• Publication Date:
  • Publication Type:
    Final Rule
  • Fed Register #:
    71:10099-10385
  • Standard Number:
  • Title:
    Occupational Exposure to Hexavalent Chromium
    [Federal Register: February 28, 2006 (Volume 71, Number 39)][Rules and Regulations]               [Page 10099-10385]
    From the Federal Register Online via GPO Access [wais.access.gpo.gov]
    [DOCID:fr28fe06-25]                         
     
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    Part II
    
    Department of Labor
    
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    Occupational Safety and Health Administration
    
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    29 CFR Parts 1910, 1915, et al.
    
    Occupational Exposure to Hexavalent Chromium; Final Rule
    
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    DEPARTMENT OF LABOR
    
    Occupational Safety and Health Administration
    
    29 CFR Parts 1910, 1915, 1917, 1918, and 1926
    
    [Docket No. H054A]
    RIN 1218-AB45
    
     
    Occupational Exposure to Hexavalent Chromium
    
    AGENCY: Occupational Safety and Health Administration (OSHA), 
    Department of Labor.
    
    ACTION: Final rule.
    
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    SUMMARY: The Occupational Safety and Health Administration (OSHA) is 
    amending the existing standard which limits occupational exposure to 
    hexavalent chromium (Cr(VI)). OSHA has determined based upon the best 
    evidence currently available that at the current permissible exposure 
    limit (PEL) for Cr(VI), workers face a significant risk to material 
    impairment of their health. The evidence in the record for this 
    rulemaking indicates that workers exposed to Cr(VI) are at an increased 
    risk of developing lung cancer. The record also indicates that 
    occupational exposure to Cr(VI) may result in asthma, and damage to the 
    nasal epithelia and skin.
        The final rule establishes an 8-hour time-weighted average (TWA) 
    exposure limit of 5 micrograms of Cr(VI) per cubic meter of air (5 
    [mu]g/m\3\). This is a considerable reduction from the previous PEL of 
    1 milligram per 10 cubic meters of air (1 mg/10 m\3\, or 100 [mu]g/
    m\3\) reported as CrO3, which is equivalent to a limit of 52 
    [mu]g/m\3\ as Cr(VI). The final rule also contains ancillary provisions 
    for worker protection such as requirements for exposure determination, 
    preferred exposure control methods, including a compliance alternative 
    for a small sector for which the new PEL is infeasible, respiratory 
    protection, protective clothing and equipment, hygiene areas and 
    practices, medical surveillance, recordkeeping, and start-up dates that 
    include four years for the implementation of engineering controls to 
    meet the PEL.
        The final standard separately regulates general industry, 
    construction, and shipyards in order to tailor requirements to the 
    unique circumstances found in each of these sectors.
        The PEL established by this rule reduces the significant risk posed 
    to workers by occupational exposure to Cr(VI) to the maximum extent 
    that is technologically and economically feasible.
    
    DATES: This final rule becomes effective on May 30, 2006. Start-up 
    dates for specific provisions are set in Sec.  1910.1026(n) for general 
    industry; Sec.  1915.1026(l) for shipyards; and Sec.  1926.1126(l) for 
    construction. However, affected parties do not have to comply with the 
    information collection requirements in the final rule until the 
    Department of Labor publishes in the Federal Register the control 
    numbers assigned by the Office of Management and Budget (OMB). 
    Publication of the control numbers notifies the public that OMB has 
    approved these information collection requirements under the Paperwork 
    Reduction Act of 1995.
    
    ADDRESSES: In compliance with 28 U.S.C. 2112(a), the Agency designates 
    the Associate Solicitor for Occupational Safety and Health, Office of 
    the Solicitor, Room S-4004, U.S. Department of Labor, 200 Constitution 
    Avenue, NW., Washington, DC 20210, as the recipient of petitions for 
    review of these standards.
    
    FOR FURTHER INFORMATION CONTACT: Mr. Kevin Ropp, Director, OSHA Office 
    of Communications, Room N-3647, U.S. Department of Labor, 200 
    Constitution Avenue, NW., Washington, DC 20210; telephone (202) 693-
    1999.
    
    SUPPLEMENTARY INFORMATION: The following table of contents lays out the 
    structure of the preamble to the final standards. This preamble 
    contains a detailed description of OSHA's legal obligations, the 
    analyses and rationale supporting the Agency's determination, including 
    a summary of and response to comments and data submitted during the 
    rulemaking.
    
    I. General
    II. Pertinent Legal Authority
    III. Events Leading to the Final Standard
    IV. Chemical Properties and Industrial Uses
    V. Health Effects
        A. Absorption, Distribution, Metabolic Reduction and Elimination
        1. Deposition and Clearance of Inhaled Cr(VI) From the 
    Respiratory Tract
        2. Absorption of Inhaled Cr(VI) Into the Bloodstream
        3. Dermal Absorption of Cr(VI)
        4. Absorption of Cr(VI) by the Oral Route
        5. Distribution of Cr(VI) in the Body
        6. Metabolic Reduction of Cr(VI)
        7. Elimination of Cr(VI) From the Body
        8. Physiologically-Based Pharmacokinetic Modeling
        9. Summary
        B. Carcinogenic Effects
        1. Evidence From Chromate Production Workers
        2. Evidence From Chromate Pigment Production Workers
        3. Evidence From Workers in Chromium Plating
        4. Evidence From Stainless Steel Welders
        5. Evidence From Ferrochromium Workers
        6. Evidence From Workers in Other Industry Sectors
        7. Evidence From Experimental Animal Studies
        8. Mechanistic Considerations
        C. Non-Cancer Respiratory Effects
        1. Nasal Irritation, Nasal Tissue Ulcerations and Nasal Septum 
    Perforations
        2. Occupational Asthma
        3. Bronchitis
        4. Summary
        D. Dermal Effects
        E. Other Health Effects
    VI. Quantitative Risk Assessment
        A. Introduction
        B. Study Selection
        1. Gibb Cohort
        2. Luippold Cohort
        3. Mancuso Cohort
        4. Hayes Cohort
        5. Gerin Cohort
        6. Alexander Cohort
        7. Studies Selected for the Quantitative Risk Assessment
        C. Quantitative Risk Assessments Based on the Gibb Cohort
        1. Environ Risk Assessments
        2. National Institute for Occupational Safety and Health (NIOSH) 
    Risk Assessment
        3. Exponent Risk Assessment
        4. Summary of Risk Assessments Based on the Gibb Cohort
        D. Quantitative Risk Assessments Based on the Luippold Cohort
        E. Quantitative Risk Assessments Based on the Mancuso, Hayes, 
    Gerin, and Alexander Cohorts
        1. Mancuso Cohort
        2. Hayes Cohort
        3. Gerin Cohort
        4. Alexander Cohort
        F. Summary of Risk Estimates Based on Gibb, Luippold, and 
    Additional Cohorts
        G. Issues and Uncertainties
        1. Uncertainty With Regard to Worker Exposure to Cr(VI)
        2. Model Uncertainty, Exposure Threshold, and Dose Rate Effects
        3. Influence of Smoking, Race, and the Healthy Worker Survivor 
    Effect
        4. Suitability of Risk Estimates for Cr(VI) Exposures in Other 
    Industries
        H. Conclusions
    VII. Significance of Risk
        A. Material Impairment of Health
        1. Lung Cancer
        2. Non-Cancer Impairments
        B. Risk Assessment
        1. Lung Cancer Risk Based on the Gibb Cohort
        2. Lung Cancer Risk Based on the Luippold Cohort
        3. Risk of Non-Cancer Impairments
        C. Significance of Risk and Risk Reduction
    VIII. Summary of the Final Economic Analysis and Regulatory 
    Flexibility Analysis
    IX. OMB Review Under the Paperwork Reduction Act of 1995
    X. Federalism
    XI. State Plans
    XII. Unfunded Mandates
    XIII. Protecting Children from Environmental Health and Safety Risks
    XIV. Environmental Impacts
    XV. Summary and Explanation of the Standards
        (a) Scope
        (b) Definitions
        (c) Permissible Exposure Limit (PEL)
        (d) Exposure Determination
        (e) Regulated Areas
        (f) Methods of Compliance
        (g) Respiratory Protection
        (h) Protective Work Clothing and Equipment
        (i) Hygiene Areas and Practices
        (j) Housekeeping
        (k) Medical Surveillance
        (l) Communication of Chromium (VI) Hazards to Employees
        (m) Recordkeeping
        (n) Dates
    XVI. Authority and Signature
    XVII. Final Standards
    
    I. General
    
        This final rule establishes a permissible exposure limit (PEL) of 5 
    micrograms of Cr(VI) per cubic meter of air (5 [mu]g/m\3\) as an 8-hour 
    time-weighted average for all Cr(VI) compounds. After consideration of 
    all comments and evidence submitted during this rulemaking, OSHA has 
    made a final determination that a PEL of 5 [mu]g/m\3\ is necessary to 
    reduce the significant health risks posed by occupational exposures to 
    Cr(VI); it is the lowest level that is technologically and economically 
    feasible for industries impacted by this rule. A full explanation of 
    OSHA's rationale for establishing this PEL is presented in the 
    following preamble sections: V (Health Effects), VI (Quantitative Risk 
    Assessment), VII (Significance of Risk), VIII (Summary of the Final 
    Economic Analysis and Regulatory Flexibility Analysis), and XV (Summary 
    and Explanation of the Standard, paragraph (c), Permissible Exposure 
    Limit).
        OSHA is establishing three separate standards covering occupational 
    exposures to Cr(VI) for: general industry (29 CFR 1910.1026); shipyards 
    (29 CFR 1915.1026), and construction (29 CFR 1926.1126). In addition to 
    the PEL, these three standards include ancillary provisions for 
    exposure determination, methods of compliance, respiratory protection, 
    protective work clothing and equipment, hygiene areas and practices, 
    medical surveillance, communication of Cr(VI) hazards to employees, 
    recordkeeping, and compliance dates. The general industry standard has 
    additional provisions for regulated areas and housekeeping. The Summary 
    and Explanation section of this preamble (Section XV, paragraphs (d) 
    through (n)) includes a full discussion of the basis for including 
    these provisions in the final standards.
        Several major changes were made to the October 4, 2004 proposed 
    rule as a result of OSHA's analysis of comments and data received 
    during the comment periods and public hearings. The major changes are 
    summarized below and are fully discussed in the Summary and Explanation 
    section of this preamble (Section XV)
        Scope. As proposed, the standards apply to occupational exposures 
    to Cr(VI) in all forms and compounds with limited exceptions. OSHA has 
    made a final determination to exclude from coverage of these final 
    standards exposures that occur in the application of pesticides 
    containing Cr(VI) (e.g., the treatment of wood with preservatives). 
    These exposures are already covered by the Environmental Protection 
    Agency. OSHA is also excluding exposures to portland cement and 
    exposures in work settings where the employer has objective data 
    demonstrating that a material containing chromium or a specific 
    process, operation, or activity involving chromium cannot release 
    dusts, fumes, or mists of Cr(VI) in concentrations at or above 0.5 
    [mu]g/m\3\ under any expected conditions of use. OSHA believes that the 
    weight of evidence in this rulemaking demonstrates that the primary 
    risk in these two exposure scenarios can be effectively addressed 
    through existing OSHA standards for personal protective equipment, 
    hygiene, hazard communication and the PELs for portland cement or 
    particulates not otherwise regulated (PNOR).
        Permissible Exposure Limit. OSHA proposed a PEL of 1 [mu]g/m\3\ but 
    has now determined that a PEL 5 [mu]g/m\3\ is the lowest level that is 
    technologically and economically feasible.
        Exposure Determination. OSHA did not include a provision for 
    exposure determination in the proposed shipyard and construction 
    standards, reasoning that the obligation to meet the proposed PEL would 
    implicitly necessitate performance-based monitoring by the employer to 
    ensure compliance with the PEL. However, OSHA was convinced by 
    arguments presented during the rulemaking that an explicit requirement 
    for exposure determination is necessary to ensure that employee 
    exposures are adequately characterized. Therefore OSHA has included a 
    provision for exposure determination for general industry, shipyards 
    and construction in the final rule. In order to provide additional 
    flexibility in characterizing employee exposures, OSHA is allowing 
    employers to choose between a scheduled monitoring option and a 
    performance-based option for making exposure determinations.
        Methods of Compliance. Under the proposed rule employers were to 
    use engineering and work practice controls to achieve the proposed PEL 
    unless the employer could demonstrate such controls are not feasible. 
    In the final rule, OSHA has retained this exception but has added a 
    provision that only requires employers to use engineering and work 
    practice controls to reduce or maintain employee exposures to 25 [mu]g/
    m\3\ when painting aircraft or large aircraft parts in the aerospace 
    industry to the extent such controls are feasible. The employer must 
    then supplement those engineering controls with respiratory protection 
    to achieve the PEL. As discussed more fully in the Summary of the Final 
    Economic Analysis and Regulatory Flexibility Analysis (Section VIII) 
    and the Summary and Explanation (Section XV) OSHA has determined that 
    this is the lowest level achievable through the use of engineering and 
    work practice controls alone for these limited operations.
        Housekeeping. In the proposed rule, cleaning methods such as 
    shoveling, sweeping, and brushing were prohibited unless they were the 
    only effective means available to clean surfaces contaminated with 
    Cr(VI). The final standard has modified this prohibition to make clear 
    only dry shoveling, sweeping and brushing are prohibited so that 
    effective wet shoveling, sweeping, and brushing would be allowed. OSHA 
    is also adding a provision that allows the use of compressed air to 
    remove Cr(VI) when no alternative method is feasible.
        Medical Surveillance. As proposed and continued in these final 
    standards, medical surveillance is required to be provided to employees 
    experiencing signs or symptoms of the adverse health effects associated 
    with Cr(VI) exposure or exposed in an emergency. In addition, for 
    general industry, employees exposed above the PEL for 30 or more days a 
    year were to be provided medical surveillance. In the final standard, 
    OSHA has changed the trigger for medical surveillance to exposure above 
    the action level (instead of the PEL) for 30 days a year to take into 
    account the existing risks at the new PEL. This provision has also been 
    extended to the standards for shipyards and construction since those 
    employers now will be required to perform an exposure determination and 
    thus will be able to determine which employees are exposed above the 
    action level 30 or more days a year.
        Communication of Hazards. In the proposed standard, OSHA specified 
    the sign for the demarcation of regulated areas in general industry and 
    the label for contaminated work clothing or equipment and Cr(VI) 
    contaminated waste and debris. The proposed standard also listed the 
    various elements to be covered for employee training. In order to 
    simplify requirements under this section of the final standard and 
    reduce confusion between this standard and the Hazard Communication 
    Standard, OSHA has removed the requirement for special signs and labels 
    and the specification of employee training elements. Instead, the final 
    standard requires that signs, labels and training be in accordance with 
    the Hazard Communication Standard (29 CFR 1910.1200). The only 
    additional training elements required in the final rule are those 
    related specifically to the contents of the final Cr(VI) standards. 
    While the final standards have removed language in the communication of 
    hazards provisions to make them more consistent with OSHA's existing 
    Hazard Communication Standard, the employers obligation to mark 
    regulated areas (where regulated areas are required), to label Cr(VI) 
    contaminated clothing and wastes, and to train on the hazards of Cr(VI) 
    have not changed.
        Recordkeeping. In the proposed standards for shipyards and 
    construction there were no recordkeeping requirements for exposure 
    records since there was not a requirement for exposure determination. 
    The final standard now requires exposure determination for shipyards 
    and construction and therefore, OSHA has also added provisions for 
    exposure records to be maintained in these final standards. In keeping 
    with its intent to be consistent with the Hazard Communication 
    Standard, OSHA has removed the requirement for training records in the 
    final standards.
        Dates. In the proposed standard, the effective date of the standard 
    was 60 days after the publication date; the start-up date for all 
    provisions except engineering controls was 90 days after the effective 
    date; and the start-up date for engineering controls was two years 
    after the effective date. OSHA believes that it is appropriate to allow 
    additional time for employers, particularly small employers, to meet 
    the requirements of the final rule. The effective and start-up dates 
    have been extended as follows: the effective date for the final rule is 
    changed to 90 days after the publication date; the start-up date for 
    all provisions except engineering controls is changed to 180 days after 
    the effective date for employers with 20 or more employees; the start-
    up date for all provisions except engineering controls is changed to 
    one year after the effective date for employers with 19 or fewer 
    employees; and the start-up date for engineering controls is changed to 
    four years after the effective date for all employers.
    
    II. Pertinent Legal Authority
    
        The purpose of the Occupational Safety and Health Act, 29 U.S.C. 
    651 et seq. ("the Act") is to,
    
    * * * assure so far as possible every working man and woman in the 
    nation safe and healthful working conditions and to preserve our 
    human resources. 29 U.S.C. 651(b).
    
        To achieve this goal Congress authorized the Secretary of Labor 
    (the Secretary) to promulgate and enforce occupational safety and 
    health standards. 29 U.S.C. 654(b) (requiring employers to comply with 
    OSHA standards), 655(a) (authorizing summary adoption of existing 
    consensus and federal standards within two years of the Act's 
    enactment), and 655(b) (authorizing promulgation, modification or 
    revocation of standards pursuant to notice and comment).
        The Act provides that in promulgating health standards dealing with 
    toxic materials or harmful physical agents, such as this standard 
    regulating occupational exposure to Cr(VI), the Secretary,
    
    * * * shall set the standard which most adequately assures, to the 
    extent feasible, on the basis of the best available evidence that no 
    employee will suffer material impairment of health or functional 
    capacity even if such employee has regular exposure to the hazard 
    dealt with by such standard for the period of his working life. 29 
    U.S.C. Sec.  655(b)(5).
    
        The Supreme Court has held that before the Secretary can promulgate 
    any permanent health or safety standard, she must make a threshold 
    finding that significant risk is present and that such risk can be 
    eliminated or lessened by a change in practices. Industrial Union 
    Dept., AFL-CIO v. American Petroleum Institute, 448 U.S. 607, 641-42 
    (1980) (plurality opinion) ("The Benzene case"). The Court further 
    observed that what constitutes "significant risk" is "not a 
    mathematical straitjacket" and must be "based largely on policy 
    considerations." The Benzene case, 448 U.S. at 655. The Court gave the 
    example that if,
    
    * * * the odds are one in a billion that a person will die from 
    cancer * * * the risk clearly could not be considered significant. 
    On the other hand, if the odds are one in one thousand that regular 
    inhalation of gasoline vapors that are 2% benzene will be fatal, a 
    reasonable person might well consider the risk significant. * * * 
    Id.
    
        OSHA standards must be both technologically and economically 
    feasible. United Steelworkers v. Marshall, 647 F.2d 1189, 1264 (D.C. 
    Cir. 1980) ("The Lead I case"). The Supreme Court has defined 
    feasibility as "capable of being done." American Textile Mfrs. Inst. 
    v. Donovan, 425 U.S. 490, 509 (1981) ("The Cotton dust case"). The 
    courts have further clarified that a standard is technologically 
    feasible if OSHA proves a reasonable possibility,
    
    * * * within the limits of the best available evidence * * * that 
    the typical firm will be able to develop and install engineering and 
    work practice controls that can meet the PEL in most of its 
    operations. See The Lead I case, 647 F.2d at 1272.
    
        With respect to economic feasibility, the courts have held that a 
    standard is feasible if it does not threaten massive dislocation to or 
    imperil the existence of the industry. See The Lead case, 647 F.2d at 
    1265. A court must examine the cost of compliance with an OSHA standard 
    "in relation to the financial health and profitability of the industry 
    and the likely effect of such costs on unit consumer prices." Id.
    
        [The] practical question is whether the standard threatens the 
    competitive stability of an industry, * * * or whether any intra-
    industry or inter-industry discrimination in the standard might 
    wreck such stability or lead to undue concentration. Id. (citing 
    Industrial Union Dept., AFL-CIO v. Hodgson, 499 F.2d 467 (D.C. Cir. 
    1974)).
    
        The courts have further observed that granting companies reasonable 
    time to comply with new PEL's may enhance economic feasibility. Id. 
    While a standard must be economically feasible, the Supreme Court has 
    held that a cost-benefit analysis of health standards is not required 
    by the Act because a feasibility analysis is. The Cotton dust case, 453 
    U.S. at 509. Finally, unlike safety standards, health standards must 
    eliminate risk or reduce it to the maximum extent that is 
    technologically and economically feasible. See International Union, 
    United Automobile, Aerospace & Agricultural Implement Workers of 
    America, UAW v. OSHA, 938 F.2d 1310, 1313 (D.C. Cir. 1991); Control of 
    Hazardous Energy Sources (Lockout/Tagout), Final rule; supplemental 
    statement of reasons, (58 FR 16612, March 30, 1993).
    
    III. Events Leading to the Final Standard
    
        OSHA's previous standards for workplace exposure to Cr(VI) were 
    adopted in 1971, pursuant to section 6(a) of the Act, from a 1943 
    American National Standards Institute (ANSI) recommendation originally 
    tissues (36 FR at 10466, 5/29/71; Ex. 20-3). OSHA's general industry 
    standard set a permissible exposure limit (PEL) of 1 mg chromium 
    trioxide per 10 m\3\ air in the workplace (1 mg/10 m\3\ 
    CrO3) as a ceiling concentration, which corresponds to a 
    concentration of 52 [mu]g/m\3\ Cr(VI). A separate rule promulgated for 
    the construction industry set an eight-hour time-weighted-average PEL 
    of 1 mg/10 m3 CrO3, also equivalent to 52 [mu]g/
    m\3\ Cr(VI), adopted from the American Conference of Governmental 
    Industrial Hygienists (ACGIH) 1970 Threshold Limit Value (TLV) (36 FR 
    at 7340, 4/17/71).
        Following the ANSI standard of 1943, other occupational and public 
    health organizations evaluated Cr(VI) as a workplace and environmental 
    hazard and formulated recommendations to control exposure. The ACGIH 
    first recommended control of workplace exposures to chromium in 1946, 
    recommending a time-weighted average Maximum Allowable Concentration 
    (later called a Threshold Limit Value) of 100 [mu]g/m\3\ for chromic 
    acid and chromates as Cr2O3 (Ex. 5-37), and later 
    classified certain Cr(VI) compounds as class A1 (confirmed human) 
    carcinogens in 1974. In 1975, the NIOSH Criteria for a Recommended 
    Standard recommended that occupational exposure to Cr(VI) compounds 
    should be limited to a 10-hour TWA of 1 [mu]g/m\3\, except for some 
    forms of Cr(VI) then believed to be noncarcinogenic (Ex. 3-92). The 
    National Toxicology Program's First Annual Report on Carcinogens 
    identified calcium chromate, chromium chromate, strontium chromate, and 
    zinc chromate as carcinogens in 1980 (Ex. 35-157).
        During the 1980s, regulatory and standards organizations came to 
    recognize Cr(VI) compounds in general as carcinogens. The Environmental 
    Protection Agency (EPA) Health Assessment Document of 1984 stated that,
    
    * * * using the IARC [International Agency for Research on Cancer] 
    classification scheme, the level of evidence available for the 
    combined animal and human data would place hexavalent chromium (Cr 
    VI) compounds into Group 1, meaning that there is decisive evidence 
    for the carcinogenicity of those compounds in humans (Ex. 19-1, p. 
    7-107).
    
        In 1988 IARC evaluated the available evidence regarding Cr(VI) 
    carcinogenicity, concluding in 1990 that
    
    * * * [t]here is sufficient evidence in humans for the 
    carcinogenicity of chromium[VI] compounds as encountered in the 
    chromate production, chromate pigment production and chromium 
    plating industries, [and] sufficient evidence in experimental 
    animals for the carcinogenicity of calcium chromate, zinc chromates, 
    strontium chromate and lead chromates (Ex. 18-3, p. 213).
    
        In September 1988, NIOSH advised OSHA to consider all Cr(VI) 
    compounds as potential occupational carcinogens (Ex. 31-22-22). ACGIH 
    now classifies water-insoluble and water-soluble Cr(IV) compounds as 
    class A1 carcinogens (Ex. 35-207). Current ACGIH standards include 
    specific 8-hour time-weighted average TLVs for calcium chromate (1 
    [mu]g/m3), lead chromate (12 [mu]g/m3), strontium 
    chromate (0.5 [mu]g/m3), and zinc chromates (10 [mu]g/
    m3), and generic TLVs for water soluble (50 [mu]g/
    m3) and insoluble (10 [mu]g/m3) forms of 
    hexavalent chromium not otherwise classified, all measured as chromium 
    (Ex. 35-207).
        In July 1993, OSHA was petitioned for an emergency temporary 
    standard to reduce occupational exposures to Cr(VI) compounds (Ex. 1). 
    The Oil, Chemical, and Atomic Workers International Union (OCAW) and 
    Public Citizen's Health Research Group (Public Citizen), citing 
    evidence that occupational exposure to Cr(VI) increases workers' risk 
    of lung cancer, petitioned OSHA to promulgate an emergency temporary 
    standard to lower the PEL for Cr(VI) compounds to 0.5 [mu]g/
    m3 as an eight-hour time-weighted average (TWA). Upon review 
    of the petition, OSHA agreed that there was evidence of increased 
    cancer risk from exposure to Cr(VI) at the existing PEL, but found that 
    the available data did not show the "grave danger" required to 
    support an emergency temporary standard (Ex. 1-C). The Agency therefore 
    denied the request for an emergency temporary standard, but initiated 
    Section 6(b)(5) rulemaking and began performing preliminary analyses 
    relevant to the rule.
        In 1997, Public Citizen petitioned the United States Court of 
    Appeals for the Third Circuit to compel OSHA to complete rulemaking 
    lowering the standard for occupational exposure to Cr(VI). The Court 
    denied Public Citizen's request, concluding that there was no 
    unreasonable delay and dismissed the suit. Oil, Chemical and Atomic 
    Workers Union and Public Citizen Health Research Group v. OSHA, 145 
    F.3d 120 (3rd Cir. 1998). Afterwards, the Agency continued its data 
    collection and analytic efforts on Cr(VI) (Ex. 35-208, p. 3). In 2002, 
    Public Citizen again petitioned the Court to compel OSHA to commence 
    rulemaking to lower the Cr(VI) standard (Ex. 31-24-1). Meanwhile on 
    August 22, 2002, OSHA published a Request for Information on Cr(VI) to 
    solicit additional information on key issues related to controlling 
    exposures to Cr(VI) (FR 67 at 54389), and on December 4, 2002 announced 
    its intent to proceed with developing a proposed standard (Ex. 35-306). 
    On December 24, 2002, the Court granted Public Citizen's petition, and 
    ordered the Agency to proceed expeditiously with a Cr(VI) standard. See 
    Public Citizen Health Research Group v. Chao, 314 F.3d 143 (3rd Cir. 
    2002)). In a subsequent order, the Court established a compressed 
    schedule for completion of the rulemaking, with deadlines of October 4, 
    2004 for publication of a proposed standard and January 18, 2006 for 
    publication of a final standard (Ex. 35-304).
        In 2003, as required by the Small Business Regulatory Enforcement 
    Act (SBREFA), OSHA initiated SBREFA proceedings, seeking the advice of 
    small business representatives on the proposed rule. The SBREFA panel, 
    including representatives from OSHA, the Small Business Administration 
    (SBA), and the Office of Management and Budget (OMB), was convened on 
    December 23, 2003. The panel conferred with representatives from small 
    entities in chemical, alloy, and pigment manufacturing, electroplating, 
    welding, aerospace, concrete, shipbuilding, masonry, and construction 
    on March 16-17, 2004, and delivered its final report to OSHA on April 
    20, 2004. The Panel's report, including comments from the small entity 
    representatives (SERS) and recommendations to OSHA for the proposed 
    rule, is available in the Cr(VI) rulemaking docket (Ex. 34). The SBREFA 
    Panel made recommendations on a variety of subjects. The most important 
    recommendations with respect to alternatives that OSHA should consider 
    included: A higher PEL than the PEL of 1; excluding cement from the 
    scope of the standard; the use of SECALs for some industries; different 
    PELS for different Hexavalent chromium compounds; a multi-year phase-in 
    to the standards; and further consideration to approaches suited to the 
    special conditions of the maritime and construction industries. OSHA 
    has adapted many of these recommendations: The PEL is now 5; cement has 
    been excluded from the scope of the standard; a compliance alternative, 
    similar to a SECAL, has been used in aerospace industry; the standard 
    allows four years to phase in engineering controls; and a new 
    performance based monitoring approach for all industries, among other 
    changes, all of which should make it easier for all
    industries with changing work place conditions to meet the standard in 
    a cost effective way. A full discussion of all of the recommendations, 
    and OSHA's responses to them, is provided in Section VIII of this 
    Preamble.
        In addition to undertaking SBREFA proceedings, in early 2004, OSHA 
    provided the Advisory Committee on Construction Safety and Health 
    (ACCSH) and the Maritime Advisory Committee on Occupational Safety and 
    Health (MACOSH) with copies of the draft proposed rule for review. OSHA 
    representatives met with ACCSH in February 2004 and May 2004 to discuss 
    the rulemaking and receive their comments and recommendations. On 
    February 13, 2004, ACCSH recommended that portland cement should be 
    included within the scope of the proposed standard (Ex. 35-307, pp. 
    288-293) and that identical PELs should be set for construction, 
    maritime, and general industry (Ex. 35-307, pp. 293-297). On May 18, 
    2004, ACCSH recommended that the construction industry should be 
    included in the current rulemaking, and affirmed its earlier 
    recommendation regarding portland cement. OSHA representatives met with 
    MACOSH in March 2004. On March 3, 2004, MACOSH collected and forwarded 
    additional exposure monitoring data to OSHA to help the Agency better 
    evaluate exposures to Cr(VI) in shipyards (Ex. 35-309, p. 208). MACOSH 
    also recommended a separate Cr(VI) standard for the maritime industry, 
    arguing that maritime involves different exposures and requires 
    different means of exposure control than general industry and 
    construction (Ex. 35-309, p. 227).
        In accordance with the Court's rulemaking schedule, OSHA published 
    the proposed standard for hexavalent chromium on October 4, 2004 (69 FR 
    at 59306). The proposal included a notice of public hearing in 
    Washington, DC (69 FR at 59306, 59445-59446). The notice also invited 
    interested persons to submit comments on the proposal until January 3, 
    2005. In the proposal, OSHA solicited public input on 65 issues 
    regarding the human health risks of Cr(VI) exposure, the impact of the 
    proposed rule on Cr(VI) users, and other issues of particular interest 
    to the Agency (69 FR at 59306-59312).
        OSHA convened the public hearing on February 1, 2005, with 
    Administrative Law Judges John M. Vittone and Thomas M. Burke 
    presiding. At the conclusion of the hearing on February 15, 2005, Judge 
    Burke set a deadline of March 21, 2005, for the submission of post 
    hearing comments, additional information and data relevant to the 
    rulemaking, and a deadline of April 20, 2005, for the submission of 
    additional written comments, arguments, summations, and briefs. A wide 
    range of employees, employers, union representatives, trade 
    associations, government agencies and other interested parties 
    participated in the public hearing or contributed written comments. 
    Issues raised in their comments and testimony are addressed in the 
    relevant sections of this preamble (e.g., comments on the risk 
    assessment are discussed in section VI; comments on the benefits 
    analysis in section VIII). On December 22, 2005, OSHA filed a motion 
    with the U.S. Court of Appeals for the Third Circuit requesting an 
    extension of the court-mandated deadline for the publication of the 
    final rule by six weeks, to February 28, 2006 (Ex. 48-13). The Court 
    granted the request on January 17, 2006 (Ex. 48-15).
        As mandated by the Act, the final standard on occupational exposure 
    to hexavalent chromium is based on careful consideration of the entire 
    record of this proceeding, including materials discussed or relied upon 
    in the proposal, the record of the hearing, and all written comments 
    and exhibits received.
        OSHA has developed separate final standards for general industry, 
    shipyards, and the construction industry. The Agency has concluded that 
    excess exposure to Cr(VI) in any form poses a significant risk of 
    material impairment to the health of workers, by causing or 
    contributing to adverse health effects including lung cancer, non-
    cancer respiratory effects, and dermal effects. OSHA determined that 
    the TWA PEL should not be set above 5 [mu]g/m3 based on the 
    evidence in the record and its own quantitative risk assessment. The 
    TWA PEL of 5 [mu]g/m3 reduces the significant risk posed to 
    workers by occupational exposure to Cr(VI) to the maximum extent that 
    is technologically and economically feasible. (See discussion of the 
    PEL in Section XV below.)
    
    IV. Chemical Properties and Industrial Uses
    
        Chromium is a metal that exists in several oxidation or valence 
    states, ranging from chromium (-II) to chromium (+VI). The elemental 
    valence state, chromium (0), does not occur in nature. Chromium 
    compounds are very stable in the trivalent state and occur naturally in 
    this state in ores such as ferrochromite, or chromite ore 
    (FeCr2O4). The hexavalent, Cr(VI) or chromate, is 
    the second most stable state. It rarely occurs naturally; most Cr(VI) 
    compounds are man made.
        Chromium compounds in higher valence states are able to undergo 
    "reduction" to lower valence states; chromium compounds in lower 
    valence states are able to undergo "oxidation" to higher valence 
    states. Thus, Cr(VI) compounds can be reduced to Cr(III) in the 
    presence of oxidizable organic matter. Chromium can also be reduced in 
    the presence of inorganic chemicals such as iron.
        Chromium does exist in less stable oxidation (valence) states such 
    as Cr(II), Cr(IV), and Cr(V). Anhydrous Cr(II) salts are relatively 
    stable, but the divalent state (II, or chromous) is generally 
    relatively unstable and is readily oxidized to the trivalent (III or 
    chromic) state. Compounds in valence states such as (IV) and (V) 
    usually require special handling procedures as a result of their 
    instability. Cr(IV) oxide (CrO2) is used in magnetic 
    recording and storage devices, but very few other Cr(IV) compounds have 
    industrial use. Evidence exists that both Cr(IV) and Cr(V) are formed 
    as transient intermediates in the reduction of Cr(VI) to Cr(III) in the 
    body.
        Chromium (III) is also an essential nutrient that plays a role in 
    glucose, fat, and protein metabolism by causing the action of insulin 
    to be more effective. Chromium picolinate, a trivalent form of chromium 
    combined with picolinic acid, is used as a dietary supplement, because 
    it is claimed to speed metabolism.
        Elemental chromium and the chromium compounds in their different 
    valence states have various physical and chemical properties, including 
    differing solubilities. Most chromium species are solid. Elemental 
    chromium is a steel gray solid, with high melting and boiling points 
    (1857 [deg]C and 2672 [deg]C, respectively), and is insoluble in water 
    and common organic solvents. Chromium (III) chloride is a violet or 
    purple solid, with high melting and sublimation points (1150 [deg]C and 
    1300 [deg]C, respectively), and is slightly soluble in hot water and 
    insoluble in common organic solvents. Ferrochromite is a brown-black 
    solid; chromium (III) oxide is a green solid; and chromium (III) 
    sulfate is a violet or red solid, insoluble in water and slightly 
    soluble in ethanol. Chromium (III) picolinate is a ruby red crystal 
    soluble in water (1 part per million at 25 [deg]C). Chromium (IV) oxide 
    is a brown-black solid that decomposes at 300 [deg]C and is insoluble 
    in water.
        Cr(VI) compounds have mostly lemon yellow to orange to dark red 
    hues. They are typically crystalline, granular, or powdery although one 
    compound (chromyl chloride) exists in liquid form. For example, chromyl 
    chloride is a dark red liquid that decomposes into chromate ion and 
    hydrochloric acid in water. Chromic acids are dark red crystals that are 
    very soluble in water. Other examples of soluble chromates are sodium 
    chromate (yellow crystals) and sodium dichromate (reddish to bright orange 
    crystals). Lead chromate oxide is typically a red crystalline powder. Zinc 
    chromate is typically seen as lemon yellow crystals which decompose in 
    hot water and are soluble in acids and liquid ammonia. Other chromates 
    such as barium, calcium, lead, strontium, and zinc chromates vary in 
    color from light yellow to greenish yellow to orange-yellow and exist 
    in solid form as crystals or powder.
        The Color Pigments Manufacturers Association (CPMA) provided 
    additional information on lead chromate and some other chromates used 
    in their pigments (Ex. 38-205, pp. 12-13). CPMA describes two main lead 
    chromate color groups: the chrome yellow pigments and the orange to red 
    varieties known as molybdate orange pigments. The chrome yellow 
    pigments are solid solution crystal compositions of lead chromate and 
    lead sulfate. Molybdate orange pigments are solid solution crystal 
    compositions of lead chromate, lead sulfate, and lead molybdate (Ex. 
    38-205, p. 12). CPMA also describes a basic lead chromate called 
    "chrome orange," and a lead chromate precipitated "onto a core" of 
    silica (Ex. 38-205, p. 13).
        OSHA re-examined available information on solubility values in 
    light of comments from the CPMA and Dominion Color Corporation (DCC) on 
    qualitative solubility designations and CPMA's claim of low 
    bioavailability of lead chromate due to its extremely low solubility 
    (Exs. 38-201-1, p. 4; 38-205, p. 95). There was not always agreement or 
    consistency with the qualitative assignments of solubilities. 
    Quantitative values for the same compound also differ depending on the 
    source of information.
        The Table IV-1 is the result of OSHA's re-examination of 
    quantitative water solubility values and qualitative designations. 
    Qualitative designations as well as quantitative values are listed as 
    they were provided by the source. As can be seen by the Table IV-1, 
    qualitative descriptions vary by the descriptive terminology chosen by 
    the source.
    BILLING CODE 4510-26-P
Table IV-1

 

Table IV-1 Part 2

 

    
    BILLING CODE 4510-26-C
        OSHA has made some generalizations to describe the water 
    solubilities of chromates in subsequent sections of this Federal 
    Register notice. OSHA has divided Cr(VI) compounds and mixtures into 
    three categories based on solubility values. Compounds and mixtures 
    with water solubilities less than 0.01 g/l are referred to as water 
    insoluble. Compounds and mixtures between 0.01 g/l and 500 g/l are 
    referred to as slightly soluble. Compounds and mixtures with water 
    solubility values of 500 g/l or greater are referred to as highly 
    water soluble. It should be noted that these boundaries for insoluble, 
    slightly soluble, and highly soluble are arbitrary designations for the 
    sake of further description elsewhere in this document. Quantitative 
    values take precedence over qualitative designations. For example, zinc 
    chromates would be slightly soluble where their solubility values exceed 0.01 g/l.
        Some major users of chromium are the metallurgical, refractory, and 
    chemical industries. Chromium is used by the metallurgical industry to 
    produce stainless steel, alloy steel, and nonferrous alloys. Chromium 
    is alloyed with other metals and plated on metal and plastic substrates 
    to improve corrosion resistance and provide protective coatings for 
    automotive and equipment accessories. Welders use stainless steel 
    welding rods when joining metal parts.
        Cr(VI) compounds are widely used in the chemical industry in 
    pigments, metal plating, and chemical synthesis as ingredients and 
    catalysts. Chromates are used as high quality pigments for textile 
    dyes, paints, inks, glass, and plastics. Cr(VI) can be produced during 
    welding operations even if the chromium was originally present in 
    another valence state. While Cr(VI) is not intentionally added to 
    portland cement, it is often present as an impurity.
        Occupational exposures to Cr(VI) can occur from inhalation of mists 
    (e.g., chrome plating, painting), dusts (e.g., inorganic pigments), or 
    fumes (e.g., stainless steel welding), and from dermal contact (e.g., 
    cement workers).
        There are about thirty major industries and processes where Cr(VI) 
    is used. These include producers of chromates and related chemicals 
    from chromite ore, electroplating, welding, painting, chromate pigment 
    production and use, steel mills, and iron and steel foundries. A 
    detailed discussion of the uses of Cr(VI) in industry is found in 
    Section VIII of this preamble.
    
    V. Health Effects
    
        This section summarizes key studies of adverse health effects 
    resulting from exposure to hexavalent chromium (Cr(VI)) in humans and 
    experimental animals, as well as information on the fate of Cr(VI) in 
    the body and laboratory research that relates to its toxic mode of 
    action. The primary health impairments from workplace exposure to 
    Cr(VI) are lung cancer, asthma, and damage to the nasal epithelia and 
    skin. While this chapter on health effects does not describe all of the 
    many studies that have been conducted on Cr(VI) toxicity, it includes a 
    selection of those that are relevant to the rulemaking and 
    representative of the scientific literature on Cr(VI) health effects.
    
    A. Absorption, Distribution, Metabolic Reduction and Elimination
    
        Although chromium can exist in a number of different valence 
    states, Cr(VI) is the form considered to be the greatest health risk. 
    Cr(VI) enters the body by inhalation, ingestion, or absorption through 
    the skin. For occupational exposure, the airways and skin are the 
    primary routes of uptake. The following discussion summarizes key 
    aspects of Cr(VI) uptake, distribution, metabolism, and elimination.
    
    1. Deposition and Clearance of Inhaled Cr(VI) From the Respiratory 
    Tract
    
        Various anatomical, physical and physiological factors determine 
    both the fractional and regional deposition of inhaled particulate 
    matter. Due to the airflow patterns in the lung, more particles tend to 
    deposit at certain preferred regions in the lung. It is therefore 
    possible to have a buildup of chromium at certain sites in the 
    bronchial tree that could create areas of very high chromium 
    concentration. A high degree of correspondence between the efficiency 
    of particle deposition and the frequency of bronchial tumors at sites 
    in the upper bronchial tree was reported in research by Schlesinger and 
    Lippman that compared the distribution of cancer sites in published 
    reports of primary bronchogenic tumors with experimentally determined 
    particle deposition patterns (Ex. 35-102).
        Large inhaled particles (>5 [mu]m) are efficiently removed from the 
    air-stream in the extrathoracic region (Ex. 35-175). Particles greater 
    than 2.5 [mu]m are generally deposited in the tracheobronchial regions, 
    whereas particles less than 2.5 [mu]m are generally deposited in the 
    pulmonary region. Some larger particles (>2.5 [mu]m) can reach the 
    pulmonary region. The mucociliary escalator predominantly clears 
    particles that deposit in the extrathoracic and the tracheobronchial 
    region of the lung. Individuals exposed to high particulate levels of 
    Cr(VI) may also have altered respiratory mucociliary clearance. 
    Particulates that reach the alveoli can be absorbed into the 
    bloodstream or cleared by phagocytosis.
    2. Absorption of Inhaled Cr(VI) Into the Bloodstream
        The absorption of inhaled chromium compounds depends on a number of 
    factors, including physical and chemical properties of the particles 
    (oxidation state, size, solubility) and the activity of alveolar 
    macrophages (Ex. 35-41). The hexavalent chromate anions 
    (CrO4)2- enter cells via facilitated diffusion 
    through non-specific anion channels (similar to phosphate and sulfate 
    anions). As demonstrated in research by Suzuki et al., a portion of 
    water soluble Cr(VI) is rapidly transported to the bloodstream in rats 
    (Ex. 35-97). Rats were exposed to 7.3-15.9 mg Cr(VI)/m\3\ as potassium 
    dichromate for 2-6 hours. Following exposure to Cr(VI), the ratio of 
    blood chromium/lung chromium was 1.440.30 at 0.5 hours, 
    0.810.10 at 18 hours, 0.850.20 at 48 hours, and 
    0.960.22 at 168 hours after exposure.
        Once the Cr(VI) particles reach the alveoli, absorption into the 
    bloodstream is greatly dependent on solubility. More soluble chromates 
    are absorbed faster than water insoluble chromates, while insoluble 
    chromates are poorly absorbed and therefore have longer resident time 
    in the lungs. This effect has been demonstrated in research by Bragt 
    and van Dura on the kinetics of three Cr(VI) compounds: highly soluble 
    sodium chromate, slightly soluble zinc chromate and water insoluble 
    lead chromate (Ex. 35-56). They instilled \51\chromium-labeled 
    compounds (0.38 mg Cr(VI)/kg as sodium chromate, 0.36 mg Cr(VI)/kg as 
    zinc chromate, or 0.21 mg Cr(VI)/kg as lead chromate) intratracheally 
    in rats. Peak blood levels of \51\chromium were reached after 30 
    minutes for sodium chromate (0.35 [mu]g chromium/ml), and after 24 
    hours for zinc chromate (0.60 [mu]g chromium/ml) and lead chromate 
    (0.007 [mu]g chromium/ml). At 30 minutes after administration, the 
    lungs contained 36, 25, and 81% of the respective dose of the sodium, 
    zinc, and lead chromate. On day six, >80% of the dose of all three 
    compounds had been cleared from the lungs, during which time the 
    disappearance from lungs followed linear first-order kinetics. The 
    residual amount left in the lungs on day 50 or 51 was 3.0, 3.9, and 
    13.9%, respectively. From these results authors concluded that zinc 
    chromate, which is less soluble than sodium chromate, is more slowly 
    absorbed from the lungs. Lead chromate was more poorly and slowly 
    absorbed, as indicated by very low levels in blood and greater 
    retention in the lungs. The authors also noted that the kinetics of 
    sodium and zinc chromates were very similar. Zinc chromate, which is 
    less soluble than sodium chromate, was slowly absorbed from the lung, 
    but the maximal blood levels were higher than those resulting from an 
    equivalent dose of sodium chromate. The authors believe that this was 
    probably the result of hemorrhages macroscopically visible in the lungs 
    of zinc chromate-treated rats 24 hours following intratracheal administration. 
    Boeing Corporation commented that this study does not show that the highly water 
    soluble sodium chromate is cleared more rapidly or retained in the lung for 
    shorter periods than the less soluble zinc chromate (Ex. 38-106-2, p. 
    18-19). This comment is addressed in the Carcinogenic Effects 
    Conclusion Section V.B.9 dealing with the carcinogenicity of slightly 
    soluble Cr(VI) compounds.
        Studies by Langard et al. and Adachi et al. provide further 
    evidence of absorption of chromates from the lungs (Exs. 35-93; 189). 
    In Langard et al., rats exposed to 2.1 mg Cr(VI)/m\3\ as zinc chromate 
    for 6 hours/day achieved steady state concentrations in the blood after 
    4 days of exposure (Ex. 35-93). Adachi et al. studied rats that were 
    subject to a single inhalation exposure to chromic acid mist generated 
    from electroplating at a concentration of 3.18 mg Cr(VI)/m\3\ for 30 
    minutes which was then rapidly absorbed from the lungs (Ex. 189). The 
    amount of chromium in the lungs of these rats declined from 13.0 mg 
    immediately after exposure to 1.1 mg after 4 weeks, with an overall 
    half-life of five days.
        Several other studies have reported absorption of chromium from the 
    lungs after intratracheal instillation (Exs. 7-9; 9-81; Visek et al. 
    1953 as cited in Ex. 35-41). These studies indicated that 53-85% of 
    Cr(VI) compounds (particle size < 5 [mu]m) were cleared from the lungs 
    by absorption into the bloodstream or by mucociliary clearance in the 
    pharynx; the rest remained in the lungs. Absorption of Cr(VI) from the 
    respiratory tract of workers has been shown in several studies that 
    identified chromium in the urine, serum and red blood cells following 
    occupational exposure (Exs. 5-12; 35-294; 35-84).
        Evidence indicates that even chromates encapsulated in a paint 
    matrix may be released in the lungs (Ex. 31-15, p. 2). In a study of 
    chromates in aircraft spray paint, LaPuma et al. measured the mass of 
    Cr(VI) released from particles into water originating from three types 
    of paint particles: solvent-borne epoxy (25% strontium chromate 
    (SrCrO4)), water-borne epoxy (30% SrCrO4) and 
    polyurethane (20% SrCrO4) (Ex. 31-2-1). The mean fraction of 
    Cr(VI) released into the water after one and 24 hours for each primer 
    averaged: 70% and 85% (solvent epoxy), 74% and 84% (water epoxy), and 
    94% and 95% (polyurethane). Correlations between particle size and the 
    fraction of Cr(VI) released indicated that smaller particles (< 5 [mu]m) 
    release a larger fraction of Cr(VI) versus larger particles (>5 [mu]m). 
    This study demonstrates that the paint matrix only modestly hinders 
    Cr(VI) release into a fluid, especially with smaller particles. Larger 
    particles, which contain the majority of Cr(VI) due to their size, 
    appear to release proportionally less Cr(VI) (as a percent of total 
    Cr(VI)) than smaller particles. Some commenters suggested that the 
    above research shows that the slightly soluble Cr(VI) from aircraft 
    spray paint is less likely to reach and be absorbed in the 
    bronchoalveolar region of the lung than a highly soluble Cr(VI) form, 
    such as chromic acid aerosol (Exs. 38-106-2; 39-43, 44-33). This issue 
    is further discussed in the Carcinogenic Effects Conclusion Section 
    V.B.9.a and in the Quantitative Risk Assessment Section VI.G.4.a.
        A number of questions remain unanswered regarding encapsulated 
    Cr(VI) and bioavailability from the lung. There is a lack of detailed 
    information on the efficiency of encapsulation and whether all of the 
    chromate molecules are encapsulated. The stability of the encapsulated 
    product in physiological and environmental conditions over time has not 
    been demonstrated. Finally, the fate of inhaled encapsulated Cr(VI) in 
    the respiratory tract and the extent of distribution in systemic 
    tissues has not been thoroughly studied.
    3. Dermal Absorption of Cr(VI)
        Both human and animal studies demonstrate that Cr(VI) compounds are 
    absorbed after dermal exposure. Dermal absorption depends on the 
    oxidation state of chromium, the vehicle and the integrity of the skin. 
    Cr(VI) readily traverses the epidermis to the dermis (Exs. 9-49; 309). 
    The histological distribution of Cr(VI) within intact human skin was 
    studied by Liden and Lundberg (Ex. 35-80). They applied test solutions 
    of potassium dichromate in petrolatum or in water as occluded circular 
    patches of filter paper to the skin. Results with potassium dichromate 
    in water revealed that Cr(VI) penetrated beyond the dermis and 
    penetration reached steady state with resorption by the lymph and blood 
    vessels by 5 hours. About 10 times more chromium penetrated when 
    potassium dichromate was applied in petrolatum than when applied in 
    water, indicating that organic solvents facilitate the absorption of 
    Cr(VI) from the skin. Research by Baranowska-Dutkiewicz also 
    demonstrated that the absorption rates of sodium chromate solutions 
    from the occluded forearm skin of volunteers increase with increasing 
    concentration (Ex. 35-75). The rates were 1.1 [mu]g Cr(VI)/cm\2\/hour 
    for a 0.01 molar solution, 6.4 [mu]g Cr(VI)/cm\2\/hour for a 0.1 molar 
    solution, and 10 [mu]g Cr(VI)/cm\2\/hour for a 0.2 molar solution.
        Additional studies have demonstrated that the absorption of Cr(VI) 
    compounds can take place through the dermal route. Using volunteers, 
    Mali found that potassium dichromate penetrates the intact epidermis 
    (Exs. 9-49; 35-41). Wahlberg and Skog demonstrated the presence of 
    chromium in the blood, spleen, bone marrow, lymph glands, urine and 
    kidneys of guinea pigs dermally exposed to \51\chromium labeled Cr(VI) 
    compounds (Ex. 35-81).
    4. Absorption of Cr(VI) by the Oral Route
        Inhaled Cr(VI) can enter the digestive tract as a result of 
    mucocilliary clearance and swallowing. Studies indicate Cr(VI) is 
    absorbed from the gastrointestinal tract. For example, in a study by 
    Donaldson and Barreras, the six-day fecal and 24-hour urinary excretion 
    patterns of radioactivity in groups of six volunteers given Cr(VI) as 
    sodium chromate labeled with \51\chromium indicated that at least 2.1% 
    of the Cr(VI) was absorbed. After intraduodenal administration at least 
    10% of the Cr(VI) compound was absorbed. These studies also 
    demonstrated that Cr(VI) compounds are reduced to Cr(III) compounds in 
    the stomach, thereby accounting for the relatively poor 
    gastrointestinal absorption of orally administered Cr(VI) compounds 
    (Exs. 35-96; 35-41). In the gastrointestinal tract, Cr(VI) can be 
    reduced to Cr(III) by gastric juices, which is then poorly absorbed 
    (Underwood, 1971 as cited in Ex. 19-1; Ex. 35-85).
        In a study conducted by Clapp et al., treatment of rats by gavage 
    with an unencapsulated lead chromate pigment or with a silica-
    encapsulated lead chromate pigment resulted in no measurable blood 
    levels of chromium (measured as Cr(III), detection limit = 10 [mu]g/L) 
    after two or four weeks of treatment or after a two-week recovery 
    period. However, kidney levels of chromium (measured as Cr(III)) were 
    significantly higher in the rats that received the unencapsulated 
    pigment when compared to the rats that received the encapsulated 
    pigment, indicating that silica encapsulation may reduce the 
    gastrointestinal bioavailability of chromium from lead chromate 
    pigments (Ex. 11-5). This study does not address the bioavailability of 
    encapsulated chromate pigments from the lung where residence time could 
    be different.
    5. Distribution of Cr(VI) in the Body
        Once in the bloodstream, Cr(VI) is taken up into erythrocytes, 
    where it is reduced to lower oxidation states and forms chromium 
    protein complexes during reduction (Ex. 35-41). Once complexed with 
    protein, chromium cannot leave the cell and chromium ions are unable to 
    repenetrate the membrane and move back into the plasma (Exs. 7-6; 7-7; 
    19-1; 35-41; 35-52). Once inside the blood cell, the intracellular 
    Cr(VI) reduction to Cr(III) depletes Cr(VI) concentration in the red 
    blood cell (Ex. 35-89). This serves to enhance diffusion of Cr(VI) from 
    the plasma into the erythrocyte resulting in very low plasma levels of 
    Cr(VI). It is also believed that the rate of uptake of Cr(VI) by red 
    blood cells may not exceed the rate at which they reduce Cr(VI) to 
    Cr(III) (Ex. 35-99). The higher tissue levels of chromium after 
    administration of Cr(VI) than after administration of Cr(III) reflect 
    the greater tendency of Cr(VI) to traverse plasma membranes and bind to 
    intracellular proteins in the various tissues, which may explain the 
    greater degree of toxicity associated with Cr(VI) (MacKenzie et al. 
    1958 as cited in 35-52; Maruyama 1982 as cited in 35-41; Ex. 35-71).
        Examination of autopsy tissues from chromate workers who were 
    occupationally exposed to Cr(VI) showed that the highest chromium 
    levels were in the lungs. The liver, bladder, and bone also had 
    chromium levels above background. Mancuso examined tissues from three 
    individuals with lung cancer who were exposed to chromium in the 
    workplace (Ex. 124). One was employed for 15 years as a welder, the 
    second and third worked for 10.2 years and 31.8 years, respectively, in 
    ore milling and preparations and boiler operations. The cumulative 
    chromium exposures for the three workers were estimated to be 3.45, 
    4.59, and 11.38 mg/m\3\-years, respectively. Tissues from the first 
    worker were analyzed 3.5 years after last exposure, the second worker 
    18 years after last exposure, and the third worker 0.6 years after last 
    exposure. All tissues from the three workers had elevated levels of 
    chromium, with the possible exception of neural tissues. Levels were 
    orders of magnitude higher in the lungs when compared to other tissues. 
    Similar results were also reported in autopsy studies of people who may 
    have been exposed to chromium in the workplace as well as chrome 
    platers and chromate refining workers (Exs. 35-92; 21-1; 35-74; 35-88).
        Animal studies have shown similar distribution patterns after 
    inhalation exposure. For example, a study by Baetjer et al. 
    investigated the distribution of Cr(VI) in guinea pigs after 
    intratracheal instillation of slightly soluble potassium dichromate 
    (Ex. 7-8). At 24 hours after instillation, 11% of the original dose of 
    chromium from potassium dichromate remained in the lungs, 8% in the 
    erythrocytes, 1% in plasma, 3% in the kidney, and 4% in the liver. The 
    muscle, skin, and adrenal glands contained only a trace. All tissue 
    concentrations of chromium declined to low or nondetectable levels in 
    140 days, with the exception of the lungs and spleen.
    6. Metabolic Reduction of Cr(VI)
        Cr(VI) is reduced to Cr(III) in the lungs by a variety of reducing 
    agents. This serves to limit uptake into lung cells and absorption into 
    the bloodstream. Cr(V) and Cr(IV) are transient intermediates in this 
    process. The genotoxic effects produced by the Cr(VI) are related to 
    the reduction process and are further discussed in the section V.B.8 on 
    Mechanistic Considerations.
        In vivo and in vitro experiments in rats indicated that, in the 
    lungs, Cr(VI) can be reduced to Cr(III) by ascorbate and glutathione. A 
    study by Suzuki and Fukuda showed that the reduction of Cr(VI) by 
    glutathione is slower than the reduction by ascorbate (Ex. 35-65). 
    Other studies have reported the reduction of Cr(VI) to Cr(III) by 
    epithelial lining fluid (ELF) obtained from the lungs of 15 individuals 
    by bronchial lavage. The average overall reduction capacity was 0.6 
    [mu]g Cr(VI)/mg of ELF protein. In addition, cell extracts made from 
    pulmonary alveolar macrophages derived from five healthy male 
    volunteers were able to reduce an average of 4.8 [mu]g Cr(VI)/10\6\ 
    cells or 14.4 [mu]g Cr(VI)/mg protein (Ex. 35-83). Postmitochondrial 
    (S12) preparations of human lung cells (peripheral lung parenchyma and 
    bronchial preparations) were also able to reduce Cr(VI) to Cr(III) (De 
    Flora et al. 1984 as cited in Ex. 35-41).
    7. Elimination of Cr(VI) From the Body
        Excretion of chromium from Cr(VI) compounds is predominantly in the 
    urine, although there is some biliary excretion into the feces. In both 
    urine and feces, the chromium is present as low molecular weight 
    Cr(III) complexes. Absorbed chromium is excreted from the body in a 
    rapid phase representing clearance from the blood and at least two 
    slower phases representing clearance from tissues. Urinary excretion 
    accounts for over 50% of eliminated chromium (Ex. 35-41). Although 
    chromium is excreted in urine and feces, the intestine plays only a 
    minor part in chromium elimination, representing only about 5% of 
    elimination from the blood (Ex. 19-1). Normal urinary levels of 
    chromium in humans have been reported to range from 0.24-1.8 [mu]g/L 
    with a median level of 0.4 [mu]g/L (Ex. 35-79). Humans exposed to 0.01-
    0.1 mg Cr(VI)/m\3\ as potassium dichromate (8-hour time-weighted 
    average) had urinary excretion levels from 0.0247 to 0.037 mg Cr(III)/
    L. Workers exposed mainly to Cr(VI) compounds had higher urinary 
    chromium levels than workers exposed primarily to Cr(III) compounds. An 
    analysis of the urine did not detect Cr(VI), indicating that Cr(VI) was 
    rapidly reduced before excretion (Exs. 35-294; 5-48).
        A half-life of 15-41 hours has been estimated for chromium in urine 
    for four welders using a linear one-compartment kinetic model (Exs. 35-
    73; 5-52; 5-53). Limited work on modeling the absorption and deposition 
    of chromium indicates that adipose and muscle tissue retain chromium at 
    a moderate level for about two weeks, while the liver and spleen store 
    chromium for up to 12 months. The estimated half-life for whole body 
    chromium retention is 22 days for Cr(VI) (Ex. 19-1). The half-life of 
    chromium in the human lung is 616 days, which is similar to the half-
    life in rats (Ex. 7-5).
        Elimination of chromium was shown to be very slow in rats exposed 
    to 2.1 mg Cr(VI)/m\3\ as zinc chromate six hours/day for four days. 
    Urinary levels of chromium remained almost constant for four days after 
    exposure and then decreased (Ex. 35-93). After intratracheal 
    administration of sodium dichromate to rats, peak urinary chromium 
    concentrations were observed at six hours, after which the urinary 
    concentrations declined rapidly (Ex. 35-94). The more prolonged 
    elimination of the moderately soluble zinc chromate as compared to the 
    more soluble sodium dichromate is consistent with the influence of 
    Cr(VI) solubility on absorption from the respiratory tract discussed 
    earlier.
        Information regarding the excretion of chromium in humans after 
    dermal exposure to chromium or its compounds is limited. Fourteen days 
    after application of a salve containing water soluble potassium 
    chromate, which resulted in skin necrosis and sloughing at the 
    application site, chromium was found at 8 mg/L in the urine and 0.61 
    mg/100 g in the feces of one individual (Brieger 1920 as cited in Ex. 
    19-1). A slight increase over background levels of urinary chromium was 
    observed in four subjects submersed in a tub of chlorinated water containing 
    22 mg Cr(VI)/L as potassium dichromate for three hours (Ex. 31-22-6). For 
    three of the four subjects, the increase in urinary chromium excretion 
    was less than 1 [mu]g/day over the five-day collection period. Chromium 
    was detected in the urine of guinea pigs after radiolabeled sodium 
    chromate solution was applied to the skin (Ex. 35-81).
    8. Physiologically-Based Pharmacokinetic Modeling
        Physiologically-based pharmacokinetic (PBPK) models have been 
    developed that simulate absorption, distribution, metabolism, and 
    excretion of Cr(VI) and Cr(III) compounds in humans (Ex. 35-95) and 
    rats (Exs. 35-86; 35-70). The original model (Ex. 35-86) evolved from a 
    similar model for lead, and contained compartments for the lung, GI 
    tract, skin, blood, liver, kidney, bone, well-perfused tissues, and 
    slowly perfused tissues. The model was refined to include two lung 
    subcompartments for chromium, one of which allowed inhaled chromium to 
    enter the blood and GI tract and the other only allowed chromium to 
    enter the GI tract (Ex. 35-70). Reduction of Cr(VI) to Cr(III) was 
    considered to occur in every tissue compartment except bone.
        The model was developed from several data sets in which rats were 
    dosed with Cr(VI) or Cr(III) intravenously, orally or by intratracheal 
    instillation, because different distribution and excretion patterns 
    occur depending on the route of administration. In most cases, the 
    model parameters (e.g., tissue partitioning, absorption, reduction 
    rates) were estimated by fitting model simulations to experimental 
    data. The optimized rat model was validated against the 1978 Langard 
    inhalation study (Ex. 35-93). Chromium blood levels were overpredicted 
    during the four-day inhalation exposure period, but blood levels during 
    the post-exposure period were well predicted by the model. The model-
    predicted levels of liver chromium were high, but other tissue levels 
    were closely estimated.
        A human PBPK model recently developed by O'Flaherty et al. is able 
    to predict tissue levels from ingestion of Cr(VI) (Ex. 35-95). The 
    model incorporates differential oral absorption of Cr(VI) and Cr(III), 
    rapid reduction of Cr(VI) to Cr(III) in major body fluids and tissues, 
    and concentration-dependent urinary clearance. The model does not 
    include a physiologic lung compartment, but can be used to estimate an 
    upper limit on pulmonary absorption of inhaled chromium. The model was 
    calibrated against blood and urine chromium concentration data from a 
    group of controlled studies in which adult human volunteers drank 
    solutions of soluble Cr(III) or Cr(VI).
        PBPK models are increasingly used in risk assessments, primarily to 
    predict the concentration of a potentially toxic chemical that will be 
    delivered to any given target tissue following various combinations of 
    route, dose level, and test species. Further development of the 
    respiratory tract portion of the model, specific Cr(VI) rate data on 
    extracellular reduction and uptake into lung cells, and more precise 
    understanding of critical pathways inside target cells would improve 
    the model value for risk assessment purposes.
    9. Summary
        Based on the studies presented above, evidence exists in the 
    literature that shows Cr(VI) can be systemically absorbed by the 
    respiratory tract. The absorption of inhaled chromium compounds depends 
    on a number of factors, including physical and chemical properties of 
    the particles (oxidation state, size, and solubility), the reduction 
    capacity of the ELF and alveolar macrophages and clearance by the 
    mucocliary escalator and phagocytosis. Highly water soluble Cr(VI) 
    compounds (e.g. sodium chromate) enter the bloodstream more readily 
    than highly insoluble Cr(VI) compounds (e.g. lead chromate). However, 
    insoluble compounds may have longer residence time in lung. Absorption 
    of Cr(VI) can also take place after oral and dermal exposure, 
    particularly if the exposures are high.
        The chromate (CrO4) 2- enters cells via 
    facilitated diffusion through non-specific anion channels (similar to 
    phosphate and sulfate anions). Following absorption of Cr(VI) compounds 
    from various exposure routes, chromium is taken up by the blood cells 
    and is widely distributed in tissues as Cr(VI). Inside blood cells and 
    tissues, Cr(VI) is rapidly reduced to lower oxidation states and bound 
    to macromolecules which may result in genotoxic or cytotoxic effects. 
    However, in the blood a substantial proportion of Cr(VI) is taken up 
    into erythrocytes, where it is reduced to Cr(III) and becomes bound to 
    hemoglobin and other proteins.
        Inhaled Cr(VI) is reduced to Cr(III) in vivo by a variety of 
    reducing agents. Ascorbate and glutathione in the ELF and macrophages 
    have been shown to reduce Cr(VI) to Cr(III) in the lungs. After oral 
    exposure, gastric juices are also responsible for reducing Cr(VI) to 
    Cr(III). This serves to limit the amount of Cr(VI) systemically 
    absorbed.
        Absorbed chromium is excreted from the body in a rapid phase 
    representing clearance from the blood and at least two slower phases 
    representing clearance from tissues. Urinary excretion is the primary 
    route of elimination, accounting for over 50% of eliminated chromium. 
    Although chromium is excreted in urine and feces, the intestine plays 
    only a minor part in chromium elimination representing only about 5% of 
    elimination from the blood.
    
    B. Carcinogenic Effects
    
        There has been extensive study on the potential for Cr(VI) to cause 
    carcinogenic effects, particularly cancer of the lung. OSHA reviewed 
    epidemiologic data from several industry sectors including chromate 
    production, chromate pigment production, chromium plating, stainless 
    steel welding, and ferrochromium production. Supporting evidence from 
    animal studies and mechanistic considerations are also evaluated in 
    this section.
    1. Evidence from Chromate Production Workers
        The epidemiologic literature of workers in the chromate production 
    industry represents the earliest and best-documented relationship 
    between exposure to chromium and lung cancer. The earliest study of 
    chromate production workers in the United States was reported by Machle 
    and Gregorius in 1948 (Ex. 7-2). In the United States, two chromate 
    production plants, one in Baltimore, MD, and one in Painesville, OH, 
    have been the subject of multiple studies. Both plants were included in 
    the 1948 Machle and Gregorius study and again in the study conducted by 
    the Public Health Service and published in 1953 (Ex. 7-3). Both of 
    these studies reported the results in aggregate. The Baltimore chromate 
    production plant was studied by Hayes et al. (Ex. 7-14) and more 
    recently by Gibb et al. (Ex. 31-22-11). The chromate production plant 
    in Painesville, OH, has been followed since the 1950s by Mancuso with 
    his most recent follow-up published in 1997. The most recent study of 
    the Painesville plant was published by Luippold et al. (Ex. 31-18-4). 
    The studies by Gibb and Luippold present historical exposure data for 
    the time periods covered by their respective studies. The Gibb exposure 
    data are especially interesting since the industrial hygiene data were 
    collected on a routine basis and not for compliance purposes. These 
    routine air measurements may be more representative of those typically 
    encountered by the exposed workers. In Great Britain, three plants have been 
    studied repeatedly, with reports published between 1952 and 1991. Other 
    studies of cohorts in the United States, Germany, Italy and Japan are 
    also reported. The elevated lung cancer mortality reported in the great 
    majority of these cohorts and the significant upward trends with 
    duration of employment and cumulative exposure provide some of the 
    strongest evidence that Cr(VI) is carcinogenic to workers. A summary of 
    selected human epidemiologic studies in chromate production workers is 
    presented in Table V-1.
    
    BILLING CODE 4510-26-P
    
Table V-1 Part 1

 

Table V-1 Part 2

 

    
    BILLING CODE 4510-26-C
        The basic hexavalent chromate production process involves milling 
    and mixing trivalent chromite ore with soda ash, sometimes in the 
    presence of lime (Exs. 7-103; 35-61). The mixture is 'roasted' at a 
    high temperature, which oxidizes much of the chromite to hexavalent 
    sodium chromate. Depending on the lime content used in the process, the 
    roast also contains other chromate species, especially calcium
    chromate under high lime conditions. The highly water-soluble sodium 
    chromate is water-extracted from the water-insoluble trivalent chromite 
    and the less water-soluble chromates (e.g., calcium chromate) in the 
    'leaching' process. The sodium chromate leachate is reacted with 
    sulfuric acid and sodium bisulfate to form sodium dichromate. The 
    sodium dichromate is prepared and packaged as a crystalline powder to 
    be sold as final product or sometimes used as the starting material to 
    make other chromates such as chromic acid and potassium dichromate.
    
    a. Cohort Studies of the Baltimore Facility. The Hayes et al. study of 
    the Baltimore, Maryland chromate production plant was designed to 
    determine whether changes in the industrial process at one chromium 
    chemical production facility were associated with a decreased risk of 
    cancer, particularly cancer of the respiratory system (Ex. 7-14). Four 
    thousand two hundred and seventeen (4,217) employees were identified as 
    newly employed between January 1, 1945 and December 31, 1974. Excluded 
    from this initial enumeration were employees who: (1) were working as 
    of 1945, but had been hired prior to 1945 and (2) had been hired since 
    1945 but who had previously been employed at the plant. Excluded from 
    the final cohort were those employed less than 90 days; women; those 
    with unknown length of employment; those with no work history; and 
    those of unknown age. The final cohort included 2,101 employees (1,803 
    hourly and 298 salaried).
        Hayes divided the production process into three departments: (1) 
    The mill and roast or "dry end" department which consists of 
    grinding, roasting and leaching processes; (2) the bichromate 
    department which consists of the acidification and crystallization 
    processes; and (3) the special products department which produces 
    secondary products including chromic acid. The bichromate and special 
    products departments are referred to as the "wet end".
        The construction of a new mill and roast and bichromate plant that 
    opened during 1950 and 1951 and a new chromic acid and special products 
    plant that opened in 1960 were cited by Hayes as "notable production 
    changes" (Ex. 7-14). The new facilities were designed to "obtain 
    improvements in process technique and in environmental control of 
    exposure to chromium bearing dusts * * *" (Ex. 7-14).
        Plant-related work and health histories were abstracted for each 
    employee from plant records. Each job on the employee's work history 
    was characterized according to whether the job exposure occurred in (1) 
    a newly constructed facility, (2) an old facility, or (3) could not be 
    classified as having occurred in the new or the old facility. Those who 
    ever worked in an old facility or whose work location(s) could not be 
    distinguished based upon job title were considered as having a high or 
    questionable exposure. Only those who worked exclusively in the new 
    facility were defined for study purposes as "low exposure". Data on 
    cigarette smoking were abstracted from plant records, but were not 
    utilized in any analyses since the investigators thought them "not to 
    be of sufficient quality to allow analysis."
        One thousand one hundred and sixty nine (1,169) cohort members were 
    identified as alive, 494 not individually identified as alive and 438 
    as deceased. Death certificates could not be located for 35 reported 
    decedents. Deaths were coded to the 8th revision of the International 
    Classification of Diseases.
        Mortality analysis was limited to the 1,803 hourly employees 
    calculating the standardized mortality ratios (SMRs) for specific 
    causes of death. The SMR is a ratio of the number of deaths observed in 
    the study population to the number that would be expected if that study 
    population had the same specific mortality rate as a standard reference 
    population (e.g., age-, gender-, calendar year adjusted U.S. 
    population). The SMR is typically multiplied by 100, so a SMR greater 
    than 100 represents an elevated mortality in the study cohort relative 
    to the reference group. In the Hayes study, the expected number of 
    deaths was based upon Baltimore, Maryland male mortality rates 
    standardized for age, race and time period. For those where race was 
    unknown, the expected numbers were derived from mortality rates for 
    whites. Cancer of the trachea, bronchus and lung accounted for 69% of 
    the 86 cancer deaths identified and was statistically significantly 
    elevated (O=59; E=29.16; SMR=202; 95% CI: 155-263).
        Analysis of lung cancer deaths among hourly workers by year of 
    initial employment (1945-1949; 1950-1959 and 1960-1974), exposure 
    category (low exposure or questionable/high exposure) and duration of 
    employment (short term defined as 90 days-2 years; long term defined as 
    3 years +) was also conducted. For those workers characterized as 
    having questionable/high exposure, the SMRs were significantly elevated 
    for the 1945-1949 and the 1950-1959 hire periods and for both short- 
    and long-term workers (not statistically significant for the short-term 
    workers initially hired 1945-1949). For those characterized as low 
    exposure, there was an elevated SMR for the long-term workers hired 
    between 1950 and 1959, but based only on three deaths (not 
    statistically significant). No lung cancer cases were observed for 
    workers hired 1960-1974.
        Case-control analyses of (1) a history of ever having been employed 
    in selected jobs or combinations of jobs or (2) a history of specified 
    morbid conditions and combinations of conditions reported on plant 
    medical records were conducted. Cases were defined as decedents (both 
    hourly and salaried were included in the analyses) whose underlying or 
    contributing cause of death was lung cancer. Controls were defined as 
    deaths from causes other than malignant or benign tumors. Cases and 
    controls were matched on race (white/non-white), year of initial 
    employment (+/-3 years), age at time of initial employment (+/-5 years) 
    and total duration of employment (90 days-2 years; 3-4 years and 5 
    years +). An odds ratio (OR) was determined where the ratio is the odds 
    of employment in a job involving Cr(VI) exposure for the cases relative 
    to the controls.
        Based upon matched pairs, analysis by job position showed 
    significantly elevated odds ratios for special products (OR=2.6) and 
    bichromate and special products (OR=3.3). The relative risk for 
    bichromate alone was also elevated (OR=2.1, not statistically 
    significant).
        The possible association of lung cancer and three health conditions 
    (skin ulcers, nasal perforation and dermatitis) as recorded in the 
    plant medical records was also assessed. Of the three medical 
    conditions, only the odds ratio for dermatitis was statistically 
    significant (OR=3.0). When various combinations of the three conditions 
    were examined, the odds ratio for having all three conditions was 
    statistically significantly elevated (OR=6.0).
        Braver et al. used data from the Hayes study discussed above and 
    the results of 555 air samples taken during the period 1945-1950 by the 
    Baltimore City Health Department, the U.S. Public Health Service, and 
    the companies that owned the plant, in an attempt to examine the 
    relationship between exposure to Cr(VI) and the occurrence of lung 
    cancer (Ex. 7-17). According to the authors, methods for determining 
    the air concentrations of Cr(VI) have changed since the industrial 
    hygiene data were collected at the Baltimore plant between 1945 and 
    1959. The authors asked the National Institute for Occupational Safety 
    and Health (NIOSH) and the Occupational Safety and Health
    Administration (OSHA) to review the available documents on the methods 
    of collecting air samples, stability of Cr(VI) in the sampling media 
    after collection and the methods of analyzing Cr(VI) that were used to 
    collect the samples during that period.
        Air samples were collected by both midget impingers and high volume 
    samplers. According to the NIOSH/OSHA review, high volume samplers 
    could have led to a "significant" loss of Cr(VI) due to the reduction 
    of Cr(VI) to Cr(III) by glass or cellulose ester filters, acid 
    extraction of the chromate from the filter, or improper storage of 
    samples. The midget impinger was "less subject" to loss of Cr(VI) 
    according to the panel since neither filters nor acid extraction from 
    filters was employed. However, if iron was present or if the samples 
    were stored for too long, conversion from Cr(VI) to Cr(III) may have 
    occurred. The midget impinger can only detect water soluble Cr(VI). The 
    authors noted that, according to a 1949 industrial hygiene survey by 
    the U.S. Public Health Service, very little water insoluble Cr(VI) was 
    found at the Baltimore plant. One NIOSH/OSHA panel member characterized 
    midget impinger results as "reproducible" and "accuracy * * * fairly 
    solid unless substantial reducing agents (e.g., iron) are present" 
    (Ex. 7-17, p. 370). Based upon the panel's recommendations, the authors 
    used the midget impinger results to develop their exposure estimates 
    even though the panel concluded that the midget impinger methods "tend 
    toward underestimation" of Cr(VI).
        The authors also cite other factors related to the industrial 
    hygiene data that could have potentially influenced the accuracy of 
    their exposure estimates (either overestimating or underestimating the 
    exposure). These include: Measurements may have been taken primarily in 
    "problem" areas of the plant; the plants may have been cleaned or 
    certain processes shut down prior to industrial hygiene monitoring by 
    outside groups; respirator use; and periodic high exposures (due to 
    infrequent maintenance operations or failure of exposure control 
    equipment) which were not measured and therefore not reflected in the 
    available data.
        The authors estimated exposure indices for cohorts rather than for 
    specific individuals using hire period (1945-1949 or 1950-1959) and 
    duration of exposure, defined as short (at least 90 days but less than 
    three years) and long (three years or more). The usual exposure to 
    Cr(VI) for both the short- and long-term workers hired 1945-1949 was 
    calculated as the average of the mean annual air concentration for 
    1945-1947 and 1949 (data were missing for 1948). This was estimated to 
    be 413 [mu]g/m3. The usual exposure to Cr(VI) was estimated 
    to be 218 [mu]g/m3 for the short and long employees hired 
    between 1950 and 1959 based on air measurements in the older facility 
    in the early 1950s.
        Cumulative exposure was calculated as the usual exposure level 
    times average duration. Short-term workers, regardless of length of 
    employment, were assumed to have received 1.6 years of exposure 
    regardless of hire period. For long-term workers, the average length of 
    exposure was 12.3 years. Those hired 1945-1949 were assigned five years 
    at an exposure of 413 [mu]g/m3 and 7.3 years at an exposure 
    of 218 [mu]g/m3. For the long-term workers hired between 
    1950 and 1959, the average length of exposure was estimated to be 13.4 
    years. The authors estimated that the cumulative exposures at which 
    "significant increases in lung cancer mortality" were observed in the 
    Hayes study were 0.35, 0.67, 2.93 and 3.65 mg/m3--years. The 
    association seen by the authors appears more likely to be the result of 
    duration of employment rather than the magnitude of exposure since the 
    variation in the latter was small.
        Gibb et al. relied upon the Hayes study to investigate mortality in 
    a second cohort of the Baltimore plant (Ex. 31-22-11). The Hayes cohort 
    was composed of 1,803 hourly and 298 salaried workers newly employed 
    between January 1, 1945 and December 31, 1974. Gibb excluded 734 
    workers who began work prior to August 1, 1950 and included 990 workers 
    employed after August 1, 1950 who worked less than 90 days, resulting 
    in a cohort of 2,357 males followed for the period August 1, 1950 
    through December 31, 1992. Fifty-one percent (1,205) of the cohort was 
    white; 36% (848) nonwhite. Race was unknown for 13% (304) of the 
    cohort. The plant closed in 1985.
        Deaths were coded according to the 8th revision of the 
    International Classification of Diseases. Person years of observation 
    were calculated from the beginning of employment until death or 
    December 31, 1992, whichever came earlier. Smoking data (yes/no) were 
    available for 2,137 (93.3%) of the cohort from company records.
        Between 1950 and 1985, approximately 70,000 measurements of 
    airborne Cr(VI) were collected utilizing several different sampling 
    methods. The program of routine air sampling for Cr(VI) was initiated 
    to "characterize 'typical/usual exposures' of workers" (Ex. 31-22-11, 
    p. 117). Area samples were collected during the earlier time periods, 
    while both area and personal samples were collected starting in 1977. 
    Exposure estimates were derived from the area sampling systems and were 
    adjusted to "an equivalent personal exposure estimate using job-
    specific ratios of the mean area and personal sampling exposure 
    estimates for the period 1978-1985 * * *" (Ex. 31-22-11, p. 117). 
    According to the author, comparison of the area and personal samples 
    showed "no significant differences" for about two-thirds of the job 
    titles. For several job titles with a "significant point source of 
    contamination" the area sampling methods "significantly 
    underestimated" personal exposure estimates and were adjusted "by the 
    ratio of the two" (Ex. 31-22-11, p. 118).
        A job exposure matrix (JEM) was constructed, where air sampling 
    data were available, containing annual average exposure for each job 
    title. Data could not be located for the periods 1950-1956 and 1960-
    1961. Exposures were modeled for the missing data using the ratio of 
    the measured exposure for a job title to the average of all measured 
    job titles in the same department. For the time periods where 
    "extensive" data were missing, a simple straight line interpolation 
    between years with known exposures was employed.
        To estimate airborne Cr(III) concentrations, 72 composite dust 
    samples were collected at or near the fixed site air monitoring 
    stations about three years after the facility closed. The dust samples 
    were analyzed for Cr(VI) content using ion chromatography. Cr(III) 
    content was determined through inductively coupled plasma spectroscopic 
    analysis of the residue. The Cr(III):Cr(VI) ratio was calculated for 
    each area corresponding to the air sampling zones and the measured 
    Cr(VI) air concentration adjusted based on this ratio. Worker exposures 
    were calculated for each job title and weighted by the fraction of time 
    spent in each air-monitoring zone. The Cr(III):Cr(VI) ratio was derived 
    in this manner for each job title based on the distribution of time 
    spent in exposure zones in 1978. Cr(VI) exposures in the JEM were 
    multiplied by this ratio to estimate Cr(III) exposures.
        Information on smoking was collected at the time of hire for 
    approximately 90% of the cohort. Of the 122 lung cancer cases, 116 were 
    smokers and four were non smokers at the time of hire. Smoking status 
    was unknown for two lung cancer cases. As discussed below, these data 
    were used by the study authors to adjust for smoking in their 
    proportional hazards regression models used to determine whether lung 
    cancer mortality in the worker cohort increased with increasing cumulative
    Cr(VI) exposure.
        A total of 855 observed deaths (472 white; 323 nonwhite and 60 race 
    unknown) were reported. SMRs were calculated using U.S. rates for 
    overall mortality. Maryland rates (the state in which the plant was 
    located) were used to analyze lung cancer mortality in order to better 
    account for regional differences in disease fatality. SMRs were not 
    adjusted for smoking. In the public hearing, Dr. Gibb explained that it 
    was more appropriate to adjust for smoking in the proportional hazards 
    models than in the SMRs, because the analyst must make more assumptions 
    to adjust the SMRs for smoking than to adjust the regression model (Tr. 
    124).
        A statistically significant lung cancer SMR, based on the national 
    rate, was found for whites (O=71; SMR=186; 95% CI: 145-234); nonwhites 
    (O=47; SMR=188; 95% CI: 138-251) and the total cohort (O=122; SMR=180; 
    95% CI: 149-214). The ratio of observed to expected lung cancer deaths 
    (O/E) for the entire cohort stratified by race and cumulative exposure 
    quartile were computed. Cumulative exposure was lagged five years (only 
    exposure occurring five years before a given age was counted). The cut 
    point for the quartiles divided the cohort into four equal groups based 
    upon their cumulative exposure at the end of their working history (0-
    0.00149 mgCrO\3\/m3-yr; 0.0015-0.0089 mgCrO3/m\3\-yr; 0.009-
    0.0769 mgCrO3/m\3\-yr; and 0.077-5.25 mgCrO3/
    m\3\-yr). For whites, the relative risk of lung cancer was 
    significantly elevated for the second through fourth exposure quartiles 
    with O/E values of 0.8, 2.1, 2.1 and 1.7 for the four quartiles, 
    respectively. For nonwhites, the O/E values by exposure quartiles were 
    1.1, 0.9, 1.2 and 2.9, respectively. Only the highest exposure quartile 
    was significantly elevated. For the total cohort, a significant 
    exposure-response trend was observed such that lung cancer mortality 
    increased with increasing cumulative Cr(VI) exposure.
        Proportional hazards models were used to assess the relationship 
    between chromium exposure and the risk of lung cancer. The lowest 
    exposure quartile was used as the reference group. The median exposure 
    in each quartile was used as the measure of cumulative Cr(VI) exposure. 
    When smoking status was included in the model, relative lung cancer 
    risks of 1.83, 2.48 and 3.32 for the second, third and fourth exposure 
    quartiles respectively were estimated. Smoking, Cr(III) exposure, and 
    work duration were also significant predictors of lung cancer risk in 
    the model.
        The analysis attempted to separate the effects into two 
    multivariate proportionate hazards models (one model incorporated the 
    log of cumulative Cr(VI) exposure, the log of cumulative Cr(III) 
    exposure and smoking; the second incorporated the log of cumulative 
    Cr(VI), work duration and smoking). In either regression model, lung 
    cancer mortality remained significantly associated (p <  .05) with 
    cumulative Cr(VI) exposure even after controlling for the combination 
    of smoking and Cr(III) exposure or the combination of smoking and work 
    duration. On the other hand, lung cancer mortality was not 
    significantly associated with cumulative Cr(III) or work duration in 
    the multivariate analysis indicating lung cancer risk was more strongly 
    correlated with cumulative Cr(VI) exposure than the other variables.
        Exponent, as part of a larger submission from the Chrome Coalition, 
    submitted comments on the Gibb paper prior to the publication of the 
    proposed rule. These comments asked that OSHA review methodological 
    issues believed by Exponent to impact upon the usefulness of the Gibb 
    data in a risk assessment analysis. While Exponent states that the Gibb 
    study offers data that "are substantially better for cancer risk than 
    the Mancuso study * * * they believe that further scrutiny of some of 
    the methods and analytical procedures is necessary (Ex. 31-18-15-1, p. 
    5).
        The issues raised by Exponent and the Chrome Coalition (Ex. 31-18-
    14) concerning the Gibb paper are: selection of the appropriate 
    reference population for compilation of expected numbers for use in the 
    SMR analysis; inclusion of short term workers (<  1 year); expansion of 
    the number of exposure groupings to evaluate dose response trends; 
    analyzing dose response by peak JEM exposure levels; analyzing dose-
    response at exposures above and below the current PEL and calculating 
    smoking-adjusted SMRs for use in dose-response assessments. Exponent 
    obtained the original data from the Gibb study. The data were 
    reanalyzed to address the issues cited above. Exponent's findings are 
    presented in Exhibit 31-18-15-1 and are discussed below.
        Exponent suggested that Gibb's use of U.S. and Maryland mortality 
    rates for developing expectations for the SMR analysis was 
    inappropriate. It suggested that Baltimore city mortality rates would 
    have been the appropriate standard to select since those mortality 
    rates would more accurately reflect the mortality experience of those 
    who worked at the plant. Exponent reran the SMR analysis to compare the 
    SMR values reported by Gibb (U.S. mortality rates for SMR analysis) 
    with the results of an SMR analysis using Maryland mortality rates and 
    Baltimore mortality rates. Gibb reported a lung cancer SMR of 1.86 (95% 
    CI: 1.45-2.34) for white males based upon 71 lung cancer deaths using 
    U.S. mortality rates. Reanalysis of the data produced a lung cancer SMR 
    of 1.85 (95% CI: 1.44-2.33) for white males based on U.S. mortality 
    rates, roughly the same value obtained by Gibb. When Maryland and 
    Baltimore rates are used, the SMR drops to 1.70 and 1.25 respectively.
        Exponent suggested conducting sensitivity analysis that excludes 
    short-term workers (defined as those with one year of employment) since 
    the epidemiologic literature suggests that the mortality of short-term 
    workers is different than long-term workers. Short-term workers in the 
    Gibb study comprise 65% of the cohort and 54% of the lung cancers. The 
    Coalition also suggested that data pertaining to short-term employees' 
    information are of "questionable usefulness for assessing the 
    increased cancer risk from chronic occupational exposure to Cr(VI)" 
    (Ex. 31-18-15-1, p. 5).
        Lung cancer SMRs were calculated for those who worked for less than 
    one year and for those who worked one year or more. Exponent defined 
    short-term workers as those who worked less than one year "because it 
    is consistent with the inclusion criteria used by others studying 
    chromate chemical production worker cohorts" (Ex. 31-18-15-1, p. 12). 
    Exponent also suggested that Gibb's breakdown of exposure by quartile 
    was not the most "appropriate" way of assessing dose-response since 
    cumulative Cr(VI) exposures remained near zero until the 50th to 60th 
    percentile, "so there was no real distinction between the first two 
    quartiles * * * (Ex. 31-18-15-1, p. 24). They also suggested that 
    combining "all workers together at the 75th quartile * * * does not 
    properly account for the heterogeneity of exposure in this group" (Ex. 
    31-18-15-1, p. 24). The Exponent reanalysis used six cumulative 
    exposure levels of Cr(VI) compared with the four cumulative exposure 
    levels of Cr(VI) in the Gibb analysis. The lower levels of exposure 
    were combined and "more homogeneous" categories were developed for 
    the higher exposure levels.
        Using these re-groupings and excluding workers with less than one 
    year of employment, Exponent reported that the highest SMRs are seen in 
    the highest exposure group (1.5-< 5.25 mg CrO3/m\3\-years) for both white 
    and nonwhite, based on either the Maryland or the Baltimore mortality rates.
    The authors did not find "that the inclusion of short-term workers had a 
    significant impact on the results, especially if Baltimore rates are used 
    in the SMR calculations' (Ex. 31-18-15-1, p. 28).
        Analysis of length of employment and "peak" (i.e., highest 
    recorded mean annual) exposure level to Cr(VI) was conducted. Exponent 
    reported that approximately 50% of the cohort had "only very low" 
    peak exposure levels (<7.2 [mu]g CrO3/m\3\ or approximately 
    3.6 [mu]g/m\3\ of Cr(VI)). The majority of the short-term workers had 
    peak exposures of <100 [mu]g CrO3/m\3\. There were five peak 
    Cr(VI) exposure levels (<7.2 [mu]g CrO3/m\3\; 7.2-<19.3 
    [mu]g CrO3/m\3\; 19.3-<48.0 [mu]g CrO3/m\3\; 
    48.0-<105 [mu]g CrO3/m\3\; 105-<182 [mu]g CrO3/
    m\3\; and 182-<806 [mu]g CrO3/m\3\) included in the 
    analyses. Overall, the lung cancer SMRs for the entire cohort grouped 
    according to the six peak exposure categories were slightly higher 
    using Maryland reference rates compared to Baltimore reference rates.
        The Exponent analysis of workers who were ever exposed above the 
    current PEL versus those never exposed above the current PEL produced 
    slightly higher SMRs for those ever exposed, with the SMRs higher using 
    the Maryland standard rather than the Baltimore standard. The only 
    statistically significant result was for all lung cancer deaths 
    combined.
        Assessment was made of the potential impact of smoking on the lung 
    cancer SMRs since Gibb did not adjust the SMRs for smoking. Exponent 
    stated that the smoking-adjusted SMRs are more appropriate for use in 
    the risk assessment than the unadjusted SMRs. It should be noted that 
    smoking adjusted SMRs could not be calculated using Baltimore reference 
    rates. As noted by the authors, the smoking adjusted SMRs produced 
    using Maryland reference rates are, by exposure, "reasonably 
    consistent with the Baltimore-referenced SMRs" (Ex. 31-18-15-1, p. 
    41).
        Gibb et al. included workers regardless of duration of employment, 
    and the cohort was heavily weighted by those individuals who worked 
    less than 90 days. In an attempt to clarify this issue, Exponent 
    produced analyses of short-term workers, particularly with respect to 
    exposures. Exponent redefined short-term workers as those who worked 
    less than one year, to be consistent with the definition used in other 
    studies of chromate producers. OSHA finds this reanalysis excluding 
    short-term workers to be useful. It suggests that including cohort 
    workers employed less than one year did not substantively alter the 
    conclusions of Gibb et al. with regard to the association between 
    Cr(VI) exposure and lung cancer mortality. It should be noted that in 
    the Hayes study of the Baltimore plant, the cohort is defined as anyone 
    who worked 90 days or more.
        Hayes et al. used Baltimore mortality rates while Gibb et al. used 
    U.S. mortality rates to calculate expectations for overall SMRs. To 
    calculate expectations for the analysis of lung cancer mortality and 
    exposure, Gibb et al. used Maryland state mortality rates. The SMR 
    analyses provided by Exponent using both Maryland and Baltimore rates 
    are useful. The data showed that using Baltimore rates raised the 
    expected number of lung cancer deaths and, thus, lowered the SMRs. 
    However, there remained a statistically significant increase in lung 
    cancer risk among the exposed workers and a significant upward trend 
    with cumulative Cr(VI) exposure. The comparison group should be as 
    similar as possible with respect to all other factors that may be 
    related to the disease except the determinant under study. Since the 
    largest portion of the cohort (45%) died in the city of Baltimore, and 
    even those whose deaths occurred outside of Baltimore (16%) most likely 
    lived in proximity to the city, the use of Baltimore mortality rates as 
    an external reference population is preferable.
        Gibb's selection of the cut points for the exposure quartiles was 
    accomplished by dividing the workers in the cohort into four equal 
    groups based on their cumulative exposure at the end of their working 
    history. Using the same method but excluding the short-term workers 
    would have resulted in slightly different cumulative exposure 
    quartiles. Exponent expressed a preference for a six-tiered exposure 
    grouping. The impact of using different exposure groupings is further 
    discussed in section VI.C of the quantitative risk assessment.
        The exposure matrix of Gibb et al. utilizes an unusually high-
    quality set of industrial hygiene data. Over 70,000 samples taken to 
    characterize the "typical/usual" working environment is more 
    extensive industrial hygiene data then is commonly available for most 
    exposure assessments. However, there are several unresolved issues 
    regarding the exposure assessment, including the impact of the 
    different industrial hygiene sampling techniques used over the sampling 
    time frame, how the use of different sampling techniques was taken into 
    account in developing the exposure assessment and the use of area vs. 
    personal samples.
        Exponent and the Chrome Coalition also suggested that the SMRs 
    should have been adjusted for smoking. According to Exponent, smoking 
    adjusted SMRs based upon the Maryland mortality rates produced SMRs 
    similar to the SMRs obtained using Baltimore mortality rates (Ex. 31-
    18-15-1). The accuracy of the smoking data is questionable since it 
    represents information obtained at the time of hire. Hayes abstracted 
    the smoking data from the plant medical records, but "found it not to 
    be of sufficient quality to allow analysis." One advantage to using 
    the Baltimore mortality data may be to better control for the potential 
    confounding of smoking.
        The Gibb study is one of the better cohort mortality studies of 
    workers in the chromium production industry. The quality of the 
    available industrial hygiene data and its characterization as 
    "typical/usual" makes the Gibb study particularly useful for risk 
    assessment.
    
    b. Cohort Studies of the Painesville Facility. The Ohio Department of 
    Health conducted epidemiological and environmental studies at a plant 
    in Painesville that manufactured sodium bichromate from chromite ore. 
    Mancuso and Hueper (Ex. 7-12) reported an excess of respiratory cancer 
    among chromate workers when compared to the county in which the plant 
    was located. Among the 33 deaths in males who had worked at the plant 
    for a minimum of one year, 18.2% were from respiratory cancer. In 
    contrast, the expected frequency of respiratory cancer among males in 
    the county in which the plant was located was 1.2%. Although the 
    authors did not include a formal statistical comparison, the lung 
    cancer mortality rate among the exposed workers would be significantly 
    greater than the county rate.
        Mancuso (Ex. 7-11) updated his 1951 study of 332 chromate 
    production workers employed during the period 1931-1937. Age adjusted 
    mortality rates were calculated by the direct method using the 
    distribution of person years by age group for the total chromate 
    population as the standard. Vital status follow-up through 1974 found 
    173 deaths. Of the 66 cancer deaths, 41 (62.1%) were lung cancers. A 
    cluster of lung cancer deaths was observed in workers with 27-36 years 
    since first employment.
        Mancuso used industrial hygiene data collected in 1949 to calculate 
    weighted average exposures to water-soluble (presumed to be Cr(VI)), 
    insoluble (presumed to be principally Cr(III)) and
    total chromium (Ex. 7-98). The age-adjusted lung cancer death rate 
    increased from 144.6 (based upon two deaths) to 649.6 (based upon 14 
    deaths) per 100,000 in five exposure categories ranging from a low of 
    0.25-0.49 to a high of 4.0+ mg/m\3\-years for the insoluble Cr(III) 
    exposures. For exposure to soluble Cr(VI), the age adjusted lung cancer 
    rates ranged from 80.2 (based upon three deaths) to 998.7 (based upon 
    12 deaths) in five exposure categories ranging from < 0.25 to 2.0+ mg/
    m\3\-years. For total chromium, the age-adjusted death rates ranged 
    from 225.7 (based upon three deaths) to 741.5 (based upon 16 deaths) 
    for exposures ranging from 0.50-0.99 mg/m\3\-years to 6.0+ mg/m\3\-
    years.
        Age-adjusted lung cancer death rates also were calculated by 
    classifying workers by the levels of insoluble Cr(III) and total 
    chromium exposure. From the data presented, it appears that for a fixed 
    level of insoluble Cr(III), the lung cancer risk appears to increase as 
    the total chromium increases (Ex. 7-11).
        Mancuso (Ex. 23) updated the 1975 study. As of December 31, 1993, 
    283 (85%) cohort members had died and 49 could not be found. Of the 102 
    cancer deaths, 66 were lung cancers. The age-adjusted lung cancer death 
    rate per 100,000 ranged from 187.9 (based upon four deaths) to 1,254.1 
    (based upon 15 deaths) for insoluble Cr(III) exposure categories 
    ranging from 0.25-0.49 to 4.00-5.00 mg/m\3\ years. For the highest 
    exposure to insoluble Cr(III) (6.00+ mg/m\3\ years) the age-adjusted 
    lung cancer death rate per 100,000 fell slightly to 1,045.5 based upon 
    seven deaths.
        The age-adjusted lung cancer death rate per 100,000 ranged from 
    99.7 (based upon five deaths) to 2,848.3 (based upon two deaths) for 
    soluble Cr(VI) exposure categories ranging from < 0.25 to 4.00+ mg/m\3\ 
    years. For total chromium, the age-adjusted lung cancer death rate per 
    100,000 ranged from 64.7 (based upon two deaths) to 1,106.7 (based upon 
    21 deaths) for exposure categories ranging from < 0.50 to 6.00+ mg/m\3\ 
    years.
        To investigate whether the increase in the lung cancer death rate 
    was due to one form of chromium compound (presumed insoluble Cr(III) or 
    soluble Cr(VI)), age-adjusted lung cancer mortality rates were 
    calculated by classifying workers by the levels of exposure to 
    insoluble Cr(III) and total chromium. For a fixed level of insoluble 
    Cr(III), the lung cancer rate appears to increase as the total chromium 
    increases for each of the six total chromium exposure categories, 
    except for the 1.00-1.99 mg/m\3\-years category. For the fixed exposure 
    categories for total chromium, increasing exposures to levels of 
    insoluble Cr(III) showed an increased age-adjusted death rate from lung 
    cancer in three of the six total chromium exposure categories.
        For a fixed level of soluble Cr(VI), the lung cancer death rate 
    increased as total chromium categories of exposure increased for three 
    of the six gradients of soluble Cr(VI). For the fixed exposure 
    categories of total chromium, the increasing exposure to specific 
    levels of soluble Cr(VI) led to an increase in two of the six total 
    chromium exposure categories. Mancuso concluded that the relationship 
    of lung cancer is not confined solely to either soluble or insoluble 
    chromium. Unfortunately, it is difficult to attribute these findings 
    specifically to Cr(III) [as insoluble chromium] and Cr(VI) [as soluble 
    chromium] since it is likely that some slightly soluble and insoluble 
    Cr(VI) as well as Cr(III) contributed to the insoluble chromium 
    measurement.
        Luippold et al. conducted a retrospective cohort study of 493 
    former employees of the chromate production plant in Painesville, Ohio 
    (Ex. 31-18-4). This Painesville cohort does not overlap with the 
    Mancuso cohort and is defined as employees hired beginning in 1940 who 
    worked for a minimum of one year at Painesville and did not work at any 
    other facility owned by the same company that used or produced Cr(VI). 
    An exception to the last criterion was the inclusion of workers who 
    subsequently were employed at a company plant in North Carolina (number 
    not provided). Four cohort members were identified as female. The 
    cohort was followed for the period January 1, 1941 through December 31, 
    1997. Thirty-two percent of the cohort worked for 10 or more years.
        Information on potential confounders was limited. Smoking status 
    (yes/no) was available for only 35% of the cohort from surveys 
    administered between 1960 and 1965 or from employee medical files. For 
    those employees where smoking data were available, 78% were smokers 
    (responded yes on at least one survey or were identified as smokers 
    from the medical file). Information on race also was limited, the death 
    certificate being the primary source of information.
        Results of the vital status follow-up were: 303 deaths; 132 
    presumed alive and 47 vital status unknown. Deaths were coded to the 
    9th revision of the International Classification of Diseases. Cause of 
    death could not be located for two decedents. For five decedents the 
    cause of death was only available from data collected by Mancuso and 
    was recoded from the 7th to the 9th revision of the ICD. There were no 
    lung cancer deaths among the five recoded deaths.
        SMRs were calculated based upon two reference populations: The U.S. 
    (white males) and the state of Ohio (white males). Lung cancer SMRs 
    stratified by year of hire, duration of exposure, time since first 
    employment and cumulative exposure group also were calculated.
        Proctor et al. analyzed airborne Cr(VI) levels throughout the 
    facility for the years 1943 to 1971 (the plant closed April 1972) from 
    800 area air sampling measurements from 21 industrial hygiene surveys 
    (Ex. 35-61). A job exposure matrix (JEM) was constructed for 22 
    exposure areas for each month of plant operation. Gaps in the matrix 
    were completed by computing the arithmetic mean concentration from area 
    sampling data, averaged by exposure area over three time periods (1940-
    1949; 1950-1959 and 1960-1971) which coincided with process changes at 
    the plant (Ex. 31-18-1)
        The production of water-soluble sodium chromate was the primary 
    operation at the Painesville plant. It involved a high lime roasting 
    process that produced a water insoluble Cr(VI) residue (calcium 
    chromate) as byproduct that was transported in open conveyors and 
    likely contributed to worker exposure until the conveyors were covered 
    during plant renovations in 1949. The average airborne soluble Cr(VI) 
    from industrial hygiene surveys in 1943 and 1948 was 0.72 mg/m\3\ with 
    considerable variability among departments. During these surveys, the 
    authors believe the reported levels may have underestimated total 
    Cr(VI) exposure by 20 percent or less for some workers due to the 
    presence of insoluble Cr(VI) dust.
        Reductions in Cr(VI) levels over time coincided with improvements 
    in the chromate production process. Industrial hygiene surveys over the 
    period from 1957 to 1964 revealed average Cr(VI) levels of 270 [mu]g/
    m\3\. Another series of plant renovations in the early 1960s lowered 
    average Cr(VI) levels to 39 [mu]g/m\3\ over the period from 1965 to 
    1972. The highest Cr(VI) concentrations generally occurred in the 
    shipping, lime and ash, and filtering operations while the locker 
    rooms, laboratory, maintenance shop and outdoor raw liquor storage 
    areas had the lowest Cr(VI) levels.
        The average cumulative Cr(VI) exposure (mg/m\3\-yrs) for the cohort 
    was 1.58 mg/m\3\-yrs and ranged from 0.006 to 27.8 mg/m\3\-yrs. For 
    those who died from lung cancer, the average Cr(VI) exposure was 3.28 
    mg/m\3\-yrs and ranged from 0.06 to 27.8 mg/m\3\-yrs.
    According to the authors, 60% of the cohort accumulated an estimated 
    Cr(VI) exposure of 1.00 mg/m\3\-yrs or less.
        Sixty-three per cent of the study cohort was reported as deceased 
    at the end of the follow-up period (December 31, 1997). There was a 
    statistically significant increase for the all causes of death category 
    based on both the national and Ohio state standard mortality rates 
    (national: O=303; E=225.6; SMR=134; 95% CI: 120-150; state: O=303; 
    E=235; SMR=129; 95% CI: 115-144). Fifty-three of the 90 cancer deaths 
    were cancers of the respiratory system with 51 coded as lung cancer. 
    The SMR for lung cancer is statistically significant using both 
    reference populations (national O= 51; E=19; SMR 268; 95% CI: 200-352; 
    state O=51; E=21.2; SMR 241; 95% CI: 180-317).
        SMRs also were calculated by year of hire, duration of employment, 
    time since first employment and cumulative Cr(VI) exposure, mg/m\3\-
    years. The highest lung cancer SMRs were for those hired during the 
    earliest time periods. For the period 1940-1949, the lung cancer SMR 
    was 326 (O=30; E=9.2; 95% CI: 220-465); for 1950-1959, the lung cancer 
    SMR was 275 (O=15; E=5.5; 95% CI: 154-454). For the period 1960-1971, 
    the lung cancer SMR was just under 100 based upon six deaths with 6.5 
    expected.
        Lung cancer SMRs based upon duration of employment (years) 
    increased as duration of employment increased. For those with one to 
    four years of employment, the lung cancer SMR was 137 based upon nine 
    deaths (E=6.6; 95% CI: 62-260); for five to nine years of employment, 
    the lung cancer SMR was 160 (O=8; E=5.0; 95% CI: 69-314). For those 
    with 10-19 years of employment, the lung cancer SMR was 169 (O=7; 
    E=4.1; 95% CI: 68-349), and for those with 20 or more years of 
    employment, the lung cancer SMR was 497 (O=27; E=5.4; 95% CI: 328-723).
        Analyses of cumulative Cr(VI) exposure found the lung cancer SMR 
    (based upon the Ohio standard) in the highest exposure group (2.70-
    27.80 mg/m\3\-yrs) was 463 (O=20; E=4.3; 95% CI: 183-398). In the 1.05-
    2.69 mg/m\3\-yrs cumulative exposure group, the lung cancer SMR was 365 
    based upon 16 deaths (E=4.4; 95% CI: 208-592). For the cumulative 
    exposure groups 0.49-1.04, 0.20-0.48 and 0.00-0.19, the lung cancer 
    SMRs were 91 (O=4; E=4.4; 95% CI: 25-234; 184 (O=8; E=4.4; 95% CI: 79-
    362) and 67 (O=3; E=4.5; 95% CI: 14-196). A test for trend showed a 
    strong relationship between lung cancer mortality and cumulative Cr(VI) 
    exposure (p=0.00002). The authors claim that the SMRs are also 
    consistent with a threshold effect since there was no statistically 
    significant trend for excess lung cancer mortality with cumulative 
    Cr(VI) exposures less than about 1 mg/m\3\-yrs. The issue of whether 
    the cumulative Cr(VI) exposure-lung cancer response is best represented 
    by a threshold effect is discussed further in preamble section VI on 
    the quantitative risk assessment.
        The Painesville cohort is small (482 employees). Excluded from the 
    cohort were six employees who worked at other chromate plants after 
    Painesville closed. However, exceptions were made for employees who 
    subsequently worked at the company's North Carolina plant (number not 
    provided) because exposure data were available from the North Carolina 
    plant. Subsequent exposure to Cr(VI) by other terminated employees is 
    unknown and not taken into account by the investigators. Therefore, the 
    extent of the bias introduced is unknown.
        The 10% lost to follow-up (47 employees) in a cohort of this size 
    is striking. Four of the forty-seven had "substantial" follow-up that 
    ended in 1997 just before the end date of the study. For the remaining 
    43, most were lost in the 1950s and 1960s (most is not defined). Since 
    person-years are truncated at the time individuals are lost to follow 
    up, the potential implication of lost person years could impact the 
    width of the confidence intervals.
        The authors used U.S. and Ohio mortality rates for the standards to 
    compute the expectations for the SMRs, stating that the use of Ohio 
    rates minimizes bias that could occur from regional differences in 
    mortality. It is unclear why county rates were not used to address the 
    differences in regional mortality.
    c. Other Cohort Studies. The first study of cancer of the respiratory 
    system in the U.S. chromate producing industry was reported by Machle 
    and Gregorius (Ex. 7-2). The study involved a total of 11,000 person-
    years of observation between 1933 and 1947. There were 193 deaths; 42 
    were due to cancer of the respiratory system. The proportion of 
    respiratory cancer deaths among chromate workers was compared with 
    proportions of respiratory cancer deaths among Metropolitan Life 
    Insurance industrial policyholders. A non-significant excess 
    respiratory cancer among chromate production workers was found. No 
    attempt was made to control for confounding factors (e.g., age). While 
    some exposure data are presented, the authors state that one cannot 
    associate tumor rates with tasks (and hence specific exposures) because 
    of "shifting of personnel" and the lack of work history records.
        Baetjer reported the results of a case-control study based upon 
    records of two Baltimore hospitals (Ex. 7-7). A history of working with 
    chromates was determined from these hospital records and the proportion 
    of lung cancer cases determined to have been exposed to chromates was 
    compared with the proportion of controls exposed. Of the lung cancer 
    cases, 3.4% had worked in a chromate manufacturing plant, while none of 
    the controls had such a history recorded in the medical record. The 
    results were statistically significant and Baetjer concluded that the 
    data confirmed the conclusions reached by Machle and Gregorius that 
    "the number of deaths due to cancer of the lung and bronchi is greater 
    in the chromate-producing industry than would normally be expected" 
    (Ex. 7-7, p. 516).
        As a part of a larger study carried out by the U.S. Public Health 
    Service, the morbidity and mortality of male workers in seven U.S. 
    chromate manufacturing plants during the period 1940-1950 was reported 
    (Exs. 7-1; 7-3). Nearly 29 times as many deaths from respiratory cancer 
    (excluding larynx) were found among workers in the chromate industry 
    when compared to mortality rates for the total U.S. for the period 
    1940-1948. The lung cancer risk was higher at the younger ages (a 40-
    fold risk at ages 15-45; a 30-fold risk at ages 45-54 and a 20-fold 
    risk at ages 55-74). Analysis of respiratory cancer deaths (excluding 
    larynx) by race showed an observed to expected ratio of 14.29 for white 
    males and 80 for nonwhite males.
        Taylor conducted a mortality study in a cohort of 1,212 chromate 
    workers followed over a 24 year (1937-1960) period (Ex. 7-5). The 
    workers were from three chromate plants that included approximately 70% 
    of the total population of U.S. chromate workers in 1937. In addition, 
    the plants had been in continuous operation for the study period 
    (January 1, 1937 to December 31, 1960). The cohort was followed 
    utilizing records of Old Age and Survivors Disability Insurance 
    (OASDI). Results were reported both in terms of SMRs and conditional 
    probabilities of survival to various ages comparing the mortality 
    experience of chromate workers to the U.S. civilian male population. No 
    measures of chromate exposure were reported although results are 
    provided in terms of duration of employment. Taylor concluded that not 
    only was there an excess in mortality from respiratory cancer, but from 
    other causes as well, especially as duration of employment increased.
        In a reanalysis of Taylor's data, Enterline excluded those workers 
    born prior to 1889 and analyzed the data by follow-up period using U.S. 
    rates (Ex. 7-4). The SMR for respiratory cancer for all time periods 
    showed a nine-fold excess (O=69 deaths; E=7.3). Respiratory cancer 
    deaths comprised 28% of all deaths. Two of the respiratory cancer 
    deaths were malignant neoplasms of the maxillary sinuses, a number 
    according to Enterline, "greatly in excess of that expected based on 
    the experience of the U.S. male population." Also slightly elevated 
    were cancers of the digestive organs (O=16; E=10.4) and non-malignant 
    respiratory disease (O=13; E=8.9).
        Pastides et al. conducted a cohort study of workers at a North 
    Carolina chromium chemical production facility (Ex. 7-93). Opened in 
    1971, this facility is the largest chromium chemical production 
    facility in the United States. A low-lime process was used since the 
    plant began operation. Three hundred and ninety eight workers employed 
    for a minimum of one year between September 4, 1971 and December 31, 
    1989 comprised the study cohort. A self-administered employee 
    questionnaire was used to collect data concerning medical history, 
    smoking, plant work history, previous employment and exposure to other 
    potential chemical hazards. Personal air monitoring results for Cr(VI) 
    were available from company records for the period February 1974 
    through April 1989 for 352 of the 398 cohort members. A job matrix 
    utilizing exposure area and calendar year was devised. The exposure 
    means from the matrix were linked to each employee's work history to 
    produce the individual exposure estimates by multiplying the mean 
    Cr(VI) value from the matrix by the duration (time) in a particular 
    exposure area (job). Annual values were summed to estimate total 
    cumulative exposure.
        Personal air monitoring indicated that TWA Cr(VI) air 
    concentrations were generally very low. Roughly half the samples were 
    less than 1 [mu]g/m3, about 75 percent were below 3 [mu]g/
    m3, and 96 percent were below 25 [mu]g/m3. The 
    average worker's age was 42 years and mean duration of employment was 
    9.5 years. Two thirds of the workers had accumulated less than 0.01 
    [mu]g/m3-yr cumulative Cr(VI) exposure. SMRs were computed 
    using National, State (not reported) and county mortality rates (eight 
    adjoining North Carolina counties, including the county in which the 
    plant is located). Two of the 17 recorded deaths in the cohort were 
    from lung cancers. The SMRs for lung cancer were 127 (95% CI: 22-398) 
    and 97 (95% CI: 17-306) based on U.S. and North Carolina county 
    mortality rates, respectively. The North Carolina cohort is still 
    relatively young and not enough time has elapsed to reach any 
    conclusions regarding lung cancer risk and Cr(VI) exposure.
        In 2005, Luippold et al. published a study of mortality among two 
    cohorts of chromate production workers with low exposures (Ex. 47-24-
    2). Luippold et al. studied a total of 617 workers with at least one 
    year of employment, including 430 at the North Carolina plant studied 
    by Pastides et al. (1994) ("Plant 1") and 187 hired after the 1980 
    institution of exposure-reducing process and work practice changes at a 
    second U.S. plant ("Plant 2"). A high-lime process was never used at 
    Plant 1, and workers drawn from Plant 2 were hired after the 
    institution of a low lime process, so that exposures to calcium 
    chromate in both cohorts were likely minimal. Personal air-monitoring 
    measures available from 1974 to 1988 for the first plant and from 1981 
    to 1998 for the second plant indicated that exposure levels at both 
    plants were low, with overall geometric mean concentrations below 1.5 
    [mu]g/m3 and area-specific average personal air sampling 
    values not exceeding 10 [mu]g/m3 for most years (Ex. 47-24-
    2, p. 383).
        Workers were followed through 1998. By the end of follow-up, which 
    lasted an average of 20.1 years for workers at Plant 1 and 10.1 years 
    at Plant 2, 27 cohort members (4%) were deceased. There was a 41% 
    deficit in all-cause mortality when compared to all-cause mortality 
    from age-specific state reference rates, suggesting a strong healthy 
    worker effect. Lung cancer was 16% lower than expected based on three 
    observed vs. 3.59 expected cases, also using age-specific state 
    reference rates (Ex. 47-24-2, p. 383). The authors stated that "[t]he 
    absence of an elevated lung cancer risk may be a favorable reflection 
    of the postchange environment", but cautioned that longer follow-up 
    allowing an appropriate latency for the entire cohort would be required 
    to confirm this conclusion (Ex. 47-24-2, p. 381). OSHA received several 
    written testimony regarding this cohort during the post-hearing comment 
    period. These are discussed in section VI.B.7 on the quantitative risk 
    assessment.
        A study of four chromate producing facilities in New Jersey was 
    reported by Rosenman (Ex. 35-104). A total of 3,408 individuals were 
    identified from the four facilities over different time periods (plant 
    A from 1951-1954; plant B from 1951-1971; plant C from 1937-1964 and 
    plant D 1937-1954). No Cr(VI) exposure data was collected for this 
    study. Proportionate mortality ratios (PMRs) and proportionate cancer 
    mortality ratios (PCMRs), adjusted by race, age, and calendar year, 
    were calculated for the three companies (plants A and B are owned by 
    one company). Unlike SMRs, PMRs are not based on the expected mortality 
    rates in a standardized population but, instead, merely represent the 
    proportional distribution of deaths in the cohort relative to the 
    general U.S. population. Analyses were done evaluating duration of work 
    and latency from first employment.
        Significantly elevated PMRs were seen for lung cancer among white 
    males (170 deaths, PMR=1.95; 95% CI: 1.67-2.27) and black males (54 
    deaths, PMR=1.88; 95% CI: 1.41-2.45). PMRs were also significantly 
    elevated (regardless of race) for those who worked 1-10, 11-20 and >20 
    years and consistently higher for white and black workers 11-20 years 
    and >20 years since first hire. The results were less consistent for 
    those with 10 or fewer years since first hire.
        Bidstrup and Case reported the mortality experience of 723 workers 
    at three chromate producing factories in Great Britain (Ex. 7-20). Lung 
    cancer mortality was 3.6 times that expected (O=12; E=3.3) for England 
    and Wales. Alderson et al. conducted a follow-up of workers from the 
    three plants in the U.K. (Bolton, Rutherglen and Eaglescliffe) 
    originally studied by Bidstrup (Ex. 7-22). Until the late 1950s, all 
    three plants operated a "high-lime" process. This process potentially 
    produced significant quantities of calcium chromate as a by-product as 
    well as the intended sodium dichromate. Process changes occurred during 
    the 1940s and 1950s. The major change, according to the author, was the 
    introduction of the "no-lime" process, which eliminated unwanted 
    production of calcium chromate. The no-lime process was introduced at 
    Eaglescliffe 1957-1959 and by 1961 all production at the plant was by 
    this process. Rutherglen operated a low-lime process from 1957/1959 
    until it closed in 1967. Bolton never changed to the low lime process. 
    The plant closed in 1966. Subjects were eligible for entry into the 
    study if they had received an X-ray examination at work and had been 
    employed for a minimum of one year between 1948 and 1977. Of the 3,898 
    workers enumerated at the three plants, 2,715 met the cohort entrance 
    criteria, (alive: 1,999; deceased: 602; emigrated: 35; and lost to 
    follow-up: 79). Those lost to follow-up were not included in the 
    analyses. Eaglescliffe contributed the greatest number of subjects to 
    the study (1,418). Rutherglen contributed the largest number of total 
    deaths (369, or 61%). Lung cancer comprised the majority of cancer deaths
    and was statistically significantly elevated for the entire cohort 
    (O=116; E=47.96; SMR= 240; p < 0.001). Two deaths from nasal cancer were
    observed, both from Rutherglen.
        SMRs were computed for Eaglescliffe by duration of employment, 
    which was defined based upon plant process updates (those who only 
    worked before the plant modification, those who worked both before and 
    after the modifications, or those who worked only after the 
    modifications were completed). Of the 179 deaths at the Eaglescliffe 
    plant, 40 are in the pre-change group; 129 in the pre-/post-change and 
    10 in the post-change. A total of 36 lung cancer deaths occurred at the 
    plant, in the pre-change group O=7; E=2.3; SMR=303; in the pre-/post-
    change group O=27; E=13; SMR=2.03 and in the post-change group O=2; 
    E=1.07; SMR=187.
        In an attempt to address several potential confounders, regression 
    analysis examined the contributions of various risk factors to lung 
    cancer. Duration of employment, duration of follow-up and working 
    before or after plant modification appear to be greater risk factors 
    for lung cancer, while age at entry or estimated degree of chromate 
    exposure had less influence.
        Davies updated the work of Alderson, et al. concerning lung cancer 
    in the U.K. chromate producing industry (Ex. 7-99). The study cohort 
    included payroll employees who worked a minimum of one year during the 
    period January 1, 1950 and June 30, 1976 at any of the three facilities 
    (Bolton, Eaglescliffe or Rutherglen). Contract employees were excluded 
    unless they later joined the workforce, in which case their contract 
    work was taken into account.
        Based upon the date of hire, the workers were assigned to one of 
    three groups. The first, or "early" group, consists of workers hired 
    prior to January 1945 who are considered long term workers, but do not 
    comprise a cohort since those who left or died prior to 1950 are 
    excluded. The second group, "pre-change" workers, were hired between 
    January 1, 1945 to December 31, 1958 at Rutherglen or to December 31, 
    1960 at Eaglescliffe. Bolton employees starting from 1945 are also 
    termed pre-change. The cohort of pre-change workers is considered 
    incomplete since those leaving 1946-1949 could not be included and 
    because of gaps in the later records. For those who started after 1953 
    and for all men staying 5+ years, this subcohort of pre-change workers 
    is considered complete. The third group, "post-change" workers, 
    started after the process changes at Eaglescliffe and Rutherglen became 
    fully effective and are considered a "complete" cohort. A "control" 
    group of workers from a nearby fertilizer facility, who never worked in 
    or near the chromate plant, was assembled.
        A total of 2,607 employees met the cohort entrance criteria. As of 
    December 31, 1988, 1,477 were alive, 997 dead, 54 emigrated and 79 
    could not be traced (total lost to follow-up: 133). SMRs were 
    calculated using the mortality rates for England and Wales and the 
    mortality rates for Scotland. Causes of death were ascertained for all 
    but three decedents and deaths were coded to the revision of the 
    International Classification of Diseases in effect at the time of 
    death. Lung cancer in this study is defined as those deaths where the 
    underlying cause of death is coded as 162 (carcinoma of the lung) or 
    239.1 (lung neoplasms of unspecified nature) in the 9th revision of the 
    ICD. Two deaths fell into the latter category. The authors attempted to 
    adjust the national mortality rates to allow for differences based upon 
    area and social class.
        There were 12 lung cancer deaths at Bolton, 117 at Rutherglen, 75 
    at Eaglescliffe and one among staff for a total of 205 lung cancer 
    deaths. A statistically significant excess of lung cancer deaths (175 
    deaths) among early and pre-change workers is seen at Rutherglen and 
    Eaglescliffe for both the adjusted and unadjusted SMRs. For Rutherglen, 
    for the early period based upon 68 observed deaths, the adjusted SMR 
    was 230 while the unadjusted SMR was 347 (for both SMRs p< 0.001). For 
    the 41 pre-change lung cancer deaths at Rutherglen, the adjusted SMR 
    was 160 while the unadjusted SMR was 242 (for both SMRs p< 0.001). At 
    Eaglescliffe, there were 14 lung cancer deaths in the early period 
    resulting in an adjusted SMR of 196 and an unadjusted SMR of 269 (for 
    both SMRs p< 0.05). For the pre-change period at Eaglescliffe, the 
    adjusted SMR was 195 and the unadjusted was 267 (p< 0.001 for both 
    SMRs). At Bolton there is a non-significant excess among pre-change 
    men. There are no apparent excesses in the post-change groups, the 
    staff groups or in the non-exposed fertilizer group.
        There is a highly significant overall excess of nasal cancers with 
    two cases at Eaglescliffe and two cases at Rutherglen (O=4, 
    Eadjusted=0.26; SMR=1538). All four men with nasal cancer had more than 
    20 years of exposure to chromates.
        Aw reported on two case-control studies conducted at the previously 
    studies Eaglescliffe plant (Ex. 245). In 1960, the plant, converted 
    from a "high-lime" to a "no-lime" process, reducing the likelihood 
    of calcium chromate formation. As of March 1996, 2,672 post-change 
    workers had been employed, including 891 office personnel. Of the post-
    change plant personnel, 56% had been employed for more than one year. 
    Eighteen lung cancer cases were identified among white male post-change 
    workers (13 deceased; five alive). Duration of employment for the cases 
    ranged from 1.5 to 25 years with a mean of 14.4. Sixteen of the lung 
    cancer cases were smokers.
        In the first case-control study reported, the 15 lung cancer cases 
    identified up to September 1991 were matched to controls by age and 
    hire date (five controls per case). Cases and controls were compared 
    based upon their job categories within the plant. The results showed 
    that cases were more likely to have worked in the kiln area than the 
    controls. Five of the 15 cases had five or more years in the kiln area 
    where Cr(VI) exposure occurred vs. six of the 75 controls. A second 
    case-control study utilized the 18 lung cancer cases identified in post 
    change workers up to March 1996. Five controls per case were matched by 
    age (+/-5 years), gender and hire date. Both cases and controls had a 
    minimum of one year of employment. A job exposure matrix was being 
    constructed that would allow the investigators to "estimate exposure 
    to hexavalent chromates for each worker in the study for all the jobs 
    done since the start of employment at the site until 1980." Starting 
    in 1970 industrial hygiene sampling was performed to determine exposure 
    for all jobs at the plant. Cr(VI) exposure levels for the period 
    between 1960 and 1969 were being estimated based on the recall of 
    employees regarding past working conditions relative to current 
    conditions from a questionnaire. The author stated that preliminary 
    analysis suggests that the maximum recorded or estimated level of 
    exposure to Cr(VI) for the cases was higher than that of the controls. 
    However, specific values for the estimated Cr(VI) exposures were not 
    reported.
        Korallus et al. conducted a study of 1,140 active and retired 
    workers with a minimum of one year of employment between January 1, 
    1948 and March 31, 1979 at two German chromate production plants (Ex. 
    7-26). Workers employed prior to January 1, 1948 (either active or 
    retired) and still alive at that date were also included in the cohort. 
    The primary source for determining cause of death was medical
    records. Death certificates were used only when medical records could 
    not be found. Expected deaths were calculated using the male population 
    of North Rhineland-Westphalia. Elevated SMRs for cancer of the 
    respiratory system (50 lung cancers and one laryngeal cancer) were seen 
    at both plants (O=21; E=10.9; SMR=192 and O=30; E=13.4; SMR=224).
        Korallus et al. reported an update of the study. The cohort 
    definition was expanded to include workers with one year of employment 
    between January 1, 1948 and December 31, 1987 (Ex. 7-91). One thousand 
    four hundred and seventeen workers met the cohort entrance criteria and 
    were followed through December 31, 1988. While death certificates were 
    used, where possible, to obtain cause of death, a majority of the cause 
    of death data was obtained from hospital, surgical and general 
    practitioner reports and autopsies because of Germany's data protection 
    laws. Smoking data for the cohort were incomplete.
        Process modifications at the two plants eliminated the high-lime 
    process by January 1, 1958 at one location and January 1, 1964 at the 
    second location. In addition, technical measures were introduced which 
    led to reductions in the workplace air concentrations of chromate 
    dusts. Cohort members were divided into pre- and post-change cohorts, 
    with subcohorts in the pre-change group. SMRs were computed with the 
    expected number of deaths derived from the regional mortality rates 
    (where the plants are located). One plant had 695 workers (279 in the 
    pre-change group and 416 in the post change group). The second plant 
    had 722 workers (460 in the pre-change group and 262 in the post-change 
    group). A total of 489 deaths were ascertained (225 and 264 deaths). Of 
    the cohort members, 6.4% were lost to follow-up.
        Lung cancer is defined as deaths coded 162 in the 9th revision of 
    the International Classification of Diseases. There were 32 lung cancer 
    deaths at one plant and 43 lung cancer deaths at the second plant. Lung 
    cancer SMRs by date of entry (which differ slightly by plant) show 
    elevated but declining SMRs for each plant, possibly due to lower 
    Cr(VI) exposure as a result of improvements in production process. The 
    lung cancer SMR for those hired before 1948 at Plant 1 is statistically 
    significant (O=13; SMR=225; 95% CI: 122-382). The overall lung cancer 
    SMR for Plant 1 is also statistically significantly elevated based upon 
    32 deaths (SMR=175; 95% CI: 120-246). At Plant 2, the only lung cancer 
    SMR that is not statistically significant is for those hired after 1963 
    (based upon 1 death). Lung cancer SMRs for those hired before 1948 
    (O=23; SMR=344; 95% CI: 224-508) and for those hired between 1948 and 
    1963 (O=19; SMR=196; 95% CI: 1.24-2.98) are statistically significantly 
    elevated. The overall lung cancer SMR at Plant 2 based upon 43 deaths 
    is 239 (95% CI: 177-317). No nasal cavity neoplasms were found. A 
    statistically significant SMR for stomach cancer was observed at Plant 
    2 (O=12; SMR=192; 95% CI: 104-324).
        Recently, the mortality experience of the post-change workers 
    identified by Korallus et al. was updated in a study by Birk et al. 
    (Ex. 48-4). The study cohort consisted of 901 post-change male workers 
    from two German chromate production plants (i.e. 472 workers and 262 
    workers, respectively) employed for at least one year. Review of 
    employment records led to the addition of employees to the previous 
    Korallus cohort. Mortality experience of the cohort was evaluated 
    through 1998. A total of 130 deaths were ascertained, of which 22 were 
    due to cancer of the lung. Four percent of the cohort was lost to 
    follow-up. Specific cause of death could not be determined for 14 
    decedents. The mean duration of Cr(VI) exposure was 10 years and the 
    mean time since first exposure was 17 years. The proportion of workers 
    who ever smoked was 65 percent.
        The cohort lacked sufficient job history information and air 
    monitoring data to develop an adequate job-exposure matrix required to 
    estimate individual airborne exposures (Ex. 48-1-2). Instead, the 
    researchers used the over 12,000 measurements of urinary chromium from 
    routine biomonitoring of plant employees collected over the entire 
    study period to derive individual cumulative urinary chromium estimates 
    as an exposure surrogate. The approximate geometric average of all 
    urinary chromium measurements in the two German plants from 1960 to 
    1998 was 7-8 [mu]g/dl (Ex. 48-1-2, Table 5). There was a general plant-
    wide decline in average urinary chromium over time from 30 to 50 [mu]g/
    dl in the 1960s to less than 5 [mu]g/dl in the 1990s (Ex. 48-4, Figure 
    1). However, there was substantial variation in urinary chromium by 
    work location and job group.
        The study reported a statistically significant deficit in all cause 
    mortality (SMR=80 95% CI: 67-95) and mortality due to heart disease 
    (SMR=66 95% CI: 45-93) based on the age- and calendar year-adjusted 
    German national population rates indicating a healthy worker 
    population. However, the SMR for lung cancer mortality was elevated 
    (SMR=148 95% CI: 93-225) against the same reference population (Ex. 48-
    4, Table 2). There was a statistically significant two-fold excess lung 
    cancer mortality (SMR=209; 95% CI: 108-365; 12 observed lung cancer 
    deaths) among workers in the highest cumulative exposure grouping (i.e. 
    >200 [mu]g Cr/L-yr). There was no increase in lung cancer mortality in 
    the lower exposure groups, but the number of lung cancer deaths was 
    small (i.e. < =5 deaths) and the confidence intervals were wide.
        There were no obvious trends in lung cancer mortality with 
    employment duration or time since first employed, but the results were, 
    again, limited by the small number of study subjects per group. 
    Logistic regression analysis showed that cumulative urinary chromium >= 
    200 [mu]g Cr/L-yr was associated with a significantly higher risk of 
    lung cancer death (OR=6.9; 95% CI: 2.6-18.2) when compared against 
    workers exposed to lower cumulative urinary chromium exposures. This 
    risk was unchanged after controlling for smoking status indicating that 
    the elevated risks were unlikely to be confounded by smoking. Including 
    a peak exposure score to the regression analysis did not result in 
    additional risk beyond that associated with cumulative exposure alone. 
    Some commenters felt this German post-change cohort provided evidence 
    for an exposure threshold below which there is no risk of lung cancer. 
    This issue is addressed in Section VI.B.7 of the quantitative risk 
    assessment.
        DeMarco et al. conducted a cohort study of chromate production 
    workers in northern Italy to assess the existence of excess risk of 
    respiratory cancer, specifically lung cancer (Ex. 7-54). The cohort was 
    defined as males who worked for a minimum of one year from 1948 to 1985 
    and had at least 10 years of follow-up. Five hundred forty workers met 
    the cohort definition. Vital status follow-up, carried out through June 
    30, 1985, found 427 cohort members alive, 110 dead and three lost to 
    follow-up. Analysis utilizing SMRs based on Italian national rates was 
    conducted. Of the 110 deaths, 42 were cancer deaths. The statistically 
    significant SMR for lung cancer based upon 14 observed deaths with 6.46 
    expected was 217 (95% CI: 118-363).
        Exposure estimates were based upon the duration of cumulative 
    exposure and upon a risk score (low, medium, high and not assessed) 
    assigned to the department in which the worker was primarily employed. 
    A committee assigned the scores, based upon knowledge of the production 
    process or on industrial hygiene surveys taken in 1974, 1982 and 1984. 
    The risk score is a surrogate for the workplace concentrations of Cr(VI)
    in the different plant departments. Since no substantial changes had been 
    made since World War II, the assumption was made that exposures remained 
    relatively stable. Lung cancer SMRs based upon type of exposure increased 
    with level of exposure (Low: O=1; E=1.43; SMR=70; Medium: O=5; E=202; SMR=2.48; 
    High: O=6; E=1.4; SMR=420; Not Assessed: O=2; E=1.6; SMR=126). Only the SMR 
    for those classified as having worked in departments characterized as high 
    exposure was statistically significant at the p< 0.05 level.
        A cohort study of workers at a chromium compounds manufacturing 
    plant in Tokyo, Japan by Satoh et al. included males employed between 
    1918 and 1975 for a minimum of one year and for whom the necessary data 
    were available (Ex. 7-27). Date and cause of death data were obtained 
    from the death certificate (85%) or from other "reliable" written 
    testimony (15%). Of the 1,061 workers identified, 165 were excluded 
    from the study because information was missing. A total of 896 workers 
    met the cohort inclusion criteria and were followed through 1978. The 
    causes of 120 deaths were ascertained. SMRs based on age-cause specific 
    mortality for Japanese males were calculated for four different time 
    periods (1918-1949; 1950-1959; 1960-1969 and 1970-1978) and for the 
    entire follow-up period (1918-1978). An elevated SMR for lung cancer is 
    seen for the entire follow-up period (O=26; E=2.746; SMR=950). A 
    majority of the lung cancer deaths (20) occurred during the 1970-1978 
    interval.
        Results from the many studies of chromate production workers from 
    different countries indicate a relationship between exposure to 
    chromium and malignant respiratory disease. The epidemiologic studies 
    done between 1948 and 1952 by Machle and Gregorius (Ex. 7-2), Mancuso 
    and Hueper (Ex. 7-12) and Brinton, et al. (Ex. 7-1) suggest a risk for 
    respiratory cancer among chromate workers between 15 and 29 times 
    expectation. Despite the potential problems with the basis for the 
    calculations of the expectations or the particular statistical methods 
    employed, the magnitude of the difference between observed and expected 
    is powerful enough to overcome these potential biases.
        It is worth noting that the magnitude of difference in the relative 
    risks reported in a mortality study among workers in three chromate 
    plants in the U.K. (Ex.7-20) were lower than the relative risks 
    reported for chromate workers in the U.S. during the 1950s and 1960s. 
    The observed difference could be the result of a variety of factors 
    including different working conditions in the two countries, a shorter 
    follow-up period in the British study, the larger lost-to-follow-up in 
    the British study or the different statistical methods employed. While 
    the earlier studies established that there was an excess risk for 
    respiratory cancer from exposure to chromium, they were unable to 
    specify either a specific chromium compound responsible or an exposure 
    level associated with the risk. Later studies were able to use superior 
    methodologies to estimate standardized lung cancer mortality ratios 
    between chromate production cohorts and appropriate reference 
    populations (Exs. 7-14; 7-22; 7-26; 7-99; 7-91). These studies 
    generally found statistically increased lung cancer risk of around two-
    fold. The studies usually found trends with duration of employment, 
    year of hire, or some production process change that tended to 
    implicate chromium exposure as the causative agent.
        Some of the most recent studies were able to use industrial hygiene 
    data to reconstruct historical Cr(VI) exposures and show statistically 
    significant associations between cumulative airborne Cr(VI) and lung 
    cancer mortality (Exs. 23; 31-22-11; Ex. 31-18-4). Gibb et al. found 
    the significant association between Cr(VI) and lung cancer was evident 
    in models that accounted for smoking. The exposure'response 
    relationship from these chromate production cohorts provide strong 
    evidence that occupational exposure to Cr(VI) dust can increase cancer 
    in the respiratory tract of workers.
        The Davies, Korallus, (German cohort), Luippold (2003), and 
    Luippold (2005) studies examine mortality patterns at chromate 
    producing facilities where one production process modification involved 
    conversion from a high-lime to a low-lime or a lime-free process (Exs. 
    7-99; 7-91; 31-18-4). In addition to process modification, technical 
    improvements also were implemented that lowered Cr(VI) exposure. One of 
    the plants in the Davies study retained the high-lime process and is 
    not discussed. The lung cancer SMRs for one British plant and both of 
    the German plants decline from early, to pre-change to post change time 
    periods. In the remaining British plants, the lung cancer SMR is 
    basically identical for the early and pre-change period, but does 
    decline in the post-change time period. The lung cancer SMR in the 
    Luippold 2003 cohort also declined over time as the amount of lime was 
    reduced in the roasting process. Other modifications at the Painesville 
    plant that reduced airborne Cr(VI) exposure, such as installation of 
    covered conveyors and conversion from batch to continuous process, 
    occurred at the same time (Ex. 35-61). The workers in the Luippold 
    (2005) study were not exposed to Cr(VI) in facilities using a high-lime 
    process. This study did not show excess risk; however, this may be a 
    consequence of short follow-up time (<  20 years for most workers) or 
    the small size of the study (<  4 expected lung cancers), as discussed 
    further in Section VI.B.7. In general, it is not clear whether reduced 
    levels of the high-lime byproduct, calcium chromate, or the roasting/
    leaching end product, sodium dichromate, that resulted from the various 
    process changes is the reason for the decrease in lung cancer SMRs in 
    these cohorts. It should be noted that increased lung cancer risk was 
    experienced by workers at the Baltimore plant (e.g., Hayes and Gibb 
    cohorts) even though early air monitoring studies suggest that a high 
    lime process was probably not used at this facility (Ex. 7-17).
    2. Evidence From Chromate Pigment Production Workers
        Chromium compounds are used in the manufacture of pigments to 
    produce a wide range of vivid colors. Lead and zinc chromates have 
    historically been the predominant hexavalent chromium pigments, 
    although others such as strontium and barium chromate have also been 
    produced. These chromates vary considerably in their water solubility 
    with lead and barium chromates being the most water insoluble. All of 
    the above chromates are less water-soluble than the highly water-
    soluble sodium chromate and dichromate that usually serve as the 
    starting material for chromium pigment production. The reaction of 
    sodium chromate or dichromate with the appropriate zinc or lead 
    compound to form the corresponding lead or zinc chromate takes place in 
    solution. The chromate pigment is then precipitated, separated, dried, 
    milled, and packaged. Worker exposures to chromate pigments are 
    greatest during the milling and packaging stages.
        There have been a number of cohort studies of chromate pigment 
    production workers from the United States, the United Kingdom, France, 
    Germany, the Netherlands, Norway and Japan. Most of the studies found 
    significantly elevated lung cancers in workers exposed to Cr(VI) 
    pigments over many years when compared against standardized reference 
    populations. In general, the studies of chromate pigment workers lack 
    the historical exposure data found in some of the chromate production 
    cohorts. The consistently higher lung cancers across several worker 
    cohorts exposed to the less water-soluble Cr(VI) compounds complements 
    the lung cancer findings from the studies of workers producing highly 
    water soluble chromates and adds to the further evidence that occupational 
    exposure to Cr(VI) compounds should be regarded as carcinogenic. A summary 
    of selected human epidemiologic studies in chromate production workers is 
    presented in Table V-2.
    BILLING CODE 4510-26-P
Table V-2

 

    
    BILLING CODE 4510-26-C
        Langard and Vigander updated a cohort study of lung cancer 
    incidence in 133 workers employed by a chromium pigment production 
    company in Norway (Ex. 7-36). The cohort was originally studied by 
    Langard and Norseth (Ex. 7-33). Twenty four men had more than three 
    years of exposure to chromate dust. From 1948, when the company was 
    founded, until 1951, only lead chromate pigment was produced.
    From 1951 to 1956, both lead chromate and zinc chromate pigments were 
    produced and from 1956 to the end of the study period in 1972 only zinc 
    chromate was produced. Workers were exposed to chromates both as the 
    pigment and its raw material, sodium dichromate.
        The numbers of expected lung cancers in the workers were calculated 
    using the age-adjusted incidence rates for lung cancer in the Norwegian 
    male population for the period 1955-1976. Follow-up using the Norwegian 
    Cancer Registry through December 1980, found the twelve cancers of 
    which seven were lung cancers. Six of the seven lung cancers were 
    observed in the subcohort of 24 workers who had been employed for more 
    than three years before 1973. There was an increased lung cancer 
    incidence in the subcohort based on an observed to expected ratio of 44 
    (O=6; E=0.135). Except for one case, all lung cancer cases were exposed 
    to zinc chromates and only sporadically to other chromates. Five of the 
    six cases were known to be smokers or ex-smokers. Although the authors 
    did not report any formal statistical comparisons, the extremely high 
    age-adjusted standardized incidence ratio suggests that the results 
    would likely be statistically significant.
        Davies reported on a cohort study of English chromate pigment 
    workers at three factories that produced chromate pigments since the 
    1920s or earlier (Ex. 7-41). Two of the factories produced both zinc 
    and lead chromate. Both products were made in the same sheds and all 
    workers had mixed exposure to both substances. The only product at the 
    third factory was lead chromate.
        Cohort members are defined as males with a minimum of one year of 
    employment first hired between 1933 and 1967 at plant A; 1948 and 1967 
    at plant B and 1946-1961 at plant C. The analysis excludes men who 
    entered employment later than 1967 because of the short follow-up 
    period. Three hundred and ninety six (396) men from Factory A, 136 men 
    from Factory B and 114 men from Factory C were followed to mid-1977. 
    Ninety-four workers with 3-11 months employment during 1932-1945 at 
    Factory A were also included. Expectations were based upon calendar 
    time period-, gender- and age-specific national cancer death rates for 
    England and Wales. The author adjusted the death rates for each factory 
    for local differences, but the exact methods of adjustment were not 
    explicit.
        Exposure to chromates was assigned as high for those in the dry 
    departments where pigments were ground, blended and packed; medium for 
    those in the wet departments where precipitates were washed, pressed 
    and stove dried and in maintenance or cleaning which required time in 
    various departments; or low for those jobs which the author states 
    involved "slight exposure to chromates such as most laboratory jobs, 
    boiler stoking, painting and bricklaying" (Ex. 7-41, p. 159). The high 
    and medium exposure categories were combined for analytical purposes.
        For those entering employment from 1932 to 1954 at Factory A, there 
    were 18 lung cancer deaths in the high/medium exposure group, with 8.2 
    deaths expected. The difference is significant at p< .01. In the low 
    exposure group, the number of observed and expected lung cancer deaths 
    was equal (two deaths). There were no lung cancer deaths at Factory A 
    for those hired between 1955-1960 and 1961-1967.
        For those entering employment between 1948 and 1967 at Factory B, 
    there were seven observed lung cancer deaths in the high/medium 
    exposure group with 1.4 expected which is statistically significant at 
    p< .001. At Factory C (which manufactured only lead chromate), there was 
    one death in the high/medium exposure group and one death in the low 
    exposure group for those beginning employment between 1946 and 1967.
        The author points out that:
    
        There has been no excess lung cancer mortality amongst workers 
    with chromate exposure rated as "low", nor among those exposed 
    only to lead chromate. High and medium exposure-rated workers who in 
    the past had mixed exposure to both lead and zinc chromate have 
    experienced a marked excess of lung cancer deaths, even if employed 
    for as little as one year (Ex. 7-41, p. 157).
    
        It is the author's opinion that the results "suggest that the 
    manufacture of zinc chromate may involve a lung cancer hazard" (Ex. 7-
    41, p. 157).
        Davies updated the lung cancer mortality at the three British 
    chromate pigment production factories (Ex. 7-42). The follow-up was 
    through December 31, 1981. The cohort was expanded to include all male 
    workers completing one year of service by June 30, 1975 but excluded 
    office workers.
        Among workers at Factory A with high and medium exposure, mortality 
    was statistically significantly elevated over the total follow-up 
    period among entrants hired from 1932 to 1945 (O/E=2.22). A similar, 
    but not statistically significant, excess was seen among entrants hired 
    from 1946 to 1954 (O/E=2.23). The results for Factory B showed 
    statistically significantly elevated lung cancer mortality among 
    workers classified with medium exposures entering service during the 
    period from 1948 to 1960 (O/E=3.73) and from 1961 to 1967 (O/E=5.62). 
    There were no lung cancer deaths in the high exposure group in either 
    time period. At Factory C, analysis by entry date (early entrant and 
    the period 1946-1960) produced no meaningful results since the number 
    of deaths was small. When the two periods are combined, the O/E was 
    near unity. The author concluded that in light of the apparent absence 
    of risk at Factory C, "it seems reasonable to suggest that the hazard 
    affecting workers with mixed exposures at factories A and B * * * is 
    attributable to zinc chromates" (Ex. 7-42, p. 166). OSHA disagrees 
    with this conclusion, as discussed in section V.9.
        Davies also studied a subgroup of 57 chromate pigment workers, 
    mostly employed between 1930 and 1945, who suffered clinical lead 
    poisoning (Ex. 7-43). Followed through 1981, there was a statistically 
    significantly elevated SMR for lung cancer based upon four cases (O=4; 
    E=2.8; SMR=145).
        Haguenoer studied 251 French zinc and lead chromate pigment workers 
    employed for six months or more between January 1, 1958 and December 
    31, 1977 (Ex. 7-44). As of December 31, 1977, 50 subjects were 
    identified as deceased. Cause of death was obtained for 30 of the 50 
    deaths (60%). Lung cancer mortality was significantly elevated based on 
    11 fatalities (SMR=461; 95% CI: 270-790). The mean time from first 
    employment until detection of cancer was 17 years. The mean duration of 
    employment among cases was 15 years.
        The Haguenoer cohort was followed up in a study by Deschamps et al. 
    (Ex. 234). Both lead and zinc chromate pigments were produced at the 
    plant until zinc chromate production ceased in 1986. The cohort 
    consisted of 294 male workers employed for at least six months between 
    1958 and 1987. At the end of the follow-up, 182 cohort members were 
    alive, 16 were lost to follow-up and 96 were dead. Because of French 
    confidentiality rules, the cause of death could not be obtained from 
    the death certificate; instead physicians and hospital records were 
    utilized. Using cause of death data from sources other than death 
    certificates raises the potential for misclassification bias. Cause of 
    death could not be obtained for five decedents. Data on smoking habits 
    was not available for a number of workers and was not used in the 
    analysis.
        Since individual work histories were not available, the authors 
    made the assumption that the exposure level was the same for all 
    workers during their employment at the plant. Duration of employment 
    was used as a surrogate for exposure. Industrial hygiene measurements 
    taken in 1981 provide some idea of the exposure levels at the plant. 
    In the filtration department, Cr(VI) levels were between 2 and 3 [mu]g/m\3\; 
    in the grinding department between 6 and 165 [mu]g/m\3\; in the drying and 
    sacking department between 6 and 178 [mu]g/m\3\; and in the sacks 
    marking department more than 2000 [mu]g/m\3\.
        The expected number of deaths for the SMR analysis was computed 
    from age-adjusted death rates in the northern region of France where 
    the plant was located. There was a significant increase in lung cancer 
    deaths based on 18 fatalities with five expected (SMR=360; 95% CI: 213-
    568). Using duration of employment as a surrogate for exposure, 
    statistically significant SMRs were seen for the 10-15 years of 
    exposure (O=6, SMR=720, 95% CI: 264-1568), 15-20 years (O=4, SMR=481, 
    95% CI: 131-1231), and 20+ years (O=6, SMR=377, 95% CI: 1.38-8.21) time 
    intervals. There was a significantly elevated SMR for brain cancer 
    based upon two deaths (SMR=844, 95% CI: 102-3049). There was a non-
    statistically significant increase for digestive tract cancer (O=9, 
    SMR=130) consisting of three esophageal cancers, two stomach cancers 
    and four colon cancers.
        Equitable Environmental Health, Inc., on behalf of the Dry Color 
    Manufacturers Association, undertook a historical prospective mortality 
    study of workers involved in the production of lead chromate (Exs. 2-D-
    3; 2-D-1). The cohort was defined as male employees who had been 
    exposed to lead chromate for a minimum of six months prior to December 
    1974 at one of three facilities in West Virginia, Kentucky or New 
    Jersey. The New Jersey facility had a unit where zinc chromate was 
    produced dating back to 1947 (Ex. 2-D-3). Most workers rotated through 
    this unit and were exposed to both lead and zinc chromates. Two men 
    were identified at the New Jersey facility with exposure solely to lead 
    chromate; no one with exposure only to zinc chromate was identified.
        Subsequent review of the data found that the Kentucky plant also 
    produced zinc chromates from the late 1930s to early 1964. During the 
    period 1961-1962, zinc chromates accounted for approximately 12% of 
    chromate production at the plant. In addition, strontium chromate and 
    barium chromate also were produced at the plant.
        The cohort consisted of 574 male employees from all three plants 
    (Ex. 2-D-1). Eighty-five deaths were identified with follow up through 
    December 1979. Six death certificates were not obtained. SMRs were 
    reported based on U.S. white male death rates. There were 53 deaths 
    from the New Jersey plant including a statistically significant SMR for 
    cancer of the trachea, bronchus and lung based upon nine deaths (E=3.9; 
    SMR=231; 95% CI: 106-438). One lung cancer decedent worked solely in 
    the production of lead chromates. Three of the lung cancer deaths were 
    black males. In addition, there were six deaths from digestive system 
    cancers, five of which were stomach cancers reported at the New Jersey 
    plant. The SMR for stomach cancer was statistically significantly 
    elevated (O=5; E=0.63; SMR=792; 99% CI: 171-2243). There were 21 deaths 
    from the West Virginia plant, three of which were cancer of the 
    trachea, bronchus and lung (E=2.3; SMR=130; 95% CI: 27-381). There were 
    11 deaths at the Kentucky plant, two of which were cancer of the 
    trachea, bronchus and lung (E=0.9; SMR=216; 95% CI: 26-780).
        Sheffet et al. examined the lung cancer mortality among 1,946 male 
    employees in a chromate pigment factory in Newark, NJ, who were exposed 
    to both lead chromate and zinc chromate pigments (Ex. 7-48). The men 
    worked for a minimum of one month between January 1, 1940 and December 
    31, 1969. As of March 31, 1979, a total of 321 cohort members were 
    identified as deceased (211 white males and 110 non-white males). Cause 
    of death could not be ascertained for 37 white males and 12 non-white 
    males. The proportion of the cohort lost to follow up was high (15% of 
    white males and 20% of non-white males).
        Positions at the plant were classified into three categories 
    according to intensity of exposure: high (continuous exposure to 
    chemical dust), moderate (occasional exposure to chemical dust or to 
    dry or wet pigments) and low (infrequent exposure by janitors or office 
    workers). Positions were also classified by type of chemical exposure: 
    chromates, other inorganic substances, and organics. The authors state 
    that in almost all positions individuals "who were exposed to any 
    chemicals were also exposed to hexavalent chromium in the form of 
    airborne lead and zinc chromates (Ex. 7-48, p. 46)." The proportion of 
    lead chromate to zinc chromate was approximately nine to one. 
    Calculations, based upon air samples during later years, give an 
    estimate for the study period of more than 2000 [mu]g airborne 
    chromium/m\3\ for the high exposure category, between 500 and 2000 
    [mu]g airborne chromium/m\3\ and less than 100 [mu]g airborne chromium/
    m\3\ for the low exposure category. Other suspected carcinogens present 
    in the workplace air at much lower levels were nickel sulfate and 
    nickel carbonate.
        Because of the large proportion of workers lost to follow-up (15% 
    of white males and 20% of non-white males) and the large numbers of 
    unknown cause of death (21% of white males and 12% of non-white males), 
    the authors calculated three separate mortality expectations based upon 
    race-, gender-, age-, and time-specific U.S. mortality ratios. The 
    first expectation was calculated upon the assumption that those lost to 
    follow-up were alive at the end of the study follow-up period. The 
    second expectation was calculated on the assumption that those whose 
    vital status was unknown were lost to follow-up as of their employment 
    termination date. The third expectation was calculated excluding those 
    of unknown vital status from the cohort. Deaths with unknown cause were 
    distributed in the appropriate proportions among known causes of death 
    which served as an adjustment to the observed deaths. The adjusted 
    deaths were used in all of the analyses.
        A statistically significant ratio for lung cancer deaths among 
    white males (O/E=1.6) was observed when using the assumption that 
    either the lost to follow-up were assumed lost as of their termination 
    date or were excluded from the cohort (assumptions two and three 
    above). The ratio for lung cancer deaths for non-white males results in 
    an identical O/E of 1.6 for all three of the above scenarios, none of 
    which was statistically significant.
        In addition, the authors also conducted Proportionate Mortality 
    Ratio (PMR) and Proportionate Cancer Mortality Ratio (PCMR) analyses. 
    For white males, the lung cancer PMR was 200 and the lung cancer PCMR 
    was 160 based upon 25.5 adjusted observed deaths (21 actual deaths). 
    Both were statistically significantly elevated at the p< .05 level. For 
    non-white males, the lung cancer PMR was 200 and the lung cancer PCMR 
    was 150 based upon 11.2 adjusted observed deaths (10 actual deaths). 
    The lung cancer PMR for non-white males was statistically significantly 
    elevated at the p< .05 level. Statistically significantly elevated PMRs 
    and PCMRs for stomach cancer in white males were reported (PMR=280; 
    PCMR=230) based upon 6.1 adjusted observed deaths (five actual).
        The Sheffet cohort was updated in a study by Hayes et al. (Ex. 7-
    46). The follow up was through December 31, 1982. Workers employed as 
    process operators or in other jobs which involved direct exposure to 
    chromium dusts were classified as having exposure to chromates. Airborne 
    chromium concentrations taken in "later years" were estimated to be 
    >500 [mu]g g/m\3\ for "exposed" jobs and >2000 [mu]g/m\3\ for 
    "highly exposed" jobs.
        The cohort included 1,181 white and 698 non-white males. Of the 453 
    deaths identified by the end of the follow-up period, 41 were lung 
    cancers. For the entire study group, no statistically significant 
    excess was observed for lung cancer (SMR=116) or for cancer at any 
    other site. Analysis by duration of employment found a statistically 
    significant trend (p=.04) for lung cancer SMRs (67 for those employed 
    < 1 year; 122 for those employed 1-9 years and 151 for those employed 
    10+ years).
        Analysis of lung cancer deaths by duration of employment in 
    chromate dust associated jobs found no elevation in risk for subjects 
    who never worked in these jobs (SMR=92) or for subjects employed less 
    than one year in these jobs (SMR=93). For those with cumulative 
    employment of 1-9 and 10+ years in jobs with chromate dust exposure, 
    the SMRs were 176 (nine deaths) and 194 (eight deaths) respectively.
        Frentzel-Beyme studied the mortality experience of 1,396 men 
    employed for more than six months in one of five factories producing 
    lead and zinc chromate pigments located in Germany and the Netherlands 
    (Ex. 7-45). The observed deaths from the five factories were compared 
    with the expected deaths calculated on the basis of mortality figures 
    for the region in which the plant was located. Additional analysis was 
    conducted on relevant cohorts which included workers with a minimum of 
    10 years exposure, complete records for the entire staff, and exclusion 
    of foreign nationals. Jobs were assigned into one of three exposure 
    categories: High (drying and milling of the filtered pigment paste), 
    medium (wet processes including precipitation of the pigment, filtering 
    and maintenance, craftsmen and cleaning) and low or trivial exposure 
    (storage, dispatch, laboratory personnel and supervisors).
        There were 117 deaths in the entire cohort of which 19 were lung 
    cancer deaths (E=9.3). The lung cancer SMRs in the relevant cohort 
    analyses were elevated at every plant; however, in only one instance 
    was the increased lung cancer SMR statistically significant, based upon 
    three deaths (SMR=386, p< 0.05). Analysis by type of exposure is not 
    meaningful due to the small number of lung cancer deaths per plant per 
    exposure classification.
        Kano et al. conducted a study of five Japanese manufacturers who 
    produced lead chromates, zinc chromate, and/or strontium chromate to 
    assess if there was an excess risk of lung cancer (Ex. 7-118). The 
    cohort consisted of 666 workers employed for a minimum of one year 
    between 1950 and 1975. At the end of 1989, 604 subjects were alive, 
    five lost to follow-up and 57 dead. Three lung cancer deaths were 
    observed in the cohort with 2.95 expected (SMR=102; 95% CI: 0.21-2.98). 
    Eight stomach cancer deaths were reported with a non-statistically 
    significant SMR of 120.
        Following the publication of the proposed rule, the Color Pigment 
    Manufacturers Association requested that OSHA reconsider its 
    preliminary conclusions with respect to the health effects of lead 
    chromate color pigments (Ex. 38-205). They relied on the Davies (Ex. 7-
    43), Cooper [Equitable Environmental Health, Inc] (Ex. 2-D-1) and Kano 
    (Ex. 14-1-B) epidemiologic studies as the only available data on worker 
    cohorts exposed to lead chromate in the absence of other chromates 
    commonly found in pigment production (e.g., zinc chromate). The CPMA's 
    comments regarding the Davies, Cooper and Kano studies and OSHA's 
    response to them are discussed in section V.B.9.a.
    3. Evidence from Workers in Chromium Plating
        Chrome plating is the process of depositing chromium metal onto the 
    surface of an item using a solution of chromic acid. The items to be 
    plated are suspended in a diluted chromic acid bath. A fine chromic 
    acid mist is produced when gaseous bubbles, released by the 
    dissociation of water, rise to the surface of the plating bath and 
    burst. There are two types of chromium electroplating. Decorative or 
    "bright" involves depositing a thin (0.5-1 [mu]m) layer of chromium 
    over nickel or nickel-type coatings to provide protective, durable, 
    non-tarnishable surface finishes. Decorative chrome plating is used for 
    automobile and bicycle parts. Hard chromium plating produces a thicker 
    (exceeding 5 [mu]m) coating which makes it resistant and solid where 
    friction is usually greater, such as in crusher propellers and in 
    camshafts for ship engines. Limited air monitoring indicates that 
    Cr(VI) levels are five to ten times higher during hard plating than 
    decorative plating (Ex. 35-116).
        There are fewer studies that have examined the lung cancer 
    mortality of chrome platers than of soluble chromate production and 
    chromate pigment production workers. The largest and best described 
    cohort studies investigated chrome plating cohorts in the United 
    Kingdom (Exs. 7-49; 7-57; 271; 35-62). They generally found elevated 
    lung cancer mortality among the chrome platers, especially those 
    engaged in chrome bath work, when compared to various reference 
    populations. The studies of British chrome platers are summarized in 
    Table V-3.
    BILLING CODE 4510-26-P
Table V-3

 

    
    BILLING CODE 4510-26-C
        Cohort studies of chrome platers in Italy, the United States, and 
    Japan are also discussed in this subsection. Co-exposure to nickel, 
    another suspected carcinogen, during plating operations can complicate 
    evaluation of an association between Cr(VI) and an increased risk of 
    lung cancer in chrome platers. Despite this, the International Agency 
    for Research on Cancer concluded that the epidemiological
    studies provide sufficient evidence for carcinogenicity of Cr(VI) as 
    encountered in the chromium plating industry; the same conclusion 
    reached for chromate production and chromate pigment production (Exs. 
    18-1; 35-43). The findings implicate the highly water-soluble chromic 
    acid as an occupational carcinogen. This adds to the weight of evidence 
    that water-soluble (e.g., sodium chromates, chromic acid) and water-
    insoluble forms (e.g., lead and zinc chromates) of Cr(VI) are able to 
    cause cancer of the lower respiratory tract.
        Royle reported on a cohort mortality study of 1,238 chromium 
    platers employed for a minimum of three consecutive months between 
    February 20, 1969 and May 31, 1972 in 54 plating plants in West Riding, 
    Yorkshire, England (Ex. 7-49). A control population was enumerated from 
    other departments of the larger companies where chromium plating was 
    only a portion of the companies' activities and from the former and 
    current employees of two industrial companies in York where information 
    on past workers was available. Controls were matched for gender, age 
    (within two years) and date last known alive. In addition, 229 current 
    workers were matched for smoking habits.
        As of May 1974, there were 142 deaths among the platers (130 males 
    and 12 females) and 104 deaths among the controls (96 males and 8 
    females). Among the male platers, there were 24 deaths from cancer of 
    the lung and pleura compared to 13 deaths in the control group. The 
    difference was not statistically significant. There were eight deaths 
    from gastrointestinal cancer among male platers versus four deaths in 
    the control group. The finding was not statistically significant.
        The Royle cohort was updated by Sorahan and Harrington (Ex. 35-62). 
    Chrome plating was the primary activity at all 54 plants, however 49 of 
    the plants used nickel and 18 used cadmium. Also used, but in smaller 
    quantities according to the authors, were zinc, tin, copper, silver, 
    gold, brass or rhodium. Lead was not used at any of the plants. Four 
    plants, including one of the largest, only used chromium. Thirty-six 
    chrome platers reported asbestos exposure versus 93 comparison workers.
        Industrial hygiene surveys were carried out at 42 plants during 
    1969-1970. Area air samples were done at breathing zone height. With 
    the exception of two plants, the chromic acid air levels were less than 
    30 [mu]g/m\3\. The two exceptions were large plants, and in both the 
    chromic acid levels exceeded 100 [mu]g/m\3\.
        The redefined cohort consisted of 1087 platers (920 men and 167 
    women) from 54 plants employed for a minimum of three months between 
    February 1969 and May 31, 1972 who were alive on May 31, 1972. 
    Mortality data were also available for a comparison group of 1,163 
    workers (989 men and 174 women) with no chromium exposure. Both groups 
    were followed for vital status through 1997.
        The lung cancer SMR for male platers was statistically significant 
    (O=60; E=32.5; SMR=185; 95% CI: 141-238). The lung cancer SMR for the 
    comparison group, while elevated, was not statistically significant 
    (O=47; E=36.9; SMR=127; 95% CI: 94-169). The only statistically 
    significant SMR in the comparison group was for cancer of the pleura 
    (O=7; E=0.57; SMR=1235; 95% CI: 497-2545).
        Internal regression analyses were conducted comparing the mortality 
    rates of platers directly with those of the comparison workers. For 
    these analyses, lung cancers mentioned anywhere on the death 
    certificate were considered cases. The redefinition resulted in four 
    additional lung cancer cases in the internal analyses. There was a 
    statistically significant relative risk of 1.44 (p< 0.05) for lung 
    cancer mortality among chrome platers that was slightly reduced to 1.39 
    after adjustment for smoking habits and employment status. There was no 
    clear trend between lung cancer mortality and duration of Cr(VI) 
    exposure. However, any positive trend may have been obscured by the 
    lack of information on worker employment post-1972 and the large 
    variation in chromic acid levels among the different plants.
        Sorahan reported the experience of a cohort of 2,689 nickel/
    chromium platers from the Midlands, U.K. employed for a minimum of six 
    months between 1946 and 1975 and followed through December 1983 (Ex. 7-
    57). There was a statistically significant lung cancer SMR for males 
    (O=63; E=40; SMR=158; p< 0.001). The lung cancer SMR for women, while 
    elevated (O=9; E=8.1; SMR=111), was not statistically significant. 
    Other statistically significant cancer SMRs for males included: stomach 
    (O=21; E=11.3; SMR=186; p< 0.05); liver (O=4; E=0.6; SMR=667; p< 0.01); 
    and nasal cavities (O=2; E=0.2; SMR=1000; p< 0.05). While there were 
    several elevated SMRs for women, none were statistically significant. 
    There were nine lung cancers and one nasal cancer among the women.
        Analysis by type of first employment (i.e., chrome bath workers vs. 
    other chrome work) resulted in a statistically significant SMR for lung 
    cancer of 199 (O=46; E=23.1; p< 0.001) for chrome bath workers and a SMR 
    of 101 for other chrome work. The SMR for cancer of the stomach for 
    male chrome bath workers was also statistically significantly elevated 
    (O=13; E=6.3; SMR=206; p< 0.05); for stomach cancer in males doing other 
    chrome work, the SMR was 160 with 8 observed and 5 expected. Both of 
    the nasal cancers in males and the one nasal cancer in women were 
    chrome bath workers. The nasal cancer SMR for males was statistically 
    significantly elevated (O=2; E=0.1; SMR=2000; p< 0.05).
        Regression analysis was used to examine evidence of association of 
    several types of cancers and Cr(VI) exposure duration among the cohort. 
    There was a significant positive association between lung cancer 
    mortality and exposure duration as a chrome bath worker controlling for 
    gender as well as year and age at the start of employment. There was no 
    evidence of an association between other cancer types and duration of 
    Cr(VI) exposure. There was no positive association between duration of 
    exposure to nickel bath work and cancer of the lung. The two largest 
    reported SMRs were for chrome bath workers 10-14 years (O=13; E=3.8; 
    SMR=342; p< 0.001) and 15-19 years (O=12; E=4.9; SMR=245; p< 0.01) after 
    starting employment. The positive associations between lung cancer 
    mortality and duration of chrome bath work suggests Cr(VI) exposure may 
    be responsible for the excess cancer risk.
        Sorahan et al. reported the results of a follow-up to the nickel/
    chromium platers study discussed above (Ex. 271). The cohort was 
    redefined and excluded employees whose personnel records could not be 
    located (650); those who started chrome work prior to 1946 (31) and 
    those having no chrome exposure (236). The vital status experience of 
    1,762 workers (812 men and 950 women) was followed through 1995. The 
    expected number of deaths was based upon the mortality of the general 
    population of England and Wales.
        There were 421 deaths among the men and 269 deaths among the women, 
    including 52 lung cancers among the men and 17 among the women. SMRs 
    were calculated for different categories of chrome work: Period from 
    first chrome work; year of starting chrome work, and cumulative 
    duration of chrome work categories. Poison regression modeling was 
    employed to investigate lung cancer in relation to type of chrome work 
    and cumulative duration of work.
        A significantly elevated lung cancer SMR was seen for male workers 
    with some period of chrome bath work (O=40; E=25.4; SMR=157; 95% CI: 113-
    214, p< 0.01). Lung cancer was not elevated among male workers engaged 
    in other chrome work away from the chromic acid bath (O=9; E=13.7; 
    SMR=66; 95% CI: 30-125). Similar lung cancer mortality results were 
    found for female chrome bath workers (O=15; E=8.6; SMR=175; 95% CI: 98-
    285; p< 0.06). After adjusting for sex, age, calendar year, year 
    starting chrome work, period from first chrome work, and employment 
    status, regression modeling showed a statistically significant positive 
    trend (p< 0.05) between duration of chrome bath work and lung cancer 
    mortality risk. The relative lung cancer risk for chrome bath workers 
    with more than five years of Cr(VI) exposure (i.e., relative to the 
    risk of those without any chrome bath work) was 4.25 (95% CI: 1.83-
    9.37).
        Since the Sorahan cohort consists of nickel/chromium workers, the 
    question arises of the potential confounding of nickel. In the earlier 
    study, 144 of the 564 employees with some period of chrome bath work 
    had either separate or simultaneous periods of nickel bath employment. 
    According to the authors, there was no clear association between cancer 
    deaths from stomach, liver, respiratory system, nose and larynx, and 
    lung and bronchus and the duration of nickel bath employment. In the 
    follow-up report, the authors re-iterate this result stating, 
    "findings for lung cancer in a cohort of nickel platers (without any 
    exposure to chrome plating) from the same factory are unexceptional" 
    (Ex. 35-271, p. 241).
        Silverstein et al. reported the results of a cohort study of hourly 
    employees and retirees with at least 10 years of credited pension 
    service in a Midwestern plant manufacturing hardware and trim 
    components for use primarily in the automobile industry (Ex. 7-55). Two 
    hundred thirty eight deaths occurred between January 1, 1974 and 
    December 31, 1978. Proportional Mortality Ratio (PMR) analysis adjusted 
    for race, gender, age and year of death was conducted. For white males, 
    the PMR for cancer of the lung and pleura was 1.91 (p< 0.001) based upon 
    28 deaths. For white females, the PMR for cancer of the lung and pleura 
    was 3.70 (p< 0.001) based upon 10 deaths.
        White males who worked at the plant for less than 15 years had a 
    lung cancer PMR of 1.65. Those with 15 or more years at the plant had a 
    lung cancer PMR of 2.09 (p< 0.001). For white males with less than 22.5 
    years between hire and death (latency) the lung cancer PMR was 1.78 
    (p< 0.05) and for those with 22.5 or more years, the PMR was 2.11 
    (p< 0.01).
        A case-control analysis was conducted on the Silverstein cohort to 
    examine the association of lung cancer risk with work experience. 
    Controls were drawn from cardiovascular disease deaths (ICD 390-458, 
    8th revision). The 38 lung cancer deaths were matched to controls for 
    race and gender. Odds ratios (ORs) were calculated by department 
    depending upon the amount of time spent in the department (ever/never; 
    more vs. less than one year; and more vs. less than five years). Three 
    departments showed increasing odds ratios with duration of work; 
    however, the only statistically significant result was for those who 
    worked more than five years in department 5 (OR=9.17, p=0.04, Fisher's 
    exact test). Department 5 was one of the major die-casting and plating 
    areas of the plant prior to 1971.
        Franchini et al. conducted a mortality study of employees and 
    retirees from nine chrome plating plants in Parma, Italy (Ex. 7-56). 
    Three plants produced hard chrome plating. The remaining six plants 
    produced decorative chromium plates. A limited number of airborne 
    chromium measurements were available. Out of a total of 10 measurements 
    at the hard chrome plating plants, the air concentrations of chromium 
    averaged 7 [mu]g/m\3\ (range of 1-50 [mu]g/m\3\) as chromic acid near 
    the baths and 3 [mu]g/m\3\ (range of 0-12 [mu]g/m\3\) in the middle of 
    the room.
        The cohort consisted of 178 males (116 from the hard chromium 
    plating plants and 62 from the bright chromium plating plants) who had 
    worked for at least one year between January 1, 1951 and December 31, 
    1981. In order to allow for a 10-year latency period, only those 
    employed before January 1972 were included in further analysis. There 
    were three observed lung cancer deaths among workers in the hard chrome 
    plating plants, which was significantly greater than expected (O=3; 
    E=0.6; p< 0.05). There were no lung cancer deaths among decorative 
    chrome platers.
        Okubo and Tsuchiya conducted a study of plating firms with five or 
    more employees in Tokyo (Exs. 7-51; 7-52). Five hundred and eighty nine 
    firms were sent questionnaires to ascertain information regarding 
    chromium plating experience. The response rate was 70.5%. Five thousand 
    one hundred seventy platers (3,395 males and 1,775 females) met the 
    cohort entrance criteria and were followed from April 1, 1970 to 
    September 30, 1976. There were 186 deaths among the cohort; 230 people 
    were lost to follow-up after retirement. The cohort was divided into 
    two groups: Chromium platers who worked six months or more and a 
    control group with no exposure to chromium (clerical, unskilled 
    workers). There were no deaths from lung cancer among the chromium 
    platers.
        The Okubo cohort was updated by Takahashi and Okubo (Ex. 265). The 
    cohort was redefined to consist of 1,193 male platers employed for a 
    minimum of six months between April 1970 and September 1976 in one of 
    415 Tokyo chrome plating plants and who were alive and over 35 years of 
    age on September 30, 1976. The only statistically significant SMR was 
    for lung cancer for all platers combined (O=16; E=8.9; SMR=179; 95% CI: 
    102-290). The lung cancer SMR for the chromium plater subcohort was 187 
    based upon eight deaths and 172 for the nonchromium plater subcohort, 
    also based upon eight deaths. The cohort was followed through 1987. 
    Itoh et al. updated the Okubo metal plating cohort through December 
    1992 (Ex. 35-163). They reported a lung cancer SMR of 118 (95% CI: 99-
    304).
    4. Evidence From Stainless Steel Welders
        Welding is a term used to describe the process for joining any 
    materials by fusion. The fumes and gases associated with the welding 
    process can cause a wide range of respiratory exposures which may lead 
    to an increased risk of lung cancer. The major classes of metals most 
    often welded include mild steel, stainless and high alloy steels and 
    aluminum. The fumes from stainless steel, unlike fumes from mild steel, 
    contain nickel and Cr(VI). There are several cohort and case-control 
    studies as well as two meta analyses of welders potentially exposed to 
    Cr(VI). In general, the studies found an excess number of lung cancer 
    deaths among stainless steel welders. However, few of the studies found 
    clear trends with Cr(VI) exposure duration or cumulative Cr(VI). In 
    most studies, the reported excess lung cancer mortality among stainless 
    steel welders was no greater than mild steel welders, even though 
    Cr(VI) exposure is much greater during stainless steel welding. This 
    weak association between lung cancer and indices of exposure limits the 
    evidence provided by these studies. Other limitations include the co-
    exposures to other potential lung carcinogens, such as nickel, 
    asbestos, and cigarette smoke, as well as possible healthy worker 
    effects and exposure misclassification in some studies, which may 
    obscure a relationship betweeen Cr(VI) and lung cancer risk. These 
    limitations are discussed further in sections VI.B.5, VI.E.3, and 
    VI.G.4.
    Nevertheless, these studies add some further support to the much 
    stronger link between Cr(VI) and lung cancer found in soluble chromate 
    production workers, chromate pigment production workers, and chrome 
    platers. The key studies are summarized in Table V-4.
    BILLING CODE 4510-26-P

Table V-4 Part 1

 

Table V-4 Part 2

 

    
    BILLING CODE 4510-26-C
        Sjogren et al. reported on the mortality experience in two cohorts 
    of welders (Ex. 7-95). The cohort characterized as "high exposure"
    consisted of 234 male stainless steel welders with a minimum of 5 years 
    of employment between 1950 and 1965. An additional criterion for 
    inclusion in the study was assurance from the employer that asbestos 
    had not been used or had been used only occasionally and never in a 
    dust-generating way. The cohort characterized as "low exposure" 
    consisted of 208 male railway track welders working at the Swedish 
    State Railways for at least 5 years between 1950 and 1965. In 1975, air 
    pollution in stainless steel welding was surveyed in Sweden. The median 
    time weighted average (TWA) value for Cr(VI) was 110 [mu]g 
    CrO3/m\3\ (57 [mu]g/m\3\ measured as CrVI). The highest 
    concentration was 750 [mu]g CrO3/m\3\ (390 [mu]g/m\3\ 
    measured as CrVI) found in welding involving coated electrodes. For 
    gas-shielded welding, the median Cr(VI) concentration was 10 [mu]g 
    CrO3/m\3\ (5.2 [mu]g/m\3\ measured as CrVI) with the highest 
    concentration measured at 440 [mu]g CrO3/m\3\ (229 [mu]g/
    m\3\ measured as CrVI). Follow-up for both cohorts was through December 
    1984. The expected number of deaths was based upon Swedish male death 
    rates. Of the 32 deaths in the "high exposure" group, five were 
    cancers of the trachea, bronchus and lung (E=2.0; SMR=249; 95% CI: 
    0.80-5.81). In the low exposure group, 47 deaths occurred, one from 
    cancer of the trachea, bronchus and lung.
        Polednak compiled a cohort of 1,340 white male welders who worked 
    at the Oak Ridge nuclear facilities from 1943 to 1977 (Ex. 277). One 
    thousand fifty-nine cohort members were followed through 1974. The 
    cohort was divided into two groups. The first group included 536 
    welders at a facility where nickel-alloy pipes were welded; the second 
    group included 523 welders of mild steel, stainless steel and aluminum 
    materials. Smoking data were available for 33.6% of the total cohort. 
    Expectations were calculated based upon U.S. mortality rates for white 
    males. There were 17 lung cancer deaths in the total cohort (E=11.37; 
    SMR=150; 95% CI: 87-240). Seven of the lung cancer deaths occurred in 
    the group which routinely welded nickel-alloy materials (E=5.65; 
    SMR=124; 95% CI: 50-255) versus 10 lung cancer deaths in the "other" 
    welders (E=6.12; SMR=163; 95% CI: 78-300).
        Becker et al. compiled a cohort of 1,213 stainless steel welders 
    and 1,688 turners from 25 German metal processing factories who had a 
    minimum of 6 months employment during the period 1950-1970 (Exs. 227; 
    250; 251). The data collected included the primary type of welding 
    (e.g., arc welding, gas-shielded welding, etc.) used by each person, 
    working conditions, average daily welding time and smoking status. The 
    most recent follow-up of the cohort was through 1995. Expected numbers 
    were developed using German mortality data. There were 268 deaths among 
    the welders and 446 deaths among the turners. An elevated, but non-
    statistically significant, lung cancer SMR (O=28; E=23; SMR=121.5; 95% 
    CI: 80.7-175.6) was observed among the welders. There were 38 lung 
    cancer deaths among the turners with 38.6 expected, resulting in a SMR 
    slightly below unity. Seven deaths from cancer of the pleura (all 
    mesotheliomas) occurred among the welders with only 0.6 expected 
    (SMR=1,179.9; 95% CI: 473.1-2,430.5), compared to only one death from 
    cancer of the pleura among the turners, suggesting that the welders had 
    exposure to asbestos. Epidemiological studies have shown that asbestos 
    exposure is a primary cause of pleural mesotheliomas.
        The International Agency for Research on Cancer (IARC) and the 
    World Health Organization (WHO) cosponsored a study on welders. IARC 
    and WHO compiled a cohort of 11,092 male welders from 135 companies in 
    nine European countries to investigate the relationship between the 
    different types of exposure occurring in stainless steel, mild steel 
    and shipyard welding and various cancer sites, especially lung cancer 
    (Ex. 7-114). Cohort entrance criteria varied by country. The expected 
    number of deaths was compiled using national mortality rates from the 
    WHO mortality data bank.
        Results indicated the lung cancer deaths were statistically 
    significant in the total cohort (116 cases; E=86.81; SMR=134; 95% CI: 
    110-160). Cohort members were assigned to one of four subcohorts based 
    upon type of welding activity. While the lung cancer SMRs were elevated 
    for all of the subcohorts, the only statistically significant SMR was 
    for the mild steel-only welders (O=40; E=22.42; SMR=178; 95% CI: 127-
    243). Results for the other subgroups were: shipyard welders (O=36; 
    E=28.62; SMR=126; 95% CI: 88-174); ever stainless steel welders (O=39; 
    E=30.52; SMR=128; 95% CI: 91-175); and predominantly stainless steel 
    welders (O=20; E=16.25; SMR=123; 95% CI: 75-190). When analyzed by 
    subcohort and time since first exposure, the SMRs increased over time 
    for every group except shipyard welders. For the predominantly 
    stainless steel welder subcohort, the trend to increase with time was 
    statistically significant (p < .05).
        An analysis was conducted of lung cancer mortality in two stainless 
    steel welder subgroups (predominantly and ever) with a minimum of 5 
    years of employment. Cumulative Cr(VI) was computed from start of 
    exposure until 20 years prior to death. A lung cancer SMR of 170, based 
    upon 14 cases, was observed in the stainless steel ever subgroup for 
    those welders with >=0.5 mg-years/m\3\ Cr(VI) exposure; the lung cancer 
    SMR for those in the < 0.5 mg-years/m\3\ Cr(VI) exposure group was 123 
    (based upon seven cases). Neither SMR was statistically significant. 
    For the predominantly stainless steel welders, which is a subset of the 
    stainless steel ever subgroup, the corresponding SMRs were 167 (>=0.5 
    mg-years/m\3\ Cr(VI) exposure) based upon nine cases and 191 (< 0.5 mg-
    years/m\3\ Cr(VI) exposure) based upon three cases. Neither SMR was 
    statistically significant.
        In conjunction with the IARC/WHO welders study, Gerin et al. 
    reported the development of a welding process exposure matrix relating 
    13 combinations of welding processes and base metals used to average 
    exposure levels for total welding fumes, total chromium, Cr(VI) and 
    nickel (Ex. 7-120). Quantitative estimates were derived from the 
    literature supplemented by limited monitoring data taken in the 1970s 
    from only 8 of the 135 companies in the IARC/WHO mortality study. An 
    exposure history was constructed which included hire and termination 
    dates, the base metal welded (stainless steel or mild steel), the 
    welding process used and changes in exposure over time. When a detailed 
    welding history was not available for an individual, the average 
    company welding practice profile was used. In addition, descriptions of 
    activities, work force, welding processes and parameters, base metals 
    welded, types of electrodes or rods, types of confinement and presence 
    of local exhaust ventilation were obtained from the companies.
        Cumulative dose estimates in mg/m\3\ years were generated for each 
    welder's profile (number of years and proportion of time in each 
    welding situation) by applying a welding process exposure matrix 
    associating average concentrations of welding fumes (mg/m\3\) to each 
    welding situation. The corresponding exposure level was multiplied by 
    length of employment and summed over the various employment periods 
    involving different welding situations. No dose response relationship 
    was seen for exposure to Cr(VI) for either those who were "ever 
    stainless steel welders" or those who were "predominantly stainless 
    steel welders". The authors note that if their exposure estimates are 
    correct, the study had the power to detect a significant result in the 
    high exposure group for Cr(VI). However, OSHA believes that there is 
    likely to be substantial exposure misclassification in this study, as 
    discussed further in section VI.G.4.
        The IARC/WHO multicenter study is the sole attempt to undertake 
    even a semi-quantified exposure analysis of stainless steel welders' 
    potential exposure to nickel and Cr(VI) for <5 and >=0.5 mg-years/
    m3 Cr(VI) exposures. The IARC/WHO investigators noted that 
    there was more than a twofold increase in SMRs between the long (>=20 
    years since first exposure) and short (< 20 years since first exposure) 
    observation groups for the predominantly stainless steel welders 
    "suggesting a relation of lung cancer mortality with the occupational 
    environment for this group" (Ex. 7-114, p. 152). The authors conclude 
    that the increase in lung cancer mortality does not appear to be 
    related to either duration of exposure or cumulative exposure to total 
    fume, chromium, Cr(VI) or nickel.
        Moulin compiled a cohort of 2,721 French male welders and an 
    internal comparison group of 6,683 manual workers employed in 13 
    factories (including three shipyards) with a minimum of one year of 
    employment from 1975 to 1988 (Ex. 7-92). Three controls were selected 
    at random for each welder. Smoking data were abstracted from medical 
    records for 86.6% of welders and 86.5% of the controls. Smoking data 
    were incorporated in the lung cancer mortality analysis using methods 
    suggested by Axelson. Two hundred and three deaths were observed in the 
    welders and 527 in the comparison group. A non-statistically 
    significant increase was observed in the lung cancer SMR (O=19; 
    E=15.33; SMR=124; 95% CI: 0.75-1.94) for the welders. In the control 
    group, the lung cancer SMR was in deficit (O=44; E=46.72; SMR=94; 95% 
    CI: 0.68-1.26). The resulting relative risk was a non-significant 1.3. 
    There were three deaths from pleural cancer in the comparison group and 
    none in the welders, suggesting asbestos exposure in the comparison 
    group. The welders were divided into four subgroups (shipyard welders, 
    mild steel only welders, ever stainless steel welders and stainless 
    steel predominantly Cr(VI) welders). The highest lung cancer SMR was 
    for the mild steel welders O=9; SMR of 159). The lowest lung cancer 
    SMRs were for ever stainless steel welders (O=3; SMR= 92) and for 
    stainless steel predominantly Cr(VI) welders (O=2; SMR= 103). None of 
    the SMRs are statistically significant.
        Hansen conducted a study of cancer incidence among 10,059 male 
    welders, stainless steel grinders and other metal workers from 79 
    Danish companies (Ex. 9-129). Cohort entrance criteria included: alive 
    on April 1, 1968; born before January 1, 1965; and employed for at 
    least 12 months between April 1, 1964 and December 31, 1984. Vital 
    status follow-up found 9,114 subjects alive, 812 dead and 133 
    emigrated. A questionnaire was sent to subjects and proxies for 
    decedents/emigrants in an attempt to obtain information about lifetime 
    occupational exposure, smoking and drinking habits. The overall 
    response rate was 83%. The authors stated that no major differences in 
    smoking habits were found between exposure groups with or without a 
    significant excess of lung cancer.
        The expected number of cancers was based on age-adjusted national 
    cancer incidence rates from the Danish Cancer Registry. There were 
    statistically significantly elevated Standardized Incidence Ratios 
    (SIRs) for lung cancer in the welding (any kind) group (O=51; E=36.84; 
    SIR=138; 95% CI: 103-181) and in the mild steel only welders (O=28; 
    E=17.42; SIR=161; 95% CI: 107-233). The lung cancer SIR for mild steel 
    ever welders was 132 (O=46; E=34.75; 95% CI: 97-176); for stainless 
    steel ever welders 119 (O=23; E=19.39; 95% CI: 75-179) and for 
    stainless steel only welders 238 (O=5; E=2.10; 95% CI: 77-555).
        Laurtitsen reported the results of a nested case-control conducted 
    in conjunction with the Hansen cancer incidence study discussed above 
    (Exs. 35-291; 9-129). Cases were defined as the 94 lung cancer deaths. 
    Controls were defined as anyone who was not a case, but excluded deaths 
    from respiratory diseases other than lung cancer (either as an 
    underlying or a contributing cause of death), deaths from "unknown 
    malignancies" and decedents who were younger than the youngest case. 
    There were 439 decedents eligible for use as controls.
        The crude odds ratio (OR) for welding ever (yes/no) was 1.7 (95% 
    CI: 1.0-2.8). The crude OR for mild steel welding only was 1.3 (95% CI: 
    0.8-2.3) and for stainless steel welding only the crude OR was 1.3 (95% 
    CI: 0.3-4.3). When analyzed by number of years exposed, "ever" 
    stainless steel welding showed no relationship with increasing number 
    of years exposed. The highest odds ratio (2.9) was in the lowest 
    category (1-5 years) based upon seven deaths; the lowest odds ratio was 
    in the highest category (21+ years) based upon three deaths.
        Kjuus et al. conducted a hospital-based case-control study of 176 
    male incident lung cancer cases and 186 controls (matched for age, +/-5 
    years) admitted to two county hospitals in southeast Norway during 
    1979-1983 (Ex. 7-72). Subjects were classified according to exposure 
    status of main occupation and number of years in each exposure category 
    and assigned into one of three exposure groups according to potential 
    exposure to respiratory carcinogens and other contaminants. A 
    statistically significantly elevated risk ratio for lung cancer 
    (adjusted for smoking) for the exposure factor "welding, stainless, 
    acid proof" of 3.3 (p< 0.05) was observed based upon 16 lung cancer 
    deaths. The unadjusted odds ratio is not statistically significant 
    (OR=2.8). However, the appropriateness of the analysis is questionable 
    since the exposure factors are not discrete (a case or a control may 
    appear in multiple exposure factors and therefore is being compared to 
    himself). In addition, the authors note that several exposure factors 
    were highly correlated and point out specifically that one-half of the 
    cases "exposed to either stainless steel welding fumes or fertilizers 
    also reported moderate to heavy asbestos exposure." When put into a 
    stepwise logistic regression model, exposure to stainless steel fumes, 
    which was initially statistically significant, loses its significance 
    when smoking and asbestos are first entered into the model.
        Hull et al. conducted a case-control study of lung cancer in white 
    male welders aged 20-65 identified through the Los Angeles County tumor 
    registry (Southern California Cancer Surveillance Program) for the 
    period 1972 to 1987 (Ex. 35-243). Controls were welders 40 years of age 
    or older with non-pulmonary malignancies. Interviews were conducted to 
    obtain information about sociodemographic data, smoking history, 
    employment history and occupational exposures to specific welding 
    processes, metals welded, asbestos and confined space welding. 
    Interviews were completed for 90 (70%) of the 128 lung cancer cases and 
    116 (66%) of the controls. Analysis was conducted using 85 deceased 
    cases and 74 deceased controls after determining that the subject's 
    vital status influenced responses to questions concerning occupational 
    exposures. The crude odds ratio (ever vs. never exposed) for stainless 
    steel welding, based upon 34 cases, was 0.9 (95% CI: 0.3-1.4). For 
    manual metal arc welding on stainless steel, the crude odds ratio
    was 1.3 (95% CI: 0.6-2.3) based upon 61 cases.
        While the relative risk estimates in both cohort and case-control 
    of stainless steel welders are elevated, none are statistically 
    significant. However, when combined in two meta-analyses, a small but 
    statistically significant increase in lung cancer risk was reported. 
    Two meta-analyses of welders have been published. Moulin carried out a 
    meta-analysis of epidemiologic studies of lung cancer risk among 
    welders, taking into account the role of asbestos and smoking (Ex. 35-
    285). Studies published between 1954 and 1994 were reviewed. The 
    inclusion criteria were clearly defined: only the most recent updates 
    of cohort studies were used and only the mortality data from mortality/
    morbidity studies were included. Studies that did not provide the 
    information required by the meta-analysis were excluded.
        Five welding categories were defined (shipyard welding, non-
    shipyard welding, mild steel welding, stainless steel welding and all 
    or unspecified welding). The studies were assigned to a welding 
    category (or categories) based upon the descriptions provided in the 
    paper's study design section. The combined relative risks (odds ratios, 
    standardized mortality ratios, proportionate mortality ratios and 
    standardized incidence ratios) were calculated separately for the 
    population-based studies, case-control studies, and cohort studies, and 
    for all the studies combined.
        Three case-control studies (Exs. 35-243; 7-120; 7-72) and two 
    cohort studies (Exs. 7-114; 35-277) were included in the stainless 
    steel welding portion of the meta-analysis. The combined relative risk 
    was 2.00 (O=87; 95% CI: 1.22-3.28) for the case-control studies and 
    1.23 (O=27; 95% CI: 0.82-1.85) for the cohort studies. When all five 
    studies were combined, the relative risk was 1.50 (O=114; 95% CI: 1.10-
    2.05).
        By contrast, the combined risk ratio for the case-control studies 
    of mild steel welders was 1.56 (O=58; 95% CI: 0.82-2.99) (Exs. 7-120; 
    35-243). For the cohort studies, the risk ratio was 1.49 (O=79; 95% CI: 
    1.15-1.93) (Exs. 35-270; 7-114). For the four studies combined, the 
    risk ratio was 1.50 (O=137; 95% CI: 1.18-191). The results for the 
    stainless steel welders and the mild steel welders are basically the 
    same.
        The meta-analysis by Sjogren of exposure to stainless steel welding 
    fumes and lung cancer included studies published between 1984 and 1993, 
    which took smoking and potential asbestos exposure into account (Ex. 7-
    113). Five studies met the author's inclusion criteria and were 
    included in the meta-analysis: two cohort studies, Moulin et al. (Ex. 
    35-283) and Sjogren et al. (Ex. 7-95); and three case-control studies, 
    Gerin, et al. (Ex. 7-120, Hansen et al. (Ex. 9-129) and Kjuus et al. 
    (Ex. 7-72). The calculated pooled relative risk for welders exposed to 
    stainless steel welding fumes was 1.94 (95% CI: 1.28-2.93).
    5. Evidence from Ferrochromium Workers
        Ferrochromium is produced by the electrothermal reduction of 
    chromite ore with coke in the presence of iron in electric furnaces. 
    Some of the chromite ore is oxidized into Cr(VI) during the process. 
    However, most of the ore is reduced to chrome metal. The manufacture of 
    ferroalloys results in a complex mixture of particles, fumes and 
    chemicals including nickel, Cr(III) and Cr(VI). Polycyclic aromatic 
    hydrocarbons (PAH) are released during the manufacturing process. The 
    co-exposure to other potential lung carcinogens combined with the lack 
    of a statistically significant elevation in lung cancer mortality among 
    ferrochromium workers were limitations in the key studies. 
    Nevertheless, the observed increase in the relative risks of lung 
    cancer add some further support to the much stronger link between 
    Cr(VI) and lung cancer found in soluble chromate production workers, 
    chromate pigment production workers, and chrome platers. The key 
    studies are summarized in Table V-5.
    BILLING CODE 4510-26-P

Table V-5

 

    
    BILLING CODE 4510-26-C
        Langard et al. conducted a cohort study of male workers producing 
    ferrosilicon and ferrochromium for more than one year between 1928 and 
    1977 at a plant located on the west coast of Norway (Exs. 7-34; 7-37). The 
    cohort and study findings are summarized in Table V.5. Excluded from 
    the study were workers who died before January 1, 1953 or had an 
    unknown date of birth. The cohort was defined in the 1980 study as 976 
    male employees who worked for a minimum of one year prior to January 1, 
    1960. In the 1990 study, the cohort definition was expanded to include 
    those hired up to 1965.
        Production of ferrosilicon at the plant began in 1928 and 
    ferrochromium production began in 1932. Job characterizations were 
    compiled by combining information from company personnel lists and 
    occupational histories contained in medical records and supplemented 
    with information obtained via interview with long-term employees. Ten 
    occupational categories were defined. Workers were assigned to an 
    occupational category based upon the longest time in a given category.
        Industrial hygiene studies of the plant from 1975 indicated that 
    both Cr(III) and Cr(VI) were present in the working environment. The 
    ferrochromium furnance operators were exposed to measurements of 0.04-
    0.29 mg/m3 of total chromium. At the charge floor the mean 
    concentration of total chromium was 0.05 mg/m3, 11-33% of 
    which was water soluble. The water soluble chromium was considered to 
    be in the hexavalent state.
        Both observed and expected cases of cancer were obtained via the 
    Norwegian Cancer Registry. The observation period for cancer incidence 
    was January 1, 1953 to December 31, 1985. Seventeen incident lung 
    cancers were reported in the 1990 study (E=19.4; SIR=88). A deficit of 
    lung cancer incidence was observed in the ferrosilicon group (O=2; 
    E=5.8; SIR=35). In the ferrochromium group there were a significant 
    excess of lung cancer; 10 observed lung cancers with 6.5 expected 
    (SIR=154).
        Axelsson et al. conducted a study of 1,932 ferrochromium workers to 
    examine whether exposure in the ferrochromium industry could be 
    associated with an increased risk of developing tumors, especially lung 
    cancer (Ex. 7-62). The study cohort and findings are summarized in 
    Table V.5. The study cohort was defined as males employed at a 
    ferrochromium plant in Sweden for at least one year during the period 
    January 1, 1930 to December 31, 1975.
        The different working sites within the industry were classified 
    into four groups with respect to exposure to Cr(VI) and Cr(III). 
    Exposure was primarily to metallic and trivalent chromium with 
    estimated levels ranging from 0-2.5 mg/m3. Cr(VI) was also 
    present in certain operations with estimated levels ranging from 0-0.25 
    mg/m3. The highest exposure to Cr(VI) was in the arc-furnace 
    operations. Cr(VI) exposure also occurred in a chromate reduction 
    process during chromium alum production from 1950-1956. Asbestos-
    containing materials had been used in the plant. Cohort members were 
    classified according to length and place of work in the plant.
        Death certificates were obtained and coded to the revision of the 
    International Classification of Diseases in effect at the time of 
    death. Data on cancer incidence were obtained from the Swedish National 
    Cancer Registry. Causes of death in the cohort for the period 1951-1975 
    were compared with causes of death for the age-adjusted male population 
    in the county in which the plant was located.
        There were seven cases of cancers of the trachea, bronchus and lung 
    and the pleura with 5.9 expected (SIR=119) for the period 1958-1975. 
    Four of the seven cases in the lung cancer group were maintenance 
    workers and two of the four cases were pleural mesotheliomas. In the 
    arc furnace group, which was thought to have the highest potential 
    exposure to both Cr(III) and Cr(VI), there were two cancers of the 
    trachea, bronchus and lung and the pleura. One of the cases was a 
    mesothelioma. Of the 380 deaths that occurred during the period 1951-
    1975, five were from cancer of the trachea, bronchus and lung and the 
    pleura (E=7.2; SMR=70). For the "highly" exposed furnace workers, 
    there was one death from cancer of the trachea, bronchus and lung and 
    the pleura.
        Moulin et al. conducted a cohort mortality study in a French 
    ferrochromium/stainless steel plant to determine if exposure to 
    chromium compounds, nickel compounds and polycyclic aromatic 
    hydrocarbons (PAHs) results in an increased risk of lung cancer (Ex. 
    282). The cohort was defined as men employed for at least one year 
    between January 1, 1952 and December 31, 1982; 2,269 men met the cohort 
    entrance criteria. No quantitative exposure data were available and no 
    information on the relative amounts of Cr(VI) and Cr(III) was provided. 
    In addition, some workers were also exposed to other carcinogens, such 
    as silica and asbestos. The authors estimated that 75.7% of the cohort 
    had been exposed to combinations of PAH, nickel and chromium compounds. 
    Of the 137 deaths identified, the authors determined 12 were due to 
    cancer of the trachea, bronchus and lung (E=8.56; SMR=140; 95% CI: 
    0.72-2.45). Eleven of the 12 lung cancers were in workers employed for 
    at least one year in the ferrochromium or stainless steel production 
    workshops (E=5.4; SMR=204; 95% CI: 1.02-3.64).
        Pokrovskaya and Shabynina conducted a cohort mortality study of 
    male and female workers employed "some time" between 1955 and 1969 at 
    a chromium ferroalloy production plant in the U.S.S.R (Ex. 7-61). 
    Workers were exposed to both Cr(III) and Cr(VI) as well as to benzo [a] 
    pyrene. Neither the number of workers nor the number of cancer deaths 
    by site were provided. Death certificates were obtained and the deaths 
    were compared with municipal mortality rates by gender and 10 year age 
    groups. The investigators state that they were able to exclude those in 
    the comparison group who had chromium exposures in other industries. 
    The lung cancer SMR for male chromium ferroalloy workers was 440 in the 
    30-39 year old age group and 660 in the 50-59 year old age group 
    (p=0.001). There were no lung cancer deaths in the 40-49 and the 60-69 
    year old age groups. The data suggest that these ferrochromium workers 
    may have been had an excess risk of lung cancer.
        The association between Cr(VI) exposure in ferrochromium workers 
    and the incidence of respiratory tract cancer these studies is 
    difficult to assess because of co-exposures to other potential 
    carcinogens (e.g., asbestos, PAHs, nickel, etc.), absence of a clear 
    exposure-response relationship and lack of information on smoking. 
    There is suggestive evidence of excess lung cancer mortality among 
    Cr(VI)-exposed ferrochromium workers in the Norwegian (Langard) cohort 
    when compared to a similar unexposed cohort of ferrosilicon workers. 
    However, there is little consistency for this finding in the Swedish 
    (Axelsson) or French (Moulin) cohorts.
    6. Evidence From Workers in Other Industry Sectors
        There are several other epidemiological studies that do not fit 
    into the five industry sectors previously reviewed. These include 
    worker cohorts in the aerospace industry, paint manufacture, and 
    leather tanning operations, among others. The two cohorts of aircraft 
    manufacturing workers are summarized in Table V-6. All of the cohorts 
    had some Cr(VI) exposure, but certain cohorts may have included a 
    sizable number of workers with little or no exposure to Cr(VI). This 
    creates an additional complexity in assessing whether the study 
    findings support a Cr(VI) etiology for cancer of the respiratory system.
    BILLING CODE 4510-26-P

Table V-6

 

    
    BILLING CODE 4510-26-C
        Alexander et al. conducted a cohort study of 2,429 aerospace 
    workers with a minimum of six months of cumulative employment in jobs 
    involving chromate exposure during the period 1974 through 1994 (Ex. 31-16-3). 
    Exposure estimates were based on industrial hygiene measurements and work 
    history records. Jobs were classified into categories of "high" 
    (spray painters, decorative painters), "moderate" (sanders/maskers, 
    maintenance painters) and "low" (chrome platers, surface processors, 
    tank tenders, polishers, paint mixers) exposure. Each exposure category 
    was assigned a summary TWA exposure based upon the weighted TWAs and 
    information from industrial hygienists. The use of respiratory 
    protection was accounted for in setting up the job exposure matrix. The 
    index of cumulative total chromium exposure (reported as [mu]g/m\3\ 
    chromate TWA-years) was computed by multiplying the years in each job 
    by the summary TWAs for each exposure category.
        In addition to cumulative chromate exposure, chromate exposure jobs 
    were classified according to the species of chromate. According to the 
    authors, in painting operations the exposure is to chromate pigments 
    with moderate and low solubility such as zinc chromate, strontium 
    chromate and lead chromate; in sanding and polishing operations the 
    same chromate pigments exist as dust; while platers and tank tenders 
    are exposed to chromium trioxide, which is highly soluble.
        Approximately 26% of the cohort was lost to follow-up. Follow-up on 
    the cohort was short (average 8.9 years per cohort member). Cases were 
    identified through the Cancer Surveillance System (CSS) at the Fred 
    Hutchinson Cancer Research Center in Seattle, Washington. CSS records 
    primary cancer diagnoses in 13 counties in western Washington. Expected 
    numbers were calculated using race-, gender-, age- and calendar-
    specific rates from the Puget Sound reference population for 1974 
    through 1994. Fifteen lung cancer cases were identified with an overall 
    standardized incidence ratio (SIR) of 80 (95% CI: 0.4-1.3). The SIRs 
    for lung cancer by cumulative years of employment in the "high 
    exposure" painting job category were based upon only three deaths in 
    each of the cumulative years categories (<5 and >=5); years of 
    employment was inversely related to the risk of lung cancer. For those 
    in the "low exposure" category, the SIRs were 130 for those who 
    worked less than five years in that category (95% CI: 0.2-4.8) and 190 
    for those who worked five years or more (95% CI: 0.2-6.9). However, 
    there were only two deaths in each category. The SIR for those who 
    worked >=5 years was 270 (95% CI: 0.5-7.8), but based only on three 
    deaths.
        Boice et al. conducted a cohort mortality study of 77,965 workers 
    employed for a minimum of one year on or after January 1960 in aircraft 
    manufacturing (Ex. 31-16-4). Routine exposures to Cr(VI) compounds 
    occurred primarily while operating plating and coating process 
    equipment or when using chromate based primers or paints. According to 
    the authors, 3,634 workers, or 8% of the cohort, had the potential for 
    routine exposure to chromate and 3,809 workers, or 8.4%, had the 
    potential for intermittent exposure to chromate. Limited chromate air 
    sampling was conducted between 1978 and 1991. The mean full shift air 
    measurement was 1.5 [mu]g CrO3/m\3\ (0.78 [mu]g Cr(VI)/m\3\) 
    indicating fairly low airborne Cr(VI) in the plant (Ex. 47-19-5).
        Follow up of the cohort was through 1996. Expectations were 
    calculated based on the general population of California for white 
    workers, while general population rates for the U.S. were used for non-
    white workers. For the 3,634 cohort members who had potential for 
    routine exposure to chromates, the lung cancer SMR (race and gender 
    combined) was 102 based upon 87 deaths (95% CI: 82-126). There was a 
    slight non-significant positive trend (p value >2.0) for lung cancer 
    with duration of potential exposure. The SMR was 108 (95% CI: 75-157) 
    for workers exposed to chromate for >=5 years. Among the painters, 
    there were 41 deaths from lung cancer yielding a SMR of 111 (95% CI: 
    80-151). For those who worked as a process operator or plater the SMR 
    for lung cancer was 103 based upon 38 deaths (95% CI: 73-141).
        OSHA believes the Alexander (Ex. 31-16-3) and the Boice et al. (Ex. 
    31-16-4) studies have several limitations. The Alexander cohort has few 
    lung cancers (due in part to the young age of the population) and lacks 
    smoking data. The authors note that these factors "[limit] the overall 
    power of the study and the stability of the risk estimates, especially 
    in exposure-related subanalyses" (Ex. 31-16-3, p. 1256). Another 
    limitation of the study is the 26.3% of cohort members lost to follow-
    up. Boice et al. is a large study of workers in the aircraft 
    manufacturing industry, but was limited by a lack of Cr(VI) exposure 
    measurement during the 1960s and most of the 1970s. I was also limited 
    by a substantial healthy worker survivor effect that may have masked 
    evidence of excess lung cancer mortality in Cr(VI) exposed workers (Ex. 
    31-16-4). These studies are discussed further in section VI, including 
    section VI.B.6 (Alexander cohort) and section VI.G.4.a (Alexander and 
    Boice cohorts).
        Dalager et al. conducted a proportionate mortality study of 977 
    white male spray painters potentially exposed to zinc chromate in the 
    aircraft maintenance industry who worked at least three months and 
    terminated employment within ten years prior to July 31, 1959 (Ex. 7-
    64). Follow-up was through 1977. The expected numbers of deaths were 
    obtained by applying the cause-specific proportionate mortality of U.S. 
    white males to the total numbers of deaths in the study group by five 
    year age groups and five year time intervals. Two hundred and two 
    deaths were observed. There were 21 deaths from cancer of the 
    respiratory system (PMR=184), which was statistically significant. The 
    Proportionate Cancer Mortality Ratio for cancer of the respiratory 
    system was not statistically significant (PCMR= 146). Duration of 
    employment as a painter with the military as indicated on the service 
    record was used as an estimate of exposure to zinc chromate pigments, 
    which were used as a metal primer. The PMRs increased as duration of 
    employment increased (< 5 years, O=9, E=6.4, PMR=141; 5-9 years, O=6, 
    E=3, PMR=200; and 10+ years, O=6, E=2, PMR=300) and were statistically 
    significant for those who worked 10 or more years.
        Bertazzi et al. studied the mortality experience of 427 workers 
    employed for a minimum of six months between 1946 and 1977 in a plant 
    manufacturing paint and coatings (Ex. 7-65). According to the author, 
    chromate pigments represented the "major exposure" in the plant. The 
    mortality follow-up period was 1954-1978. There were eight deaths from 
    lung cancer resulting in a SMR of 227 on the local standard (95% CI: 
    156-633) and a SMR of 334 on the national standard (95% CI: 106-434). 
    The authors were unable to differentiate between exposures to different 
    paints and coatings. In addition, asbestos was used in the plant and 
    may be a potential confounding exposure.
        Morgan conducted a cohort study of 16,243 men employed after 
    January 1, 1946 for at least one year in the manufacture of paint or 
    varnish (Ex. 8-4). Analysis was also conducted for seven subcohorts, 
    one of which was for work with pigments. Expectations were calculated 
    based upon the mortality experience of U.S. white males. The SMR for 
    cancer of the trachea, bronchus and lung was below unity based upon 150 
    deaths. For the pigment subcohort, the SMR for cancer of the trachea, 
    bronchus and lung was 117 based upon 43 deaths. In a follow-up study of 
    the subcohorts, case-control analyses were conducted for several causes 
    of death including lung cancer (Ex. 286). The details of matching were not 
    provided. The authors state that no significant excesses of lung cancer 
    risk by job were found. No odds ratios were presented.
        Pippard et al. conducted a cohort mortality study of 833 British 
    male tannery workers employed in 1939 and followed through December 31, 
    1982 (Ex. 278). Five hundred and seventy three men worked in tanneries 
    making vegetable tanned leathers and 260 men worked in tanneries that 
    made chrome tanned leathers. The expected number of deaths was 
    calculated using the mortality rates of England and Wales as a whole. 
    The lung cancer SMR for the vegetable tanned leather workers was in 
    deficit (O=31; E=32.6; 95% CI: 65-135), while the lung cancer SMR for 
    the chrome tanned leather workers was slightly elevated but not 
    statistically significant (O=13; E=12; SMR=108; 95% CI: 58-185).
        In a different study of two U.S. tanneries, Stern et al. 
    investigated mortality in a cohort of all production workers employed 
    from January 1, 1940 to June 11, 1979 at tannery A (N=2,807) and from 
    January 1, 1940 to May 1, 1980 at tannery B (N=6,558) (Ex. 7-68). Vital 
    status was followed through December 31, 1982. There were 1,582 deaths 
    among workers from the two tanneries. Analyses were conducted employing 
    both U.S. mortality rates and the mortality rates for the state in 
    which the plant is located. There were 18 lung/pleura cancer deaths at 
    tannery A and 42 lung/pleura cancer deaths at tannery B. The lung 
    cancer/pleura SMRs were in deficit on both the national standard and 
    the state standard for both tanneries. The authors noted that since the 
    1940s most chrome tanneries have switched to the one-bath tanning 
    method in which Cr(VI) is reduced to Cr(III).
        Blot et al. reported the results of a cohort study of 51,899 male 
    workers of the Pacific Gas & Electric Company alive in January 1971 and 
    employed for at least six months before the end of 1986 (Ex. 239). A 
    subset of the workers were involved in gas generator plant operations 
    where Cr(VI) compounds were used in open and closed systems from the 
    1950s to early 1980s. One percent of the workers (513 men) had worked 
    in gas generator jobs, with 372 identified from post-1971 listing at 
    the company's three gas generator plants and 141 from gas generator job 
    codes. Six percent of the cohort members (3,283) had trained at one of 
    the gas generator plants (Kettleman).
        SMRs based on national and California rates were computed. Results 
    in the paper are based on the California rates, since the overall 
    results reportedly did not differ substantially from those using the 
    national rates. SMRs were calculated for the entire cohort and for 
    subsets defined by potential for gas generator plant exposure. No 
    significant cancer excesses were observed and all but one cancer SMR 
    was in deficit. There were eight lung cancer deaths in the gas 
    generator workers (SMR=81; 95% CI: 0.35-1.60) and three lung cancer 
    deaths among the Kettleman trainees (SMR=57; 95% CI: 0.12-1.67). There 
    were no deaths from nasal cancer among either the gas generator workers 
    or the Kettleman trainees. The risk of lung cancer did not increase 
    with length of employment or time since hire.
        Rafnsson and Johannesdottir conducted a study of 450 licensed 
    masons (cement finishers) in Iceland born between 1905 and 1945, 
    followed from 1951 through 1982 (Ex. 7-73). Stonecutters were excluded. 
    Expectations were based on the male population of Iceland. The SMR for 
    lung cancer was 314 and is statistically significant based upon nine 
    deaths (E=2.87; 95% CI: 1.43-5.95). When a 20 year latency was factored 
    into the analysis, the lung cancer SMR remained statistically 
    significant (O=8; E=2.19; SMR=365; 95% CI: 1.58-7.20).
        Svensson et al. conducted a cohort mortality study of 1,164 male 
    grinding stainless steel workers employed for three months or more 
    during the period 1927-1981 (Ex.266). Workers at the facility were 
    reportedly exposed to chromium and nickel in the stainless steel 
    grinding process. Records provided by the company were used to assign 
    each worker to one of three occupational categories: those considered 
    to have high exposure to chromium, nickel as well as total dust, those 
    with intermediate exposure, and those with low exposure. Mortality 
    rates for males in Blekinge County, Sweden were used as the reference 
    population. Vital status follow-up was through December 31, 1983. A 
    total of 194 deaths were observed (SMR=91). No increased risk of lung 
    cancer was observed (SMR=92). The SMR for colon/rectum cancer was 2.47, 
    but was not statistically significant.
        Cornell and Landis studied the mortality experience of 851 men who 
    worked in 26 U.S. nickel/chromium alloy foundries between 1968 and 1979 
    (Ex. 7-66). Standardized Proportionate Mortality Ratio (SPMR) analyses 
    were done using both an internal comparison group (foundry workers not 
    exposed to nickel/chromium) and the mortality experience of U.S. males. 
    The SPMR for lung cancer was 105 (O=60; E=56.9). No nasal cancer deaths 
    were observed.
        Brinton et al. conducted a case-control study of 160 patients 
    diagnosed with primary malignancies of the nasal cavity and sinuses at 
    one of four hospitals in North Carolina and Virginia between January 1, 
    1970 and December 31, 1980 (Ex. 8-8). For each case determined to be 
    alive at the time of interview, two hospital controls were selected 
    matched on vital status, hospital, year of admission (2 
    years), age (5 years), race and state economic area or 
    county or usual residence. Excluded from control selection were 
    malignant neoplasms of the buccal cavity and pharynx, esophagus, nasal 
    cavity, middle ear and accessory sinuses, larynx, and secondary 
    neoplasms. Also excluded were benign neoplasms of the respiratory 
    system, mental disorders, acute sinusitis, chronic pharyngitis and 
    nasopharyngitis, chronic sinusitis, deflected nasal septum or nasal 
    polyps. For those cases who were deceased at the time of interview, two 
    different controls were selected. One control series consisted of 
    hospital controls as described previously. The second series consisted 
    of decedents identified through state vital statistics offices matched 
    for age (5 years), sex, race, county of usual residence and 
    year of death. A total of 193 cases were identified and 160 case 
    interviews completed. For those exposed to chromates, the relative risk 
    was not significantly elevated (OR=5.1) based upon five cases. 
    According to the authors, chromate exposure was due to the use of 
    chromate products in the building industry and in painting, rather than 
    the manufacture of chromates.
        Hernberg et al. reported the results of a case-control study of 167 
    living cases of nasal or paranasal sinus cancer diagnosed in Denmark, 
    Finland and Sweden between July 1, 1977 and December 31, 1980 (Exs. 8-
    7; 7-71). Controls were living patients diagnosed with malignant tumors 
    of the colon and rectum matched for country, gender and age at 
    diagnosis (3 years) with the cases. Both cases and controls 
    were interviewed by telephone to obtain occupational histories. 
    Patients with work-related exposures during the ten years prior to 
    their illness were excluded. Sixteen cases reported exposure to 
    chromium, primarily in the "stainless steel welding" and "nickel" 
    categories, versus six controls (OR=2.7l; 95% CI: 1.1-6.6).
    7. Evidence From Experimental Animal Studies
        Most of the key animal cancer bioassays for chromium compounds were 
    conducted before 1988. These studies have been critically reviewed by the 
    IARC in the Monograph Chromium, Nickel, and Welding (Ex. 35-43). OSHA 
    reviewed the key animal cancer bioassays in the NPRM (69 FR at 59341-59347)
    and requested any additional data in experimental animals that were considered 
    important to evaluating the carcinogenicity of Cr(VI). The discussion below 
    describes these studies along with any new study information received 
    during the public hearing and comment periods.
        In the experimental studies, Cr(VI) compounds were administered by 
    various routes including inhalation, intratracheal instillation, 
    intrabronchial implantation, and intrapleural injection, as well as 
    intramuscular and subcutaneous injection. For assessing human health 
    effects from occupational exposure, the most relevant route is 
    inhalation. However, as a whole, there were very few inhalation 
    studies. In addition to inhalation studies, OSHA is also relying on 
    intrabronchial implantation and intratracheal instillation studies for 
    hazard identification because these studies examine effects directly 
    administered to the respiratory tract, the primary target organ of 
    concern, and they give insight into the relative potency of different 
    Cr(VI) compounds. In comparison to studies examining inhalation, 
    intrabronchial implantation, and intratracheal instillation, studies 
    using subcutaneous injection and intramuscular administration of Cr(VI) 
    compounds were of lesser significance but were still considered for 
    hazard identification.
        In its evaluation, OSHA took into consideration the exposure 
    regimen and experimental conditions under which the experiments were 
    performed, including the exposure level and duration; route of 
    administration; number, species, strain, gender, and age of the 
    experimental animals; the inclusion of appropriate control groups; and 
    consistency in test results. Some studies were not included if they did 
    not contribute to the weight of evidence, lacked adequate 
    documentation, were of poor quality, or were less relevant to 
    occupational exposure conditions (e.g., some intramuscular injection 
    studies).
        The summarized animal studies are organized by Cr(VI) compound in 
    order of water solubility as defined in section IV on Chemical 
    Properties (i.e., Cr(VI) compounds that are highly soluble in water; 
    Cr(VI) compounds that are slightly soluble in water, and Cr(VI) 
    compounds that insoluble in water). Solubility is an important factor 
    in determining the carcinogenicity of Cr(VI) compounds (Ex. 35-47).
    a. Highly Water Soluble Cr(VI) Compounds
        Multiple animal carcinogenicity studies have been conducted on 
    highly water soluble sodium dichromate and chromic acid. The key 
    studies are summarized in Table V-7.
    BILLING CODE 4510-26-P

Table V-7

 

    
    BILLING CODE 4510-26-C
    Chromic acid (Chromium trioxide). In a study by Adachi et al., ICR/JcI 
    mice were exposed by inhalation to 3.63 mg/m\3\ for 30 minutes per day, 
    two days per week for up to 12 months (Ex. 35-26-1). The mice were 
    observed for an additional six months. The authors used a miniaturized 
    chromium electroplating system to generate chromic acid for the study. 
    The authors found there were elevations in lung adenomas at 10-14
    months (3/14 vs. 0/10) and lung adenocarcinomas at 15-18 months (2/19 
    vs. 0/10), but the results were not statistically significant. The 
    small number of animals (e.g. 10-20 per group) used in this study 
    limited its power to detect all but a relatively high tumor incidence 
    (e.g. >20%) with statistical precision. Statistically significant 
    increases in nasal papillomas were observed in another study by Adachi 
    et al., in which C57B1 mice were exposed by inhalation to 1.81 mg/m\3\ 
    chromic acid for 120 min per day, two days per week for up to 12 months 
    (Ex. 35-26). At 18 months, the tumor incidence was 6/20 in exposed 
    animals vs. 0/20 in the control animals (p< 0.05).
        In separate but similar studies, Levy et al. and Levy and Venitt, 
    using similar exposure protocol, conducted bronchial implantation 
    experiments in which 100 male and female Porton-Wistar rats were dosed 
    with single intrabronchial implantations of 2 mg chromic acid (1.04 mg 
    Cr(VI)) mixed 50:50 with cholesterol in stainless steel mesh pellets 
    (Exs. 11-2; 11-12). The authors found no statistically significant 
    increases in lung tumors, although Levy et al. found a bronchial 
    carcinoma incidence of 2/100 in exposed rats compared with 0/100 in 
    control rats. Levy and Venitt found a bronchial carcinoma incidence of 
    1/100 accompanied by a statistically significant increase in squamous 
    metaplasia, a lesion believed capable of progressing to carcinoma. 
    There was no statistically significant increase in the incidence of 
    squamous metaplasia in control rats or rats treated with Cr(III) 
    compounds in the same study. This finding suggests that squamous 
    metaplasia is specific to Cr(VI) and is not evoked by a non-specific 
    stimuli, the implantation procedure itself, or treatment with Cr(III) 
    containing materials.
        Similar to Levy et al. and Levy and Venitt studies, Laskin et al. 
    gave a single intrabronchial implantation of 3-5 mg chromic acid mixed 
    50:50 with cholesterol in stainless steel mesh pellets to 100 male and 
    female Porton-Wistar rats (Ex. 10-1). The rats were observed for 2 
    years. No tumors were identified in the treated or control animals (0/
    100 vs. 0/24).
        Sodium dichromate. Glaser et al. exposed male Wistar rats to 
    aerosolized sodium dichromate by inhalation for 22-23 hours per day, 
    seven days per week for 18 months (Exs. 10-10; 10-11). The rats were 
    held for an additional 12 months at which point the study was 
    terminated. Lung tumor incidences among groups exposed to 25, 50, and 
    100 [mu]g Cr(VI)/m\3\ were 0/18, 0/18, and 3/19, respectively, vs. 0/37 
    for the control animals. Histopathology revealed one adenocarcinoma and 
    two adenomas in the highest group. The slightly elevated tumor 
    incidence at the highest dose was not statistically significant. A 
    small number of animals (20 per group) were used in this study limiting 
    its power to detect all but a relatively high tumor incidence (e.g. 
    >20%) with statistical precision. In addition, the administered doses 
    used in this study were fairly low, such that the maximum tolerated 
    dose (i.e., the maximum dose level that does not lead to moderate 
    reduction in body weight gain) may not have been achieved. Together, 
    these factors limit the interpretation of the study.
        In an analysis prepared by Exponent and submitted by the Chrome 
    Coalition, Exponent stated that "inhalation studies of Glaser et al. 
    support a position that exposures to soluble Cr(VI) at concentrations 
    at least as high as the current PEL (i.e., 52 [mu]g/m\3\) do not cause 
    lung cancer" (Ex. 31-18-1, page 2). However, it should be noted that 
    the Glaser et al. studies found that 15% (\3/19\) of the rats exposed 
    to an air concentration just above the current PEL developed lung 
    tumors, and that the elevated tumor incidence was not statistically 
    significant in the highest dose group because the study used a small 
    number of animals. OSHA believes the Glaser study lacks the statistical 
    power to state with sufficient confidence that Cr(VI) exposure does not 
    cause lung cancer at the current PEL, especially when given the 
    elevated incidence of lung tumors at the next highest dose level.
        Steinhoff et al. studied the carcinogenicity of sodium dichromate 
    in Sprague-Dawley rats (Ex. 11-7). Forty male and 40 female Sprague-
    Dawley rats were divided into two sets of treatment groups. In the 
    first set, doses of 0.01, 0.05 or 0.25 mg/kg body weight in 0.9% saline 
    were instilled intratracheally five times per week. In the second set 
    of treatment groups, 0.05, 0.25 or 1.25 mg/kg body weight in 0.9% 
    saline doses were instilled intratracheally once per week. Duration of 
    exposure in both treatment groups was 30 months. The total cumulative 
    dose for the lowest treatment group of animals treated once per week 
    was the same as the lowest treatment group treated five times per week. 
    Similarly, the medium and high dose groups treated once per week had 
    total doses equivalent to the medium and high dose animals treated five 
    times per week, respectively. No increased incidence of lung tumors was 
    observed in the animals dosed five times weekly. However, in the 
    animals dosed once per week, tumor incidences were 0/80 in control 
    animals, 0/80 in the 0.05 mg/kg exposure group, 1/80 in the 0.25 mg/kg 
    exposure group and 14/80 in the 1.25 mg/kg exposure group (p < 0.01). 
    The tumors were malignant in 12 of the 14 animals in the 1.25 mg/kg 
    exposure group. Tracheal instillation at the highest dose level (i.e. 
    1.25 mg/kg) caused emphysematous lesions and pulmonary fibrosis in the 
    lungs of Cr(VI)-treated rats. A similar degree of lung damage did not 
    occur at the lower dose levels. Exponent commented that the Steinhoff 
    and Glaser results are evidence that the risk of lung cancer from 
    occupational exposure does not exist below a threshold Cr(VI) air 
    concentration of approximately 20 [mu]g/m\3\ (Ex. 38-233-4). This 
    comment is addressed in Section VI.G.2.c.
        In separate but similar studies, Levy et al. and Levy and Venitt 
    implanted stainless steel mesh pellets filled with a single dose of 2 
    mg sodium dichromate (0.80 mg Cr(VI)) mixed 50:50 with cholesterol in 
    the bronchi of male and female Porton-Wistar rats (Exs. 11-2; 11-12). 
    Control groups (males and females) received blank pellets or pellets 
    loaded with cholesterol. The rats were observed for two years. Levy et 
    al. and Levy and Venitt reported a bronchial tumor incidence of 1/100 
    and 0/89, respectively, for exposed rats. However, the latter study 
    reported a statistically significant increase in squamous metaplasia, a 
    lesion believed capable of progressing to carcinoma, among exposed rats 
    when compared to unexposed rats. There were no bronchial tumors or 
    squamous metaplasia in any of the control animals and no significant 
    increases in lung tumors were observed in the two studies.
    b. Slightly Water Soluble Cr(VI) Compounds
        Animal carcinogenicity studies have been conducted on slightly 
    water soluble calcium chromate, strontium chromate, and zinc chromates. 
    The key studies are summarized in Table V-8.
    BILLING CODE 4510-26-P

Table V-8

 

    
    BILLING CODE 4510-26-C
         Calcium chromate. Nettesheim et al. conducted the only available 
    inhalation carcinogenicity study with calcium chromate showing 
    borderline statistical significance for increased lung adenomas in 
    C57B1/6 mice exposed to 13 mg/m\3\ for 5 hours per day, 5 days per week 
    over the life of the mice. The tumor incidences were 6/136 in exposed 
    male mice vs. 3/136 in control male mice and 8/136 in exposed female 
    mice vs. 2/136 in control female mice (Ex. 10-8).
        Steinhoff et al. observed a statistically significant increase in 
    lung tumors in Sprague-Dawley rats exposed by intratracheal 
    instillation to 0.25 mg/kg body weight calcium chromate in 0.9% saline 
    five times weekly for 30 months (Ex. 11-7). Tumors were found in 6/80 
    exposed animals vs. 0/80 in unexposed controls (p< 0.01). Increased 
    incidence of lung tumors was also observed in those rats exposed to 
    1.25 mg/kg calcium chromate once per week (14/80 vs. 0/80 in controls) 
    for 30 months. At the highest dose, the authors observed 11 adenomas, 
    one adenocarcinoma, and two squamous carcinomas. The total administered 
    doses for both groups of dosed animals (1 x 1.25 mg/kg and 5 x 0.25 mg/
    kg) were equal, but the tumor incidence in the rats exposed once per 
    week was approximately double the incidence in rats exposed to the same 
    weekly dose divided into five smaller doses. The authors suggested that 
    the dose-rate for calcium chromate compounds may be important in 
    determining carcinogenic potency and that limiting higher single 
    exposures may offer greater protection against carcinogenicity than 
    reducing the average exposure alone.
        Snyder et al. administered Cr(VI)-contaminated soil of defined 
    aerodynamic diameter (2.9 to 3.64 micron) intratracheally to male 
    Sprague-Dawley rats (Ex. 31-18-12). For the first six weeks of 
    treatment, the rats were instilled with weekly suspensions of 1.25 mg 
    of material per kg body weight, followed by 2.5 mg/kg every other week, 
    until treatments were terminated after 44 weeks. The investigation 
    included four exposure groups: control animals (50 rats), rats 
    administered Cr(VI)-contaminated soil (50 rats), rats administered 
    Cr(VI)-contaminated soil supplemented with calcium chromate (100 rats), 
    and rats administered calcium chromate alone (100 rats). The total 
    Cr(VI) dose for each group was: control group (0.000002 mg Cr(VI)/kg), 
    soil alone group (0.324 mg Cr(VI)/kg), soil plus calcium chromate group 
    (7.97 mg Cr(VI)/kg), and calcium chromate alone group (8.70 mg Cr(VI)/
    kg). No primary tumors were observed in the control group or the 
    chromium contaminated soil group. Four primary tumors of the lung were 
    found in the soil plus calcium chromate group and one primary lung 
    tumor was observed in the group treated with calcium chromate alone; 
    however, these incidences did not reach statistical significance.
        Statistically significant increases in the incidence of bronchial 
    carcinoma in rats exposed to calcium chromate through intrabronchial 
    instillation were reported by Levy et al. (Ex. 11-2) and Levy and 
    Venitt (Ex. 11-12). These studies, using a similar protocol, implanted 
    a single dose of 2 mg calcium chromate (0.67 mg Cr(VI)) mixed 50:50 
    with cholesterol in stainless steel pellets into the bronchi of Porton-
    Wistar rats. Levy et al. and Levy and Venitt found bronchial carcinoma 
    incidences of 25/100 and 8/84, respectively, following a 24-month 
    observation. The increased incidences were statistically significant 
    when compared to the control group. Levy and Venitt also reported 
    statistically significant increases in squamous metaplasia in the 
    calcium chromate-treated rats (Ex. 11-12).
        Laskin et al. observed 8/100 tumors in rats exposed to a single 
    dose of 3-5 mg calcium chromate mixed with cholesterol in stainless 
    steel mesh pellets implanted in the bronchi (Ex. 10-1). Animals were 
    observed for a total of 136 weeks. The sex, strain, and species of the 
    rats were not specified in the study. Tumor incidence in control 
    animals was 0/24. Although tumor incidence did not reach statistical 
    significance in this study, OSHA agrees with the IARC evaluation that 
    the incidences are due to calcium chromate itself rather than 
    background variation.
        Strontium chromate. Strontium chromate was tested by intrabronchial 
    implantation and intrapleural injection. In a study by Levy et al., two 
    strontium chromate compounds mixed 50:50 with cholesterol in stainless 
    steel mesh pellets were administered by intrabronchial instillation of 
    a 2 mg (0.48 mg Cr(VI)) dose into 100 male and female Porton-Wistar 
    rats (Ex. 11-2). Animals were observed for up to 136 weeks. The 
    strontium chromate compounds induced bronchial carcinomas in 43/99 (Sr, 
    42.2%; CrO4, 54.1%) and 62/99 rats (Sr, 43.0%; Cr, 24.3%)], 
    respectively, compared to 0/100 in the control group. These results 
    were statistically significant. The strontium chromates produced the 
    strongest carcinogenic response out of the 20 Cr(VI) compounds tested 
    by the intrabronchial implantation protocol. Boeing Corporation 
    commented that the intrabronchial implantation results with strontium 
    chromate should not be relied upon in an evaluation of carcinogenicity 
    and that the data is inconsistent with other Cr(VI) studies (Ex. 38-
    106-2, p. 26). This comment is discussed in the Carcinogenic Effects 
    Conclusion Section V.B.9 dealing with the carcinogenicity of slightly 
    soluble Cr(VI) compounds.
        In the study by Hueper, strontium chromate was administered by 
    intrapleural injection (doses unspecified) lasting 27 months (Ex. 10-
    4). Local tumors were observed in 17/28 treated rats vs. 0/34 for the 
    untreated rats. Although the authors did not examine the statistical 
    significance of tumors, the results clearly indicate a statistical 
    significance.
        Zinc chromate compounds. Animal studies have been conducted to 
    examine several zinc chromates of varying water solubilities and 
    composition. In separate, but similarly conducted studies, Levy et al. 
    and Levy and Venitt studied two zinc chromate powders, zinc potassium 
    chromate, and zinc tetroxychromate (Exs. 11-2; 11-12). Two milligrams 
    of the compounds were administered by intrabronchial implantation to 
    100 male and female Porton-Wistar rats. Zinc potassium chromate (0.52 
    mg Cr(VI)) produced a bronchial tumor incidence of 3/61 which was 
    statistically significant (p< 0.05) when compared to a control group 
    (Ex. 11-12). There was also an increased incidence of bronchial tumors 
    (5/100, p=0.04; 3/100, p=0.068) in rats receiving the zinc chromate 
    powders (0.44 mg Cr(VI)). Zinc tetroxychromate (0.18 mg Cr(VI)) did not 
    produce a statistically significant increase in tumor incidence (1/100) 
    when compared to a control group. These studies show that most slightly 
    water soluble zinc chromate compounds elevated incidences of tumors in 
    rats.
        Basic potassium zinc chromate was administered to mice, guinea pigs 
    and rabbits via intratracheal instillation (Ex. 35-46). Sixty-two 
    Strain A mice were given six injections of 0.03 ml of a 0.2% saline 
    suspension of the zinc chromate at six week intervals and observed 
    until death. A statistically significant increase in tumor incidence 
    was observed in exposed animals when compared to controls (31/62 vs. 7/
    18). Statistically significant effects were not observed among guinea 
    pigs or rabbits. Twenty-one guinea pigs (sex and strain not given) 
    received six injections of 0.3 ml of a 1% suspension of zinc chromate 
    at three monthly intervals and observed until death. Results showed 
    pulmonary adenomas in only 1/21 exposed animals vs. 0/18 in controls. 
    Seven rabbits (sex and strain not given) showed no increase in lung 
    tumors when given 3-5 injections of 1 ml of a saline suspension of 10 
    mg zinc chromate at 3-month intervals. However, as noted by IARC, the 
    small numbers of animals used in the guinea pig and rabbit experiments 
    (as few as 13 guinea pigs and 7 rabbits per group) limit the power of 
    the study to detect increases in cancer incidence.
        Hueper found that intrapleural injection of slightly water soluble 
    zinc yellow (doses were unspecified) resulted in statistically significant 
    increases in local tumors in rats (sex, strain, and age of rat 
    unspecified; dose was unspecified). The incidence of tumors in exposed 
    rats was 22/33 vs. 0/34 in controls (Ex. 10-4).
        Maltoni et al. observed increases in the incidence of local tumors 
    after subcutaneous injection of slightly water soluble zinc yellow in 
    20 male and 20 female Sprague-Dawley rats (statistical significance was 
    not evaluated) (Ex. 8-37). Tumor incidences were 6/40 in 20% 
    CrO3 dosed animals at 110 weeks and 17/40 in 40% 
    CrO3 dosed animals at 137 weeks compared to 0/40 in control 
    animals.
    c. Water Insoluble Cr(VI) Compounds
        There have been a number of animal carcinogenicity studies 
    involving implantation or injection of principally water insoluble 
    zinc, lead, and barium chromates. The key studies are summarized in 
    Table V-9.
    BILLING CODE 4510-26-P

Table V-9

 

    
    BILLING CODE 4510-26-C
        Lead chromate and lead chromate pigments. Levy et al. examined the 
    carcinogenicity of lead chromate and several lead chromate-derived 
    pigments in 100 male and female Porton-Wistar rats after a single 
    intrabronchial implantation followed by a two year observation period 
    (Ex. 11-12). The rats were dosed with two mg of a lead chromate 
    compound and lead chromate pigments, which were mixed 50:50 with
    cholesterol in stainless steel mesh pellets and implanted in the 
    bronchi of experimental animals. The lead chromate and lead chromate 
    pigment compositions consisted of the following: lead chromate (35.8% 
    CrO4; 0.32 mg Cr(VI)), primrose chrome yellow (12.6% Cr; 
    0.25 mg Cr(VI)), molybdate chrome orange (12.9% Cr; 0.26 mg Cr(VI)), 
    light chrome yellow (12.5% Cr; 0.25 mg Cr(VI)), supra LD chrome yellow 
    (26.9% CrO3; 0.28 mg Cr(VI)), medium chrome yellow (16.3% 
    Cr; 0.33 mg Cr(VI)) and silica encapsulated medium chrome yellow (10.5% 
    Cr; 0.21 mg Cr(VI)). No statistically significant tumors were observed 
    in the lead chromate group compared to controls (1/98 vs. 0/100), 
    primrose chrome yellow group (1/100 vs. 0/100), and supra LD chrome 
    yellow group (1/100 vs. 0/100). The authors also noted no tumors in the 
    molybdate chrome orange group, light chrome yellow group, and silica 
    encapsulated medium chrome yellow group.
        Maltoni (Ex. 8-25), Maltoni (Ex. 5-2), and Maltoni et al. (Ex. 8-
    37) examined the carcinogenicity of lead chromate, basic lead chromate 
    (chromium orange) and molybdenum orange in 20 male and 20 female 
    Sprague-Dawley rats by a single subcutaneous administration of the lead 
    chromate compound in water. Animals were observed for 117 to 150 weeks. 
    After injection of 30 mg lead chromate, local injection site sarcomas 
    were observed in 26/40 exposed animals vs. 0/60 and 1/80 in controls. 
    Although the authors did not examine the statistical significance of 
    sarcomas, the results clearly indicate a statistical significance. 
    Animals injected with 30 mg basic lead chromate (chromium orange) were 
    found to have an increased incidence of local injection site sarcomas 
    (27/40 vs. 0/60 and 1/80 in controls). Animals receiving 30 mg 
    molybdenum orange in 1 ml saline were also found to have an increased 
    incidence of local injection site sarcomas (36/40 vs. 0/60 controls).
        Carcinogenesis was observed after intramuscular injection in a 
    study by Furst et al. (Ex. 10-2). Fifty male and female Fischer 344 
    rats were given intramuscular injections of 8 mg lead chromate in 
    trioctanoin every month for nine months and observed up to 24 months. 
    An increase in local tumors at the injection site (fibrosarcomas and 
    rhabdomyosarcomas) was observed (31/47 in treated animals vs. 0/22 in 
    controls). These rats also had an increased incidence of renal 
    carcinomas (3/23 vs. 0/22 in controls), but IARC noted that the renal 
    tumors may be related to the lead content of the compound. In the same 
    study, 3 mg lead chromate was administered to 25 female NISH Swiss 
    weanling mice via intramuscular injection every 4 months for up to 24 
    months. In the exposed group, the authors observed three lung 
    alveologenic carcinomas after 24 months of observation and two 
    lymphomas after 16 months of observation. Two control groups were used: 
    an untreated control group (22 rats) and a vehicle injected control 
    group (22 rats). The authors noted that one alveologenic carcinoma and 
    one lymphoma were observed in each control group. The Color Pigment 
    Manufacturers Association (CPMA) commented that the lack of elevated 
    tumor incidence in the intrabronchial implantation studies confirmed 
    that lead chromate was not carcinogenic and that the positive injection 
    studies by the subcutaneous, intrapleural, and intramuscular routes 
    were of questionable relevance (Ex. 38-205, p. 93). This comment is 
    further discussed in the Carcinogenic Effects Conclusion Section V.B.9 
    dealing with the carcinogenicity of lead chromate.
        Barium chromate. Barium chromate was tested in rats via 
    intrabronchial, intrapleural and intramuscular administration. No 
    excess lung or local tumors were observed (Ex. 11-2; Ex. 10-4; Ex. 10-
    6).
        d. Summary. Several Cr(VI) compounds produced tumors in laboratory 
    animals under a variety of experimental conditions using different 
    routes of administration. The animals were generally given the test 
    material(s) by routes other than inhalation (e.g., intratracheal 
    administration, intramuscular injection, intrabronchial implantation, 
    and subcutaneous injection). Although the route of administration may 
    have differed from that found in an occupational setting, these studies 
    have value in the identification of potential health hazards associated 
    with Cr(VI) and in assessing the relative potencies of various Cr(VI) 
    compounds.
        OSHA believes that the results from Adachi et al. (Ex. 35-26-1), 
    Adachi et al. (Ex. 35-26), Glaser et al. (Ex. 10-4), Glaser et al. (Ex. 
    10-10), Levy et al. (Ex. 11-2), and Steinhoff et al. (Ex. 11-7) studies 
    provide valuable insight on the carcinogenic potency of Cr(VI) 
    compounds in laboratory animals. Total dose administered, dose rate, 
    amount of dosage, dose per administration, number of times 
    administered, exposure duration and the type of Cr(VI) compound are 
    major influences on the observed tumor incidence in animals. It was 
    found that slightly water soluble calcium, strontium, and zinc 
    chromates showed the highest incidence of lung tumors, as indicated in 
    the results of the Steinhoff and Levy studies, even when compared to 
    similar doses of the more water soluble sodium chromates and chromic 
    acid compounds. The highly insoluble lead chromates did not produce 
    lung tumors by the intrabronchial implantation procedure but did 
    produce tumors by subcutaneous injection and intramuscular injection.
    8. Mechanistic Considerations
        Mechanistic information can provide insight into the biologically 
    active form(s) of chromium, its interaction with critical molecular 
    targets, and the resulting cellular responses that trigger neoplastic 
    transformation. There has been considerable scientific study in recent 
    years of Cr(VI)-initiated cellular and molecular events believed to 
    impact development of respiratory carcinogenesis. Much of the research 
    has been generated using in vitro techniques, cell culture systems, and 
    animal administrations. The early mechanistic data were reviewed by 
    IARC in 1990 (Ex. 35-43). Recent experimental research has identified 
    several biological steps critical to the mode of action by which Cr(VI) 
    transforms normal lung cells into a neoplastic phenotype. These are: 
    (a) Cellular uptake of Cr(VI) and its extracellular reduction, (b) 
    intracellular Cr(VI) reduction to produce biologically active products, 
    (c) damage to DNA, and (d) activation of signaling pathways in response 
    to cellular stress. Each step will be described in detail below.
        a. Cellular Uptake and Extracellular Reduction. The ability of 
    different Cr(VI) particulate forms to be taken up by the 
    bronchoalveolar cells of the lung is an essential early step in the 
    carcinogenic process. Particle size and solubility are key physical 
    factors that influence uptake into these cells. Large particulates (>10 
    [mu]m) are generally deposited in the upper nasopharygeal region of the 
    respiratory tract and do not reach the bronchoalveolar region of the 
    lungs. Smaller Cr(VI) particulates will increasingly reach these lower 
    regions and come into contact with target cells.
        Once deposited in the lower respiratory tract, solubility of Cr(VI) 
    particulates becomes a major influence on disposition. Highly water 
    soluble Cr(VI), such as sodium chromate and chromic acid, rapidly 
    dissolves in the fluids lining the lung epithelia and can be taken up 
    by lung cells via facilitated diffusion mediated by sulfate/phosphate 
    anion transport channels (Ex. 35-148). This is because Cr(VI) exists in 
    a tetrahedral configuration as a chromate oxyanion similar to the 
    physiological anions, sulfate and phosphate (Ex. 35-231). Using cultured
    human epithelial cells, Liu et al. showed that soluble Cr(VI) uptake was 
    time- and dose-dependant over a range of 1 to 300 [mu]m in the medium with 
    30 percent of the Cr(VI) transported into the cells within two hours and 
    67 percent at 16 hours at the lowest concentration (Ex. 31-22-18).
        Water insoluble Cr(VI) particulates do not readily dissolve into 
    epithelial lining fluids of the bronchoalveolar region. This has led to 
    claims that insoluble chromates, such as lead chromate pigments, are 
    not bioavailable and, therefore, are unable to cause carcinogenesis 
    (Ex. 31-15). However, several scientific studies indicate that 
    insoluble Cr(VI) particulates can come in close contact with the 
    bronchoalveolar epithelial cell surface, allowing enhanced uptake into 
    cells. Wise et al. showed that respirable lead chromate particles 
    adhere to the surface of rodent cells in culture causing cell-enhanced 
    dissolution of the chromate ion as well as phagocytosis of lead 
    chromate particles (Exs. 35-68; 35-67). The intracellular accumulation 
    was both time- and dose-dependant. Cellular uptake resulted in damage 
    to DNA, apoptosis (i.e., form of programmed cell death), and neoplastic 
    transformation (Ex. 35-119). Singh et al. showed that treatment of 
    normal human lung epithelial cells with insoluble lead chromate 
    particulates (0.4 to 2.0 [mu]g/cm\2\) or soluble sodium chromate (10 
    [mu]M) for 24 hours caused Cr(VI) uptake, Cr-DNA adduct formation, and 
    apoptosis (Ex. 35-66). The proximate genotoxic agent in these cell 
    systems was determined to be the chromate rather than the lead ions 
    (Ex. 35-327). Elias et al. reported that cell-enhanced particle 
    dissolution and uptake was also responsible for the cytotoxicity and 
    neoplastic transformation in Syrian hamster embryo cells caused by 
    Cr(VI) pigments, including several complex industrial chrome yellow and 
    molybdate orange pigments (Ex. 125). These studies are key experimental 
    evidence in the determination that water-insoluble Cr(VI) compounds, as 
    well as water soluble Cr(VI) compounds, are to be regarded as 
    carcinogenic agents. This determination is further discussed in the 
    next section (see V.B.9).
        Reduction to the poorly permeable Cr(III) in the epithelial lining 
    fluid limits cellular uptake of Cr(VI). Ascorbic acid and glutathione 
    (GSH) are believed to be the key molecules responsible for the 
    extracellular reduction. Cantin et al. reported high levels of GSH in 
    human alveolar epithelial lining fluid and Susuki et al. reported 
    significant levels of ascorbic acid in rat lung lavage fluids (Exs. 35-
    147; 35-143). Susuki and Fukuda studied the kinetics of soluble Cr(VI) 
    reduction with ascorbic acid and GSH in vitro and following 
    intratracheal instillation (Ex. 35-90). They reported that the rate of 
    reduction was proportional to Cr(VI) concentration with a half-life of 
    just under one minute to several hours. They found the greatest 
    reduction rates with higher levels of reductants. Ascorbic acid was 
    more active than GSH. Cr(VI) reduction was slower in vivo than 
    predicted from in vitro and principally involved ascorbic acid, not 
    GSH. This research indicates that extracellular Cr(VI) reduction to 
    Cr(III) is variable depending on the concentration and nature of the 
    reductant in the epithelial fluid lining regions of the respiratory 
    tract. De Flora et al. determined the amount of soluble Cr(VI) reduced 
    in vitro by human bronchiolar alveolar fluid and pulmonary alveolar 
    macrophage fractions over a short period and used these specific 
    activities to estimate an "overall reducing capacity" of 0.9-1.8 mg 
    Cr(VI) and 136 mg Cr(VI) per day per individual, respectively (Ex. 35-
    140).
        De Flora, Jones, and others have interpreted the extracellular 
    reduction data to mean that very high levels of Cr(VI) are required to 
    "overwhelm" the reductive defense mechanism before target cell uptake 
    can occur and, as such, impart a "threshold" character to the 
    exposure-response (Exs. 35-139; 31-22-7). However, the threshold 
    capacity concept does not consider that facilitated lung cell uptake 
    and extracellular reduction are dynamic and parallel processes that 
    happen concurrently. If their rates are comparable then some cellular 
    uptake of Cr(VI) would be expected, even at levels that do not 
    "overwhelm" the reductive capacity. Based on the in vitro kinetic 
    data, it would appear that such situations are plausible, especially 
    when concentrations of ascorbic acid are low. Unfortunately, there has 
    been little systematic study of the dose-dependence of Cr(VI) uptake in 
    the presence of physiological levels of ascorbate and GSH using 
    experimental systems that possess active anion transport capability. 
    The implications of extracellular reduction on the shape of Cr(VI) 
    dose--lung cancer response curve is further discussed in Section 
    VI.G.2.c.
        Wise et al. did study uptake of a single concentration of insoluble 
    lead chromate particles (0.8 [mu]g/cm2) and soluble sodium 
    chromate (1.3 [mu]M) in Chinese hamster ovary cells co-treated with a 
    physiological concentration (1mM) of ascorbate (Ex. 35-68). They found 
    that the ascorbate substantially reduced, but did not eliminate, 
    chromate ion uptake over a 24 hour period. Interestingly, ascorbate did 
    not affect phagocytic uptake of lead chromate particles, although it 
    eliminated the Cr(VI)-induced clastogenesis (e.g., DNA strand breakage 
    and chromatid exchange) as measured under their experimental 
    conditions.
        Singh et al. suggested that cell surface interactions with 
    insoluble lead chromate particulates created a concentrated 
    microenvironment of chromate ions resulting in higher intracellular 
    levels of chromium than would occur from soluble Cr(VI) (Ex. 35-149). 
    Cell membrane-enhanced uptake of Cr(VI) is consistent with the 
    intratracheal and intrabronchial instillation studies in rodents that 
    show greater carcinogenicity with slightly soluble (e.g., calcium 
    chromate and strontium chromate) than with the highly water-soluble 
    chromates (e.g., sodium chromate and chromic acid) (Ex. 11-2).
        Finally, Cr(VI) deposited in the tracheobronchial and alveolar 
    regions of the respiratory tract is cleared by the mucocilliary 
    escalator (soluble and particulate Cr(VI)) and macrophage phagocytosis 
    (particulate Cr(VI) only). In most instances, these clearance processes 
    take hours to days to completely clear Cr(VI) from the lung, but it can 
    take considerably longer for particulates deposited at certain sites. 
    For example, Ishikawa et al. showed that some workers had substantial 
    amounts of chromium particulates at the bifurcations of the large 
    bronchii for more than two decades after cessation of exposure (Ex. 35-
    81). Mancuso reported chromium in the lungs of six chromate production 
    workers who died from lung cancer (as cited in Ex. 35-47). The interval 
    between last exposure to Cr(VI) until autopsy ranged from 15 months to 
    16 years. Using hollow casts of the human tracheobronchial tree and 
    comparing particle deposition with reported occurrence of bronchogenic 
    tumors, Schlesinger and Lippman were able to show good correlations 
    between sites of greatest deposition and increased incidence of 
    bronchial tumors (Ex. 35-102).
        b. Intracellular Reduction of Cr(VI). Once inside the cell, the 
    hexavalent chromate ion is rapidly reduced to intermediate oxidation 
    states, Cr(V) and Cr(IV), and the more chemically stable Cr(III). 
    Unlike Cr(VI), these other chromium forms are able to react with DNA 
    and protein to generate a variety of adducts and complexes. In 
    addition, reactive oxygen species (ROS) are produced during the 
    intracellular reduction of Cr(VI) that are also capable of damaging 
    DNA. These reactive intermediates, and not Cr(VI) itself, are considered
    to be the ultimate genotoxic agents that initiate the carcinogenic process.
        After crossing the cell membrane, Cr(VI) compounds can be non-
    enzymatically converted to Cr(III) by several intracellular reducing 
    factors (Ex. 35-184). The most plentiful electron donors in the cell 
    are GSH, and other thiols, such as cysteine, and ascorbate. Connett and 
    Wetterhahn showed that a Cr(VI)-thioester initially forms in the 
    presence of GSH (Ex. 35-206). A two-phase reduction then occurs with 
    rapid conversion to Cr(V) and glutathionyl radical followed by 
    relatively slower reduction to Cr(III) that requires additional 
    molecules of GSH. Depletion of cellular GSH and other thiols is 
    believed to retard complete reduction of Cr(VI) to Cr(III), allowing 
    buildup of intermediates Cr(V) and Cr(IV). The molecular kinetics of 
    the Cr(VI) to Cr(III) reduction with ascorbate is less well understood 
    but can also involve intermediate formation of Cr(V) and free radicals 
    (Ex. 35-184).
        Another important class of intracellular Cr(VI) reductions are 
    catalyzed by flavoenzymes, such as GSH reductase, lipoyl dehydrogenase, 
    and ferredoxin-NADP oxidoreductase. The most prominent among these is 
    GSH reductase that uses NADPH as a cofactor in the presence of 
    molecular oxygen (O2) to form Cr(V)-NADPH complexes. During 
    the reaction, O2 undergoes one electron reduction to the 
    superoxide radical (O2-) which produces hydrogen 
    peroxide (H2O2) through the action of the enzyme 
    superoxide dismutase. The Cr(V)-NADPH can then react with 
    H2O2 to regenerate Cr(VI) giving off hydroxyl 
    radicals, a highly reactive oxygen species, by a Fenton-like reaction. 
    It is, therefore, possible for a single molecule of Cr(VI) to produce 
    many molecules of potentially DNA damaging ROS through a repeated 
    reduction/oxidation cycling process. Shi and Dalal used electron spin 
    resonance (ESR) to establish formation of Cr(V)-NADPH and hydroxyl 
    radical in an in vitro system (Ex. 35-169; 35-171). Sugiyama et al. 
    reported Cr(V) formation in cultured Chinese hamster cells treated with 
    soluble Cr(VI) (Ex.35-133). Using a low frequency ESR, Liu et al. 
    provided evidence of Cr(V) formation in vivo in mice injected with 
    soluble Cr(VI) (Ex. 35-141-28).
        Several studies have documented that Cr(VI) can generate Cr(V) and 
    ROS in cultured human lung epithelial cells and that this reduction/
    oxidation pathway leads to DNA damage, activation of the p53 tumor 
    suppressor gene and stress-induced transcription factor NF-[kappa]B, 
    cell growth arrest, and apptosis (Exs. 35-125; 35-142; 31-22-18; 35-
    135). Leonard et al. used ESR spin trapping, catalase, metal chelators, 
    free radical scavengers, and O2-free atmospheres to show 
    that hydroxyl radical generation involves a Fenton-like reaction with 
    soluble potassium dichromate (Ex. 31-22-17) and insoluble lead chromate 
    (Ex.35-137) in vitro. Liu et al. showed that the Cr(IV)/Cr(V) compounds 
    are also able to generate ROS with H2O2 in a 
    Fenton reduction/oxidation cycle in vitro (Ex. 35-183).
        Although most intracellular reduction of Cr(VI) is believed to 
    occur in the cytoplasm, Cr(VI) reduction can also occur in mitochondria 
    and the endoplasmic reticulum. Cr(VI) reduction can occur in the 
    mitochondria through the action of the electron transport complex (Ex. 
    35-230). The microsomal cytochrome P-450 system in the endoplasmic 
    reticulum also enzymatically reduces Cr(VI) to Cr(V), producing ROS 
    through reduction/oxidation cycling as described above (Ex. 35-171).
        c. Genotoxicity and Damage to DNA. A large number of studies have 
    examined multiple types of genotoxicity in a wide range of experimental 
    test systems. Many of the specific investigations have been previously 
    reviewed by IARC (Ex. 35-43), Klein (Ex. 35-134), ATSDR (Ex. 35-41), 
    and the K.S. Crump Group (Ex. 35-47) and will only be briefly 
    summarized here. The body of evidence establishes that both soluble and 
    insoluble forms of Cr(VI) cause structural DNA damage that can lead to 
    genotoxic events such as mutagenisis, clastogenisis, inhibition of DNA 
    replication and transcription, and altered gene expression, all of 
    which probably play a role in neoplastic transformation. The reactive 
    intermediates and products that occur from intracellular reduction of 
    Cr(VI) cause a wide variety of DNA lesions. The type(s) of DNA damage 
    that are most critical to the carcinogenic process is an area of active 
    investigation.
        Many Cr(VI) compounds are mutagenic in bacterial and mammalian test 
    systems (Ex. 35-118). In the bacterial Salmonella typhimurium strains, 
    soluble Cr(VI) caused base pair substitutions at A-T sites as well as 
    frame shift mutations (Ex. 35-161). Nestmann et al. also reported 
    forward and frame shift mutations in Salmonella typhimurium with pre-
    solubilized lead chromate (Ex. 35-162). Several Cr(VI) compounds have 
    produced mutagenic responses at various genetic loci in mammalian cells 
    (Ex. 12-7). Clastogenic damage, such as sister chromatid exchange and 
    chromosomal aberrations, have also been reported for insoluble Cr(VI) 
    and soluble Cr(VI) (Exs. 35-132; 35-115). Mammalian cells undergo 
    neoplastic transformation following treatment with soluble Cr(VI) or 
    insoluble Cr(VI), including a number of slightly soluble zinc and 
    insoluble lead chromate pigments (Exs. 12-5; 35-186).
        Genotoxicity has been reported from Cr(VI) administration to 
    animals in vivo. Soluble Cr(VI) induced micronucleated erythrocytes in 
    mice following intraperitoneal (IP) administration (Ex. 35-150). It 
    also increased the mutation frequency in liver and bone marrow 
    following IP administration to lacZ transgenic mice (Exs. 35-168; 35-
    163). Izzotti et al. reported DNA damage in the lungs of rats exposed 
    to soluble Cr(VI) by intratracheal instillation (Ex. 35-170). 
    Intratracheal instillation of soluble Cr(VI) produced a time- and dose-
    dependant elevation in mutant frequency in the lung of Big Blue 
    transgenic mice (Ex. 35-174). Oral administration of soluble Cr(VI) in 
    animals did not produce genotoxicity in several studies probably due to 
    route-specific differences in absorption. OSHA is not aware of 
    genotoxicity studies from in vivo administration of insoluble Cr(VI). 
    Studies of chromosomal and DNA damage in workers exposed to Cr(VI) vary 
    in their findings. Some studies reported higher levels of chromosomal 
    aberrations, sister chromatid exchanges, or DNA strand breaks in 
    peripheral lymphocytes of stainless steel welders (Exs. 35-265; 35-160) 
    and electroplaters (Ex. 35-164). Other studies were not able to find 
    excess damage in DNA from the blood lymphocytes of workers exposed to 
    Cr(VI) (Exs. 35-185; 35-167). These reports are difficult to interpret 
    since co-exposure to other genotoxic agents (e.g., other metals, 
    cigarette smoke) likely existed and the extent of Cr(VI) exposures were 
    not known.
        Because of the consistent positive response across multiple assays 
    in a wide range of experimental systems from prokaryotic organisms 
    (e.g., bacteria) to human cells in vitro and animals in vivo, OSHA 
    regards Cr(VI) as an agent able to induce carcinogenesis through a 
    genotoxic mode of action. Both soluble and insoluble forms of Cr(VI) 
    are reported to cause genotoxicity and neoplastic transformation. On 
    the other hand, Cr(III) compounds do not easily cause genotoxicity in 
    intact cellular systems, presumably due to the inability of Cr(III) to 
    penetrate cell membranes (Exs. 12-7; 35-186).
        There has been a great deal of research to identify the types of 
    damage to DNA caused by Cr(VI), the reactive intermediates that are 
    responsible for the damage, and the specific genetic lesions critical to 
    carcinogenesis. It was shown that Cr(VI) was inactive in DNA binding assays 
    with isolated nuclei or purified DNA (Ex. 35-47). However, Cr(III) was able 
    to produce DNA protein cross-links, sister chromatid exchanges, and chromosomal 
    aberrations in an acellular system. Zhitkovich et al. showed that incubation of 
    Chinese hamster ovary cells with soluble Cr(VI) produced ternary complexes of 
    Cr(III) cross-linked to cysteine, other amino acids, or glutathione and 
    the DNA phosphate backbone (Ex. 312). Utilizing the pSP189 shuttle 
    vector plasmid, they showed these DNA-Cr(III)-amino acid cross-links 
    were mutagenic when introduced in human fibroblasts (Ex. 35-131).
        Another research group showed that plasmid DNA treated with Cr(III) 
    produced intrastrand crosslinks and the production of these lesions 
    correlated with DNA polymerase arrest (Ex. 35-126). The same 
    intrastrand crosslinks and DNA polymerase arrest could also be induced 
    by Cr(VI) in the presence of ascorbate as a reducing agent to form 
    Cr(III) (Ex. 35-263). These results were confirmed in a cell system by 
    treating human lung fibroblasts with soluble Cr(VI), isolating genomic 
    DNA, and demonstrating dose-dependent guanine-specific arrest in a DNA 
    polymerase assay (Ex. 35-188). Cr(V) may also form intrastrand 
    crosslinks since Cr(V) interacts with DNA in vitro (Ex. 35-178). The 
    Cr(V)-DNA crosslinks are probably readily reduced to Cr(III) in cell 
    systems. Intrastrand crosslinks have also been implicated in inhibition 
    of RNA polymerase and DNA topoisomerase, leading to cell cycle arrest, 
    apoptosis and possibly other disturbances in cell growth that 
    contribute to the carcinogenic pathway (Ex. 35-149).
        DNA strand breaks and oxidative damage result from the one electron 
    reduction/oxidation cycling of Cr(VI), Cr(V), and Cr(IV). Shi et al. 
    showed that soluble Cr(VI) in the presence of ascorbate and 
    H2O2 caused DNA double strand breaks and 8-
    hydroxy deoxyguanine (8-OHdG, a marker for oxidative DNA damage) in 
    vitro (Ex. 35-129). Leonard et al. showed that the DNA strand breaks 
    were reduced by several experimental conditions including an 
    O2-free atmosphere, catabolism of H2O2 
    by catalase, ROS depletion by free radical scavengers, and chelation of 
    Cr(V). They concluded that the strand breaks and 8-OHdG resulted from 
    DNA damage caused by hydroxyl radicals from Cr(VI) reduction/oxidation 
    cycling (Ex. 31-22-17). Generation of ROS-dependant DNA damage could 
    also be shown with insoluble Cr(VI) (Ex. 35-137). DNA strand breaks and 
    related damage caused by soluble Cr(VI) have been reported in Chinese 
    hamster cells (Ex. 35-128), human fibroblasts (Ex. 311), and human 
    prostate cells (Ex. 35-255). Pretreatment of Chinese hamster cells with 
    a metal chelator suppressed Cr(V) formation from Cr(VI) and decreased 
    DNA strand breaks (Ex. 35-197). Chinese hamster cells that developed 
    resistance to H2O2 damage also had reduced DNA 
    strand breaks from Cr(VI) treatment compared to the normal phenotype 
    (Ex. 35-176).
        Several researchers have been able to modulate Cr(VI)-induced DNA 
    damage using cellular reductants such as ascorbate, GSH and the free 
    radical scavenger tocopherol (vitamin E). This has provided insight 
    into the relationships between DNA damage, reduced chromium forms and 
    ROS. Sugiyama et al. showed that Chinese hamster cells pretreated with 
    ascorbate decreased soluble Cr(VI)-induced DNA strand damage (e.g., 
    alkali-labile sites), but enhanced DNA-amino acid crosslinks (Ex. 35-
    133). Standeven and Wetterhahn reported that elimination of ascorbate 
    from rat lung cytosol prior to in vitro incubation with soluble Cr(VI) 
    completely inhibited Cr-DNA binding (Ex. 35-180). However, not all 
    types of Cr-DNA binding are enhanced by ascorbate. Bridgewater et al. 
    found that high ratios of ascorbate to Cr(VI) actually decreased 
    intrastrand crosslinks in vitro while low ratios induced their 
    formation (Ex. 35-263). This finding is consistent with research by 
    Stearns and Watterhahn who showed that excessive ascorbate relative to 
    Cr(VI) leads to two-electron reduction of Cr(III) and formation of 
    Cr(III)-DNA monoadducts and DNA-Cr(III)-amino acid crosslinks (Ex. 35-
    166). Low amounts of ascorbate primarily cause one-electron reduction 
    to intermediates Cr(V) and Cr(IV) that form crosslinks with DNA and ROS 
    responsible for DNA strand breaks, alkali-labile sites, and clastogenic 
    damage. This explains the apparent paradox that extracellular Cr(VI) 
    reduction by ascorbate to Cr(III) reduces Cr(VI)-induced DNA binding 
    but intracellular Cr(VI) reduction by ascorbate to Cr(III) enhances Cr-
    DNA binding. The aforementioned studies used soluble forms of Cr(VI), 
    but Blankenship et al. showed that ascorbate pretreatment inhibited 
    chromosomal aberrations in Chinese hamster ovary cells caused by both 
    insoluble lead chromate particles as well as soluble Cr(VI) (Ex. 35-
    115). Pretreatment with the free radical scavenger tocopherol also 
    inhibits chromosomal aberrations and alkali-labile sites in Cr(VI)-
    treated cells (Exs. 35-115; 35-128).
        Studies of the different types of DNA damage caused by Cr(VI) and 
    the modulation of that damage inside the cell demonstrate that Cr(VI) 
    itself is not biologically active. Cr(VI) must undergo intracellular 
    reduction to Cr(V), Cr(IV), and Cr(III) before the damage to DNA can 
    occur. The evidence suggests that Cr(III) can cause DNA-Cr-amino acid, 
    DNA-Cr-DNA crosslinks and Cr-DNA monoadducts. Cr(V) and possibly Cr(IV) 
    contribute to intrastrand crosslinks and perhaps other Cr-DNA binding. 
    ROS generated during intracellular reduction of Cr(VI) lead to lesions 
    such as chromosomal aberrations, DNA strand breaks, and oxidative DNA 
    damage. The specific DNA lesions responsible for neoplastic 
    transformation have yet to be firmly established so all forms of DNA 
    damage should, at this time, be regarded as potential contributors to 
    carcinogenicity.
        d. Cr(VI)-induced Disturbances in the Regulation of Cell 
    Replication. Recent research has begun to elucidate how Cr(VI)-induced 
    oxidative stress and DNA lesions trigger cell signaling pathways that 
    regulate the cell growth cycle. The complex regulation of the cell 
    growth cycle by Cr(VI) involves activation of the p53 protein and other 
    transcription factors that respond to oxidative stress and DNA damage. 
    The cellular response ranges from a temporary pause in the cell cycle 
    to terminal growth arrest (i.e., viable cells that have lost the 
    ability to replicate) and a programmed form of cell death, known as 
    apoptosis. Apoptosis involves alterations in mitochondrial 
    permeability, release of cytochrome c and the action of several kinases 
    and caspases. Less is known about the molecular basis of terminal 
    growth arrest. Terminal growth arrest and apoptosis serve to eliminate 
    further growth of cells with unrepaired Cr(VI)-induced genetic damage. 
    However, it is believed that cells which escape these protective 
    mechanisms and regain replicative competence eventually become 
    resistant to normal growth regulation and can transform to a neoplastic 
    phenotype (Exs. 35-121; 35-122; 35-120).
        Blankenship et al. first described apoptosis as the primary mode of 
    cell death following a two hour treatment of Chinese hamster ovary 
    cells with high concentrations (>150 [mu]M) of soluble Cr(VI) (Ex. 35-
    144). Apoptosis also occurs in human lung cells following short-term 
    treatment with soluble Cr(VI)(Ex. 35-125) as well as longer term treatment
    (e.g., 24 hours) with lower concentrations of soluble Cr(VI) (e.g., 10 [mu]M)
    and insoluble Cr(VI) in the form of lead chromate (Ex. 35-166). Ye et al. 
    found that the Cr(VI) treatment that caused apoptosis also activated expression
    of p53 protein (Ex. 35-125). This apoptotic response was substantially 
    reduced in a p53-deficient cell line treated with Cr(VI), suggesting 
    that the p53 activation was required for apoptosis. Other studies using 
    p53 null cells from mice and humans confirmed that Cr(VI)-induced 
    apoptosis is p53-dependent (Ex. 35-225).
        The p53 protein is a transcription factor known to be activated by 
    DNA damage, lead to cell cycle arrest, and regulate genes responsible 
    for either DNA repair or apoptosis. Therefore, it is likely that the 
    p53 activation is a response to the Cr(VI)-induced DNA damage. 
    Apoptosis (i.e., programmed cell death) is triggered once the Cr(VI)-
    induced DNA damage becomes too extensive to successfully repair. In 
    this manner, apoptosis serves to prevent replication of genetically 
    damaged cells.
        Several researchers have gone on to further elucidate the molecular 
    pathways involved in Cr(VI)-induced apoptosis. ROS produced by 
    intracellular Cr(VI) reduction/oxidation cycling have been implicated 
    in the activation of p53 and apoptosis (Exs. 35-255; 35-122). Using 
    specific inhibitors, Pritchard et al. showed that mitochondrial release 
    of cytochrome c is critical to apoptotic death from Cr(VI) (Ex. 35-
    159). Cytochrome c release from mitochondria could potentially result 
    from either direct membrane damage caused by Cr(VI)-induced ROS or 
    indirectly by enhanced expression of the p53-dependent apoptotic 
    proteins, Bax and Nova, known to increase mitochondrial membrane 
    permeability.
        Cr(VI) causes cell cycle arrest and reduces clonogenic potential 
    (i.e., normal cell growth) at very low concentrations (e.g., 1 [mu]M) 
    where significant apoptosis is not evident. Xu et al. showed that human 
    lung fibroblasts treated with low doses of Cr(VI) caused guanine-
    guanine intrastrand crosslinks, guanine-specific polymerase arrest, and 
    inhibited cell growth at the G1/S phase of the cell cycle 
    (Ex. 35-188). Zhang et al. described a dose-dependent increase in 
    growth arrest at the G2/M phase of the cell cycle in a human 
    lung epithelial cell line following 24 hour Cr(VI) treatment over a 
    concentration range of 1 to 10 [mu]M (Ex. 35-135). The cell cycle 
    arrest could be partially eliminated by reducing production of Cr(VI)-
    induced ROS. Apoptosis was not detected in these cells until a 
    concentration of 25 [mu]M Cr(VI) had been reached. These data suggest 
    that low cellular levels of Cr(VI) are able to cause DNA damage and 
    disrupt the normal cell growth cycle.
        Pritchard et al. studied the clonogenicity over two weeks of human 
    fibroblasts treated 24 hours with soluble Cr(VI) concentrations from 1 
    to 10 [mu]M (Ex. 35-120). They reported a progressive decline in cell 
    growth with increasing Cr(VI) concentration. Terminal growth arrest 
    (i.e., viable cells that have lost the ability to replicate) was 
    primarily responsible for the decrease in clonogenic survival below 4 
    [mu]M Cr(VI). At higher Cr(VI) concentrations, apoptosis was 
    increasingly responsible for the loss in clonogenicity. Pritchard et 
    al. and other research groups have suggested that a subset of cells 
    that continue to replicate following Cr(VI) exposure could contain 
    unrepaired genetic damage or could have become intrinsically resistant 
    to processes (e.g., apoptosis, terminal growth arrest) that normally 
    control their growth (Exs. 35-121; 35-122; 35-120). These surviving 
    cells would then be more prone to neoplastic progression and have 
    greater carcinogenic potential.
        e. Summary. Respirable chromate particulates are taken up by target 
    cells in the bronchoalveolar region of the lung, become intracellularly 
    reduced to several reactive genotoxic species able to damage DNA, 
    disrupt normal regulation of cell division and cause neoplastic 
    transformation. Scientific studies indicate that both water soluble and 
    insoluble Cr(VI) can be transported into the cell. In fact, cell 
    surface interactions with slightly soluble and insoluble chromates may 
    create a concentrated microenvironment of chromate ion, especially in 
    the case of the slightly soluble Cr(VI) compounds that more readily 
    dissociate. The higher concentration of chromate ion in close proximity 
    to the lung cells will likely result in higher intracellular Cr(VI) 
    than would occur from the highly water-soluble chromates. This is 
    consistent with the studies of respiratory tract carcinogenesis in 
    animals that indicate the most tumorigenic chromates had low to 
    moderate water solubility. Once inside the cell, Cr(VI) is converted to 
    several lower oxidation forms able to bind to and crosslink DNA. ROS 
    are produced during intracellular reduction/oxidation of Cr(VI) that 
    further damage DNA. These structural lesions are functionally 
    translated into a impaired DNA replication, mutagenesis, and altered 
    gene expression that ultimately lead to neoplastic transformation.
    9. Conclusion
        In the NRPM, OSHA preliminarily concluded that the weight of 
    evidence supports the determination that all Cr(VI) compounds should be 
    regarded as carcinogenic to workers (69 FR at 59351). This conclusion 
    included the highly water soluble chromates, such as sodium chromate, 
    sodium dichromate, and chromic acid; chromates of slight and 
    intermediate water solubility such as calcium chromate, strontium 
    chromates, and many zinc chromates (e.g. zinc yellow); and chromates 
    that have very low water solubility and are generally considered to be 
    water insoluble such as barium chromate and lead chromates. The 
    strongest evidence supporting this conclusion comes from the many 
    cohort studies reporting excess lung cancer mortality among workers 
    engaged in the production of soluble chromates (Exs. 7-14; 31-22-11; 
    23; 31-18-4), chromate pigments (Exs. 7-36; 7-42; 7-46), and chrome 
    plating (Exs. 35-62; 35-271). Chromate production workers were 
    principally exposed to the highly soluble sodium chromate and 
    dichromate (Ex. 35-61) although lesser exposure to other chromates, 
    such as highly soluble chromic acid and slightly soluble calcium 
    chromate probably occurred. Pigment production workers were principally 
    exposed Cr(VI) in the form of lead and zinc chromates. Significantly 
    elevated lung cancer mortality was found in two British chromium 
    electroplating cohorts (Exs. 35-62; 35-271). These workers were exposed 
    to Cr(VI) in the form of chromic acid mist. Therefore, significantly 
    elevated lung cancer rates have been observed in working populations 
    exposed to a broad range of Cr(VI) compounds.
        Cellular research has shown that both highly water soluble (e.g. 
    sodium chromate) Cr(VI) and water insoluble (e.g. lead chromate) Cr(VI) 
    enter lung cells (see Section V.8.a) and undergo intracellular 
    reduction to several lower oxidation forms able to bind to and 
    crosslink DNA as well as generate reactive oxygen species that can 
    further damage DNA (see Section V.8.b). Soluble and insoluble Cr(VI) 
    compounds are reported to cause mutagenesis, clastogenesis, and 
    neoplastic transformation across multiple assays in a wide range of 
    experimental systems from prokaryotic organisms to human cells in vitro 
    and animals in vivo (see Section V.8.c).
        The carcinogenicity of various Cr(VI) compounds was examined after 
    instillation in the respiratory tract of rodents. Slightly water 
    soluble Cr(VI) compounds, strontium chromate, calcium chromate, and some 
    zinc chromates produced a greater incidence of respiratory tract tumors than 
    highly water soluble (e.g. sodium dichromate and chromic acid) and 
    water insoluble (e.g. barium chromate and lead chromates) Cr(VI) 
    compounds under similar experimental protocol and conditions (see 
    Section V.7). This likely reflects the greater tendency for chromates 
    of intermediate water solubility to provide a persistent high local 
    concentration of solubilized Cr(VI) in close proximity to the target 
    cell. Highly soluble chromates rapidly dissolve and diffuse in the 
    aqueous fluid lining the epithelia of the lung. Thus, these chromates 
    are less able to achieve the higher local concentrations within close 
    proximity of the lung cell surface than the slightly water soluble 
    chromates. However, it has been shown that water-soluble Cr(VI) can 
    still enter lung cells, damage DNA, and cause cellular effects 
    consistent with carcinogenesis (Ex. 31-22-18; 35-125; 35-135; 35-142). 
    Like the slightly water soluble chromates, water insoluble Cr(VI) 
    particulates are able to come in close contact with the lung cell 
    surface and slowly dissolve into readily absorbed chromate ion. For 
    example, water insoluble lead chromate has been shown to enter human 
    airway cells both through extracellular solubilization as chromate ion 
    (Exs. 35-66; 35-327; 47-12-3) as well as internalization as 
    unsolubilized particulate (Exs. 35-66; 47-19-7). However, the rate of 
    solubilization and uptake of water insoluble Cr(VI) is expected to be 
    more limited than chromates with moderate solubility. Once chromate ion 
    is inside lung cells, studies have shown that similar cellular events 
    believed critical to initiating neoplastic transformation occur 
    regardless of whether the source is a highly soluble or insoluble 
    Cr(VI) compound (Ex. 35-327).
    a. Public Comment on the Carcinogenicity of Cr(VI) Compounds
        In the NRPM, OSHA requested comment on whether currently available 
    epidemiologic and experimental studies supported the determination that 
    all Cr(VI) compounds possess carcinogenic potential and solicited 
    additional information that should be considered in evaluating relative 
    carcinogenic potency of the different Cr(VI) compounds (69 FR 59307). 
    Several comments supported the view that sufficient scientific evidence 
    exists to regard all Cr(VI) compounds as potential occupational 
    carcinogens (Exs. 38-106-2; 38-222; 39-73-2; 40-10-2; 42-2). The AFL-
    CIO stated that " * * * the agency has fully demonstrated that Cr(VI) 
    is a human carcinogen and that exposed workers are at risk of 
    developing lung cancer" (Ex. 38-222). NIOSH stated that "the 
    epidemiologic and experimental studies cited by OSHA support the 
    carcinogenic potential of all Cr(VI) compounds (i.e. water soluble, 
    insoluble, and slightly soluble)" (Ex. 40-10-2, p. 4). Peter Lurie of 
    Public Citizen testified:
    
        As we heard repeatedly in the course of this hearing, scientific 
    experts, in fact, agree. They agree that the most reasonable 
    approach to the regulation is to consider them all [Cr(VI) 
    compounds] to be carcinogenic (Tr. 710).
    
        Several commenters agreed that the evidence supported the 
    qualitative determination that Cr(VI) compounds were carcinogenic but 
    wished to make clear that the information was inadequate to support 
    quantitative statements about relative potency of the individual 
    chromates (Exs. 38-106-2; 40-10-2; 42-2). For example, the Boeing 
    Company in their technical comments stated:
    
        The available data does support the conclusion that the low 
    solubility hexavalent chromium compounds [e.g. strontium chromate] 
    can cause cancer but evidence to support a quantitative comparison 
    of carcinogenic potency based on differences in solubility is 
    lacking (Ex. 38-106-2, p. 18).
    
    Pigment Manufacturers' Comments on Carcinogenicity of Lead Chromate--
    One group that did not regard all Cr(VI) compounds as occupational 
    carcinogens was the color pigment manufacturers who manufacture and 
    market lead chromate pigments which are primarily used in industrial 
    coatings and colored plastic articles. The color pigment manufacturers 
    maintain that their lead chromate products are unreactive in biological 
    systems, are not absorbed into the systemic circulation by any route, 
    and can not enter lung cells (Ex. 38-205, p. 14). Their principal 
    rationale is that lead chromate is virtually insoluble in water, is 
    unable to release chromate ion into aqueous media, and therefore, is 
    incapable of interacting with biological systems (Exs. 38-205, p. 95; 
    38-201-1, p. 9). The color pigment manufacturers assert that their lead 
    chromate pigment products are double encapsulated in a resin/plastic 
    matrix surrounded by a silica coating and that the encapsulated pigment 
    becomes even less "bioavailable" than unencapsulated "less 
    stabilized" lead chromates. They believe the extreme stability and 
    non-bioavailable nature of their products makes them a non-carcinogenic 
    form of Cr(VI) (Ex. 38-205, p. 106).
        According to the Color Pigment Manufacturers Association (CPMA), 
    several pieces of scientific evidence support their position, namely, 
    the lack of a significant excess of lung cancer mortality in three 
    cohorts of pigment workers engaged in the production of water-insoluble 
    lead chromate (Ex. 38-205, pp. 88-91) and the lack of statistically 
    significant elevated tumor incidence following a single instillation of 
    lead chromate in the respiratory tract of rats (Ex. 38-205, pp. 88-92). 
    They dismiss as irrelevant other animal studies that produced 
    statistically significant increases in tumors when lead chromate was 
    repeatedly injected by other routes. In addition, CPMA claims that the 
    lead chromate used in cellular studies that report genotoxicity was 
    reagent grade, was contaminated with soluble chromate, and was 
    inappropriately solubilized using strong acids and bases prior to 
    treatment (Exs. 38-205, pp. 93-94; 47-31, pp. 9-13). They are 
    especially critical of studies conducted by the Environmental and 
    Genetic Toxicology group at the University of Southern Maine that 
    report lead chromate particulates to be clastogenic in human lung cells 
    (Exs. 34-6-1; 38-205, pp. 98-102 & appendix D; 47-22). Instead, they 
    rely on two in vitro studies of lead chromate pigments that report a 
    lack of genotoxicity in cultured bacterial and hamster ovary cells, 
    respectively (Exs. 47-3 Appendix C; 38-205, p. 94).
        OSHA addresses many of the CPMA claims in other sections of the 
    preamble. The bioavailability issue of encapsulated lead chromate is 
    addressed in Section V.A.2. The CPMA request to consider the lack of 
    excess lung cancer mortality among pigment workers exposed exclusively 
    to lead chromate is discussed in Section V.B.2. The CPMA assertions 
    that animal studies are evidence that lead chromates are not 
    carcinogenic to workers are addressed in Section V.B.7. The studies 
    documenting uptake of lead chromate into lung cells are described in 
    Section V.B.8.a. Section V.B.8.c describes evidence that lead chromate 
    is genotoxic. As requested by CPMA, OSHA will pull these responses 
    together and expand on their concerns below.
        Lung Cancer Mortality in Pigments Workers Exposed to Lead 
    Chromate--Comments and testimony from NIOSH and others cite evidence of 
    excess lung cancer among pigment workers and support the results of 
    OSHA's preliminary risk assessment for color pigments in general and 
    for lead chromate in particular (Tr. 135-146, 316, 337, Ex. 40-18-1, p. 
    2). However, comments submitted by the CPMA and the Dominion Colour 
    Corporation (DCC) attributed the excess lung cancer risk observed in 
    pigment worker studies to zinc chromate (Tr. 1707, 1747, Exs. 38-201-1, 
    p. 13; 38-205, p. 90; 40-7, p. 92). For example, the CPMA stated that:
    
        When lead chromate and zinc chromate exposures occur 
    simultaneously, there appears to be a significant cancer hazard. 
    However, when lead chromate pigments alone are the source of 
    chromium exposure, a significant carcinogenic response has never 
    been found (Ex. 40-7, p. 92).
    
    The latter statement refers to the Davies et al. (1984) study of 
    British pigment workers, the Cooper et al. (1983) study of U.S. pigment 
    workers, and the Kano et al. (1993) study of pigment workers in Japan, 
    all of which calculated separate observed and expected lung cancer 
    deaths for workers exposed exclusively to lead chromate (Ex. 38-205, p. 
    89). DCC and the Small Business Administration's Office of Advocacy 
    similarly stated that the excess lung cancer risk observed among 
    workers exposed to both zinc chromate and lead chromate cannot 
    necessarily be attributed to lead chromate (Exs. 38-201-1, p. 13; 38-7, 
    p. 4).
        OSHA agrees with CPMA and DCC that the excess lung cancer observed 
    in most pigment worker studies taken alone cannot be considered 
    conclusive evidence that lead chromate is carcinogenic. Given that the 
    workers were exposed to both zinc chromate and lead chromate, it is not 
    possible to draw strong conclusions about the effects of either 
    individual compound using only these studies. However, based on the 
    overall weight of available evidence, OSHA believes that the excess 
    lung cancer found in these studies is most likely attributable to lead 
    chromate as well as zinc chromate exposure. Lead chromate was the 
    primary source of Cr(VI) for several worker cohorts with excess lung 
    cancer (e.g., Davies et al. (1984), Factory A; Hayes et al. (1989); and 
    Deschamps et al. (1995)) (Exs. 7-42; 7-46; 35-234), and as previously 
    discussed, there is evidence from animal and mechanistic studies 
    supporting the carcinogenicity of both zinc chromate and lead chromate. 
    Considered in this context, the elevated risk of lung cancer observed 
    in most chromate pigment workers is consistent with the Agency's 
    determination that all Cr(VI) compounds--including lead chromate--
    should be regarded as carcinogenic.
        Moreover, OSHA disagrees with the CPMA and DCC interpretation of 
    the data on workers exposed exclusively to lead chromate. In the 
    Preamble to the Proposed Rule, OSHA stated that "[t]he number of lung 
    cancer deaths [in the Davies, Cooper, and Kano studies] is too small to 
    be meaningful" with respect to the Agency's determination regarding 
    the carcinogenicity of lead chromate (FR 69 at 59332). The CPMA 
    subsequently argued that:
    
        [b]y this rationale, OSHA could never conclude that a compound 
    such as lead chromate pigment exhibits no carcinogenic potential 
    because there can never be enough lung cancer deaths to produce a 
    "meaningful" result. This is an arbitrary and obviously biased 
    assessment which creates an insurmountable barrier. Since the lead 
    chromate pigments did not create an excess of lung cancer, there 
    cannot be a significant enough mortality from lung cancer to be 
    meaningful (Ex. 38-205, p. 90).
    
    OSHA believes that these comments reflect a misunderstanding of the 
    sense in which the Davies, Cooper, and Kano studies are too small to be 
    meaningful, and also a misunderstanding of the Agency's position.
        Contrary to CPMA's argument, a study with no excess in lung cancer 
    mortality can provide evidence of a lack of carcinogenic effect if the 
    confidence limits for the measurement of effect are close to the null 
    value. In other words, the measured effect must be close to the null 
    and the study must have a high level of precision. In the case of the 
    Davies, Cooper, and Kano studies, the standardized mortality ratio 
    (SMR) is the measurement of interest and the null value is an SMR of 1. 
    Table V.10 below shows that the SMRs for these study populations are 
    near or below 1; however, the 95% confidence intervals for the SMRs are 
    quite wide, indicating that the estimated SMRs are imprecise. The Kano 
    data, for example, are statistically consistent with a "true" SMR as 
    low as 0.01 or as high as 2.62. The results of these studies are too 
    imprecise to provide evidence for or against the hypothesis that lead 
    chromate is carcinogenic.

Table V-10

 

    
        This lack of precision may be partly explained by the small size of 
    the studies, as reflected in the low numbers of expected lung cancers. 
    However, it is the issue of precision, and not the number of lung 
    cancer deaths per se, that led OSHA to state in the preamble to the 
    proposed rule that the Davies, Cooper, and Kano studies cannot serve as 
    the basis of a meaningful analysis of lead chromate carcinogenicity 
    (Exs. 7-42; 2-D-1; 7-118). In contrast, a study population that has 
    confidence limits close to or below 1 would provide evidence to support 
    the DCC claim that " * * * if lead chromate pigments possess any 
    carcinogenic potential at all, it must be extremely small" (Ex. 38-
    201-1, p. 14) at the exposure levels experienced by that population. 
    While this standard of evidence has not been met in the epidemiological 
    literature for pigment workers exposed exclusively to lead chromate 
    (i.e., the Davies, Cooper, and Kano studies), it is hardly an 
    "insurmountable barrier" that sets up an impossible standard of proof 
    for those who contend that lead chromate is not carcinogenic.
        Some comments suggested that the Davies, Cooper, and Kano studies 
    should be combined to derive a summary risk measure for exposure to 
    lead chromate (see e.g. Ex. 38-201-1, pp. 13-14). However, OSHA 
    believes that these studies do not provide a suitable basis of meta-analysis.
    There is little information with which to assess factors recognized by 
    epidemiologists as key to meta-analysis, for example sources of bias or 
    confounding in the individual studies and comparability of exposures and 
    worker characteristics across studies, and to verify certain conditions 
    required for comparability of SMRs across these studies (see e.g. Modern 
    Epidemiology, Rothman and Greenland, p. 655). In addition, the 
    inclusion criteria and length of follow-up differ across the three 
    studies. Finally, each of the studies is extremely small. Even if it 
    were appropriate to calculate a 'summary' SMR based on them, the 
    precision of this SMR would not be much improved compared to those of 
    the original studies.
        In their written testimony, DCC suggested that OSHA should 
    aggregate the data from the Davies, Cooper, and Kano studies in order 
    to determine whether there is a discrepancy between the results of 
    these three studies, taken together, and OSHA's preliminary risk 
    assessment (Ex. 38-201-1, pp. 13-14). DCC performed a calculation to 
    compare OSHA's risk model with the observed lung cancer in the three 
    cohorts. DCC stated that:
    
        OSHA estimates a chromate worker's risk of dying from lung 
    cancer due to occupational exposure as about one chance in four * * 
    * [Assuming that there were about] 200 workers in the Kano study, 
    the total in the three studies would be 600. A calculation of one 
    quarter would be 150 deaths. To compensate for a working life of 
    less than OSHA's 45 years [an assumption of 20 years] provides * * * 
    a refined estimate of about 70 deaths. An observed number less than 
    this could be due either to exposures already in practice averaging 
    much less than the current PEL of 52, or to lead chromate having 
    much less potential (if any) for carcinogenicity than other 
    chromates. In any event the actual incidence of death from lung 
    cancer would appear to be no more than one tenth of OSHA's best 
    estimate (Ex. 38-201-1, pp. 15-16).
    
    The method suggested by DCC is not an appropriate way to assess the 
    carcinogenicity of lead chromate, to identify a discrepancy between the 
    pigment cohort results and OSHA's risk estimates, or to determine an 
    exposure limit for lead chromate. Among other problems, DCC's 
    calculation does not make a valid comparison between OSHA's risk 
    estimates and the results of the Davies, Cooper, and Kano studies. 
    OSHA's 'best estimate' of lung cancer risk for any given Cr(VI)-exposed 
    population depends strongly on factors including exposure levels, 
    exposure duration, population age, and length of follow-up. The 'one in 
    four' prediction cited by DCC applies to one specific risk scenario 
    (lifetime risk from 45 years of occupational exposure at the previous 
    PEL of 52 [mu]g/m\3\). OSHA's best estimate of risk would be lower for 
    a population with lower exposures (as noted by DCC), shorter duration 
    of exposure, or less than a lifetime of follow-up. Without adequate 
    information to adjust for each of these factors, a valid comparison 
    cannot be drawn between OSHA's risk predictions and the results of the 
    lead chromate cohort studies.
        The importance of accounting for cohort age and follow-up time may 
    be illustrated using information provided in the Cooper et al. study. 
    As shown in Table V-11 below, approximately three-fourths of the Cooper 
    et al. Plant 1 cohort members were less than 60 years old at the end of 
    follow-up.

Table V-11

 

    
        For a population of 600 with approximately the same distribution of 
    follow-up time as described in the Cooper et al. publication (e.g., 
    0.4% of workers are followed to age 84, 2% to age 79, etc.), OSHA's 
    risk model predicts about 3-15 excess lung cancers (making the DCC 
    assumption that workers are exposed for 20 years at 52 [mu]g/m\3\), 
    rather than the 70 deaths calculated by the DCC. If the workers were 
    typically exposed for less than 20 years or at levels lower than 52 
    [mu]g/m\3\, OSHA s model would predict still lower risk. A precise 
    comparison between OSHA's risk model and the observed lung cancer risk 
    in the Davies, Cooper and Kano cohorts is not possible without 
    demographic, work history and exposure information on the lead chromate 
    workers. (In particular, note that year 2000 background lung cancer 
    rates were used in the calculation above, as it was not feasible to 
    reconstruct appropriate reference rates without work history 
    information on the cohorts.) However, this exercise illustrates that 
    DCC's assertion of a large discrepancy between OSHA's risk model and 
    the available data on workers exposed exclusively to lead chromate is 
    not well-founded. To make a valid comparison between the OSHA risk
    model and the lung cancer observed in the lead chromate cohorts would 
    require more information on exposure and follow-up than is available 
    for these cohorts.
        OSHA received comments and testimony from NIOSH and others 
    supporting of the Agency's interpretation of the epidemiological 
    literature on Cr(VI) color pigments, including lead chromate (Tr. 135-
    146, 316, 337, Ex. 40-18-1, p. 2). At the hearing, Mr. Robert Park of 
    NIOSH stated that the available studies of workers exposed to chromate 
    pigments show " * * * a general pattern of excess [lung cancer] * * * 
    " and pointed out that "[i]n several of the studies, lead [chromate] 
    was by far the major component of production, like 90 percent * * * So 
    I don't think there is any epidemiological evidence at this point that 
    gets lead off the hook" (Tr. 337). Regarding the lack of statistically 
    significant excess lung cancer in several pigment worker cohorts, Mr. 
    Park identified study attributes that may have obscured an excess in 
    lung cancer, such as the high percentage of workers lost to follow-up 
    among immigrant workers in the Davies et al. study (Tr. 337) or a 
    healthy worker effect in the Hayes et al. study (Tr. 316). Dr. Paul 
    Schulte of NIOSH explained that
    
        * * * a lot of these studies that appear to be negative were 
    either of low power or had [some] other kind of conflicting 
    situation [so] that we can't really consider them truly negative 
    studies (Tr. 338).
    
    Dr. Herman Gibb testified that the epidemiological studies relied on by 
    CPMA and DCC to question the carcinogenicity of lead chromate have very 
    low expected numbers of lung cancer deaths, so they " * * * really 
    don't have a lot of ability to be able to detect a risk" (Tr. 135-
    136). Public Citizen agreed with OSHA's preliminary conclusion that 
    lead chromate is carcinogenic. Based on the major pigment worker 
    cohorts identified by OSHA in the Preamble to the Proposed Rule, Public 
    Citizen's Health Research Group concluded that
    
        * * * inadequately-powered studies, the standardized mortality 
    ratios for exposed workers are significantly elevated (range 1.5-
    4.4) and a relationship between extent of exposure (whether measured 
    by duration of exposure or factory) generally emerges; [moreover,] 
    [t]hese studies must be placed in the context * * * of the animal 
    carcinogenicity studies * * * and the mechanistic studies reviewed 
    by OSHA (Ex. 40-18-1, p. 2).
    
    Tumor Incidence in Experimental Animals Administered Lead Chromate--
    CPMA also claims that the absence of evidence for carcinogenicity found 
    among the three cited cohorts of lead chromate pigment workers " * * * 
    is further confirmed by the rat implantation studies of Levy" (Ex. 38-
    205, p. 98). They argue that these studies which involved implantation 
    into rat lungs " * * * indicated no increased incidence of tumors for 
    lead chromate pigment, although more soluble chromates exhibited 
    varying degrees of carcinogenicity" (Ex. 38-205, p. 93). They 
    dismissed other animal studies involving intramuscular and subcutaneous 
    injection of lead chromate which did report increased incidence of 
    tumors because they believe these techniques
    
        * * * are of questionable relevance in relation to human 
    workplace exposure conditions in industry, whereas tests involving 
    implantation in rat lung * * * are relevant to inhalation in 
    industrial exposures (Ex. 38-205, p. 93).
    
    In a more recent submission, CPMA remarked that the intramuscular and 
    subcutaneous injection studies with lead chromate were contradictory 
    and " * * * problematic in that false positive results frequently 
    occur during the study procedure (Ex. 47-31, p. 13).
        The rat implantation studies of Levy involved the surgical 
    placement of a Cr(VI)-containing pellet in the left bronchus of an 
    anesthetized rat (Exs. 10-1; 11-12; 11-2). This pellet procedure was an 
    attempt to deliver Cr(VI) compounds directly to the bronchial 
    epithelium and mimic continuous chronic in vivo dosing at the tissue 
    target site in order to assess the relative ability of different Cr(VI) 
    compounds to induce bronchogenic carcinoma. Histopathological 
    evaluation of the rat lung was conducted after a two year exposure 
    time. In most cases, approximately 100 rats were implanted with a 
    single pellet for each Cr(VI) test compound. The total lifetime dose of 
    Cr(VI) received by the animal was generally between 0.2 and 1.0 mg 
    depending on the compound. The amount of Cr(VI) that actually leached 
    from the cholesterol pellet and remained near the lung tissue was never 
    determined. At least 20 different commercially relevant Cr(VI) 
    compounds ranging from water insoluble to highly water soluble were 
    tested using this intrabronchial implantation protocol.
        The results of these studies are described in preamble section 
    V.B.7 and tables V-7, V-8, and V-9. Reagent grade lead chromate and six 
    different lead chromate pigments were tested. The lead chromate 
    pigments were a variety of different chrome yellows, including a silica 
    encapsulated chrome yellow, and molybdenum orange. The incidence of 
    bronchogenic cancer in the rats under this set of experimental 
    conditions was one percent or less for all the lead chromates tested. 
    This incidence was not statistically different from the negative 
    controls (i.e. rats implanted with a cholesterol pellet containing no 
    test compound) or rats administered either the water-insoluble barium 
    chromate or the highly soluble chromic acid and sodium dichromate. The 
    percent incidence of bronchogenic cancer in lead chromate-treated rats 
    was substantially less than that of rats treated with slightly soluble 
    strontium chromates (about 52 percent) and calcium chromate (24 
    percent). The type of bronchogenic cancer induced in these experiments 
    was almost entirely squamous cell carcinomas.
        OSHA does not agree with the CPMA position that absence of a 
    significant tumor incidence in the intrabronchial implantation studies 
    confirms that lead chromates lack carcinogenic activity and, therefore, 
    should not be subject to the OSHA Cr(VI) standard. The bioassay 
    protocol used approximately 100 test animals per experimental group. 
    This small number of animals limits the power of the bioassay to detect 
    tumor incidence below three to four percent with an acceptable degree 
    of statistical confidence. Three of the lead chromates, in fact, 
    produced a tumor incidence of about one percent (e.g. 1 tumor in 100 
    rats examined) which was not statistically significant. The researchers 
    only applied a single 2 mg [approximately 0.3 mg Cr(VI)] dose of lead 
    chromate to the bronchus of the rats. Since it was not experimentally 
    confirmed that the lead chromate pigments were able to freely leach 
    from the cholesterol pellet, the amount of Cr(VI) actually available to 
    the lung tissue is not entirely clear. Therefore, OSHA believes a more 
    appropriate interpretation of the study findings is that lead chromates 
    delivered to the respiratory tract at a dose of about 0.3 mg Cr(VI) 
    (maybe lower) lead to a less than three percent tumor incidence.
        However, OSHA agrees that the intrabronchial implantation protocol 
    does provide useful information regarding the relative carcinogenicity 
    of different Cr(VI) compounds once they are delivered and deposited in 
    the respiratory tract. No other study examines the carcinogenicity of 
    such a broad range of commercial Cr(VI) compounds under the same 
    experimental conditions in the relevant target organ to humans (i.e. 
    respiratory tract) following in vivo administration. OSHA agrees with 
    CPMA that the results of this study provide credible
    evidence that water insoluble lead chromates are less carcinogenic than 
    some of the more moderately soluble chromates. Specifically, this 
    includes the slightly soluble zinc chromates (e.g. zinc yellow, zinc 
    potassium chromates, basic zinc chromates) as well as strontium 
    chromate and calcium chromate. Intrabronchial implantation of chromic 
    acid and other highly soluble Cr(VI) salts, such as sodium chromates, 
    did not induce a significant number of tumors. Therefore, these 
    experiments do not indicate lead chromate are less carcinogenic than 
    the highly water soluble Cr(VI) compounds.
        If the histopathology data from the intrabronchial implantation is 
    examined more closely, all lead chromates increased the incidence of 
    squamous metaplasia relative to controls, and, for some lead chromates, 
    squamous dysplasia of the bronchial epithelium occurred (Table 2, Ex. 
    11-2). Squamous metaplasia and dysplasia are generally considered to be 
    transformed cellular states from which a neoplasm (e.g. carcinomas) can 
    arise (Ex. 11-12). Increased squamous metaplasia was common among all 
    tested Cr(VI) compounds but not among Cr(III)-containing materials or 
    the negative controls (Ex. 11-12). The increased metaplasia induced by 
    lead chromates is unlikely to be due to bronchial inflammation since 
    the degree of inflammation was no greater than that observed in the 
    cholesterol-implanted controls (Table 2, Ex. 11-2).
        The squamous metaplasia and dysplasia in the rat lung model 
    following low dose lead chromate administration is consistent with a 
    low carcinogenic response (e.g. incidence of one percent or less) not 
    able to be detected under the conditions of the animal bioassay. This 
    explanation is supported by studies (discussed later in the section) 
    that show lead chromate can enter lung cells, damage DNA, and cause 
    genotoxic events leading to neoplastic transformation.
        Lead chromate carcinogenicity is also supported by the animal 
    studies that CPMA dismisses as problematic and of questionable 
    relevance. These studies administered lead chromates to rodents by 
    either the subcutaneous (Exs. 8-25, 5-2, 8-37) or intramuscular routes 
    (Ex. 10-2). While OSHA agrees that these routes may be less relevant to 
    occupational inhalation than implantation in the respiratory tract, the 
    studies exposed rats to a larger dose of lead chromate. The higher 
    amounts of Cr(VI) produced a significant incidence of tumors at the 
    injection site (see section V.B.7.c).
        The lead chromate pigments, chrome yellow and chrome orange, 
    induced injection site rhabdomyosarcomas and fibrosarcomas in 65 
    percent of animals following a single 30 mg injection in a saline 
    suspension (Ex. 8-37). The rats received a roughly ten fold higher dose 
    of Cr(VI) than in the intrabronchial bioassay. Rats injected with 
    saline alone did not develop injection site tumors. Only two percent or 
    less of rats receiving equal quantities of the inorganic pigments iron 
    yellow and iron red developed these tumors. The iron oxides are not 
    considered to be carcinogenic and do not give a significant neoplastic 
    response in this bioassay. OSHA has no reason to believe the 
    experimental procedure was problematic or given to frequent false 
    positives.
        A similarly high incidence (i.e. 70 percent) of the same injection 
    site sarcomas were found in an independent study in which rats were 
    injected intramuscularly with reagent grade lead chromate once a month 
    for nine months (Ex. 10-2). Each injection contained approximately 1.3 
    mg of Cr(VI) and the total dose administered was over 30 times higher 
    than the intrabronchial implantation. The lead chromate was 
    administered in a glycerin vehicle. The vehicle produced less than a 
    two percent incidence of injection site sarcomas when administered 
    alone.
        Contrary to statements by Eurocolour (Ex. 44-3D), lead chromate did 
    produce a low incidence of site-of-contact tumors in rats in an earlier 
    study when administered by either intramuscular or intrapleural 
    implantation (Ex. 10-4). There was no tumor incidence in the control 
    animals. The dose of lead chromate in this early publication was not 
    stated.
        Based on the increase in pre-neoplastic changes from the single low 
    dose intrabronchial implantation and the high incidence of malignant 
    tumors resulting from larger doses administered by subcutaneous and 
    intramuscular injection, it is scientifically reasonable to expect that 
    larger doses of lead chromate may have produced a higher incidence of 
    tumors in the more relevant intrabronchial implantation procedure. The 
    highly soluble sodium dichromate produced a small (statistically 
    insignificant) incidence of squamous cell carcinoma (i.e. one percent) 
    upon single low dose intrabronchial implantation similar to the lead 
    chromates (Ex. 11-2). In another study, sodium dichromate caused a 
    significant 17 percent increase in the incidence of respiratory tract 
    tumors when instilled once a week for 30 months in the trachea of rats 
    (Ex. 11-7). The weekly-administered dose for this repeated instillation 
    was about \1/5\th the dose of that used in the intrabronchial 
    implantation assay but the total administered dose after 30 months was 
    about 25 times higher. Rats that received a lower total dose of sodium 
    dichromate or the same total dose in more numerous instillations (i.e. 
    lower dose rate) developed substantially fewer tumors that were 
    statistically indistinguishable from the saline controls. A third study 
    found a 15 percent increase (not statistically significant) in lung 
    tumor incidence when rats repeatedly inhaled aerosolized sodium 
    dichromate for 18 months at the highest air concentrations tested (Ex. 
    10-11). These sodium dichromate studies are further described in 
    section V.B.7.a. The findings suggest that the lack of significant 
    carcinogenic activity in the intrabronchial implantation study 
    reflects, in part, the low administered dose employed in the bioassay.
        In his written testimony to OSHA, Dr. Harvey Clewell directly 
    addressed the issue of interpreting the absence of carcinogenicity in 
    an animal study as it relates to significant risk.
    
        First, the ability to detect an effect depends on the power of 
    the study design. A statistically-based No Observed Adverse Effect 
    Level (NOAEL) in a toxicity study does not necessarily mean that 
    there is no risk of adverse effect. For example, it has been 
    estimated that a NOAEL in a typical animal study can actually be 
    associated with the presence of an effect in as many as 10% to 30% 
    of the animals. Thus the failure to observe a statistically 
    significant increase in tumor incidence at a particular exposure 
    does not rule out the presence of a substantial carcinogenic effect 
    at that exposure * * *. Similarly the failure of Levy et al. (1986) 
    to detect an increase in tumors following intrabronchial 
    instillation of lead chromate does not in itself demonstrate a lack 
    of carcinogenic activity for that compound. It only demonstrates a 
    lower activity than for other compounds that showed activity in the 
    same experimental design. Presumably this lower activity is 
    primarily due to its low solubility; evidence of solubilization, 
    cellular uptake, and carcinogenic activity of this compound [i.e. 
    lead chromate] is provided in other studies (Maltoni et al. 1974, 
    Furst et al., 1976, Blankenship et al., 1997; Singh et al., 1999; 
    Wise et al., 2004) (Ex. 44.5, p. 13-14).
    
        OSHA agrees with Dr. Clewell that the inability to detect a 
    statistically significant incidence of tumors in one study that 
    administers a single low dose of lead chromate to a limited number of 
    animals is not evidence that this Cr(VI) compound lacks carcinogenic 
    activity. This is especially true when there exists an elevation in 
    pre-neoplastic lesions and other studies document significant
    tumor incidence in animals administered higher doses of lead chromate.
        Cellular Uptake and Genotoxicity of Lead Chromate--CPMA disputes 
    the many studies that report lead chromate to be genotoxic or 
    clastogenic in cellular test systems (Exs. 35-162; 12-5; 35-119; 35-
    188; 35-132; 35-68; 35-67; 35-115; 35-66; 47-22-1; 47-12-3; 35-327; 35-
    436). They claim that the studies inappropriately solubilized the lead 
    chromate " * * * in non-biological conditions such as strong alkali or 
    strong acid that causes the chemical breakdown of the lead chromate 
    crystal" (Ex. 38-205, p. 94) and the "lead chromate had been 
    dissolved * * * using aggressive substances" (Ex. 38-205, p. 99). In a 
    later submission, CPMA states state that some of the cellular studies 
    used reagent grade lead chromate that is only >=98 percent pure and may 
    contain up to 2 percent soluble chromate (Ex. 47-31, p. 11). They 
    speculate that the interactions (e.g. chromate ion uptake, chromosomal 
    aberrations, DNA adducts, etc.) described in studies using cell 
    cultures treated with lead chromate are either due to the presumed 
    contamination of soluble chromate or some other undefined "reactive 
    nature" of lead chromate. CPMA adds that " * * * the studies 
    referenced by OSHA [that use reagent grade lead chromate] have no 
    relevance to occupational exposures to commercial lead chromate 
    pigments" (Ex. 38-205, p. 11-12).
        OSHA agrees that studies involving lead chromate pre-solubilized in 
    solutions of hydrochloric acid, sodium hydroxide or other strong acids 
    and bases prior to treatment with cells are not particularly relevant 
    to the inhalation of commercial lead chromate particulates. However, 
    several relevant cellular studies have demonstrated that lead chromate 
    particulates suspended in biological media and not can enter lung 
    cells, damage DNA, and cause altered gene expression as described 
    below.
        Beginning in the late 1980s, there has been a consistent research 
    effort to characterize the genotoxic potential of lead chromate 
    particulate in mammalian cells. The lead chromate was not pre-
    solubilized prior to cell treatment in any of these investigations. In 
    most of the studies, lead chromate particles were rinsed with water and 
    then acetone. The rinses cleansed the particles of water- and acetone-
    soluble contaminants before cell treatment. This served to remove any 
    potential water-soluble Cr(VI) present that might confound the study 
    results. In most instances, the lead chromate particles were filtered, 
    stirred or sonicated in suspension to break up the aggregated particles 
    into monomeric lead chromate particulates. These lead chromate 
    particulates were primarily less than 5 [mu]m in diameter. This is 
    consistent with the inhaled particle size expected to deposit in the 
    bronchial and alveolar regions of the lung where lung cancer occurs. 
    Air-dried lead chromate particulates were introduced to the cell 
    cultures in a suspension of either saline-based media or acetone. Lead 
    chromate particulate is considered to be insoluble in both solvents so 
    significant solubilization is not expected during the process of 
    creating a homogenous suspension.
        The initial research showed that lead chromate particulate 
    morphologically transformed mouse and hamster embryo cells (Exs. 35-
    119; 12-5). One study tested a variety of lead chromate pigments of 
    different types (e.g. chrome yellows, chrome oranges, molybdate 
    oranges) as well as reagent grade lead chromate (Ex. 12-5). The 
    transformed cells displayed neoplastic properties (e.g. growth in soft 
    agar) and were tumorigenic when injected into animals (Ex. 35-119; 12-
    5). While lead chromate particulate transformed mouse embryo cells, it 
    is important to note that lead chromate particulate was not found to be 
    mutagenic in these cells suggesting that other types of genetic lesions 
    (e.g. clastogenicity) may be involved (Ex. 35-119).
        Follow-on research established that lead chromate particulate 
    caused DNA-protein crosslinks, DNA strand breaks, and chromosomal 
    aberrations (i.e. chromatid deletions and achromatic lesions combined) 
    in mammalian cells rather than DNA nucleotide binding often associated 
    with base substitution and frameshift mutations captured in a standard 
    Ames assay (Exs. 35-132; 35-188). This distinguishes lead chromate 
    particulate from high concentrations of soluble Cr(VI) compounds or 
    pre-solubilized lead chromate which can cause these mutations.
        Lead chromate particulate enters mammalian embryo cells by two 
    distinct pathways (Ex. 35-68). It partially dissolves in the culture 
    medium (i.e. biological saline solution) to form chromate ion, which is 
    then transported into the cell. The rate of particle dissolution was 
    shown to be time- and concentration-dependent. The measured chromate 
    ion concentration was consistent with that predicted from the lead 
    chromate solubility constant in water. Lead chromate particulates were 
    shown to adhere to the embryo cell surface enhancing chromate ion 
    solubilization leading to sustained intracellular chromium levels and 
    measurable chromosomal damage (Ex. 35-67).
        Lead chromate particulates are also internalized into embryo cells, 
    without dissolution, by a phagocytic process (Ex. 35-68). The lead 
    chromate particles appeared to remain undissolved in tight vacuoles 
    (i.e. phagosomes) within the cell over a 24 hour period. Treatment of 
    embryo cells with lead chromate particulates in the presence of a 
    reducing agent (i.e. ascorbate) substantially reduced cellular uptake 
    of dissolved chromate ions and the chromosomal damage, but did not 
    impact the internalization of lead chromate particulates (Ex. 35-68). 
    This suggests that chromosomal damage by lead chromate was the result 
    of extracellular particle dissolution and not internalization under the 
    particular experimental conditions. Embryo cell treatment with large 
    amounts of lead glutamate that produced high intracellular lead in the 
    absence of Cr(VI) did not cause chromosomal damage further implicating 
    intracellular chromium as the putative clastogenic agent (Ex. 35-67).
        As the ability to maintain human tissue cells in culture improved 
    in the 1990s, dissolution and internalization of lead chromate 
    particulates, uptake of chromate ion, and the resulting chromosomal 
    damage were verified in human lung cells (Exs. 35-66; 47-22-1; 47-12-3; 
    35-327; 35-436). Lead chromate particulates are internalized, form 
    chromium adducts with DNA, and trigger dose-dependent apoptosis in 
    human small airway epithelial cells (Ex. 35-66). They also cause dose-
    dependent increases in intracellular chromium, internalized lead 
    chromate particulates and chromosomal damage in human lung fibroblasts 
    (Exs. 47-22-1; 47-12-3). The chromosomal damage from lead chromate in 
    these human lung cells is dependent on the extracellular dissolution 
    and cell uptake of the chromate, rather than lead, in a manner similar 
    to dilute concentrations of the highly soluble sodium chromate (Ex. 47-
    12-3; 35-327). Another water insoluble Cr(VI) compound, barium chromate 
    particulate, produces very similar responses in human lung fibroblasts 
    (Ex. 35-328). Human lung macrophages can phagocytize lead chromate 
    particulates and trigger oxidation-reduction of Cr(VI) to produce 
    reactive oxygen species capable of damaging DNA and altering gene 
    expression (Ex. 35-436).
        OSHA finds these recent studies to be carefully conceived and 
    executed by reputable academic laboratories. The scientific findings 
    have been published in well-respected peer reviewed
    molecular cancer and toxicology journals, such as Carcinogenesis (Exs. 
    12-5, 35-68), Cancer Research (Ex. 35-119), Toxicology and Applied 
    Pharmacology (Exs. 35-66; 25-115), and Mutation Research (Exs. 35-132; 
    47-22-1; 35-327). Contrary to statements by CPMA, the results indicate 
    that lead chromate particulates are able to dissociate in the presence 
    of biological media without the aid of aggressive substances. The 
    resulting chromate ion is bioavailable to enter lung cells, damage 
    genetic material and initiate events critical to carcinogenesis. These 
    effects can not be attributed to small amounts of soluble chromate 
    contaminants since these substances are usually removed as part of the 
    test compound preparation prior to cell treatment.
        As one of the study authors, Dr. John Wise of the University of 
    Southern Maine, stated in his post-hearing comments:
    
        At no time did we dissolve lead chromate particles prior to 
    administration. At the initial onset of the administration of lead 
    chromate particles in our studies, the cells encountered intact lead 
    chromate particles. Any dissolution that occurred was the natural 
    result of the fate of lead chromate particles in a biological 
    environment (Ex. 47-12, p. 3).
    
    Other scientists concurred that the methods and findings of the 
    cellular research with lead chromate were reasonable. Dr. Kathleen 
    MacMahon, a biologist from NIOSH stated:
    
        NIOSH believes that the methods that were used in the [lead 
    chromate] studies were credible and we support the results and 
    conclusions from those studies (Tr. 342).
    
    Dr. Clewell said:
    
        As I recall, it [lead chromate particles] was suspended in 
    acetone and ultrasonically shaken to reduce it to submicron 
    particles, which seems like a reasonably good thing to do. There are 
    actually a couple of studies besides the Wise studies that have 
    looked at the question of the uptake of lead chromate. I have looked 
    at those studies and I don't really see any basic flaws in what they 
    did. It is obviously a challenge to reproduce inhalation exposure in 
    vitro (Tr. 180-181).
    
    Chromosal Aberrations and Lead Chromate--Several submissions contained 
    testimony from another researcher, Dr. Earle Nestmann of CANTOX Health 
    Sciences International, that criticized the methodology and findings of 
    a study published by the research group at the University of Southern 
    Maine (Exs. 34-6-1; 38-205D; 47-12-1; 47-22). Dr. Nestmann viewed as 
    inappropriate the practice of combining the chromatid deletions and 
    achromatic lesions together as chromosomal aberrations. He indicated 
    the standard practice was to score these two types of lesions 
    separately and that only the deletions had biological relevance. 
    According to Dr. Nestmann, achromatic lesions are chromatid gaps (i.e. 
    lesion smaller than the width of one chromatid) that have no 
    clastogenic significance and serve to inflate the percentage of cells 
    with chromosomal aberrations (i.e. chromatid deletions or breaks). Dr. 
    Nestmann criticized the studies for not including a positive control 
    group that shows the experimental system responds to a 'true' 
    clastogenic effect (i.e. a compound that clearly increases chromosomal 
    deletions without contribution from chromatid gaps).
        Dr. John Wise, the Director of the research laboratory at the 
    University of Southern Maine, responded that distinguishing chromatid 
    gaps from breaks is a subjective distinction (e.g. requiring judgment 
    as to the width of a lesion relative to the width of a chromatid) and 
    pooling these lesions simply reduces this potential bias (Ex. 47-12; 
    47-12-1). He stated that there is no consensus on whether gaps should 
    or should not be scored as a chromosomal aberration and that gaps have 
    been included as chromosomal aberrations in other publications. Dr. 
    Wise also points out that achromatic lesions have not been shown to 
    lack biological significance and that the most recent research 
    indicates that they may be related to DNA strand breaks, a 
    scientifically accepted genotoxic endpoint. Dr. Wise further believed 
    that a positive control was unnecessary in his experiments since the 
    purpose was not to determine whether lead chromate was a clastogenic 
    agent, which had already been established by other research. Rather, 
    the purpose of his studies was to assess Cr(VI) uptake and chromosomal 
    damage caused by water-insoluble lead chromate compared to that of 
    highly water soluble sodium chromate using a relevant in vitro cell 
    model (i.e. human lung cells).
        OSHA is not in a position to judge whether achromatic lesions 
    should be scored as a chromosomal aberration. However, OSHA agrees with 
    Dr. Nestmann that combining gaps and breaks together serves to increase 
    the experimental response rate in the studies. Given the lack of 
    consensus on the issue, it would have been of value to record these 
    endpoints separately. OSHA is not aware of data that show achromatic 
    gaps to be of no biological significance. The experimental data cited 
    above indicate that soluble and insoluble Cr(VI) compounds clearly 
    increase achromatic gaps in a concentration-dependent manner. The 
    chromatid lesions (gaps and breaks) may be chromosomal biomarkers 
    indicative of genetic damage that is critical to neoplastic 
    transformation. Furthermore, OSHA agrees with Dr. Wise that other 
    evidence establishes lead chromate as an agent able to cause DNA damage 
    and transform cells. The Agency considers the use of sodium chromate-
    treated cells in the above set of experiments to be the appropriate 
    comparison group and does not find the absence of an additional 
    positive control group to be a technical deficiency of the studies. 
    OSHA considers the research conducted at the University of Southern 
    Maine documenting chromosomal damage in human lung cells following 
    treatment with lead chromate particulates to be consistent with results 
    from other studies (see Section V.B.8) and, thus, contributes to the 
    evidence that water insoluble lead chromate, like other chromates, is 
    able to enter lung cells and damage DNA.
        In post-hearing comments, CPMA provided a Canadian research 
    laboratory report that tested the lead chromate Pigment Yellow 34 for 
    chromosomal aberrations in a hamster embryo cell system (Ex. 47-3, 
    appendix C). The research was sponsored by DCC and its representative 
    Dr. Nestmann. Lead chromate particles over the concentration range of 
    0.1 [mu]/cm2 to 10 [mu]/cm2 were reported to not 
    induce chromosomal aberrations under the experimental test conditions. 
    Chromatid structural and terminal gaps were not scored as aberrations 
    in this study, even though the percentage of cells with these lesions 
    increased in a dose-dependent manner from two percent in the absence of 
    lead chromate to over thirteen percent in cells treated with 1 [mu]/
    cm2 lead chromate pigment particles.
        This result is consistent with other experimental data that show 
    lead chromate particulates cause chromosomal lesions when administered 
    to mammalian embryo cells (Exs. 35-188; 35-132; 35-68; 35-67). The key 
    difference is how the various researchers interpreted the data. The 
    George Washington University group (i.e. Pateirno, Wise, Blankenship et 
    al.) considered the dose-dependent achromatic lesions (i.e. chromatid 
    gaps) as a clastogenic event and included them as chromosomal damage. 
    The Canadian test laboratory (i.e. Nucrotechnics) reported achromatic 
    lesions but did not score them as chromosomal aberrations. Reporting 
    achromatic lesions but not scoring them as chromosomal aberrations is 
    consistent with regulatory test guidelines as currently recommended by 
    EPA and OECD. The Nucrotechnics data suggest that the tested lead chromate 
    pigment caused a similar degree of chromosomal damage (i.e. dose-dependent 
    achromatic lesions and chromosomal aberrations combined) in mammalian cells. 
    This result was similar to results produced by reagent grade lead chromate in 
    previous studies.
        Mutagenicity and Lead Chromate--CPMA also relied on a study that 
    reported a lack of mutagenicity for lead chromate pigments in a 
    bacterial assay using Salmonella Typhimurium TA 100 (Ex. 11-6). As 
    previously mentioned, this assay specifically measures point and 
    frameshift mutations usually caused by DNA adduct formation. The assay 
    is not sensitive to chromosomal damage, DNA strand breaks, or DNA 
    crosslinks most commonly found with low concentrations of Cr(VI) 
    compounds. Large amounts (50 to 500 [mu]g/plate) of highly soluble 
    sodium dichromate and slightly soluble calcium, strontium, and zinc 
    chromates, were found to be mutagenic in the study, but not the water 
    insoluble barium chromate and lead chromate pigments. However, 
    mutagenicity was observed when the acidic chelating agent, 
    nitrilotriacetic acid (NTA), was added to the assay to help solubilize 
    the water insoluble Cr(VI) compounds. The chelating agent was unable to 
    solubilize sufficient amounts of lead chromate pigments to cause 
    bacterial mutagenicity, if these pigments were more than five percent 
    encapsulated (weight to weight) with amorphous silica.
        OSHA finds the results of this study to be consistent with the 
    published literature that shows Cr(VI) mutagenicity requires high 
    concentrations of solubilized chromate ion (Exs. 35-118; 35-161). Large 
    amounts of water-soluble and slightly soluble Cr(VI) compounds produce 
    a mutagenic response in most studies since these Cr(VI) compounds can 
    dissociate to achieve a high concentration of chromate ion. Insoluble 
    lead chromate usually needs to be pre-solubilized under acidic or 
    alkaline conditions to achieve sufficient chromate ion to cause 
    mutagenicity (Ex. 35-162). The above study found highly and slightly 
    soluble chromates to be mutagenic as well as water insoluble lead 
    chromate pigments pre-solubilized with NTA. The lack of mutagenicity 
    for silica encapsulated lead chromate pigments under these experimental 
    conditions is likely the result of their greater resistance to acidic 
    digestion than unencapsulated lead chromate pigment.
        Failure to elicit a mutagenic response in a bacterial assay, with 
    or without NTA, is not a convincing demonstration that chromate ion can 
    not partially dissociate from encapsulated lead chromate in biological 
    media, enter mammalian cells, and elicit other types of genotoxicity. 
    As described above, chromosomal damage, believed to result from DNA 
    strand breaks and crosslinks, appears to be the critical genotoxic 
    endpoint for low concentrations of Cr(VI) compounds. Research has shown 
    that lead chromate and lead chromate pigment particulates in biological 
    media can cause chromosomal lesions and cell transformation without the 
    aid of strongly acidic or basic substances (Exs. 12-5; 35-119; 35-188; 
    35-132; 35-68; 35-67; 47-12-3; 35-327). While silica-encapsulated lead 
    chromate pigments have not been as thoroughly investigated as the 
    unencapsulated pigments or reagent grade lead chromate, one study 
    reported that lead silicochromate particles did have low solubility in 
    biological culture media and transformed hamster embryo cells (Ex. 12-
    5).
        Information is not available in the record to adequately 
    demonstrate the efficiency and stability of the encapsulation process, 
    despite OSHA statements that such information would be of value in its 
    health effects evaluation and its request for such information (69 FR 
    59315-59316, 10/4/2004; Ex. 2A). In the absence of data to the 
    contrary, OSHA believes it prudent and plausible that encapsulated lead 
    chromate pigments are able to partially dissociate into chromate ion 
    available for lung cell uptake and/or be internalized in a manner 
    similar to other lead chromate particulates. The resulting 
    intracellular Cr(VI) leads to genotoxic damage and cellular events 
    critical to carcinogenesis.
        Public Comments on Carcinogenicity of Slightly Water Soluble Cr(VI) 
    Compounds--In its written comments to the NPRM, Boeing Corporation 
    stated that "there is no persuasive scientific evidence for OSHA's 
    repeated assertion that low solubility hexavalent chromium compounds 
    [e.g. strontium and zinc chromates] are more potent carcinogens than 
    [highly] soluble [Cr(VI)] compounds" (Ex. 38-106, p. 2). Boeing and 
    others in the aerospace industry are users of certain slightly soluble 
    Cr(VI) compounds, particularly strontium chromate, found in the 
    protective coatings applied to commercial and military aircraft.
        Boeing argues that OSHA, along with IARC, ACGIH and others, have 
    exclusively relied on intrabronchial implantation studies in animals 
    that are both not representative of inhalation exposures in the 
    workplace and are not consistent with the available animal inhalation 
    data (Ex. 38-106-2, p. 26). Boeing asserts that there is no evidence 
    that slightly soluble chromates behave differently in terms of their 
    absorption kinetics than highly soluble chromates when instilled in the 
    lungs of rats (Ex. 38-106-2, p. 19). Boeing believes the OSHA position 
    that slightly soluble Cr(VI) compounds are retained in the lung, 
    associate with cells, and cause high uptake or high local 
    concentrations to be inconsistent with other data showing these Cr(VI) 
    compounds quickly disperse in water (Ex. 38-106-2, p. 26). Boeing 
    concludes:
    
        There is no basis for the conclusion that low solubility [i.e. 
    slightly soluble] chromates could be more potent than [highly] 
    soluble, and some evidence the opposite may be the case. As a worst 
    case OSHA should conclude that there is inadequate evidence to 
    conclude that [highly] soluble and low-solubility compounds differ 
    in carcinogenic potency. It is critical that OSHA maintain a 
    distinction between low-solubility chromates and highly insoluble 
    chromates based on this data. (Ex. 38-106-2, p. 26)
    
        As noted earlier, OSHA as well as other commenters agree with 
    Boeing that the animal intrabronchial and intratracheal instillation 
    studies are not appropriate for quantitatively predicting lung cancer 
    risk to a worker breathing Cr(VI) dust and aerosols. However, many 
    stakeholders disagreed with the Boeing view and believed these animal 
    studies can be relied upon as qualitative evidence of relative 
    carcinogenic potency. CPMA, which relies on the rat intrabronchial 
    implantation results as evidence that lead chromate is non-
    carcinogenic, states "tests involving implantation in rat lung, as 
    carried out by Levy et al. in 1986, are relevant to inhalation in 
    industrial exposures" (Ex. 38-205, p. 93). In their opening statement 
    NIOSH agreed with the preliminary OSHA determination that "the less 
    water soluble [Cr(VI)] compounds may be more potent than the more water 
    soluble [Cr(VI)] compounds" (Tr. 299). NIOSH identified the rat 
    intrabronchial implantation findings as the basis for their position 
    that the slightly soluble Cr(VI) compounds appear to be more 
    carcinogenic than the more soluble and insoluble Cr(VI) compounds (Tr. 
    334). Dr. Clewell testified that:
    
        Some animal studies suggest the solubility of hexavalent 
    chromium compounds influences their carcinogenic potency with 
    slightly soluble compounds having the higher potencies than highly 
    soluble or insoluble compounds. However, the evidence is inadequate 
    to conclude that specific hexavalent chromium compounds are not 
    carcinogenic. Moreover the designs of the studies were not 
    sufficient to quantitatively estimate comparative potencies (Ex. 44-5, p. 15).
    
    Respiratory Tract Instillation of Slightly Soluble Cr(VI) Compounds in 
    Rats--OSHA agrees that animal intrabronchial and intratracheal 
    implantation studies provide persuasive evidence that slightly soluble 
    Cr(VI) are more carcinogenic than the highly soluble Cr(VI) compounds. 
    As mentioned previously, these studies provide useful information 
    regarding the relative carcinogenicity of different Cr(VI) compounds 
    once they are delivered and deposited in the respiratory tract. For 
    example, one study examined the carcinogenicity of over twenty 
    different Cr(VI) compounds in rats, spanning a broad range of 
    solubilities, under the same experimental conditions in the relevant 
    target organ to humans (i.e. respiratory tract) following in vivo 
    administration (Ex. 11-2). A single administration of each Cr(VI) test 
    compound was instilled in the lower left bronchus of approximately 100 
    rats. The results were dramatic. Roughly 50 and 25 percent of the rats 
    receiving the slightly soluble strontium and calcium chromates, 
    respectively, developed bronchogenic carcinoma. No other Cr(VI) 
    compounds produced more than five percent tumor incidence. The highly 
    soluble sodium dichromate under the same experimental conditions caused 
    bronchogenic carcinoma in only a single rat.
        The higher relative potency of the slightly soluble calcium 
    chromate compared to the highly soluble sodium dichromate was confirmed 
    in another study in which each test compound was instilled at a low 
    dose level (i.e., 0.25 mg/kg) in the trachea of 80 rats five times 
    weekly for 30 months (Ex. 11-7). Using this experimental protocol, 7.5 
    percent of the slightly soluble calcium chromate-treated animals 
    developed brochioalveolar adenomas while none of the highly soluble 
    sodium dichromate-treated rats developed tumors. The tumor incidence at 
    this lower dose level occurred in the absence of serious lung pathology 
    and is believed to reflect the tumorigenic potential of the two Cr(VI) 
    compounds at workplace exposures of interest to OSHA. On the other 
    hand, a five-fold higher dose level that caused severe damage and 
    chronic inflammation to the rat lungs produced a similar fifteen 
    percent lung tumor incidence in both calcium and sodium chromate 
    treated rats. OSHA, as well as the study authors, believe the later 
    tumor response with the higher dose level did not result from direct 
    Cr(VI) interaction with cellular genes, but, instead, was primarily 
    driven by the cellular hyperplasia secondary to the considerable damage 
    to the lung tissue. Boeing also seems to attribute this result to 
    tissue damage stating "most of the tumors were found in areas of 
    chronic inflammation and scarring, suggesting an effect that is 
    secondary to tissue damage" (Ex. 38-106-2, p. 21).
        OSHA does not agree with some study interpretations advanced by 
    Boeing in support of their position that slightly soluble Cr(VI) 
    compounds are no more carcinogenic than highly soluble Cr(VI). For 
    example, Boeing claims that the intrabronchial implantation experiments 
    cannot be relied upon because the results do not correspond to findings 
    from animal inhalation studies (Ex. 38-106-2, p. 24-25). The primary 
    basis for the Boeing comparison were two rodent bioassays that reported 
    tumor incidence from the inhalation of different Cr(VI) compounds (Exs. 
    10-8; 10-11). In one study over 200 mice inhaled slightly soluble 
    calcium chromate powder for five hours per day, five days per week for 
    roughly two years (Ex. 10-8). In the other study, 19 rats inhaled an 
    aqueous sodium dichromate liquid aerosol virtually around the clock for 
    22 hours a day, seven days a week for eighteen months (Ex. 10-11). The 
    two studies reported a similar tumor incidence despite the lower total 
    weekly Cr(VI) dose of sodium dichromate in the second study. OSHA 
    believes the vastly different experimental protocols employed in these 
    studies do not allow for a legitimate comparison of carcinogenic 
    potency between Cr(VI) compounds. First, mouse and rat strains can 
    differ in their susceptibility to chemical-induced lung tumors. Second, 
    the proportion of respirable Cr(VI) may differ between a liquid aerosol 
    of aqueous sodium dichromate mist and an aerosol solid calcium chromate 
    particles suspended in air. Third, the opportunity for Cr(VI) clearance 
    will undoubtedly differ between a Cr(VI) dose inhaled nearly 
    continuously (e.g., 22 hours per day, seven days a week) and inhaled 
    intermittently (e.g., five hours a day, five days a week) over the 
    course of a week. These experimental variables can be expected to have 
    a major influence on tumor response and, thus, will obscure a true 
    comparison of carcinogenic potency. Boeing acknowledges that "these 
    [inhalation] studies used very different protocols and are not directly 
    comparable" (Ex. 38-106-2, p.24). On the other hand, slightly soluble 
    Cr(VI) compounds were found to cause a greater incidence of lung tumors 
    than highly soluble Cr(VI) compounds in two independent studies in 
    which the test compounds were instilled under the same dosing regime in 
    the same rodent models in research specifically designed to assess 
    relative Cr(VI) carcinogenic potency (Exs. 11-2; 11-7). Therefore, OSHA 
    believes any apparent lack of correspondence between animal inhalation 
    and instillation studies is due to an inability to compare inhalation 
    data from vastly different experimental protocols and should not 
    diminish the relevance of the instillation findings.
        Epidemiological Studies of Slightly Soluble Cr(VI) Compounds--
    Boeing further argues that the greater carcinogenic potency experienced 
    by rats intrabronchially instilled with slightly soluble chromates 
    compared to rats instilled with highly soluble and water-insoluble 
    Cr(VI) compounds "do not correspond qualitatively to observed lung 
    cancer in occupational exposure" (Ex. 38-106-2, p. 21). Several other 
    industry stakeholders disagree. In explaining the excess lung cancer 
    mortality among pigment production workers, CPMA commented:
    
        [water-insoluble] Lead chromate pigments must be differentiated 
    from [slightly soluble] zinc chromate corrosion inhibitor additives, 
    which are consistently shown to be carcinogenic in various studies. 
    When [water insoluble] lead chromate and [slightly soluble] zinc 
    chromate exposures occur simultaneously, there appears to be a 
    significant cancer hazard. However, when lead chromate pigments 
    alone are the source of chromium exposure, a significant cancer 
    response has never been found (Ex. 38-205, p. 91).
    
    In explaining the excess lung cancer mortality among chromate 
    production workers in the Gibb and Luippold cohorts, the Electric Power 
    Research Institute states that:
    
        One important distinction is that workers of the historical 
    chromate production industry were exposed to sparingly soluble forms 
    of calcium chromate in the roast mix, which are recognized to have 
    greater carcinogenic potential as compared to soluble forms of 
    Cr(VI) based on animal implantation studies (Ex. 38-8, p. 12).
    
    Deborah Proctor of Exponent also testified:
    
        Several studies of chromate production worker cohorts have 
    demonstrated that the excess cancer risk is reduced when less lime 
    is added to the roast mixture, reducing worker exposure to the 
    sparingly soluble calcium chromate compounds" (Ex. 40-12-5).
    
        OSHA believes there is merit to the above comments that workplace 
    exposure to slightly soluble Cr(VI) compounds may have contributed to 
    the higher lung cancer mortality in both pigments workers producing 
    mixed zinc and lead chromate pigments as well as
    chromate production workers exposed to calcium chromate from high lime 
    production processes in the 1930s and 1940s. Other factors, such as 
    greater Cr(VI) exposure, probably also contributed to the higher lung 
    cancer mortality observed in these cohorts. In any case, these 
    epidemiological findings support the Boeing contention that the 
    epidemiological findings are inconsistent with the results from animal 
    intrabronchial implantation studies (Ex. 38-106-2, p. 26).
        Clearance, Retention, and Dissolution of Slightly Soluble Cr(VI) 
    Compounds in the Lung--Boeing argues that animal experiments that 
    examined the absorption, distribution and excretion of Cr(VI) compounds 
    after intratracheal instillation of Cr(VI) compounds in rats do not 
    show that highly soluble Cr(VI) is cleared more rapidly or retained in 
    the lung for shorter periods than slightly soluble Cr(VI) compounds 
    (Ex. 38-106-2, p. 18-19). The results of one study found that larger 
    amounts of water-insoluble lead chromate were retained in the lungs of 
    rats at both 30 minutes and at 50 days after instillation than for 
    highly soluble sodium chromate or slightly soluble zinc chromate (Ex. 
    35-56). Although the authors concluded that slightly soluble zinc 
    chromate was more slowly absorbed from the lung than the highly soluble 
    sodium chromate, the excretion and distribution of the absorbed 
    chromium from the zinc and sodium chromate instillations was similar. 
    Furthermore, there was little difference in the amounts of zinc and 
    sodium chromate retained by the lung at the two extreme time points 
    (e.g., 30 minutes and 50 days) measured in the study. OSHA agrees with 
    Boeing that these findings indicate slower clearance and longer 
    retention in the lung of the water insoluble lead chromate relative to 
    highly soluble sodium chromate, but not in the case of the slightly 
    soluble zinc chromate. Slower clearance and longer residence time in 
    the lung will generally enhance carcinogenic potential assuming other 
    dosimetric variables such as lung deposition, Cr(VI) concentration at 
    the lung cell surface, and dissociation into chromate ion are 
    unchanged.
        Boeing asserts that a study of strontium chromate dissociation from 
    paint primer contradicts the notion that slightly soluble are more 
    likely than highly soluble Cr(VI) compounds to concentrate and 
    dissociate at the lung cell surface (Ex. 38-106-2, p. 25). This 
    experimental research found that roughly 75 and 85 percent of strontium 
    chromate contained in metal surface primer coating particles was 
    solubilized in water after one and 24 hours, respectively (Ex. 31-2-1). 
    The primer particles were generated using a high volume, low pressure 
    spray gun according to manufacturer specifications, and collected in 
    water impingers. The authors concluded that their study demonstrated 
    that chromate dissociation from primer particles into the aqueous fluid 
    lining lung cells would be modestly hindered relative to highly water 
    soluble Cr(VI) aerosols.
        The slower dissociation of the slightly soluble Cr(VI) compound, 
    strontium chromate, plausibly explains its higher carcinogenicity in 
    animal implantation studies. The 'modest hindrance' allows the 
    undissociated chromate to achieve higher concentrations at the surface 
    of the lung cells facilitating chromate transport into the cell. The 
    unhindered, instantaneous dispersion of highly water soluble chromates 
    in aqueous fluid lining of the respiratory tract is less likely to 
    achieve a high chromate concentration at the lung cell membrane. OSHA 
    believes the results of the above study support, not contradict, that 
    slightly soluble Cr(VI) may lead to higher chromium uptake into lung 
    cells than highly soluble Cr(VI) compounds.
        In summary, slightly soluble Cr(VI) compounds have consistently 
    caused higher lung tumor incidence in animal instillation studies 
    specifically designed to examine comparative carcinogenic potency in 
    the respiratory tract. The higher carcinogenic activity of slightly 
    soluble Cr(VI) is consistent with cellular studies that indicate that 
    chromate dissociation in close proximity to the lung cell surface may 
    be a critical feature to efficient chromate ion uptake. This is 
    probably best achieved by Cr(VI) compounds that have intermediate water 
    solubility rather than by highly water-soluble Cr(VI) that rapidly 
    dissolves and diffuses in the aqueous fluid layers lining the 
    respiratory tract. The higher carcinogenicity of slightly soluble 
    Cr(VI) may contribute, along with elevated Cr(VI) workplace exposures, 
    to the greater lung cancer mortality in certain occupational cohorts 
    exposed to both slightly soluble and other forms of Cr(VI). The vastly 
    different study protocols employed in the few animal inhalation 
    bioassays do not allow a valid comparison of lung tumor incidence 
    between slightly soluble and highly soluble Cr(VI) compounds.
    b. Summary of Cr(VI) Carcinogenicity
        After carefully considering all the epidemiological, animal and 
    mechanistic evidence presented in the rulemaking record, OSHA regards 
    all Cr(VI) compounds as agents able to induce carcinogenesis through a 
    genotoxic mode of action. This position is consistent with findings of 
    IARC, EPA, and ACGIH that classified Cr(VI) compounds as known or 
    confirmed human carcinogens. Based on the above animal and experimental 
    evidence, OSHA believes that slightly soluble Cr(VI) compounds are 
    likely to exhibit a greater degree of carcinogenicity than highly water 
    soluble or water insoluble Cr(VI) when the same dose is delivered to 
    critical target cells in the respiratory tract of the exposed worker. 
    In its evaluation of different Cr(VI) compounds, ACGIH recommended 
    lower occupational exposure limits for the slightly soluble strontium 
    chromate (TLV of 0.5 [mu]g/m\3\) and calcium chromate (TLV of 1 [mu]g/
    m\3\) than either water insoluble (TLV of 10 [mu]g/m\3\) or water 
    soluble (TLV of 50 [mu]g/m\3\) forms of Cr(VI) based on the animal 
    instillation studies cited above. While these animal instillation 
    studies are useful for hazard identification and qualitative 
    determinations of relative potency, they cannot be used to determine a 
    reliable quantitative estimate of risk for human workers breathing 
    these chromates during occupational exposure. This was due to use of 
    inadequate number of dose levels (e.g., single dose level) or a less 
    appropriate route of administration (e.g., tracheal instillation).
        It is not clear from the animal or cellular studies whether the 
    carcinogenic potency of water insoluble Cr(VI) compounds would be 
    expected to be more or less than highly water soluble Cr(VI). However, 
    it was found that a greater percentage of water insoluble lead chromate 
    remains in the lungs of rats for longer periods than the highly water 
    soluble sodium chromate when instilled intratracheally at similar doses 
    (Ex. 35-56). Since water insoluble lead chromate can persist for long 
    periods in the lung and increase intracellular levels of Cr and damage 
    DNA in human lung cells at low doses (e.g., 0.1 [mu]g/cm\2\), OSHA 
    believes that based on the scientific evidence discussed above it is 
    reasonable to regard the water insoluble Cr(VI) to be of similar 
    carcinogenic potency to highly soluble Cr(VI) compounds. No convincing 
    scientific evidence was introduced into the record that shows lead 
    chromate to be less carcinogenic than highly soluble chromate 
    compounds.
    
    C. Non-cancer Respiratory Effects
    
        The following sections describe the evidence from the literature on 
    nasal irritation, nasal ulcerations, nasal perforations, asthma, and 
    bronchitis following inhalation exposure to water
    soluble Cr(VI) compounds. The evidence clearly demonstrates that 
    workers can develop impairment to the respiratory system (nasal 
    irritation, nasal ulceration, nasal perforation, and asthma) after 
    workplace exposure to Cr(VI) compounds below the previous PEL.
        It is very clear from the evidence that workers may develop nasal 
    irritation, nasal tissue ulcerations, and nasal septum perforations at 
    occupational exposures level at or below the current PEL of 52 [mu]g/
    m\3\. However, it is not clear what occupational exposure levels lead 
    to the development of occupational asthma or bronchitis.
    1. Nasal Irritation, Nasal Tissue Ulcerations and Nasal Septum 
    Perforations
        Occupational exposure to Cr(VI) can lead to nasal tissue 
    ulcerations and nasal septum perforations. The nasal septum separates 
    the nostrils and is composed of a thin strip of cartilage. The nostril 
    tissue consists of an overlying mucous membrane known as the mucosa. 
    The initial lesion after Cr(VI) exposure is characterized by localized 
    inflammation or a reddening of the affected mucosa, which can later 
    lead to atrophy. This may progress to an ulceration of the mucosa layer 
    upon continued exposure (Ex. 35-1; Ex. 7-3). If exposure is 
    discontinued, the ulcer progression will stop and a scar may form. If 
    the tissue damage is sufficiently severe, it can result in a 
    perforation of the nasal septum, sometimes referred to chrome hole. 
    Individuals with nasal perforations may experience a range of signs and 
    symptoms, such as a whistling sound, bleeding, nasal discharge, and 
    infection. Some individuals may experience no noticeable effects.
        Several cohort and cross-sectional studies have described nasal 
    lesions from airborne exposure to Cr(VI) at various electroplating and 
    chrome production facilities. Most of these studies have been reviewed 
    by the Center for Disease Control's Agency for Toxic Substances and 
    Disease Registry (ATSDR) toxicological profile for chromium (Ex. 35-
    41). OSHA reviewed the studies summarized in the profile, conducted its 
    own literature search, and evaluated studies and comments submitted to 
    the rulemaking record. In its evaluation, OSHA took into consideration 
    the exposure regimen and experimental conditions under which the 
    studies were performed, including exposure levels, duration of 
    exposure, number of animals, and the inclusion of appropriate control 
    groups. Studies were not included if they did not contribute to the 
    weight of evidence either because of inadequate documentation or 
    because of poor quality. This section only covers some of the key 
    studies and reviews. OSHA has also identified two case reports 
    demonstrating the development of nasal irritation and nasal septum 
    perforations, and these case reports are summarized as well. One case 
    report shows how a worker can develop the nasal perforations from 
    direct contact (i.e., touching the inner surface of the nose with 
    contaminated fingers).
        Lindberg and Hedenstierna examined the respiratory symptoms and 
    effects of 104 Swedish electroplaters (Ex. 9-126). Of the 104 
    electroplaters, 43 were exposed to chromic acid by inhalation. The 
    remaining 61 were exposed to a mixture of chromic acid and nitric acid, 
    hydrochloric acid, boric acid, nickel, and copper salts. The workers 
    were evaluated for respiratory symptoms, alterations in the condition 
    of the nasal tissue, and lung function. All workers were asked to fill 
    out a detailed questionnaire on their history of respiratory symptoms 
    and function. Physicians performed inspections of the nasal passages of 
    each worker. Workers were given a pulmonary function test to assess 
    lung function. For those 43 workers exposed exclusively to chromic 
    acid, the median exposure time was 2.5 years, ranging from 0.2 to 23.6 
    years. The workers were divided into two groups, a low exposure group 
    (19 workers exposed to eight-hour time weighted average levels below 2 
    [mu]g/m\3\) and a high exposure group (24 workers exposed to eight-hour 
    time weighted average levels above 2 [mu]g/m\3\). Personal air sampling 
    was conducted on 11 workers for an entire week at stations close to the 
    chrome baths to evaluate peak exposures and variations in exposure on 
    different days over the week. Nineteen office employees who were not 
    exposed to Cr(VI) were used as controls for nose and throat symptoms, 
    and 119 auto mechanics (no car painters or welders) whose lung function 
    had been evaluated using similar techniques to those used on Cr(VI) 
    exposed workers were used as controls for lung function.
        The investigators reported nasal tissue ulcerations and septum 
    perforations in a group of workers exposed to chromic acid as Cr(VI) at 
    peak exposure ranging from 20 [mu]g/m\3\ to 46 [mu]g/m\3\. The 
    prevalence of ulceration/perforation was statistically higher than the 
    control group. Of the 14 individuals in the 20-46 [mu]g/m\3\ exposure 
    group, 7 developed nasal ulcerations. In addition to nasal ulcerations, 
    2 of the 7 also had nasal perforations. Three additional individuals in 
    this group developed nasal perforations in the absence of ulcerations. 
    None of the 14 workers in the 20-46 [mu]g/m\3\ exposure group were 
    reported to have nasal tissue atrophy in the absence of the more 
    serious ulceration or perforation.
        At average exposure levels from 2 [mu]g/m\3\ to 20 [mu]g/m\3\, half 
    of the workers complained of "constantly running nose," "stuffy 
    nose," or "there was a lot to blow out." (Authors do not provide 
    details of each complaint). Nasal tissue atrophy, in the absence of 
    ulcerations or perforations, was observed in 66 percent of 
    occupationally exposed workers (8 of 12 subjects) at relatively low 
    peak levels ranging from 2.5 [mu]g/m\3\ to 11 [mu]g/m\3\. No one 
    exposed to levels below 1 [mu]g/m\3\ (time-weighted average, TWA) 
    complained of respiratory symptoms or developed lesions.
        The authors also reported that in the exposed workers, both forced 
    vital capacity and forced expiratory volume in one second were reduced 
    by 0.2 L, when compared to controls. The forced mid-expiratory flow 
    diminished by 0.4 L/second from Monday morning to Thursday afternoon in 
    workers exposed to chromic acid as Cr(VI) at daily TWA average levels 
    of 2 [mu]g/m\3\ or higher. The effects were small, not outside the 
    normal range and transient. Workers recovered from the effects after 
    two days. There was no difference between the control and exposed group 
    after the weekend. The workers exposed to lower levels (2 [mu]g/m\3\ or 
    lower, TWA) showed no significant changes.
        Kuo et al. evaluated nasal septum ulcerations and perforations in 
    189 electroplaters in 11 electroplating factories (three factories used 
    chromic acid, six factories used nickel-chromium, and two factories 
    used zinc) in Taiwan (Ex. 35-10). Of the 189 workers, 26 used Cr(VI), 
    129 used nickel-chromium, and 34 used zinc. The control group consisted 
    of electroplaters who used nickel and zinc. All workers were asked to 
    fill out a questionnaire and were given a nasal examination including a 
    lung function test by a certified otolaryngologist. The authors 
    determined that 30% of the workers (8/26) that used chromic acid 
    developed nasal septum perforations and ulcerations and 38% (10/26) 
    developed nasal septum ulcers. Using the Mantel Extension Test for 
    Trends, the authors also found that chromium electroplaters had an 
    increased likelihood of developing nasal ulcers and perforations 
    compared to electroplating workers using nickel-chromium and zinc. 
    Personal sampling of airborne Cr(VI) results indicated the highest 
    levels (32 [mu]g/m\3\  35 [mu]g/m\3\, ranging from 0.1 
    [mu]g/m\3\-119 [mu]g/m\3\) near the electroplating tanks of the Cr(VI) 
    electroplating
    factories (Ex. 35-11). Much lower personal sampling levels were 
    reported in the "other areas in the manufacturing area" and in the 
    "administrative area" (TWA 0.16  0.10 [mu]g/m\3\) of the 
    Cr(VI) electroplating plant. The duration of sampling was not 
    indicated. The lung function tests showed that Cr(VI) electroplaters 
    had significantly lower forced vital capacity and forced expiratory 
    volume when compared to other exposure groups.
        Cohen et al. examined respiratory symptoms of 37 electroplaters 
    following inhalation exposure to chromic acid (Ex. 9-18). The mean 
    length of employment for the 37 electroplaters was 26.9 months (range 
    from 0.3 to 132 months). Fifteen workers employed in other parts of the 
    plant were randomly chosen for the control group (mean length of 
    employment was 26.1 months; range from 0.1 to 96). All workers were 
    asked to fill out a questionnaire on their respiratory history and to 
    provide details about their symptoms. An otolaryngologist then examined 
    each individual's nasal passages and identified ulcerations and 
    perforations. Air samples to measure Cr(VI) were collected for 
    electroplaters. The air sampling results of chromic acid as Cr(VI) 
    concentrations for electroplaters was a mean of 2.9 [mu]g/m\3\ (range 
    from non-detectable to 9.1 [mu]g/m\3\). The authors found that 95% of 
    the electroplaters developed pathologic changes in nasal mucosa. 
    Thirty-five of the 37 workers who were employed for more than 1 year 
    had nasal tissue damage. None of these workers reported any previous 
    job experience involving Cr(VI) exposure. Four workers developed nasal 
    perforations, 12 workers developed ulcerations and crusting of the 
    septal mucosa, 11 workers developed discoloration of the septal mucosa, 
    and eight workers developed shallow erosion of septal mucosa. The 
    control group consisted of 15 workers who were not exposed to Cr(VI) at 
    the plant. All but one had normal nasal mucosa. The one individual with 
    an abnormal finding was discovered to have had a previous Cr(VI) 
    exposure while working in a garment manufacturing operation as a fabric 
    dyer for three years. In addition to airborne exposure, the authors 
    observed employees frequently wiping their faces and picking their 
    noses with contaminated hands and fingers. Many did not wear any 
    protective gear, such as gloves, glasses, or coveralls.
        Lucas and Kramkowsi conducted a Health Hazard Evaluation (HHE) on 
    11 chrome platers in an industrial electroplating facility (Ex. 3-84). 
    The electroplaters worked for about 7.5 years on average. Physicians 
    evaluated each worker for chrome hole scars, nasal septum ulceration, 
    mucosa infection, nasal redness, perforated nasal septum, and wheezing. 
    Seventeen air samples for Cr(VI) exposure were collected in the chrome 
    area. Cr(VI) air concentrations ranged from 1 to 20 [mu]g/m\3\, with an 
    average of 4 [mu]g/m\3\. In addition to airborne exposure, the authors 
    observed workers being exposed to Cr(VI) by direct "hand to nose" 
    contact, such as touching the nose with contaminated hands. Five 
    workers had nasal mucosa that became infected, two workers had nasal 
    septum ulcerations, two workers had atrophic scarring (author did not 
    provide explanation), possibly indicative of presence of past 
    ulcerations, and four workers had nasal septum perforations.
        Gomes evaluated 303 employees from 81 electroplating operations in 
    Sao Paulo, Brazil (Ex. 9-31). Results showed that more than two-thirds 
    of the workers had nasal septum ulcerations and perforations following 
    exposure to chromic acid at levels greater than 100 [mu]g/m\3\, but 
    less than 600 [mu]g/m\3\ (precise duration of exposure was not stated). 
    These effects were observed within one year of employment.
        Lin et al. examined nasal septum perforations and ulcerations in 79 
    electroplating workers from seven different chromium electroplating 
    factories in Taipei, Taiwan (Ex.35-13). Results showed six cases of 
    nasal septum perforations, four having scar formations, and 38 cases of 
    nasal septum ulcerations following inhalation exposure to chromic acid. 
    Air sampling near the electroplating tanks had the highest range of 
    chromic acid as Cr(VI) (mean of 28 [mu]g/m\3\; range from 0.7 to 168.3 
    [mu]g/m\3\). In addition to airborne exposures, the authors also 
    observed direct "hand to nose" contact where workers placed 
    contaminated fingers in their nose. The authors attributed the high 
    number of cases to poor industrial hygiene practices in the facilities. 
    Five of the seven factories did not have adequate ventilation systems 
    in place. Workers did not wear any PPE, including respirators.
        Bloomfield and Blum evaluated nasal tissue damage and nasal septum 
    perforations in 23 workers employed at six chromium electroplating 
    plants (Ex. 9-13). They found that daily exposure to chromic acid as 
    Cr(VI) at levels of 52 [mu]g/m\3\ or higher can lead to nasal tissue 
    damage. Three workers developed nasal ulcerations, two workers had 
    nasal perforations, nine workers had nose bleeds, and nine workers had 
    inflamed mucosa.
        Kleinfeld and Rosso found that seven out of nine of chrome 
    electroplaters had nasal septum ulcerations (Ex. 9-41). The nine 
    workers were exposed to chromic acid as Cr(VI) by inhalation at levels 
    ranging from 93 [mu]g/m\3\ to 728 [mu]g/m\3\. Duration of exposure 
    varied from two weeks to one year. Nasal septum ulcerations were noted 
    in some workers who had been employed for only one month.
        Royle, using questionnaire responses from 997 British 
    electroplaters exposed to chromic acid, reported a significant increase 
    in the prevalence of nasal ulcerations. The prevalence increased the 
    longer the worker was exposed to chromic acid (e.g., from 14 cases with 
    exposure less than one year to 62 cases with exposure over five years) 
    (Ex. 7-50). In all but 2 cases, air samples revealed chromic acid 
    concentrations of 0.03 mg/m\3\ (i.e., 30 [mu]g/m\3\).
        Gibb et al. reported nasal irritations, nasal septum bleeding, 
    nasal septum ulcerations and perforations among a cohort of 2,350 
    chrome production workers in a Baltimore plant (Ex. 31-22-12). A 
    description of the cohort is provided in detail in the cancer health 
    effects section V.B. of this preamble. The authors found that more than 
    60% of the cohort had experienced nasal ulcerations and irritations, 
    and that the workers developed these effects for the first time within 
    the first three months of being hired (median). Gibb et al. found that 
    the median annual exposure to Cr(VI) during first diagnosis of 
    irritated and/or ulcerated nasal septum was 10 [mu]g/m\3\. About 17% of 
    the cohort reported nasal perforations. Based on historical data, the 
    authors believe that the nasal findings are attributable to Cr(VI) 
    exposure.
        Gibb et al. also used a Proportional Hazard Model to evaluate the 
    relationship between Cr(VI) exposure and the first occurrence of each 
    of the clinical findings. Cr(VI) data was entered into the model as a 
    time dependent variable. Other explanatory variables were calendar year 
    of hire and age of hire. Results of the model indicated that airborne 
    Cr(VI) exposure was associated with the occurrence of nasal septum 
    ulceration (p = 0.0001). The lack of an association between airborne 
    Cr(VI) exposure and nasal perforation and bleeding nasal septum may 
    reflect the fact that Cr(VI) concentrations used in the model represent 
    annual averages for the job, in which the worker was involved in at the 
    time of the findings, rather than a short-term average. Annual averages 
    do not factor in day-to-day fluctuations or extreme episodic 
    occurrences. Also, the author believed that poor housekeeping
    and hygiene practices may have contributed to these health effects as 
    well as Cr(VI) air borne concentrations.
        Based on their hazard model, Gibb et al. estimated the relative 
    risks for nasal septum ulcerations would increase 1.2 for each 52 [mu]g 
    of Cr(VI)/m\3\ increase in Cr(VI) air levels. They found a reduction in 
    the incidence of nasal findings in the later years. They found workers 
    from the earlier years who did not wear any PPE had a greater risk of 
    developing respiratory problems. They believe that the reduction in 
    ulcerations was possibly due to an increased use of respirators and 
    protective clothing and improved industrial hygiene practices at the 
    facility.
        The U.S. Public Health Service conducted a study of 897 chrome 
    production workers in seven chromate producing plants in the early 
    1950s (Ex. 7-3). The findings of this study were used in part as 
    justification for the current OSHA PEL. Workers were exposed by 
    inhalation to various water soluble chromates and bichromate compounds. 
    The total mean exposure to the workers was a TWA of 68 [mu]g/m\3\. Of 
    the 897 workers, 57% (or 509 workers) were found to have nasal septum 
    perforations. Nasal septum perforations were even observed in workers 
    during their first year on the job.
        Case reports provide further evidence that airborne exposure and 
    direct "hand to nose" contact of Cr(VI) compounds lead to the 
    development of nasal irritation and nasal septum perforations.
        For example, a 70-year-old man developed nasal irritation, 
    incrustation, and perforation after continuous daily exposure by 
    inhalation to chromium trioxide (doses were not specified, but most 
    likely quite high given the nature of his duties). This individual 
    inhaled chromium trioxide daily by placing his face directly over an 
    electroplating vessel. He worked in this capacity from 1934 to 1982. 
    His symptoms continued to worsen after he stopped working. By 1991, he 
    developed large perforations of the nasal septum and stenosis (or 
    constriction) of both nostrils by incrustation (Ex. 35-8).
        Similarly, a 30-year-old female jigger (a worker who prepares the 
    items prior to electroplating by attaching the items to be plated onto 
    jigs or frames) developed nasal perforation in her septum following 
    continuous exposure (doses in this case were not provided) to chromic 
    acid mists. She worked adjacent to the automated Cr(VI) electroplating 
    shop. She was also exposed to chromic acid from direct contact when she 
    placed her contaminated fingers in her nose. Her hands became 
    contaminated by handling wet components in the jigging and de-jigging 
    processes (Ex. 35-24).
        Evidence of nasal septum perforations has also been demonstrated in 
    experimental animals. Adachi exposed 23 C57BL mice to chromic acid by 
    inhalation at concentrations of 1.81 mg Cr(VI)/m\3\ for 120 min per 
    day, twice a week and 3.63 mg Cr(VI)/m\3\ for 30 minutes per day, two 
    days per week for up to 12 months (Ex. 35-26). Three of the 23 mice 
    developed nasal septum perforations in the 12 month exposure group.
        Adachi et al. also exposed 50 ICR female mice to chromic acid by 
    inhalation at concentrations of 3.18 mg Cr(VI)/m\3\ for 30 minutes per 
    day, two days per week for 18 months (Ex. 35-26-1). The authors used a 
    miniaturized chromium electroplating system to mimic electroplating 
    processes and exposures similar to working experience. Nasal septum 
    perforations were found in six mice that were sacrificed after 10 
    months of exposure. Of those mice that were sacrificed after 18 months 
    of exposure, nasal septum perforations were found in three mice.
    2. Occupational Asthma
        Occupational asthma is considered "a disease characterized by 
    variable airflow limitation and/or airway hyperresponsiveness due to 
    causes and conditions attributable to a particular occupational 
    environment and not to stimuli encountered outside the workplace" (Ex. 
    35-15). Asthma is a serious illness that can damage the lungs and in 
    some cases be life threatening. The common symptoms associated with 
    asthma include heavy coughing while exercising or when resting after 
    exercising, shortness of breath, wheezing sound, and tightness of chest 
    (Exs. 35-3; 35-6).
        Cr(VI) is considered to be an airway sensitizer. Airway sensitizers 
    cause asthma through an immune response. The sensitizing agent 
    initially causes production of specific antibodies that attach to cells 
    in the airways. Subsequent exposure to the sensitizing agent, such as 
    Cr(VI), can trigger an immune-mediated narrowing of the airways and 
    onset of bronchial inflammation. All exposed workers do not become 
    sensitized to Cr(VI) and the asthma only occurs in sensitized 
    individuals. It is not clear what occupational exposure levels of 
    Cr(VI) compounds lead to airway sensitization or the development of 
    occupational asthma.
        The strongest evidence of occupational asthma has been demonstrated 
    in four case reports. OSHA chose to focus on these four case reports 
    because the data from other occupational studies do not exclusively 
    implicate Cr(VI). The four case reports have the following in common: 
    (1) The worker has a history of occupational exposure exclusively to 
    Cr(VI); (2) a physician has confirmed a diagnosis that the worker has 
    symptoms consistent with occupational asthma; and (3) the worker 
    exhibits functional signs of air restriction (e.g., low forced 
    expiratory volume in one second or low peak expiratory flow rate) upon 
    bronchial challenge with Cr(VI) compounds. These case reports 
    demonstrate, through challenge tests, that exposure to Cr(VI) compounds 
    can cause asthmatic responses. The other general case reports below did 
    not use challenge tests to confirm that Cr(VI) was responsible for the 
    asthma; however, these reports came from workers similarly exposed to 
    Cr(VI) such that Cr(VI) is likely to have been a contributing factor in 
    the development of their asthmatic symptoms.
        DaReave reported the case of a 48-year-old cement floorer who 
    developed asthma from inhaling airborne Cr(VI) (Ex. 35-7). This worker 
    had been exposed to Cr(VI) as a result of performing cement flooring 
    activities for more than 20 years. The worker complained of dyspnea, 
    shortness of breath, and wheezing after work, especially after working 
    in enclosed spaces. The Cr(VI) content in the cement was about 12 ppm. 
    A bronchial challenge test with potassium dichromate produced a 50% 
    decrease in forced expiratory volume in one second. The occupational 
    physician concluded that the worker's asthmatic condition, triggered by 
    exposure to Cr(VI) caused the worker to develop bronchial constriction.
        LeRoyer reported a case of a 28-year-old roofer who developed 
    asthma from breathing dust while sawing material made of corrugated 
    fiber cement containing Cr(VI) for nine years (Ex. 35-12). This worker 
    demonstrated symptoms such as wheezing, shortness of breath, coughing, 
    rhinitis, and headaches while working. Skin prick tests were all 
    negative. Several inhalation challenges were performed by physicians 
    and immediate asthmatic reactions were observed after nebulization of 
    potassium dichromate. A reduction (by 20%) in the forced expiratory 
    volume in one second after exposure to fiber cement dust was noted.
        Novey et al. reported a case of a 32-year-old electroplating worker 
    who developed asthma from working with chromium sulfate and nickel 
    salts (Ex. 35-16). He began experiencing coughs,
    wheezing, and dyspnea within the first week of exposure. Separate 
    inhalation challenge tests given by physicians using chromium sulfate 
    and nickel salts resulted in positive reactions. The worker immediately 
    had difficulty breathing and started wheezing. The challenges caused 
    the forced expiratory volume in 1 second to decrease by 22% and the 
    forced expiratory volume in 1 second/forced vital capacity ratio to 
    decrease from 74.5% to 60.4%. The author believes the worker's 
    bronchial asthma was induced from inhaling chromium sulfate and nickel 
    salts. Similar findings were reported in a different individual by 
    Sastre (Ex.35-20).
        Shirakawa and Morimoto reported a case of a 50-year-old worker who 
    developed asthma while working at a metal-electroplating plant (Ex. 35-
    21). Bronchial challenge by physicians produced positive results when 
    using potassium bichromate, followed by a rapid recovery within 5 
    minutes, when given no exposures. The worker's forced expiratory volume 
    in one second dropped by 37% after inhalation of potassium bichromate. 
    The individual immediately began wheezing, coughing with dyspnea, and 
    recovered without treatment within five minutes. The author believes 
    that the worker developed his asthma from inhaling potassium 
    bichromate.
        In addition to the case reports confirming that Cr(VI) is 
    responsible for the development of asthma using inhalation challenge 
    tests, there are several other case reports of Cr(VI) exposed workers 
    having symptoms consistent with asthma where the symptoms were never 
    confirmed by using inhalation challenge tests.
        Lockman reported a case of a 41-year-old woman who was 
    occupationally exposed to potassium dichromate during leather tanning 
    (Ex. 35-14). The worker developed an occupational allergy to potassium 
    dichromate. This allergy involved both contact dermatitis and asthma. 
    The physicians considered other challenge tests using potassium 
    dichromate as the test agent (i.e., peak expiratory flow rate, forced 
    expiratory volume in 1 second and methacholine or bronchodilator 
    challenge), but the subject changed jobs before the physicians could 
    administer these tests. Once the subject changed jobs, all her symptoms 
    disappeared. It was not confirmed whether the occupational exposure to 
    Cr(VI) was the cause of the asthma.
        Williams reported a 23-year-old textile worker who was 
    occupationally exposed to chromic acid. He worked near two tanks of 
    chromic acid solutions (Ex. 35-23) and inhaled fumes while frequently 
    walking through the room with the tanks. He developed both contact 
    dermatitis and asthma. He believes the tank was poorly ventilated and 
    was the source of the fumes. He stopped working at the textile firm on 
    the advice of his physician. After leaving, his symptoms improved 
    greatly. No inhalation bronchial challenge testing was conducted to 
    confirm that chromic acid was causing his asthmatic attacks. However, 
    as noted above, chromic acid exposure has been shown to lead to 
    occupational asthma, and thus, chromic acid was likely to be a 
    causative agent in the development of asthma.
        Park et al. reported a case of four workers who worked in various 
    occupations involving exposure to either chromium sulfate or potassium 
    dichromate (Ex. 35-18). Two worked in a metal electroplating factory, 
    one worked at a cement manufacturer, and the other worked in 
    construction. All four developed asthma. One individual had a positive 
    response to a bronchial provocation test (with chromium sulfate as the 
    test agent). This individual developed an immediate reaction, 
    consisting of wheezing, coughing and dyspnea, upon being given chromium 
    sulfate as the test agent. Peak expiratory flow rate decreased by about 
    20%. His physician determined that exposure to chromium sulfate was 
    contributing to his asthma condition. Two other individuals had 
    positive reactions to prick skin tests with chromium sulfate as the 
    test agent. Two had positive responses to patch tests using potassium 
    dichromate as the testing challenge agent. Only one out of four 
    underwent inhalation bronchial challenge testing (with a positive 
    result to chromium sulfate) in this report.
    3. Bronchitis
        In addition to nasal ulcerations, nasal septum perforations, and 
    asthma, there is also limited evidence from reports in the literature 
    of bronchitis associated with Cr(VI) exposure. It is not clear what 
    occupational exposure levels of Cr(VI) compounds would lead to the 
    development of bronchitis.
        Royle found that 28% (104/288) of British electroplaters developed 
    bronchitis upon inhalation exposure to chromic acid, as compared to 23% 
    (90/299) controls (Ex. 7-50). The workers were considered to have 
    bronchitis if they had symptoms of persistent coughing and phlegm 
    production. In all but two cases of bronchitis, air samples revealed 
    chromic acid at levels of 0.03 mg/m\3\. Workers were asked to fill out 
    questionnaires to assess respiratory problems. Self-reporting poses a 
    problem in that the symptoms and respiratory health problems identified 
    were not medically confirmed by physicians. Workers in this study 
    believe they were developing bronchitis, but it is not clear from this 
    study whether the development of bronchitis was confirmed by 
    physicians. It is also difficult to assess the bronchitis health 
    effects of chromic acid from this study because the study results for 
    the exposed (28%) and control groups (23%) were similar.
        Alderson et al. reported 39 deaths of chromate production workers 
    related to chronic bronchitis from three chromate producing factories 
    (Bolton, Eaglescliffe, and Rutherglen) from 1947 to 1977 (Ex. 35-2). 
    Neither the specific Cr(VI) compound nor the extent or frequency with 
    which the workers were exposed were specified. However, workers at all 
    three factories were exposed to sodium chromate, chromic acid, and 
    calcium chromate at one time or another. The authors did not find an 
    excess number of bronchitis related deaths at the Bolton and 
    Eaglescliffe factories. At Rutherglen, there was an excess number of 
    deaths (31) from chronic bronchitis with a ratio of observed/expected 
    of 1.8 (p< 0.001). It is difficult to assess the respiratory health 
    effects of Cr(VI) compounds from this study because there are no 
    exposure data, there are no data on smoking habits, nor is it clear the 
    extent, duration, and amount of specific Cr(VI) compound to which the 
    workers were exposed during the study.
        While the evidence supports an association between bronchitis and 
    Cr(VI) exposure is limited, studies in experimental animals demonstrate 
    that Cr(VI) compounds can cause lung irritation, inflammation in the 
    lungs, and possibly lung fibrosis at various exposure levels. Glaser et 
    al. examined the effects of inhalation exposure of chromium (VI) on 
    lung inflammation and alveolar macrophage function in rats (Ex. 31-18-
    9). Twenty, 5-week-old male TNO-W-74 Wistar rats were exposed via 
    inhalation to 25-200 [mu]g Cr(VI)/m3 as sodium dichromate 
    for 28 days or 90 days for 22 hours per day, 7 days per week in 
    inhalation chambers. Twenty, 5-week-old male TNO-W-74 Wistar rats also 
    served as controls. All rats were killed at the end of the inhalation 
    exposure period. The authors found increased lung weight in the 50-200 
    [mu]g/m3 groups after the 90-day exposure period. They also 
    found that 28-day exposure to levels of 25 and 50 [mu]g/m3 
    resulted in "activated" alveolar macrophages with stimulated 
    phagocytic activities. A more pronounced effect on the activation of
    alveolar macrophages was seen during the 90-day exposure period of 25 
    and 50 [mu]g/m3.
        Glaser et al. exposed 150 male, 8-week-old Wistar rats (10 rats per 
    group) continuously by inhalation to aerosols of sodium dichromate at 
    concentrations of 50, 100, 200, and 400 [mu]g Cr(VI)/m3 for 
    22 hours per day, 7 days a week, for continuous exposure for 30 days or 
    90 days in inhalation chambers (Ex. 31-18-11). Increased lung weight 
    changes were noticeable even at levels as low as 50 and 100 [mu]g 
    Cr(VI)/m3 following both 30 day and 90 day exposures. 
    Significant accumulation of alveolar macrophages in the lungs was noted 
    in all of the exposure groups. Lung fibrosis occurred in eight rats 
    exposed to 100 [mu]g Cr(VI)/m3 or above for 30 days. Most 
    lung fibrosis disappeared after the exposure period had ceased. At 50 
    [mu]g Cr(VI)/m3 or higher for 30 days, a high incidence of 
    hyperplasia was noted in the lung and respiratory tract. The total 
    protein in bronchoalveolar lavage (BAL) fluid, albumin in BAL fluid, 
    and lactate dehydrogenase in BAL fluid were significant at elevated 
    levels of 200 and 400 [mu]g Cr(VI)/m3 in both the 30 day and 
    90 day exposure groups (as compared to the control group). These 
    responses are indicative of severe injury in the lungs of animals 
    exposed to Cr(VI) dose levels of 200 [mu]g Cr(VI)/m3 and 
    above. At levels of 50 and 100 [mu]g Cr(VI)/m3, the 
    responses are indicative of mild inflammation in the lungs. The authors 
    concluded that these results suggest that the severe inflammatory 
    reaction may lead to more chronic and obstructive lesions in the lung.
    4. Summary
        Overall, there is convincing evidence to indicate that Cr(VI) 
    exposed workers can develop nasal irritation, nasal ulcerations, nasal 
    perforations, and asthma. There is also some limited evidence that 
    bronchitis may occur when workers are exposed to Cr(VI) compounds at 
    high levels. Most of the studies involved exposure to water-soluble 
    Cr(VI) compounds. It is very clear that workers may develop nasal 
    irritations, nasal ulcerations, and nasal perforations at levels below 
    the current PEL of 52 [mu]g/m3. However, it is not clear 
    what occupational exposure levels lead to disorders like asthma and 
    bronchitis.
        There are numerous studies in the literature showing nasal 
    irritations, nasal perforations, and nasal ulcerations resulting from 
    Cr(VI) inhalation exposure. It also appears that direct hand-to-nose 
    contact (i.e., by touching inner nasal surfaces with contaminated 
    fingers) can contribute to the incidence of nasal damage. Additionally, 
    some studies show that workers developed these nasal health problems 
    because they did not wear any PPE, including respiratory protection. 
    Inadequate area ventilation and sanitation conditions (lack of 
    cleaning, dusty environment) probably contributed to the adverse nasal 
    effects.
        There are several well documented case reports in the literature 
    describing occupational asthma specifically triggered by Cr(VI) in 
    sensitized workers. All involved workers who frequently suffered 
    symptoms typical of asthma (e.g. dyspnea, wheezing, coughing, etc.) 
    while working in jobs involving airborne exposure to Cr(VI). In some of 
    the reports, a physician diagnosed bronchial asthma triggered by Cr(VI) 
    after specific bronchial challenge with a Cr(VI) aerosol produced 
    characteristic symptoms and asthmatic airway responses. Several 
    national and international bodies, such as the National Institute for 
    Occupational Safety and Health, the World Health Organization's 
    International Programme on Chemical Safety, and the United Kingdom 
    Health and Safety Executive have recognized Cr(VI) as an airway 
    sensitizer that can cause occupational asthma. Despite the widespread 
    recognition of Cr(VI) as an airway sensitizer, OSHA is not aware of any 
    well controlled occupational survey or epidemiological study that has 
    found a significantly elevated prevalence of asthma among Cr(VI)-
    exposed workers. The level of Cr(VI) in the workplace that triggers the 
    asthmatic condition and the number of workers at risk are not known.
        The evidence that workers breathing Cr(VI) can develop respiratory 
    disease that involve inflammation, such as asthma and bronchitis is 
    supported by experimental animal studies. The 1985 and 1990 Glaser et 
    al. studies show that animals experience irritation and inflammation of 
    the lungs following repeated exposure by inhalation to water-soluble 
    Cr(VI) at air concentrations near the previous PEL of 52 [mu]g/
    m3.
    
    D. Dermal Effects
    
        Occupational exposure to Cr(VI) is a well-established cause of 
    adverse health effects of the skin. The effects are the result of two 
    distinct processes: (1) Irritant reactions, such as skin ulcers and 
    irritant contact dermatitis, and (2) delayed hypersensitivity 
    (allergic) reactions. Some evidence also indicates that exposure to 
    Cr(VI) compounds may cause conjunctivitis.
        The mildest skin reactions consist of erythema (redness), edema 
    (swelling), papules (raised spots), vesicles (liquid spots), and 
    scaling (Ex. 35-313, p. 295). The lesions are typically found on 
    exposed areas of the skin, usually the hands and forearms (Exs. 9-9; 9-
    25). These features are common to both irritant and allergic contact 
    dermatitis, and it is generally not possible to determine the etiology 
    of the condition based on histopathologic findings (Ex. 35-314). 
    Allergic contact dermatitis can be diagnosed by other methods, such as 
    patch testing (Ex. 35-321, p. 226). Patch testing involves the 
    application of a suspected allergen to the skin, diluted in petrolatum 
    or some other vehicle. The patch is removed after 48 hours and the skin 
    examined at the site of application to determine if a reaction has 
    occurred.
        Cr(VI) compounds can also have a corrosive, necrotizing effect on 
    living tissue, forming ulcers, or "chrome holes" (Ex. 35-315). This 
    effect is apparently due to the oxidizing properties of Cr(VI) 
    compounds (Ex. 35-318, p. 623). Like dermatitis, chrome ulcers 
    generally occur on exposed areas of the body, chiefly on the hands and 
    forearms (Ex. 35-316). The lesions are initially painless, and are 
    often ignored until the surface ulcerates with a crust which, if 
    removed, leaves a crater two to five millimeters in diameter with a 
    thickened, hardened border. The ulcers can penetrate deeply into tissue 
    and become painful. Chrome ulcers may penetrate joints and cartilage 
    (Ex. 35-317, p. 138). The lesions usually heal in several weeks if 
    exposure to Cr(VI) ceases, leaving a flat, atrophic scar (Ex. 35-318, 
    p.623). If exposure continues, chrome ulcers may persist for months 
    (Ex. 7-3).
        It is generally believed that chrome ulcers do not occur on intact 
    skin (Exs. 35-317, p. 138; 35-315; 35-25). Rather, they develop readily 
    at the site of small cuts, abrasions, insect bites, or other injuries 
    (Exs. 35-315; 35-318, p. 138). In experimental work on guinea pigs, 
    Samitz and Epstein found that lesions were never produced on undamaged 
    skin (Ex. 35-315). The degree of trauma, as well as the frequency and 
    concentration of Cr(VI) application, was found to influence the 
    severity of chrome ulcers.
        The development of chrome ulcers does not appear to be related to 
    the sensitizing properties of Cr(VI). Edmundson provided patch tests to 
    determine sensitivity to Cr(VI) in 56 workers who exhibited either 
    chrome ulcers or scars (Ex. 9-23). A positive response to the patch 
    test was found in only two of the workers examined.
        Parkhurst first identified Cr(VI) as a cause of allergic contact 
    dermatitis in 1925 (Ex. 9-55). Cr(VI) has since been
    confirmed as a potent allergen. Kligman (1966) used a maximization test 
    (a skin test for screening possible contact allergens) to assess the 
    skin sensitizing potential of Cr(VI) compounds (Ex. 35-327). Each of 
    the 23 subjects was sensitized to potassium dichromate. On a scale of 
    one to five, with five being the most potent allergen, Cr(VI) was 
    graded as five (i.e., an extreme sensitizer). This finding was 
    supported by a guinea pig maximization test, which assigned a grade of 
    four to potassium chromate using the same scale (Ex. 35-328).
    1. Prevalence of Dermal Effects
        Adverse skin effects from Cr(VI) exposure have been known since at 
    least 1827, when Cumin described ulcers in two dyers and a chromate 
    production worker (Ex. 35-317, p. 138). Since then, skin conditions 
    resulting from Cr(VI) exposure have been noted in a wide range of 
    occupations. Work with cement is regarded as the most common cause of 
    Cr(VI)-induced dermatitis (Exs. 35-313, p. 295; 35-319; 35-320). Other 
    types of work where Cr(VI)-related skin effects have been reported 
    include chromate production, chrome plating, leather tanning, welding, 
    motor vehicle assembly, manufacture of televisions and appliances, 
    servicing of railroad locomotives, aircraft production, and printing 
    (Exs. 31-22-12; 7-50; 9-31; 9-100; 9-63; 9-28; 9-95; 9-54; 35-329; 9-
    97; 9-78; 9-9; 35-330). Some of the important studies on Cr(VI)-related 
    dermal effects in workers are described below.
    a. Cement Dermatitis
        Many workers develop cement dermatitis, including masons, tile 
    setters, and cement workers (Ex. 35-318, p. 624). Cement, the basic 
    ingredient of concrete, may contain several possible sources of 
    chromium (Exs. 35-317, p.148; 9-17). Clay, gypsum, and chalk that serve 
    as ingredients may contain traces of chromium. Ingredients may be 
    crushed using chrome steel grinders that, with wear, contribute to the 
    chromium content of the concrete. Refractory bricks in the kiln and ash 
    residues from the burning of coal or oil to heat the kiln serve as 
    additional sources. Trivalent chromium from these sources can be 
    converted to Cr(VI) in the kiln (Ex. 35-317. p. 148).
        The prevalence of cement dermatitis in groups of workers with 
    regular contact with wet cement has been reported to be from 8 to 45 
    percent depending on the countries of origin, type of construction 
    industry, and criteria used to diagnose dermatitis (Exs. 46-74, 9-131; 
    35-317, 9-57, 40-10-10). Cement dermatitis can be caused by direct 
    irritation of the skin, by sensitization to Cr(VI), or both (Ex. 35-
    317, p. 147). The reported proportion of allergic and irritant contact 
    dermatitis varies considerably depending on the information source. In 
    a review of 16 different data sets, Burrows (1983) found that, on 
    average, 80% of cement dermatitis cases were sensitized to Cr(VI) (Ex. 
    35-317, p. 148). The studies were mostly conducted prior to 1970 on 
    European construction workers. More recent occupational studies suggest 
    that Cr(VI) allergy may make up a smaller proportion of all dermatitis 
    in construction workers, depending on the Cr(VI) content of the cement. 
    For example, examination of 1238 German and Austrian construction 
    workers in dermatitis units found about half those with occupational 
    dermatitis were skin sensitized to Cr(VI) (Ex. 40-10-10). Several other 
    epidemiological investigations conducted in the 1980s and 1990s also 
    reported that allergic contact dermatitis made up 50 percent or less of 
    all dermatitis cases in various groups of construction workers exposed 
    to wet cement (Ex. 46-74).
        Cement is alkaline, abrasive, and hydroscopic (water-absorbing), 
    and it is likely that the irritant effect resulting from these 
    properties interferes with the skin's defenses, permitting penetration 
    and sensitization to take place more readily (Ex. 35-318, p. 624). Dry 
    cement is considered relatively innocuous because it is not as alkaline 
    as wet cement (Exs. 35-317, p. 147; 9-17). When water is mixed with 
    cement the water liberates calcium hydroxide, causing a rise in pH (Ex. 
    35-317, p. 147).
        Flyvholm et al. (1996) noted a correlation between the Cr(VI) 
    concentration in the local cement and the frequency of allergic contact 
    dermatitis (Ex. 35-326, p. 278). Because the Cr(VI) content depends 
    partially upon the chromium concentration in raw materials, there is a 
    great variability in the Cr(VI) content in cement from different 
    geographical regions. In locations with low Cr(VI) content, the 
    prevalence of Cr(VI)-induced allergic contact dermatitis was reported 
    to be approximately one percent, while in regions with higher chromate 
    concentrations the prevalence was reported to rise to between 9 to 11% 
    of those exposed (Ex. 35-326, p. 278). For example, only one of 35 U.S. 
    construction workers with confirmed cement dermatitis was reported to 
    have a positive Cr(VI) patch test in a 1970 NIOSH study (Ex. 9-57). 
    However, the same study revealed a low Cr(VI) content in 42 
    representative cement samples from U.S. companies (e.g 80 percent of 
    the samples with C(VI) <  2 [mu]g/g).
        The relationship between Cr(VI) content in cement and the 
    prevalence of Cr(VI)-induced allergic contact dermatitis is supported 
    by the findings of Avnstorp (1989) in a study of Danish workers who had 
    daily contact with wet cement during the manufacture of pre-fabricated 
    concrete products (Ex. 9-131). Beginning in September of 1981, low 
    concentrations of ferrous sulfate were added to all cement sold in 
    Denmark to reduce Cr(VI) to trivalent chromium. Two hundred and twenty 
    seven workers were examined in 1987 for Cr(VI)-related skin effects. 
    The findings from these examinations were compared to the results from 
    190 workers in the same plants who were examined in 1981. The 
    prevalence of hand eczema had declined from 11.7% to 4.4%, and the 
    prevalence of Cr(VI) sensitization had declined from 10.5% to 2.6%. 
    While the two-to four-fold drop in prevalence was statistically 
    significant, the magnitude of the reduction may be overstated because 
    the amount of exposure time was less in the 1987 than the 1981 group. 
    There is also the possibility that other factors, in addition to 
    ferrous sulfate, may have led to less dermal contact to Cr(VI), such as 
    greater automation or less construction work. However, the study found 
    no significant change in the frequency of irritant dermatitis.
        Another study also found lower prevalence of allergic contact 
    dermatitis among Finish construction workers following the 1987 
    decision to reduce Cr(VI) content of cement used in Finland to less 
    than 2 ppm (Ex. 48-8). Ferrous sulfate was typically added to the 
    cement to meet this requirement. There was a significantly decreased 
    risk of allergic Cr(VI) contact dermatitis reported to the Finnish 
    Occupational Disease Registry post-1987 as compared to pre-1987 
    (OR=0.4, 95% CI: 0.2-0.7) indicating the occurrence of disease dropped 
    one-third after use of the low Cr(VI) content cement. On the other 
    hand, the occurrence of irritant dermatitis remained stable throughout 
    the study period. Time of exposure was not a significant explanatory 
    variable in the analysis. However, the findings may have been somewhat 
    confounded by changes in diagnostic procedure over time. The Finnish 
    study retested patients previously diagnosed with prior patch test 
    protocols and found several false positives (i.e. false diagnosis of 
    Cr(VI) allergy).
        In 2003, the Norwegian National Institute of Occupational Health 
    sponsored an expert peer review of 24
    key epidemiological investigations addressing; (1) whether exposure to 
    wet cement containing water soluble Cr(VI) caused allergic contact 
    dermatitis, and (2) whether there was a causal association between 
    reduction of Cr(VI) in cement and reduction in the prevalence of the 
    disease (Ex. 46-74). The panel of four experts concluded that, despite 
    the documented limitations of each individual study, the collective 
    evidence was consistent in supporting "fairly strong associations 
    between Cr(VI) content in cement and the occurrence of allergic 
    dermatitis * * * it seems unlikely that all these associations reported 
    in the reviewed papers are due to systematic errors only" (Ex. 46-74, 
    p. 42).
        Even though the Norwegian panel felt that the available evidence 
    indicated a relationship between reduced Cr(VI) content of wet cement 
    and lower occurrence of allergic dermatitis, they stated that the 
    epidemiological literature was "not sufficient to conclude that there 
    is a causal association" (Ex. 46-74, p. 42). This is somewhat 
    different than the view expressed in a written June 2002 opinion by the 
    Scientific Committee on Toxicity, Ecotoxicity and the Environment 
    (CSTEE) to the European Commission, Directorate for General Health and 
    Consumer Protection (Ex. 40-10-7). In responding to the question of 
    whether it is scientifically justified to conclude that cement 
    containing less than 2 ppm Cr(VI) content could substantially reduce 
    the risk of skin sensitization, the CSTEE stated that "the available 
    information clearly demonstrates that reduction of chromium VI in 
    cement to less than 2 ppm * * * will reduce the prevalence of allergic 
    contact eczema in workers" (Ex. 40-10-7, p. 5)
    b. Dermatitis Associated With Cr(VI) From Sources Other Than Cement
        In 1953 the U.S. Public Health Service reported on hazards 
    associated with the chromium-producing industry in the United States 
    (Ex. 7-3). Workers were examined for skin effects from Cr(VI) exposure. 
    Workers' eyes were also examined for possible effects from splashes of 
    Cr(VI)-containing compounds that had been observed in the plants. Of 
    the 897 workers examined, 451 had skin ulcers or scars of ulcers. 
    Seventeen workers were reported to have skin lesions suggestive of 
    chrome dermatitis. The authors noted that most plants provided adequate 
    washing facilities, and had facilities for providing clean work 
    clothes. A statistically significant increase in congestion of the 
    conjunctiva was also reported in Cr(VI)-exposed workers when compared 
    with non-exposed workers (38.7% vs. 25.8%).
        In the Baltimore, Maryland chromate production plant examined by 
    Gibb et al. (2000), a substantial number of workers were reported to 
    have experienced adverse skin effects (Ex. 31-22-12). The authors 
    identified a cohort of 2,357 workers first employed at the plant 
    between 1950 and 1974. Clinic and first aid records were examined to 
    identify findings of skin conditions. These clinical findings were 
    identified by a physician as a result of routine examinations or visits 
    to the medical clinic by members of the cohort. Percentages of the 
    cohort with various clinical findings were as follows:
    
    Irritated skin: 15.1%
    Dermatitis: 18.5%
    Ulcerated skin: 31.6%
    Conjunctivitis: 20.0%
    
        A number of factors make these results difficult to interpret. The 
    reported findings are not specifically related to Cr(VI) exposure. They 
    may have been the result of other workplace exposures, or non-workplace 
    factors. The report also indicates the percentage of workers who were 
    diagnosed with a condition during their tenure at the plant; however, 
    no information is presented to indicate the expected incidence of these 
    conditions in a population that is not exposed to Cr(VI).
        Measurements of Cr(VI) air concentrations by job title were used to 
    estimate worker exposures. Based on these estimates, the authors used a 
    proportional hazards model to find a statistically significant 
    correlation (p=0.004) between ulcerated skin and airborne Cr(VI) 
    exposure. Statistically significant correlations between year of hire 
    and findings of ulcerated skin and dermatitis were also reported. 
    Exposures to Cr(VI) in the plant had generally dropped over time. 
    Median exposure to Cr(VI) at the time of occurrence for most of the 
    findings was said to be about 10 [mu]g/m\3\ Cr(VI) (reported as 20 
    [mu]g/m\3\ CrO3). It is unclear, however, what contribution 
    airborne Cr(VI) exposures may have had to dermal effects. Direct dermal 
    contact with Cr(VI) compounds in the plant may have been a contributing 
    factor in the development of these conditions.
        Mean and median times on the job prior to initial diagnosis were 
    also reported. The mean time prior to diagnosis of skin or eye effects 
    ranged from 373 days for ulcerated skin to 719 days for irritated skin. 
    Median times ranged from 110 days for ulcerated skin to 221 days for 
    conjunctivitis. These times are notable because many workers in the 
    plant stayed for only a short time. Over 40% worked for less than 90 
    days. Because these short-term workers did not remain in the workplace 
    for the length of time that was typically necessary for these effects 
    to occur, the results of this study may underestimate the incidence 
    that would occur with a more stable worker population.
        Lee and Goh (1988) examined the skin condition of 37 workers who 
    maintained chrome plating baths and compared these workers with a group 
    of 37 control subjects who worked in the same factories but were not 
    exposed to Cr(VI) (Ex. 35-316). Mean duration of employment as a chrome 
    plater was 8.1 (SD7.9) years. Fourteen (38%) of the chrome 
    platers had some occupational skin condition; seven had chrome ulcers, 
    six had contact dermatitis and one had both. A further 16 (43%) of the 
    platers had scars suggestive of previous chrome ulcers. Among the 
    control group, no members had ulcers or scars of ulcers, and three had 
    dermatitis.
        Where ulcers or dermatitis were noted, patch tests were 
    administered to determine sensitization to Cr(VI) and nickel. Of the 
    seven workers with chrome ulcers, one was allergic to Cr(VI). Of the 
    six workers with dermatitis, two were allergic to Cr(VI) and one to 
    nickel. The worker with ulceration and dermatitis was not sensitized to 
    either Cr(VI) or nickel. Although limited by a relatively small study 
    population, this report clearly indicates that Cr(VI)-exposed workers 
    face an increased risk of adverse skin effects. The fact that the 
    majority of workers with dermatitis were not sensitized to Cr(VI) 
    indicates that irritant factors play an important role in the 
    development of dermatitis in chrome plating operations.
        Royle (1975) also investigated the occurrence of skin conditions 
    among workers involved in chrome plating (Ex. 7-50). A questionnaire 
    survey completed by 997 chrome platers revealed that 21.8% had 
    experienced skin ulcers, and 24.6% had suffered from dermatitis. No 
    information was presented to indicate the expected incidence in a 
    comparable population that was not exposed to Cr(VI). Of the 54 plants 
    involved in the study, 49 used nickel, another recognized cause of 
    allergic contact dermatitis.
        The author examined the relationship between the incidence of these 
    conditions and length of exposure. The plater population was divided 
    into three groups: those with less than one year of Cr(VI) exposure, 
    those with one to five years of Cr(VI) exposure, and those with over 
    five years of Cr(VI) exposure. A statistically significant trend was 
    found between length of Cr(VI) exposure and incidence of skin ulcers. The 
    incidence of dermatitis, on the other hand, bore no relationship to 
    length of exposure.
        In 1973, researchers from NIOSH reported on the results of a health 
    hazard investigation of a chrome plating establishment (Ex. 3-5). In 
    the plating area, airborne Cr(VI) concentrations ranged from less than 
    0.71 to 9.12 [mu]g/m\3\ (mean 3.24 [mu]g/m\3\; SD=2.48 [mu]g/m\3\). Of 
    the 37 exposed workers who received medical examinations, five were 
    reported to have chrome-induced lesions on their hands. Hygiene and 
    housekeeping practices in this facility were reportedly deficient, with 
    the majority of workers not wearing gloves, not washing their hands 
    before eating or leaving the plant, and consuming food and beverages in 
    work areas.
        Gomes (1972) examined Cr(VI)-induced skin lesions among 
    electroplaters in Sao Paulo, Brazil (Ex. 9-31). A clinical examination 
    of 303 workers revealed 88 (28.8%) had skin lesions, while 175 (58.0%) 
    had skin and mucus membrane lesions. A substantial number of employers 
    (26.6%) also did not provide personal protective equipment to workers. 
    The author attributed the high incidence of skin ulcers on the hands 
    and arms to inadequate personal protective equipment, and lack of 
    training for employees regarding hygiene practices.
        Fleeger and Deng (1990) reported on an outbreak of skin ulcerations 
    among workers in a facility where enamel paints containing chromium 
    were applied to kitchen range parts (Ex. 9-97). A ground coat of paint 
    was applied to the parts, which were then placed on hooks and 
    transported through a curing oven. In some cases, small parts were 
    places on hooks before paint application. Tiny holes in the oven coils 
    apparently resulted in improper curing of the paint, leaving sharp 
    edges and a Cr(VI)-containing residue on the hooks. Most of the workers 
    who handled the hooks reportedly did not wear gloves, because the 
    gloves were said to reduce dexterity and decrease productivity. As a 
    result, cuts from the sharp edges allowed the Cr(VI) to penetrate the 
    skin, leading to ulcerations (Ex. 9-97).
    2. Prognosis of Dermal Effects
        Cr(VI)-related dermatitis tends to become more severe and 
    persistent with continuing exposure. Once established, the condition 
    may persist even if occupational exposure ceases. Fregert followed up 
    on cases of occupational contact dermatitis diagnosed over a 10-year 
    period by a dermatology service in Sweden. Based on responses to 
    questionnaires completed two to three years after treatment, only 7% of 
    women and 10% of men with Cr(VI)-related allergic contact dermatitis 
    were reported to be healed (Ex. 35-322). Burrows reviewed the condition 
    of patients diagnosed with work-related dermatitis 10-13 years earlier. 
    Only two of the 25 cases (8%) caused by exposure to cement had cleared 
    (Ex. 35-323).
        Hogan et al. reviewed the literature regarding the prognosis of 
    contact dermatitis, and reported that the majority of patients had 
    persistent dermatitis (Ex. 35-324). It was reported that job changes 
    did not usually lead to a significant improvement for most patients. 
    The authors surveyed contact dermatitis experts around the world to 
    explore their experience with the prognosis of patients suffering from 
    occupational contact dermatitis of the hands. Seventy-eight percent of 
    the 51 experts who responded to the survey indicated that chromate was 
    one of the allergens associated with the worst possible prognosis.
        Halbert et al. reviewed the experience of 120 patients diagnosed 
    with occupational chromate dermatitis over a 10-year period (Ex. 35-
    320). The time between initial diagnosis and the review ranged from a 
    minimum of six months to a maximum of nine years. Eighty-four (70%) of 
    patients were reviewed two or more years after initial diagnosis, and 
    40 (33%) after five years or more. In the majority of cases (78, or 
    65%), the dermatitis was attributed to work with cement. For the study 
    population as a whole, 76% had ongoing dermatitis at the time of the 
    review.
        When the review was conducted, 62 (58%) patients were employed in 
    the same occupation as when initially diagnosed. Fifty-five (89%) of 
    these workers continued to suffer from dermatitis. Fifty-eight patients 
    (48%) changed occupations after their initial diagnosis. Each of these 
    individuals indicated that they had changed occupations because of 
    their dermatitis. In spite of the change, dermatitis persisted in 40 
    members of this group (69%).
        Lips et al. found a somewhat more favorable outcome among 88 
    construction workers with occupational chromate dermatitis who were 
    removed from Cr(VI) exposure (Ex. 35-325). Follow-up one to five years 
    after removal indicated that 72% of the patients no longer had 
    dermatitis. The authors speculated that this result might be due to 
    strict avoidance of Cr(VI) contact. Nonetheless, the condition 
    persisted in a substantial portion of the affected population.
    3. Thresholds for Dermal Effects
        In a response to OSHA's RFI submitted on behalf of the Chrome 
    Coalition, Exponent indicated that the findings of Fowler et al. (1999) 
    and others provide evidence of a threshold for elicitation of allergic 
    contact dermatitis (Ex. 31-18-1, p. 27). Exponent also stated that 
    because chrome ulcers did not develop in the Fowler et al. study, 
    "more aggressive" exposures appear to be necessary for the 
    development of chrome ulcers.
        The Fowler et al. study involved the dermal exposure of 26 
    individuals previously sensitized to Cr(VI) who were exposed to water 
    containing 25 to 29 mg/L Cr(VI) as potassium dichromate (pH 9.4) (Ex. 
    31-18-5). Subjects immersed one arm in the Cr(VI) solution, while the 
    other arm was immersed in an alkaline buffer solution as a control. 
    Exposure lasted for 30 minutes and was repeated on three consecutive 
    days. Based on examination of the skin, the authors concluded that the 
    skin response experienced by subjects was not consistent with either 
    irritant or allergic contact dermatitis.
        The exposure scenario in the Fowler et al. study, however, does not 
    take into account certain skin conditions often encountered in the 
    workplace. While active dermatitis, scratches, and skin lesions served 
    as criteria for excluding both initial and continuing participation in 
    the study, it is reasonable to expect that individuals with these 
    conditions will often continue to work. Cr(VI)-containing mixtures and 
    compounds used in the workplace may also pose a greater challenge to 
    the integrity of the skin than the solution used by Fowler et al. Wet 
    cement, for example, may have a pH higher than 9.4, and may be capable 
    of abrading or otherwise damaging the skin. As damaged skin is liable 
    to make exposed workers more susceptible to Cr(VI)-induced skin 
    effects, the suggested threshold is likely to be invalid. The absence 
    of chrome ulcers in the Fowler et al. study is not unexpected, because 
    subjects with "fissures or lesions" on the skin were excluded from 
    the study (Ex. 31-18-5). As discussed earlier, chrome ulcers are not 
    believed to occur on intact skin.
    4. Conclusions
        OSHA believes that adverse dermal effects from exposure to Cr(VI), 
    including irritant contact dermatitis, allergic contact dermatitis, and 
    skin ulceration, have been firmly established. The available evidence 
    is not sufficient to relate these effects to any given Cr(VI) air 
    concentration. Rather, it appears that direct dermal contact with 
    Cr(VI) is the most relevant factor in the development of dermatitis and 
    ulcers. Based on the findings of Gibb et al. (Ex. 32-22-12) and U.S. 
    Public Health Service (Ex. 7-3), OSHA believes that conjunctivitis may 
    result from direct eye contact with Cr(VI).
        OSHA does not believe that the available evidence is sufficient to 
    establish a threshold concentration of Cr(VI) below which dermal 
    effects will not occur in the occupational environment. This finding is 
    supported not only by the belief that the exposure scenario of Fowler 
    et al. is not consistent with occupational exposures, but by experience 
    in the workplace as well. As summarized by Flyvholm et al. (1996), 
    numerous reports have indicated that allergic contact dermatitis occurs 
    in cement workers exposed to Cr(VI) concentrations below the threshold 
    suggested by Fowler et al. (1999). OSHA considers the evidence of 
    Cr(VI)-induced allergic contact dermatitis in these workers to indicate 
    that the threshold for elicitation of response suggested by Fowler et 
    al. (1999) is not applicable to the occupational environment.
    
    E. Other Health Effects
    
        OSHA has examined the possibility of health effect outcomes 
    associated with Cr(VI) exposure in addition to such effects as lung 
    cancer, nasal ulcerations and perforations, occupational asthma, and 
    irritant and allergic contact dermatitis. Unlike the Cr(VI)-induced 
    toxicities cited above, the data on other health effects do not 
    definitively establish Cr(VI)-related impairments of health from 
    occupational exposure at or below the previous OSHA PEL.
        There is some positive evidence that workplace inhalation of Cr(VI) 
    results in gastritis and gastrointestinal ulcers, especially at high 
    exposures (generally over OSHA's previous PEL) (Ex. 7-12). This is 
    supported by ulcerations in the gastrointestinal tract of mice 
    breathing high Cr(VI) concentration for long periods (Ex. 10-8). Other 
    studies reported positive effects but significant information was not 
    reported or the confounders made it difficult to draw positive 
    conclusions (Ex. 3-84; Sassi 1956 as cited in Ex. 35-41). Other studies 
    reported negative results (Exs. 7-14; 9-135).
        Likewise, several studies reported increases in renal proteins in 
    the urine of chromate production workers and chrome platers (Exs. 35-
    107; 5-45; 35-105; 5-57). The Cr(VI) air levels recorded in these 
    workers were usually below the previous OSHA PEL (Exs. 35-107; 5-45). 
    Workers with the highest urinary chromium levels tended to also have 
    the largest elevations in renal markers (Ex. 35-107). One study 
    reported no relationship between chromium in urine and renal function 
    parameters, no relationship with age or with duration of exposure, and 
    no relationship between the presence of chromium skin ulcers and 
    chromium levels in urine or renal function parameters (Ex. 5-57). In 
    most studies, the elevated renal protein levels were restricted to only 
    one or two proteins out of several examined per study, generally 
    exhibited small increases (Ex. 35-105) and the effects appeared to be 
    reversible (Ex. 5-45). In addition, it has been stated that low 
    molecular weight proteinuria can occur from other reasons and cannot by 
    itself be considered evidence of chronic renal disease (Ex. 35-195). 
    Other human inhalation studies reported no changes in renal markers 
    (Exs. 7-27; 35-104). Animal inhalation studies did not report kidney 
    damage (Exs. 9-135; 31-18-11; 10-11; 31-18-10; 10-10). Some studies 
    with Cr(VI) administered by drinking water or gavage were positive for 
    increases in renal markers as well as some cell and tissue damage (Exs. 
    9-143; 11-10). However, it is not clear how to extrapolate such 
    findings to workers exposed to Cr(VI) via inhalation. Well-designed 
    studies of effects in humans via ingestion were not found.
        OSHA did not find information to clearly and sufficiently 
    demonstrate that exposures to Cr(VI) result in significant impairment 
    to the hepatic system. Two European studies, positive for an excess of 
    deaths from cirrhosis of the liver and hepatobiliarity disorders, were 
    not able to separate chromium exposures from exposures to the many 
    other substances present in the workplace. The authors also could not 
    rule out the role of alcohol use as a possible contributor to the 
    disorder (Ex. 7-92; Sassi as cited in Ex. 35-41). Other studies did not 
    report any hepatic abnormalities (Exs. 7-27; 10-11).
        The reproductive studies showed mixed results. Some positive 
    reproductive effects occurred in some welding studies. However, it is 
    not clear that Cr(VI) is the causative agent in these studies (Exs. 35-
    109; 35-110; 35-108; 35-202; 35-203). Other positive studies were 
    seriously lacking in information. Information was not given on 
    exposures, the nature of the reproductive complications, or the women's 
    tasks (Shmitova 1980, 1978 as cited in Ex. 35-41, p. 52). ATSDR states 
    that because these studies were generally of poor quality and the 
    results were poorly reported, no conclusions can be made on the 
    potential for chromium to produce adverse reproductive effects in 
    humans (Ex. 35-41, p. 52). In animal studies, where Cr(VI) was 
    administered through drinking water or diet, positive developmental 
    effects occurred in offspring (Exs. 9-142; 35-33; 35-34; 35-38). 
    However, the doses administered in drinking water or given in the diet 
    were high (i.e., 250, 500, and 750 ppm). Furthermore, strong studies 
    showing reproductive or developmental effects in other situations where 
    employees were working exclusively with Cr(VI) were not found. In fact, 
    the National Toxicology Program (NTP) (Exs. 35-40; 35-42; 35-44) 
    conducted an extensive multigenerational reproductive assessment by 
    continuous breeding where the chromate was administered in the diet. 
    The assessment yielded negative results (Exs. 35-40; 35-42; 35-44). 
    Animal inhalation studies were also negative (Exs. 35-199; 9-135; 10-
    10; Glaser 1984 as cited in Ex. 31-22-33;). Thus, it cannot be 
    concluded that Cr(VI) is a reproductive toxin for normal working 
    situations.
    
    VI. Quantitative Risk Assessment
    
    A. Introduction
    
        The Occupational Safety and Health (OSH) Act and some landmark 
    court cases have led OSHA to rely on quantitative risk assessment, 
    where possible, to support the risk determinations required to set a 
    permissible exposure limit (PEL) for a toxic substance in standards 
    under the OSH Act. Section 6(b)(5) of the Act states that "The 
    Secretary [of Labor], in promulgating standards dealing with toxic 
    materials or harmful agents under this subsection, shall set the 
    standard which most adequately assures, to the extent feasible, on the 
    basis of the best available evidence, that no employee will suffer 
    material impairment of health or functional capacity even if such 
    employee has regular exposure to the hazard dealt with by such standard 
    for the period of his working life." (29 U.S.C. 651 et seq.)
        In a further interpretation of the risk requirements for OSHA 
    standard setting, the United States Supreme Court, in the 1980 
    "benzene" decision, (Industrial Union Department, AFL-CIO v. American 
    Petroleum Institute, 448 U.S. 607 (1980)) ruled that the OSH Act 
    requires that, prior to the issuance of a new standard, a determination 
    must be made that there is a significant risk of material impairment of 
    health at the existing PEL and that issuance of a new standard will 
    significantly reduce or eliminate that risk. The Court stated that 
    "before he can promulgate any
    permanent health or safety standard, the Secretary is required to make 
    a threshold finding that a place of employment is unsafe in the sense 
    that significant risks are present and can be eliminated or lessened by 
    a change in practices" [448 U.S. 642]. The Court also stated "that 
    the Act does not limit the Secretary's power to require the elimination 
    of significant risks" [488 U.S. 644]. While the Court indicated that 
    the use of quantitative risk analysis was an appropriate means to 
    establish significant risk, they made clear that "OSHA is not required 
    to support its finding that a significant risk exists with anything 
    approaching scientific certainty."
        The Court in the Cotton Dust case, (American Textile Manufacturers 
    Institute v. Donovan, 452 U.S. 490 (1981)) found that Section 6(b)(5) 
    of the OSH Act places benefits to worker health above all other 
    considerations except those making attainment of the health benefits 
    unachievable and, therefore, only feasibility analysis of OSHA health 
    standards is required and not cost-benefit analysis. It reaffirmed its 
    previous position in the "benzene" case, however, that a risk 
    assessment is not only appropriate but should be used to identify 
    significant health risk in workers and to determine if a proposed 
    standard will achieve a reduction in that risk. Although the Court did 
    not require OSHA to perform a quantitative risk assessment in every 
    case, the Court implied, and OSHA as a matter of policy agrees, that 
    assessments should be put into quantitative terms to the extent 
    possible.
        The determining factor in the decision to perform a quantitative 
    risk assessment is the availability of suitable data for such an 
    assessment. As reviewed in section V.B. on Carcinogenic Effects, there 
    are a substantial number of occupational cohort studies that reported 
    excess lung cancer mortality in workers exposed to Cr(VI) in several 
    industrial operations. Many of these found that workers exposed to 
    higher levels of airborne Cr(VI) for a longer period of time had 
    greater standardized mortality ratios (SMRs) for lung cancer.
        OSHA believes that two recently studied occupational cohorts by 
    Gibb et al. (Ex. 31-22-11) and Luippold et al. (Ex. 33-10) have the 
    strongest data sets on which to quantify lung cancer risk from 
    cumulative Cr(VI) exposure (i.e., air concentration x exposure 
    duration). A variety of exposure-response models were fit to these 
    data, including linear relative risk, quadratic relative risk, log-
    linear relative risk, additive risk, and Cox proportional hazards 
    models. Using a linear relative risk model on these data to predict 
    excess lifetime risk, OSHA estimated that the lung cancer risk from a 
    45 year occupational exposure to Cr(VI) at an 8-hour TWA at the 
    previous PEL of 52 [mu]g/m\3\ is 101 to 351 excess deaths per 1000. 
    Quantitative lifetime risk estimates from a working lifetime exposure 
    at several lower alternative PELs under consideration by the Agency 
    were also estimated. The sections below discuss the selection of the 
    appropriate data sets and risk models, the estimation of lung cancer 
    risks based on the selected data sets and models, the uncertainty in 
    the risk estimates, and the key issues that were raised in comments 
    received during the public hearing process.
        A preliminary quantitative risk assessment was previously published 
    in the Notice of Proposed Rulemaking (69 FR at 59306, 10/4/2004). This 
    was peer-reviewed by three outside experts in the fields of 
    occupational epidemiology and risk assessment. Their comments were 
    discussed in the NPRM (69 FR at 59385-59388). They commented on the 
    suitability of several occupational data sets for exposure-response 
    analysis, the choice of exposure metric and risk model, the 
    appropriateness of the risk estimates, and the characterization of key 
    issues and uncertainties. The reviewers agreed that the soluble 
    chromate production cohorts described by Gibb et al. and Luippold et 
    al. provided the strongest data sets for quantitative risk assessment. 
    They concurred that a linear model using cumulative exposure based on 
    time-weighted average Cr(VI) air concentrations by job title and 
    employment history was the most reasonable risk assessment approach. 
    The experts showed less enthusiasm for average monthly Cr(VI) air 
    concentrations as an appropriate exposure metric or for an exposure 
    threshold below which there is no lung cancer risk. They found the 
    range of excess lifetime lung cancer risks presented by OSHA to be 
    sound and reasonable. They offered suggestions regarding issues such as 
    the impact of cigarette smoking and the healthy worker effect on the 
    assessment of risk. OSHA revised the preliminary quantitative risk 
    assessment in several respects based on these peer review comments.
        In contrast to the more extensive occupational cohort data on 
    Cr(VI) exposure-response, data from experimental animal studies are 
    less suitable for quantitative risk assessment of lung cancer. Besides 
    the obvious species difference, most of the animal studies administered 
    Cr(VI) to the respiratory tract by less relevant routes, such as 
    instillation or implantation. The few available inhalation studies in 
    animals were limited by a combination of inadequate exposure levels, 
    abbreviated durations, and small numbers of animals per dose group. 
    Despite these limitations, the animal data do provide semi-quantitative 
    information with regard to the relative carcinogenic potency of 
    different Cr(VI) compounds. A more detailed discussion can be found in 
    sections V.B.7 and V.B.9.
        The data that relate non-cancer health impairments, such as damage 
    to the respiratory tract and skin, to Cr(VI) exposure are also not well 
    suited for quantitative assessment. There are some data from cross-
    sectional studies and worker surveys that group the prevalence and 
    severity of nasal damage by contemporary time-weighted average (TWA) 
    Cr(VI) air measurements. However, there are no studies that track 
    either incidence or characterize exposure over time. Nasal damage is 
    also more likely influenced by shorter-term peak exposures that have 
    not been well characterized. While difficult to quantify, the data 
    indicate that the risk of damage to the nasal mucosa will be 
    significantly reduced by lowering the previous PEL, discussed further 
    in section VII on Significance of Risk.
        There are even less suitable exposure-response data to assess risk 
    for other Cr(VI)-induced impairments (e.g., mild renal damage, 
    gastrointestinal ulceration). With the possible exception of 
    respiratory tract effects (e.g., nasal damage, occupational asthma), 
    the risk of non-cancer adverse effects that result from inhaling Cr(VI) 
    are expected to be very low, except as a result of long-term regular 
    airborne exposure around or above the previous PEL (52 [mu]g/m\3\). 
    Since the non-cancer effects occur at relatively high Cr(VI) air 
    concentrations, OSHA has concluded that lowering the PEL to reduce the 
    risk of developing lung cancer over a working lifetime will also 
    eliminate or reduce the risk of developing these other health 
    impairments. As discussed in section V.E., adverse effects to the skin 
    primarily result from dermal rather than airborne exposure.
    
    B. Study Selection
    
        The more than 40 occupational cohort studies reviewed in Section 
    VI.B on carcinogenic effects were evaluated to determine the adequacy 
    of the exposure-response information for the quantitative assessment of 
    lung cancer risk associated with Cr(VI) exposure. The key criteria were 
    data that allowed for estimation of input variables,
    specifically levels of exposure and duration of exposure (e.g., 
    cumulative exposure in mg/m\3\-yr); observed numbers of cancers (deaths 
    or incident cases) by exposure category; and expected (background) 
    numbers of cancer deaths by exposure category.
        Additional criteria were applied to evaluate the strengths and 
    weaknesses of the available epidemiological data sets. Studies needed 
    to have well-defined cohorts with identifiable cases. Features such as 
    cohort size and length of follow-up affect the ability of the studies 
    to detect any possible effect of Cr(VI) exposure. Potential confounding 
    of the responses due to other exposures was considered. Study 
    evaluation also considered whether disease rates from an appropriate 
    reference population were used to derive expected numbers of lung 
    cancers. One of the most important factors in study evaluation was the 
    ascertainment and use of exposure information (i.e., well-documented 
    historical exposure data). Both level and duration of exposure are 
    important in determining cumulative dose, and studies are often 
    deficient with respect to the availability or use of such information.
        Two recently studied cohorts of chromate production workers, the 
    Gibb cohort and the Luippold cohort, were found to be the strongest 
    data sets for quantitative assessment (Exs. 31-22-11; 33-10). Of the 
    various studies, these two had the most extensive and best documented 
    Cr(VI) exposures spanning three or four decades. Both cohort studies 
    characterized observed and expected lung cancer mortality and reported 
    a statistically significant positive association between lung cancer 
    risk and cumulative Cr(VI) exposure. For the remainder of this preamble 
    the Gibb and Luippold cohorts are referred to as the "preferred 
    cohorts", denoting that they are the cohorts used to derive OSHA's 
    model of lung cancer risk from exposure to Cr(VI).
        Four other cohorts (Mancuso, Hayes et al., Gerin et al., and 
    Alexander et al.) had less satisfactory data for quantitative 
    assessments of lung cancer risk (Exs. 7-11; 23; 7-14; 7-120; 31-16-3). 
    These cohorts include chromate production workers, stainless steel 
    welders, and aerospace manufacturing workers. While the lung cancer 
    response in these cohorts was stratified across multiple exposure 
    groups, there were limitations to these data that affected their 
    reliability for quantitative risk assessment. OSHA therefore did not 
    consider them to be preferred cohorts (i.e., they were not used to 
    derive OSHA's model of lung cancer risk from exposure to Cr(VI)). 
    However, OSHA believes that quantitative analysis of these cohorts 
    provides valuable information to the risk assessment, especially for 
    the purpose of comparison with OSHA's risk model based on the preferred 
    Gibb and Luippold cohorts. Analyses based on the Mancuso, Hayes et al., 
    Gerin et al., and Alexander et al. cohorts, referred to as "additional 
    cohorts" for the remainder of this preamble, were compared with the 
    assessments based on the Gibb and Luippold cohorts. The strengths and 
    weaknesses of all six cohorts as a basis for exposure-response analysis 
    are discussed in more detail below.
    1. Gibb Cohort
        The Gibb et al. study was a particularly strong study for 
    quantitative risk assessment, especially in terms of cohort size and 
    historical exposure data (Exs. 31-22-11; 33-11). Gibb et al. studied an 
    updated cohort from the same Baltimore chromate production plant 
    previously studied by Hayes et al. (see section VI.B.4). The cohort 
    included 2357 male workers (white and non-white) first employed between 
    1950 and 1974. Follow-up was through the end of 1992 for a total of 
    70,736 person-years and an average length of 30 years per cohort 
    member. Smoking status and amount smoked in packs per day at the start 
    of employment was available for the majority of the cohort members.
        A significant advantage of the Gibb data was the availability of a 
    large number of personal and area sampling measurements from a variety 
    of locations and job titles which were collected over the years during 
    which the cohort members were exposed (from 1950 to 1985, when the 
    plant closed). Using these concentration estimates, a job exposure 
    matrix was constructed giving annual average exposures by job title. 
    Based on the job exposure matrix and work histories for the cohort 
    members, Gibb et al. computed the person-years of observation, the 
    observed numbers of lung cancer deaths, and the expected numbers of 
    lung cancer deaths categorized by cumulative Cr(VI) exposure and age of 
    death. They found that cumulative Cr(VI) exposure was a significant 
    predictor of lung cancer risk over the exposure range of 0 to 2.76 
    (meanSD = 0.702.75) mg/m\3\-yr. This included a 
    greater than expected number of lung cancer deaths among relatively 
    young workers. For example, chromate production workers between 40 and 
    50 years of age with mean cumulative Cr(VI) exposure of 0.41 mg 
    CrO3/m\3\-yr (equivalent to 0.21 mg Cr(VI)/m\3\-yr) were 
    about four times more likely to die of lung cancer than a State of 
    Maryland resident of similar age (Ex. 31-22-11, Table V).
        The data file containing the demographic, exposure, smoking, and 
    mortality data for the individual cohort members was made available to 
    OSHA (Ex. 295). These data were used in several reanalyses to produce 
    several different statistical exposure-response models and to explore 
    various issues raised in comments to OSHA, such as the use of linear 
    and nonlinear exposure-response models, the difference between modern 
    and historical levels of Cr(VI) exposure, and the impact of including 
    or excluding short-term workers from the exposure-response analysis. 
    The Agency's access to the dataset and to reanalyses of it performed by 
    several different analysts has been a tremendous advantage in its 
    consideration of these and other issues in the development of the final 
    risk assessment.
    2. Luippold Cohort
        The other well-documented exposure-response data set comes from a 
    second cohort of chromate production workers. Luippold et al. studied a 
    cohort of 482 predominantly white, male employees who started work 
    between 1940 and 1972 at the same Painesville, Ohio plant studied 
    earlier by Mancuso (Ex. 33-10) (see subsection VI.B.3). Mortality 
    status was followed through 1997 for a total of 14,048 person-years. 
    The average worker had 30 years of follow-up. Cr(VI) exposures for the 
    Luippold cohort were based on 21 industrial hygiene surveys conducted 
    at the plant between 1943 and 1971, yielding a total of more than 800 
    area samples (Ex. 35-61). A job exposure matrix was computed for 22 
    exposure areas for each month of plant operation starting in 1940 and, 
    coupled with detailed work histories available for the cohort members, 
    cumulative exposures were calculated for each person-year of 
    observation. Luippold et al. found significant dose-related trends for 
    lung cancer SMRs as a function of year of hire, duration of employment, 
    and cumulative Cr(VI) exposure. Risk assessments on the Luippold et al. 
    study data performed by Crump et al. had access to the individual data 
    and, therefore, had the best basis for analysis of this cohort (Exs. 
    31-18-1; 35-205; 35-58).
        While the Luippold cohort was smaller and less racially diverse 
    than the Gibb cohort, the workforce contained fewer transient, short-
    term employees. The Luippold cohort consisted entirely of workers 
    employed over one year. Fifty-five percent worked
    for more than five years. In comparison, 65 percent of the Gibb cohort 
    worked for less than a year and 15 percent for more than five years at 
    the Baltimore plant. There was less information about the smoking 
    behavior (smoking status available for only 35 percent of members) of 
    the Luippold cohort than the Gibb cohort.
        One aspect that the Luippold cohort had in common with the Gibb 
    cohort was extensive and well-documented air monitoring of Cr(VI). The 
    quality of exposure information for both the Gibb and Luippold cohorts 
    was considerably better than that for the Mancuso, Hayes et al., Gerin 
    et al., and Alexander et al. cohorts. The cumulative Cr(VI) exposures 
    for the Luippold cohort, which ranged from 0.003 to 23 (mean< plus-
    minus>SD = 1.582.50) mg Cr(VI)/m\3\-yr, were generally 
    higher but overlapped those of the Gibb cohort. The use of individual 
    work histories to define exposure categories and presentation of mean 
    cumulative doses in the exposure groups provided a strong basis for a 
    quantitative risk assessment. The higher cumulative exposure range and 
    the longer work duration of the Luippold cohort serve to complement 
    quantitative data available on the Gibb cohort.
    3. Mancuso Cohort
        Mancuso (Ex. 7-11) studied the lung cancer incidence of an earlier 
    cohort of 332 white male employees drawn from the same plant in 
    Painesville, Ohio that was evaluated by the Luippold group. The Mancuso 
    cohort was first employed at the facility between 1931 and 1937 and 
    followed up through 1972, when the plant closed. Mancuso (Ex. 23) later 
    extended the follow-up period through 1993, yielding a total of 12,881 
    person-years of observation for an average length of 38.8 years and a 
    total of 66 lung cancer deaths. Since the Mancuso workers were first 
    employed in the 1930s and the Luippold workers were first employed 
    after 1940, the two cohorts are completely different sets of 
    individuals.
        A major limitation of the Mancuso study is the uncertainty of the 
    exposure data. Mancuso relied exclusively on the air monitoring 
    reported by Bourne and Yee (Ex. 7-98) conducted over a single short 
    period of time during 1949. Bourne and Yee presented monitoring data as 
    airborne insoluble chromium, airborne soluble chromium, and total 
    airborne chromium by production department at the Painesville plant. 
    The insoluble chromium was probably Cr(III) compounds with some 
    slightly water-soluble and insoluble chromates. The soluble chromium 
    was probably highly water-soluble Cr(VI). Mancuso (Exs. 7-11; 23) 
    calculated cumulative exposures (mg/m\3\-yr) for each cohort member 
    based on the 1949 mean chromium concentrations, by production 
    department, under the assumption that those levels reflect exposures 
    during the entire duration of employment for each cohort member, even 
    though employment may have begun as early as 1931 and may have extended 
    to 1972. Due to the lack of air measurements spanning the full period 
    of worker exposure and the lack of adequate methodology to distinguish 
    chromium valence states (i.e., Cr(VI) vs. Cr(III)), the exposure data 
    associated with the Mancuso cohort were not as well characterized as 
    data from the Luippold or Gibb cohorts.
        Mancuso (Exs. 7-11; 23)reported cumulative exposure-related 
    increases in age-adjusted lung cancer death rates for soluble, 
    insoluble, or total chromium. Within a particular range of exposures to 
    insoluble chromium, lung cancer death rates also tended to increase 
    with increasing total cumulative chromium. However, the study did not 
    report whether these tendencies were statistically significant, nor did 
    it report the extent to which exposures to soluble and insoluble 
    chromium were correlated. Thus, it is possible that the apparent 
    relationship between insoluble chromium (e.g., primarily Cr(III)) and 
    lung cancer may have arisen because both insoluble chromium 
    concentrations and lung cancer death rates were positively correlated 
    with Cr(VI) concentrations. Further discussion with respect to 
    quantitative risk estimation from the Mancuso cohort is provided in 
    section VI.E.1 on additional risk assessments.
    4. Hayes Cohort
        Hayes et al. (Ex. 7-14) studied a cohort of employees at the same 
    chromate production site in Baltimore examined by Gibb et al. The Hayes 
    cohort consisted of 2101 male workers who were first hired between 1945 
    and 1974, excluding those employed for less than 90 days. The Gibb 
    cohort had different but partially overlapping date criteria for first 
    employment (1950-1974) and no 90 day exclusion. Hayes et al. reported 
    SMRs for respiratory tract cancer based on workers grouped by time of 
    hire, employment duration, and high or low exposure groups. Workers who 
    had ever worked at an older plant facility and workers whose location 
    of employment could not be determined were combined into a single 
    exposure group referred to as "high or questionable" exposure. 
    Workers known to have been employed exclusively at a newer renovated 
    facility built in 1950 and 1951 were considered to have had "low" 
    exposure. A dose-response was observed in the sense that higher SMRs 
    for respiratory cancer were observed among long-term workers (workers 
    who had worked for three or more years) than among short-term workers.
        Hayes et al. did not quantify occupational exposure to Cr(VI) at 
    the time the cohort was studied, but Braver et al. (Ex. 7-17) later 
    estimated average cumulative soluble chromium (presumed by the authors 
    to be Cr(VI)) exposures for four subgroups of the Hayes cohort first 
    employed between 1945 and 1959. The TWA Cr(VI) concentrations were 
    determined from a total of 555 midget impinger air measurements that 
    were collected at the older plant from 1945 to 1950. The cumulative 
    exposures for the subgroups were estimated from the yearly average 
    Cr(VI) exposure for the entire plant and the subgroups' average 
    duration of employment rather than job-specific Cr(VI) concentrations 
    and individual work histories. Such "group level" estimation of 
    cumulative exposure is less appropriate than the estimation based on 
    individual experiences as was done for the Gibb and Luippold cohorts.
        A more severe limitation of this study is that exposures attributed 
    to many workers in the newly renovated facility at the Baltimore site 
    throughout the 1950s were based on chromium measurements from an 
    earlier period (i.e., 1949-1950) at an older facility. Samples 
    collected at the new facility and reviewed by Gibb et al. (Exs. 25, 31-
    22-12) show that the exposures in the new facility were substantially 
    lower than assumed by Braver et al. Braver et al. (Ex. 7-17) discussed 
    a number of other potential sources of uncertainty in the Cr(VI) 
    exposure estimates, such as the possible conversion to Cr(III) during 
    sample collection and the likelihood that samples may have been 
    collected mainly in potential problem areas.
    5. Gerin Cohort
        Gerin et al. (Ex. 7-120) developed a job exposure matrix that was 
    used to estimate cumulative Cr(VI) exposures for male stainless steel 
    welders who were part of the International Agency for Research on 
    Cancer's (IARC) multi-center historical cohort study (Ex. 7-114). The 
    IARC cohort included 11,092 welders. However, the number of cohort 
    members who were stainless steel welders, for which Cr(VI) exposures 
    were estimated, could not be determined from their report. Gerin et al. 
    used occupational hygiene surveys reported in the published literature, 
    including a limited amount of data collected from 8 of the 135 
    companies that employed welders in the cohort, to estimate typical eight-hour 
    TWA Cr(VI) breathing zone concentrations for various combinations of 
    welding processes and base metal. The resulting exposure matrix was 
    then combined with information about individual work history, including 
    time and length of employment, type of welding, base metal welded, and 
    information on typical ventilation status for each company (e.g., 
    confined area, use of local exhaust ventilation, etc.) to estimate the 
    cumulative Cr(VI) exposure. Individual work histories were not 
    available for about 25 percent of the stainless steel welders. In these 
    cases, information was assumed based on the average distribution of 
    welding practices within the company. The lack of Cr(VI) air 
    measurements from most of the companies in the study and the 
    limitations in individual work practice information for this cohort 
    raise questions concerning the accuracy of the exposure estimates.
        Gerin et al. reported no upward trend in lung cancer mortality 
    across four cumulative Cr(VI) exposure categories for stainless steel 
    welders, each accumulating between 7,000 and 10,000 person-years of 
    observation. The welders were also known to be exposed to nickel, 
    another potential lung carcinogen. Co-exposure to nickel may obscure or 
    confound the Cr(VI) exposure-response relationship. As discussed 
    further in Sections VI.E.3 and VI.G.4, exposure misclassification in 
    this cohort may obscure an exposure-response relationship. This is the 
    primary reason that the Gerin et al. cohort was not considered a 
    preferred cohort (i.e., it was not used to derive OSHA's quantitative 
    risk estimates), although a quantitative analysis of this cohort was 
    performed for comparison with the preferred cohorts.
    6. Alexander Cohort
        Alexander et al. (Ex. 31-16-3) conducted a retrospective cohort 
    study of 2429 aerospace workers employed in jobs entailing chromate 
    exposure (e.g., spray painting, sanding/polishing, chrome plating, 
    etc.) between 1974 and 1994. The cohort included workers employed as 
    early as 1940. Follow-up time was short, averaging 8.9 years per cohort 
    member; in contrast, the Gibb and Luippold cohorts accumulated an 
    average 30 or more years of follow-up. Long-term follow-up of cohort 
    members is particularly important for determining the risk of lung 
    cancer, which typically has an extended latency period of twenty years 
    or more.
        Industrial hygiene data collected between 1974 and 1994 were used 
    to classify jobs in categories of "high" exposure, "moderate" 
    exposure, or "low" exposure to Cr(VI). The use of respiratory 
    protection was accounted for when setting up the job exposure matrix. 
    These exposure categories were assigned summary TWA concentrations and 
    combined with individual job history records to estimate cumulative 
    exposures for cohort members over time. As further discussed in section 
    VI.E.4, it was not clear from the study whether exposures are expressed 
    in units of Cr(VI) or chromate (CrO3). Exposures occurring 
    before 1974 were assumed to be at TWA levels assigned to the interval 
    from 1974 to 1985.
        Alexander et al. presented lung cancer incidence data for four 
    cumulative chromate exposure categories based on worker duration and 
    the three (high, moderate, low) exposure levels. Lung cancer incidence 
    rates were determined using a local cancer registry, part of the 
    National Cancer Institute (NCI) Surveillance Epidemiology and End 
    Results (SEER) program. The authors reported no positive trend in lung 
    cancer incidence with increasing Cr(VI) exposure. Limitations of this 
    cohort study include the young age of the cohort members (median = 42) 
    and lack of information on smoking. As discussed above, the follow-up 
    time (average <  9 years) was probably too short to capture lung cancers 
    resulting from Cr(VI) exposure. Finally, the available Cr(VI) air 
    measurement data did not span the entire employment period of the 
    cohort (e.g., no data for 1940 to 1974) and was heavily grouped into a 
    relatively small number of "summary" TWA concentrations that may not 
    have fully captured individual differences in workplace exposures to 
    Cr(VI). For the above reasons, in particular the insufficient follow-up 
    time for most cohort members, the Alexander cohort was not considered a 
    preferred dataset for OSHA's quantitative risk analysis. However, a 
    quantitative analysis of this cohort was performed for comparison with 
    the preferred cohorts.
    7. Studies Selected for the Quantitative Risk Assessment
        The epidemiologic database is quite extensive and contains several 
    studies with exposure and response data that could potentially be used 
    for quantitative risk assessment. OSHA considers certain studies to be 
    better suited for quantitative assessment than others. The Gibb and 
    Luippold cohorts are the preferred sources for quantitative risk 
    assessment because they are large, have extensive follow-up, and have 
    documentation of historical Cr(VI) exposure levels superior to the 
    Mancuso, Hayes, Gerin and Alexander cohorts. In addition, analysts have 
    had access to the individual job histories of cohort members and 
    associated exposure matrices. OSHA's selection of the Gibb and Luippold 
    cohorts as the best basis of exposure-response analysis for lung cancer 
    associated with Cr(VI) exposure was supported by a variety of 
    commenters, including for example NIOSH (Tr. 314; Ex. 40-10-2, p. 4), 
    EPRI (Ex. 38-8, p.6), and Exponent (Ex. 38-215-2, p. 15). It was also 
    supported by the three external peer reviewers who reviewed OSHA's 
    preliminary risk assessment, Dr. Gaylor (Ex. 36-1-4-1, p. 24), Dr. 
    Smith (Ex. 36-1-4-2 p. 28), and Dr. Hertz-Picciotto (Ex. 36-1-4-4, pp. 
    41-42).
        The Mancuso cohort and the Hayes cohort were derived from workers 
    at the same plants as Luippold and Gibb, respectively, but have 
    limitations associated with the reporting of quantitative information 
    and exposure estimates that make them less suitable for risk 
    assessment. Similarly, the Gerin and Alexander cohorts are less 
    suitable, due to limitations in exposure estimation and short follow-
    up, respectively. For these reasons, OSHA did not rely upon the 
    Mancuso, Hayes, Gerin, and Alexander cohorts to derive its exposure-
    response model for the risk of lung cancer from Cr(VI).
        Although the Agency did not rely on the Mancuso, Hayes, Gerin, and 
    Alexander studies to develop its exposure-response model, OSHA believes 
    that evaluating risk among several different worker cohorts and 
    examining similarities and differences between them adds to the overall 
    completeness and quality of the assessment. The Agency therefore 
    analyzed these datasets and compared the results with the preferred 
    Gibb and Luippold cohorts. This comparative analysis is discussed in 
    Section VI.E. In light of the extensive worker exposure-response data, 
    there is little additional value in deriving quantitative risk 
    estimates from tumor incidence results in rodents, especially 
    considering the concerns with regard to route of exposure and study 
    design.
        OSHA received a variety of public comments regarding the overall 
    quality of the Gibb and Luippold cohorts and their suitability as the 
    preferred cohorts in OSHA's quantitative risk analysis. Some commenters 
    raised concerns about the possible impact of short-term workers in the 
    Gibb cohort on the risk assessment (Tr. 123; Exs. 38-106, p. 10, 21; 
    40-12-5, p. 9). The Gibb cohort's inclusion of many workers employed 
    for short periods of time was cited as a
    "serious flaw" by one commenter, who suggested that many lung cancers 
    among short-term workers in the study were caused by unspecified other 
    factors (Ex. 38-106, p. 10, p. 21). Another commenter stated that the 
    Davies cohort of British chromate production workers "gives greater 
    credence to the Painesville cohort as it showed that brief exposures 
    (as seen in a large portion of the Baltimore cohort) did not have an 
    increased risk of lung cancer" (Ex. 39-43, p. 1). However, separate 
    analyses of the short-term (<  1 year employment) and longer-term ( 1 
    year) Gibb cohort members indicated that restriction of the cohort to 
    workers with tenures of at least one year did not substantially impact 
    estimates of excess lung cancer mortality (Ex. 31-18-15-1 , p. 29). At 
    the public hearing, Ms. Deborah Proctor of Exponent, Inc. stated that 
    "the short term workers did not affect the results of the study" (Tr. 
    1848). OSHA agrees with Ms. Proctor's conclusion, and does not believe 
    that the inclusion of short term workers in the Gibb cohort is a source 
    of substantial uncertainty in the Agency's risk estimates.
        Some commenters expressed concern that the Gibb study did not 
    control for smoking (Exs. 38-218, pp. 20-21; 38-265, p. 28; 39-74, p. 
    3). However, smoking status at the time of employment was ascertained 
    for approximately 90% of the cohort (Ex. 35-435) and was used in 
    statistical analyses by Gibb et al., Environ Inc., and Exponent Inc. to 
    adjust for the effect of smoking on lung cancer in the cohort (Exs. 25; 
    31-18-15-1; 35-435). NIOSH performed similar analyses using more 
    detailed information on smoking level (packs per day) that was 
    available for 70% of the cohort (Ex. 35-435, p.1100). OSHA believes 
    that these analyses appropriately addressed the potential confounding 
    effect of smoking in the Gibb cohort. Issues and analyses related to 
    smoking are further discussed in Section VI.G.3.
        Other issues and uncertainties raised about the Gibb and Luippold 
    cohorts include a lack of information necessary to estimate deposited 
    dose of Cr(VI) for workers in either cohort and a concern that the 
    Luippold exposure data were based on exposures to "airborne total 
    soluble and insoluble chromium* * * rather than exposures to Cr(VI)" 
    (Ex. 38-218, pp. 20-21). However, the exposure estimates for the 
    Luippold (2003) cohort were recently developed by Proctor et al. using 
    measurements of airborne Cr(VI), not the total chromium measurements 
    used previously in Mancuso et al.'s analysis (Exs. 35-58, p. 1149; 35-
    61). And, while it is true that the Gibb and Luippold (2003) datasets 
    do not lend themselves to construction of deposited dose measures, the 
    extensive Cr(VI) air monitoring data available on these cohorts are 
    more than adequate for quantitative risk assessment. In the case of the 
    Gibb cohort, the exposure dataset is extraordinarily comprehensive and 
    well-documented (Tr. 709-710; Ex. 44-4, p.2), even "exquisite" 
    according to one NIOSH expert (Tr. 312). Further discussion of the 
    quality and reliability of the Gibb and Luippold (2003) exposure data 
    and related comments appears in Section VI.G.1.
        OSHA received several comments regarding a new epidemiological 
    study conducted by Environ, Inc. for the Industrial Health Foundation, 
    Inc. of workers hired after the institution of process changes and 
    industrial hygiene practices designed to limit exposure to Cr(VI) in 
    two chromate production plants in the United States and two plants in 
    Germany (Exs. 47-24-1; 47-27, pp. 15-16; 47-35-1, pp. 7-8). These 
    commenters suggested that OSHA should use these cohorts to model risk 
    of lung cancer from low exposures to Cr(VI). Unfortunately, the public 
    did not have a chance to comment on this study because documents 
    related to it were submitted to the docket after the time period when 
    new information should have been submitted. However, OSHA reviewed the 
    study and comments that were submitted to the docket. Based on the 
    information submitted, the Agency does not believe that quantitative 
    analysis of these studies would provide additional information on risk 
    from low exposures to Cr(VI).
        A cohort analysis based on the U.S. plants is presented in an April 
    2005 publication by Luippold et al. (Ex. 47-24-2). Luippold et al. 
    studied a total of 617 workers with at least one year of employment, 
    including 430 at a plant built in the early 1970s ("Plant 1") and 187 
    hired after the 1980 institution of exposure-reducing process and work 
    practice changes in a second plant ("Plant 2"). Workers were followed 
    through 1998. Personal air-monitoring measures available from 1974 to 
    1988 for the first plant and from 1981 to 1998 for the second plant 
    indicated that exposure levels at both plants were low, with overall 
    geometric mean concentrations below 1.5 [mu]g/m3 and area-
    specific average personal air sampling values not exceeding 10 [mu]g/
    m3 for most years (Ex. 47-24-2, p. 383). By the end of 
    follow-up, which lasted an average of 20.1 years for workers at Plant 1 
    and 10.1 years at Plant 2, 27 cohort members (4%) were deceased. There 
    was a 41% deficit in all-cause mortality when compared to all-cause 
    mortality from age-specific state reference rates, suggesting a strong 
    healthy worker effect. Lung cancer was 16% lower than expected based on 
    three observed vs. 3.59 expected cases, also using age-specific state 
    reference rates (Ex. 47-24-2, p. 383). The authors concluded that 
    "[t]he absence of an elevated lung cancer risk may be a favorable 
    reflection of the postchange environment. However, longer follow-up 
    allowing an appropriate latency for the entire cohort will be needed to 
    confirm this conclusion" (Ex. 47-24-2, p. 381).
        OSHA agrees with the study authors that the follow-up in this study 
    was not sufficiently long to allow potential Cr(VI)-related lung cancer 
    deaths to occur among many cohort members. The mean times since first 
    exposure of 10 and 20 years for Plant 1 and Plant 2 employees, 
    respectively, suggest that most workers in the cohort may not have 
    completed the " * * * typical latency period of 20 years or more" 
    that Luippold et al. suggest is required for occupational lung cancer 
    to emerge (Ex. 47-24-2, p. 384). Other important limitations of this 
    study include the striking healthy worker effect on the SMR analysis, 
    and the relatively young age of most workers at the end of follow-up 
    (approximately 90% <  60 years old) (Ex. 47-24-2, p. 383). OSHA also 
    agrees with the study authors' statements that " * * * the few lung 
    cancer deaths in this cohort precluded * * * [analyses to] evaluate 
    exposure-response relationships * * * " (Ex. 47-24-2, p. 384).
        Although OSHA's model predicts high excess lung cancer risk for 
    highly exposed individuals (e.g., workers exposed for 45 years at the 
    previous PEL of 52 [mu]g/m3), the model would predict much 
    lower risks for workers with low exposures, as in the Luippold (2005) 
    cohorts. To provide a point of comparison between the results of the 
    Luippold et al. (2005) 'post-change' study and OSHA's risk model, the 
    Agency used its risk model to generate an estimate of lung cancer risk 
    for a population with exposure characteristics approximately similar to 
    the 'post-change' cohorts described in Luippold et al. (2005). It 
    should be noted that since this comparative analysis used year 2000 
    U.S. reference rates were rather than the state-, race-, and gender-
    specific historical reference mortality rates used by Luippold et al. 
    (2005), this risk calculation provides only a rough estimate of 
    expected excess lung cancer risk for the cohort. The derivation of 
    OSHA's risk model (based on the preferred Gibb and Luippold
    (2003) cohorts) is described in Sections VI.C.1 and VI.C.2.
        It is difficult to tell from the publication what the average level 
    or duration of exposure was for the cohort. However, personal sampling 
    data reported by Luippold et al. (2005) had annual geometric mean 8-
    hour TWA concentrations "much less" than 1.5 [mu]g/m3 in 
    most years (Ex. 47-24-2, p. 383). Most workers also probably had less 
    than 20 years of exposure, given the average follow-up periods of 20 
    and 10 years reported for the Luippold (2005) Plant 1 and Plant 2, 
    respectively. OSHA assumed that workers had TWA exposures of 1.5 [mu]g/
    m3 for 20 years, with the understanding that this assumption 
    would lead to somewhat higher estimates of risk than OSHA s model would 
    predict if the average exposure of the cohort was known. Using these 
    assumptions, OSHA's model predicts a 2-9% excess lung cancer risk due 
    to Cr(VI) exposure, or less than four cancers in the population the 
    size and age of the Luippold 2005 cohort.
        Since this analysis used year 2000 U.S. reference rates rather than 
    the state-, race-, and gender-specific historical reference mortality 
    rates used by Luippold et al. (2005), this risk calculation provides 
    only a rough estimate of the lung cancer risk that OSHA's model would 
    predict for the cohort. Nevertheless, it illustrates that for a 
    relatively young population with low exposures, OSHA's risk model 
    (derived from the preferred Gibb and Luippold 2003 cohorts) predicts 
    lung cancer risk similar to that observed in the low-exposure Luippold 
    2005 cohort. The small number of lung cancer deaths observed in 
    Luippold 2005 should not be considered inconsistent with the risk 
    estimates derived using models developed by OSHA based on the Gibb and 
    Luippold (2003) cohorts (Ex. 47-24-2, p. 383).
        Some commenters believed that analysis of the unpublished German 
    cohorts would demonstrate that lung cancer risk was only increased at 
    the highest Cr(VI) levels and, therefore, could form the basis for an 
    exposure threshold (Exs. 47-24-1; 47-35-1). Although no data were 
    provided to corroborate their comments, the Society of the Plastics 
    Industry requested that OSHA obtain and evaluate the German study as 
    "new and available evidence which may suggest a higher PEL than 
    proposed" (Ex. 47-24-1, p. 4).
        Following the close of the comment period, OSHA gained access to a 
    2002 final contract report by Applied Epidemiology Inc. prepared for 
    the Industrial Health Foundation (Ex. 48-1-1; 48-1-2) and a 2005 
    prepublication by ENVIRON Germany (Ex. 48-4). The 2002 report contained 
    detailed cohort descriptions, exposure assessments, and mortality 
    analyses of 'post-change' workers from the two German chromate 
    production plants referred to above and two U.S. chromate production 
    plants, one of which is plant 1 discussed in the 2005 study by Luippold 
    et al. The mortality and multivariate analyses were performed on a 
    single combined cohort from all four plants. The 2005 prepublication 
    contained a more abbreviated description and analysis of a smaller 
    cohort restricted to the two German plants only. The cohorts are 
    referred to as 'post-change' because the study only selected workers 
    employed after the participating plants switched from a high-lime to a 
    no-lime (or very low lime facility, in the case of U.S. plant 1) 
    chromate production process and implemented industrial hygiene 
    improvements that considerably reduced Cr(VI) air levels in the 
    workplace.
        The German cohort consisted of 901 post-change male workers from 
    two chromate production plants employed for at least one year. 
    Mortality experience of the cohort was evaluated through 1998. The 
    study found elevated lung cancer mortality (SMR=1.48 95% CI: 0.93-2.25) 
    when compared to the age- and calendar year-adjusted German national 
    population rates (Ex. 48-4). The cohort lacked sufficient job history 
    information and air monitoring data to develop an adequate job-exposure 
    matrix required to estimate individual airborne exposures (Ex. 48-1-2). 
    Instead, the researchers used the large amount of urinary chromium data 
    from routine biomonitoring of plant employees to analyze lung cancer 
    mortality using cumulative urinary chromium as an exposure surrogate, 
    rather than the conventional cumulative Cr(VI) air concentrations. The 
    study reported a statistically significant two-fold excess lung cancer 
    mortality (SMR=2.09; 95% CI: 1.08-3.65; 12 observed lung cancer deaths) 
    among workers in the highest cumulative exposure grouping (i.e. >200 
    [mu]g Cr/L--yr). There was no increase in lung cancer mortality in the 
    lower exposure groups, but the number of lung cancer deaths was small 
    (i.e. < 5 deaths) and the confidence intervals were wide. Logistic 
    regression modeling in the multi-plant cohort (i.e. German and U.S. 
    plants combined) showed an increased risk of lung cancer in the high 
    (OR=20.2; 95% CI: 6.2-65.4; 10 observed deaths) and intermediate 
    (OR=4.9; 95% CI: 1.5-16.0; 9 deaths) cumulative exposure groups when 
    compared to the low exposure group (Ex. 48-1-2, Table 18). The lung 
    cancer risks remained unchanged when smoking status was controlled for 
    in the model, indicating that the elevated risks were unlikely to be 
    confounded by smoking in this study.
        OSHA does not believe that the results of the German study provide 
    a basis on which to establish a threshold exposure below which no lung 
    cancer risk exists. Like the U.S. post-change cohort (i.e., Luippold 
    (2005) cohort) discussed above, small cohort size, few lung cancer 
    cases (e.g., 10 deaths in the three lowest exposure groups combined) 
    and limited follow-up (average 17 years) severely limit the power to 
    detect small increases in risk that may be present with low cumulative 
    exposures. The limited power of the study is reflected in the wide 
    confidence intervals associated with the SMRs. For example, there is no 
    apparent evidence of excess lung cancer (SMR=0.95; 95% CI: 0.26-2.44) 
    in workers exposed to low cumulative urine chromium levels between 40-
    100 [mu]g Cr/L--yr. However, the lack of precision in this estimate is 
    such that a two-fold increase in lung cancer mortality can not be ruled 
    out with a high degree of confidence. Although the study authors state 
    that the data suggest a possible threshold effect, they acknowledge 
    that "demonstrating a clear (and statistically significant) threshold 
    response in epidemiological studies is difficult especially [where], as 
    in this study, the number of available cases is relatively small, and 
    the precise estimation of small risks requires large numbers" (Ex. 48-
    4, p. 8). OSHA agrees that the number of lung cancer cases in the study 
    is too small to clearly demonstrate a threshold response or precisely 
    estimate small risks.
        OSHA has relied upon a larger, more robust cohort study for its 
    risk assessment than the German cohort. In comparison, the Gibb cohort 
    has about five times the person-years of observation (70736 vs. 14684) 
    and number of lung cancer cases (122 vs. 22). The workers, on average, 
    were followed longer (30 vs. 17 years) and a greater proportion of the 
    cohort is deceased (36% vs. 14%). Limited air monitoring from the 
    German plants indicate that average plant-wide airborne Cr(VI) roughly 
    declined from about 35 [mu]g Cr(VI)/m\3\ in the mid 1970s to 5 [mu]g 
    Cr(VI)/m\3\ in the 1990s (2002 report; Ex. 7-91). This overlaps the 
    Cr(VI) air levels in the Baltimore plant studied by Gibb et al. (Ex. 
    47-8). Furthermore, cumulative exposure estimates for members of the 
    Gibb cohort were individually reconstructed
    from job histories and Cr(VI) air monitoring data. These airborne 
    Cr(VI) exposures are better suited than urinary chromium for evaluating 
    occupational risk at the permissible exposure limits under 
    consideration by OSHA. An appropriate conversion procedure that 
    credibly predicts time-weighted average Cr(VI) air concentrations in 
    the workplace from urinary chromium measurements is not evident and, 
    thus, would undoubtedly generate additional uncertainty in the risk 
    estimates. For the above reasons, OSHA believes the Gibb cohort 
    provides a stronger dataset than the German cohort on which to assess 
    the existence of a threshold exposure. This and other issues pertaining 
    to the relationship between the cumulative exposure and lung cancer 
    risk are further discussed in section VI.G.1.a.
    
    C. Quantitative Risk Assessments Based on the Gibb Cohort
    
        Quantitative risk assessments were performed on the exposure-
    response data from the Gibb cohort by three groups: Environ 
    International (Exs. 33-15; 33-12) under contract with OSHA; the 
    National Institute for Occupational Safety and Health (Ex. 33-13); and 
    Exponent (Ex. 31-18-15-1) for the Chrome Coalition. All reported 
    similar risks for Cr(VI) exposure over a working lifetime despite using 
    somewhat different modeling approaches. The exposure-response data, 
    risk models, statistical evaluation, and risk estimates reported by 
    each group are discussed below.
    1. Environ Risk Assessments
        In 2002, Environ International (Environ) prepared a quantitative 
    analysis of the association between Cr(VI) exposure and lung cancer 
    (Ex. 33-15) , which was described in detail in the Preamble to the 
    Proposed Rule (69 FR at 59364-59365). After the completion of the 2002 
    Environ analysis, individual data for the 2357 men in the Gibb et al. 
    cohort became available. The new data included cumulative Cr(VI) 
    exposure estimates, smoking information, date of birth, race, date of 
    hire, date of termination, cause of death, and date of the end of 
    follow-up for each individual (Ex. 35-295). The individual data allowed 
    Environ to do quantitative risk assessments based on (1) redefined 
    exposure categories, (2) alternate background reference rates for lung 
    cancer mortality, and (3) Cox proportional hazards modeling (Ex. 33-
    12). These are discussed below and in the 2003 Environ analysis (Ex. 
    33-12).
        The 2003 Environ analysis presented two alternate groupings with 
    ten cumulative Cr(VI) exposure groups each, six more than reported by 
    Gibb et al. and used in the 2002 analysis. One alternative grouping was 
    designed to divide the person-years of follow-up fairly evenly across 
    groups. The other alternative allocated roughly the same number of 
    observed lung cancers to each group. These two alternatives were 
    designed to remedy the uneven distribution of observed and expected 
    cases in the Gibb et al. categories, which may have caused parameter 
    estimation problems due to the small number of cases in some groups. 
    The new groupings assigned adequate numbers of observed and expected 
    lung cancer cases to all groups and are presented in Table VI-1.
        Environ used a five-year lag to calculate cumulative exposure for 
    both groupings. This means that at any point in time after exposure 
    began, an individual's cumulative exposure would equal the product of 
    chromate concentration and duration of exposure, summed over all jobs 
    held up to five years prior to that point in time. An exposure lag is 
    commonly used in exposure-response analysis for lung cancer since there 
    is a long latency period between first exposure and the development of 
    disease. Gibb et al. found that models using five- and ten-year lags 
    provided better fit to the mortality data than lags of zero, two and 
    twenty years (Ex. 31-22-11).
    BILLING CODE 4510-26-P

Table VI-1

 

    
    BILLING CODE 4510-26-C
        The 2003 Environ analysis also derived expected cases using lung 
    cancer rates from alternative reference populations. In addition to the 
    State of Maryland lung cancer rates that were used by Gibb et al., 
    Environ used age- and race-specific rates from the city of Baltimore, 
    where the plant was located. Baltimore may represent a more appropriate 
    reference population because most of the cohort members
    resided in Baltimore and Baltimore residents may be more similar to the 
    cohort members than the Maryland or U.S. populations in their co-
    exposures and lifestyle characteristics, especially smoking habits and 
    urban-related risk factors. On the other hand, Baltimore may not be the 
    more appropriate reference population if the higher lung cancer rates 
    in the Baltimore population primarily reflect extensive exposure to 
    industrial carcinogens. This could lead to underestimation of risk 
    attributable to Cr(VI) exposure.
        The 2003 analysis used two externally standardized models, a 
    relative risk model (model E1 below) and an additive risk model (model 
    E2) defined as follows:
    
    E1. Ni = C0 * Ei * (1 + C1Di + C2Di\2\)
    E2. Ni = C0 * Ei + PYi * (C1Di + C2Di\2\)
    
    where Ni is the predicted number of lung cancers in the i 
    th group; PYi is the number of person-years for 
    group i; Ei is the expected number of lung cancers in that 
    group, based on the reference population; Di is the mean 
    cumulative dose for that group; and C0, C1, and 
    C2 are parameters to be estimated. Both models initially 
    included quadratic exposure terms (C2Di\2\ ) as 
    one way to test for nonlinearity in the exposure-response. Model E1 is 
    a relative risk model, whereas Model E2 is an additive risk model. In 
    the case of additive risk models, the exposure-related estimate of 
    excess risk is the same regardless of the age- and race-specific 
    background rate of lung cancer. For relative risk models, a dose term 
    is multiplied by the appropriate background rate of lung cancer to 
    derive an exposure-related estimate of risk, so that excess risk always 
    depends on the background.
        Maximum likelihood techniques were used to estimate the parameters 
    C0, C1, and C2. Likelihood ratio tests 
    were used to determine which of the model parameters contributed 
    significantly to the fit of the model. Parameters were sequentially 
    added to the model, starting with C1, when they contributed 
    significantly (p <  0.05) to improving the fit. Parameters that did not 
    contribute significantly, including the quadratic exposure terms 
    (C2Di\2\ ), were removed from the models.
        Two Cox proportional hazards models were also fit to the individual 
    exposure-response data. The model forms were:
    
    C1. h(t;z;D) = h0(t)*exp([beta]1z + 
    [beta]2D)
    
    C2. h(t;z;D) = h0(t)*[exp([beta]1z)][1 + 
    [beta]2D]
    
    where h is the hazard function, which expresses the age-specific rate 
    of lung cancer among workers, as estimated by the model. In addition, t 
    is age, z is a vector of possible explanatory variables other than 
    cumulative dose, D is cumulative dose, h0(t) is the baseline 
    hazard function (a function of age only), [beta]2 is the 
    cumulative dose coefficient, and [beta]1 is a vector of 
    coefficients for other possible explanatory variables--here, cigarette 
    smoking status, race, and calendar year of death (Ex. 35-57). Cox 
    modeling is an approach that uses the experience of the cohort to 
    estimate an exposure-related effect, irrespective of an external 
    reference population or exposure categorization. Because they are 
    internally standardized, Cox models can sometimes eliminate concerns 
    about choosing an appropriate reference population and may be 
    advantageous when the characteristics of the cohort under study are not 
    well matched against reference populations for which age-related 
    background rates have been tabulated. Model C1 assumes the lung cancer 
    response is nonlinear with cumulative Cr(VI) exposure, whereas C2 
    assumes a linear lung cancer response with Cr(VI) exposure. For the Cox 
    proportional hazards models, C1 and C2, the other possible explanatory 
    variables considered were cigarette smoking status, race, and calendar 
    year of death.
        The externally standardized models E1 and E2 provided a good fit to 
    the data (p>=0.40). The choice of exposure grouping had little effect 
    on the parameter estimates of either model E1 or E2. However, the 
    choice of reference rates had some effect, notably on the 
    "background" parameter, C0, which was included as a fitted 
    parameter in the models to adjust for differences in background lung 
    cancer rates between cohort members and the reference populations. For 
    example, values of C0 greater than one "inflate" the base 
    reference rates, reducing the magnitude of excess risks in the model. 
    Such an adjustment was necessary for the Maryland reference population 
    (the maximum likelihood estimate of C0 was significantly 
    higher than one), but not for the Baltimore city reference population 
    (C0 was not significantly different from one). This result 
    suggests that the Maryland lung cancer rates may be lower than the 
    cohort's background lung cancer rates, but the Baltimore city rates may 
    adequately reflect the cohort background rates. The inclusion of the 
    C0 parameter yielded a cumulative dose coefficient that 
    reflected the effect of exposure and not the effect of differences in 
    background rates, and was appropriate.
        The model results indicated a relatively consistent cumulative dose 
    coefficient, regardless of reference population. The coefficient for 
    cumulative dose in the models ranged from 2.87 to 3.48 per mg/m\3\-yr 
    for the relative risk model, E1, and from 0.0061 to 0.0071 per mg/m\3\-
    person-yr for the additive risk model, E2. These coefficients determine 
    the slope of the linear cumulative Cr(VI) exposure-lung cancer response 
    relationship. In no case did a quadratic model fit the data better than 
    a linear model.
        Based on comparison of the models' AIC values, Environ indicated 
    that the linear relative risk model E1 was preferred over the additive 
    risk model E2. OSHA agrees with Environ's conclusion. The relative risk 
    model is also preferred over an additive risk model because the 
    background rate of lung cancer varies with age. It may not be 
    appropriate to assume, as an additive model does, that increased lung 
    cancer risk at age 25, where background risk is relatively low, would 
    be the same (for the same cumulative dose) as at age 65, where 
    background rates are much higher.
        The Cox proportional hazards models, C1 and C2, also fit the data 
    well (although the fit was slightly better for model C2 than C1). 
    Recall that for the Cox proportional hazards models, C1 and C2, the 
    other possible explanatory variables considered were cigarette smoking 
    status, race, and calendar year of death. For both models, addition of 
    a term for smoking status significantly improved the fit of the models 
    to the data (p< 0.00001). The experience with model C1 indicated that 
    race (p=0.15) and year of death (p=0.4) were not significant 
    contributors when cumulative dose and smoking status were included in 
    the model. Based on results for model C1, race and year of death were 
    not considered by Environ in the linear model C2. The cumulative dose 
    coefficient, [beta]2, was 1.00 for model C1 and 2.68 for 
    model C2. A more complete description of the models and variables can 
    be found in the 2003 Environ analysis (Ex. 33-12, p. 10).
        Lifetable calculations were made of the number of extra lung 
    cancers per 1000 workers exposed to Cr(VI) based on models E1, E2, C1, 
    and C2, assuming a constant exposure from age 20 through a maximum of 
    age 65. The lifetable accounted for both lung cancer risk and competing 
    mortality through age 100. Rates of lung cancer and other mortality for 
    the lifetable calculations were based, respectively, on 2000 U.S. lung 
    cancer and all-cause mortality rates for both sexes and all races. In 
    addition to the maximum likelihood estimates, 95% confidence intervals 
    for the excess lifetime risk were derived. Details about the procedures 
    used to estimate parameters, model fit, lifetable calculations, and 
    confidence intervals are described in the 2003 Environ report (Ex. 33-12, p. 8-9).
    BILLING CODE 4510-26-P

Table VI-2

 

    
    BILLING CODE 4510-26-C
    
        Table VI-2 shows each model's predictions of excess lifetime lung 
    cancer risk from a working lifetime of exposure to various Cr(VI) air 
    levels. The estimates are very consistent regardless of model, exposure 
    grouping, or reference population. The model that appears to generate 
    results least similar to the others is C1, which yielded one of the 
    higher risk estimates at 52 [mu]g/m3, but estimated the 
    lowest risks for exposure levels of 10 [mu]g/m3 or lower. 
    The change in magnitude, relative to the other models, is a result of 
    the nonlinearity of this model. Confidence limits for all models, 
    including C1, tend to overlap, suggesting a fair degree of statistical 
    consistency.
    2. National Institute for Occupational Safety and Health (NIOSH) Risk 
    Assessment
        NIOSH (Ex. 33-13) developed a risk assessment from the Gibb cohort. 
    The NIOSH analysis, like the 2003 Environ assessment, used the cohort 
    individual data files to compute cumulative Cr(VI) exposure. However, 
    NIOSH also explored some other exposure-related assumptions. For 
    example, they performed the dose-response analysis with lag times in 
    addition to the 5-year lag used by Environ. NIOSH also analyzed dose-
    response using as many as 50 exposure categories, although their report 
    presents data in five cumulative Cr(VI) exposure groupings.
        NIOSH incorporated information on the cohort smoking behavior in 
    their quantitative assessments. They estimated (packs/day)-years of 
    cumulative smoking for each individual in the cohort, using information 
    from a questionnaire that was administered at the time of each cohort 
    member's date of hire. To estimate cumulative smoking, NIOSH assumed 
    that the cohort members maintained the level of smoking reported in the 
    questionnaire from the age of 18 through the end of follow-up. 
    Individuals with unknown smoking status were assigned a value equal to 
    the average smoking level among all individuals with known smoking 
    levels (presumably including non-smokers). Individuals who were known 
    to smoke but for whom the amount was unknown were assigned a smoking 
    level equal to the average of all smokers.
        NIOSH considered six different relative risk models, fit to the 
    Gibb cohort data by Poisson regression methods. They did not consider 
    additive risk models. The six relative risk models were externally 
    standardized using age- and race-specific U.S. lung cancer rates. Their 
    background coefficients, C0, explicitly included smoking, 
    race, and age terms to adjust for differences between the cohort and 
    the reference population. These models are described as follows:
    
    NIOSH1a: Ni = C0 * Ei * exp(C1Di)
    NIOSH1b: Ni = C0 * Ei * exp(C1Di\1/2\\)
    NIOSH1c: Ni = C0 * Ei * exp(1 + C1Di + C2Di2)
    NIOSH1d: Ni = C0 * Ei * (1 + Di)[alpha]
    NIOSH1e: Ni = C0 * Ei * (1 + C1Di)
    NIOSH1f: Ni = C0 * Ei * (1 + C1Di[alpha])
    
    where the form of the equation has been modified to match the format 
    used in the Environ reports. In addition, NIOSH fit Cox proportional 
    hazard models (not presented) to the lung cancer mortality data using 
    the individual cumulative Cr(VI) exposure estimates.
        NIOSH reported that the linear relative risk model 1e generally 
    provided a superior fit to the exposure-response data when compared to 
    the various log linear models, 1a-d. Allowing some non-linearity (e.g., 
    model 1f) did not significantly improve the goodness-of-fit, therefore, 
    they considered the linear relative risk model form 1e (analogous to 
    the Environ model E1) to be the most appropriate for determining their 
    lifetime risk calculations. A similar fit could be achieved with a log-
    linear power model (model 1d) using log-transformed cumulative Cr(VI) 
    and a piece-wise linear specification for the cumulative smoking term.
        The dose coefficient (C1) for the linear relative risk 
    model 1e was estimated by NIOSH to be 1.444 per [mu]g CrO3/
    m3-yr (Ex. 33-13, Table 4). If the exposures were converted 
    to units of [mu]g Cr(VI)/m3-yr, the estimated cumulative 
    dose coefficient would be 2.78 (95% CI: 1.04 to 5.44) per [mu]g/
    m3-yr. This value is very close to the estimates derived in 
    the Environ 2003 analysis (maximum likelihood estimates ranging from 
    2.87 to 3.48 for model E1, depending on the exposure grouping and the 
    reference population). Lifetime risk estimates based on the NIOSH-
    estimated dose coefficient and the Environ lifetable method using 2000 
    U.S. rates for lung cancer and all cause mortality are shown in Table 
    VI-3. The values are very similar to the estimates predicted by the 
    Environ 2003 analysis (Table VI-3). The small difference may be due to 
    the NIOSH adjustment for smoking in the background coefficient. NIOSH 
    found that excess lifetime risks for a 45-year occupational exposure to 
    Cr(VI) predicted by the best-fitting power model gave very similar 
    risks to the preferred linear relative risk model at TWA Cr(VI) 
    concentrations between 0.52 and 52 [mu]g/m3 (Ex. 33-13, 
    Table 5). Although NIOSH did not report the results, they stated that 
    Cox modeling produced risk estimates similar to the Poisson regression. 
    The consistency between Cox and Poisson regression modeling is 
    discussed further in section VI.C.4.
    BILLING CODE 4510-26-P

Table VI-3

 

    
    BILLING CODE 4510-26-C
        NIOSH reported a significantly higher dose-response coefficient for 
    nonwhite workers than for white workers. That is, nonwhite workers in 
    the Gibb cohort are estimated to have a higher excess risk of lung 
    cancer than white workers, given equal cumulative exposure to Cr(VI). 
    In contrast, no significant race difference was found in the Cox 
    proportional hazards analysis reported by 2003 Environ.
    
    3. Exponent Risk Assessment
        In response to OSHA's Request For Information, Exponent prepared an 
    analysis of lung cancer mortality from the Gibb cohort. Like the 2003 
    Environ and NIOSH analyses, the Exponent analysis relied on the 
    individual worker data. Exponent performed their dose-response analyses 
    based on three different sets of exposure categories using two 
    reference populations and 70,808 person-years of follow-up. A total of 
    four analyses were completed, using (1) Maryland reference rates and 
    the four Gibb et al. exposure categories; (2) Baltimore reference rates 
    and the four Gibb et al. exposure categories; (3) Baltimore reference 
    rates and six exposure groups defined by Exponent; and (4) Baltimore 
    City reference rates and five exposure categories, obtained by removing 
    the highest of the six groups defined by Exponent from the dose-
    response analysis. A linear relative risk model without a background 
    correction term (the term C0 used by Environ and NIOSH) was 
    applied in all of these cases and cumulative exposures were lagged five 
    years (as done by Environ and NIOSH). The analyses showed excess 
    lifetime risk between 6 and 14 per 1000 for workers exposed to 1 [mu]g/
    m\3\ Cr(VI) for 45 years.
        The analysis using Maryland reference lung cancer rates and the 
    Gibb et al. four-category exposure grouping yielded an excess lifetime 
    risk of 14 per 1000. This risk, which is higher than the excess 
    lifetime risk estimates by Environ and NIOSH for the same occupational 
    exposure, probably results from the absence of a background rate 
    coefficient (C0) in Exponent's model. As reported in the 
    Environ 2002 and 2003 analyses, the Maryland reference lung cancer 
    rates require a background rate coefficient greater than 1 to achieve 
    the best fit to the exposure-response data. The unadjusted Maryland 
    rates probably underestimate the cohort's background lung cancer rate, 
    leading to overestimation of the risk attributable to cumulative Cr(VI) 
    exposure.
        The two analyses that used Baltimore reference rates and either 
    Exponent's six-category exposure grouping or the Gibb et al. four-
    category grouping both resulted in an excess lifetime unit risk of 9 
    per 1000 for workers exposed to 1 [mu]g/m\3\ Cr(VI) for 45 years (Ex. 
    31-18-15-1, p. 41). This risk is close to estimates reported by Environ 
    using their relative risk model (E1) and Baltimore reference rates for 
    the same occupational exposure (Table VI-2). The Environ analysis 
    showed that, unlike the Maryland-standardized model discussed above, 
    the Baltimore-standardized models had background rate coefficients very 
    close to 1, the "default" value assumed by the Exponent relative risk 
    model. This suggests that the Baltimore reference rates may represent 
    the background lung cancer rate for this cohort more accurately than 
    the Maryland reference rates.
        The lowest excess lifetime unit risk for workers exposed to 1 
    [mu]g/m\3\ Cr(VI) for 45 years reported by Exponent, at 6 per 1000, was 
    derived from the analysis that excluded the highest of Exponent's six 
    exposure groups. While this risk value is close to the Environ and 
    NIOSH unit risk estimates, the analysis merits some concern. Exponent 
    eliminated the highest exposure group on the basis that most cumulative 
    exposures in this group were higher than exposures usually found in 
    current workplace conditions. However, eliminating this group could 
    exclude possible long-term exposures (e.g., >15 years) below the 
    previous OSHA PEL (52 [mu]g/m\3\ ) from the risk analysis. Moreover, no 
    matter what current exposures might be, data on higher cumulative 
    exposures are relevant for understanding the dose-response 
    relationships.
        In addition, the Exponent six category cumulative exposure grouping 
    may have led to an underestimate of the dose effect. The definition of 
    Exponent's six exposure groups was not related to the distribution of 
    cumulative exposure associated with individual person-years, but rather 
    to the distribution of cumulative exposure among the workers at the end 
    of their employment. This division does not result in either a uniform 
    distribution of person-years or observed lung cancer cases among 
    exposure categories. In fact, the six category exposure groupings of 
    both person-years and observed lung cancers were very uneven, with a 
    preponderance of both allocated to the lowest exposure group. This 
    skewed distribution of person-years and observed cases puts most of the 
    power for detecting significant differences from background cancer 
    rates at low exposure levels, where these differences are expected to 
    be small, and reduces the power to detect any significant differences 
    from background at higher exposure concentrations.
    4. Summary of Risk Assessments Based on the Gibb Cohort
        OSHA finds remarkable consistency among the risk estimates from the 
    various quantitative analyses of the Gibb cohort. Both Environ and 
    NIOSH determined that linear relative risk models generally provided a 
    superior fit to the data when compared to other relative risk models, 
    although the confidence intervals in the non-linear Cox model reported 
    by Environ overlapped with the confidence intervals in their linear 
    models. The Environ 2003 analysis further suggested that a linear 
    additive risk model could adequately describe the observed dose-
    response data. The risk estimates for NIOSH and Environ's best-fitting 
    models were statistically consistent (compare Tables VI-2 and VI-3).
        The choice of reference population had little impact on the risk 
    estimates. NIOSH used the entire U.S. population as the reference, but 
    included adjustment terms for smoking, age and race in its models. The 
    Environ 2003 analysis used both Maryland and Baltimore reference lung 
    cancer rates, and included a generic background coefficient 
    C0 to adjust for potential differences in background risk 
    between the reference population and the worker cohort. This term was 
    significant in the fitted model when Maryland rates were used for 
    external standardization, but not when Baltimore rates were used. Since 
    no adjustment in the model background term was required to better fit 
    the exposure-response data using Baltimore City lung cancer rates, they 
    may best represent the cohort's true background lung cancer incidence. 
    OSHA considers the inclusion of such adjustment factors, whether 
    specific to smoking, race, and age (as defined by NIOSH), or generic 
    (as defined by Environ), to be appropriate and believes they contribute 
    to accurate risk estimation by helping to correct for confounding risk 
    factors. The Cox proportional hazard models, especially the linear Cox 
    model, yielded risk estimates that were generally consistent with the 
    externally standardized models.
        Finally, the number of exposure categories used in the analysis had 
    little impact on the risk estimates. When an appropriate adjustment to 
    the background rates was included, the four exposure groups originally 
    defined by Gibb et al. and analyzed in the 2002 Environ report, the six 
    exposure groups defined by Exponent, the two alternate sets of ten 
    exposure categories as defined in the 2003 Environ analysis, and the 
    fifty groups defined and aggregated by NIOSH all gave essentially the 
    same risk estimates. The robustness of the results to various 
    categorizations of cumulative exposure adds credence to the risk 
    projections.
        Having reviewed the analyses described in this section, OSHA finds 
    that the best estimates of excess lung cancer risk to workers exposed 
    to the previous PEL (52 [mu]g Cr(VI)/m3) for a
    working lifetime are about 300 to 400 per thousand based on data from 
    the Gibb cohort. The best estimates of excess lung cancer risks to 
    workers exposed to other TWA exposure concentrations are presented in 
    Table VI-2. These estimates are consistent with predictions from 
    Environ, NIOSH and Exponent models that applied linear relative and 
    additive risk models based on the full range of cumulative Cr(VI) 
    exposures experienced by the Gibb cohort and used appropriate 
    adjustment terms for the background lung cancer mortality rates.
    
    D. Quantitative Risk Assessments Based on the Luippold Cohort
    
        As discussed earlier, Luippold et al. (Exs. 35-204; 33-10) provided 
    information about the cohort of workers employed in a chromate 
    production plant in Painesville, Ohio. Follow-up for the 482 members of 
    the Luippold cohort started in 1940 and lasted through 1997, with 
    accumulation of person-years for any individual starting one year after 
    the beginning of his first exposure. There were 14,048 total person-
    years of follow-up for the cohort. The person-years were then divided 
    into five exposure groups that had approximately equal numbers of 
    expected lung cancers in each group. Ohio reference rates were used to 
    compute expected numbers of deaths. White male rates were used because 
    the number of women was small (4 out of 482) and race was known to be 
    white for 241 of 257 members of the cohort who died and for whom death 
    certificates were available. The 1960-64 Ohio rates (the earliest 
    available) were assumed to hold for the time period from 1940 to 1960. 
    Rates from 1990-94 were assumed to hold for the period after 1994. For 
    years between 1960 and 1990, rates from the corresponding five-year 
    summary were used. There were significant trends for lung cancer SMR as 
    a function of year of hire, duration of employment, and cumulative 
    Cr(VI) exposure. The cohort had a significantly increased SMR for lung 
    cancer deaths of 241 (95% C.I. 180 to 317).

Table VI-4

 

    
        Environ conducted a risk assessment based on the cumulative Cr(VI) 
    exposure-lung cancer mortality data from Luippold et al. and presented 
    in Table VI-4 (Ex. 33-15). Cumulative Cr(VI) exposures were categorized 
    into five groups with about four expected lung cancer deaths in each 
    group. In the absence of information to the contrary, Environ assumed 
    Luippold et al. did not employ any lag time in determining the 
    cumulative exposures. The calculated
    and expected numbers of lung cancers were derived from Ohio reference 
    rates. Environ applied the relative and additive risk models, E1 and 
    E2, to the data in Table VI-4.
        Linear relative and additive risk models fit the Luippold cohort 
    data adequately (p>=0.25). The final models did not include the 
    quadratic exposure coefficient, C2, or the background rate 
    parameter, C0, as they did not significantly improve the fit 
    of the models. The maximum likelihood estimates for the Cr(VI) 
    exposure-related parameter, C1, of the linear relative and 
    additive risk models were 0.88 per mg/m3-yr and 0.0014 per 
    mg/m3-person-yr, respectively. The C1 estimates 
    based on the Luippold cohort data were about 2.5-fold lower than the 
    parameter estimates based on the Gibb cohort data. The excess lifetime 
    risk estimate calculated by Environ for a 45-year working-lifetime 
    exposure to 1 [mu]g Cr(VI)/m3 (e.g., the unit risk) for both 
    models was 2.2 per 1000 workers (95% confidence intervals from 1.3 to 
    3.5 per 1000 for the relative risk model and 1.2 to 3.4 per 1000 for 
    the additive risk model) using a lifetable analysis with 1998 U.S. 
    mortality reference rates. These risks were 2.5 to 3-fold lower than 
    the projected unit risks based on the Gibb data set for equivalent 
    cumulative Cr(VI) exposures.
        Crump et al. (Exs. 33-15; 35-58; 31-18) also performed an exposure-
    response analysis from the Painesville data. In a Poisson regression 
    analysis, cumulative exposures were grouped into ten exposure 
    categories with approximately two expected lung cancer deaths in each 
    group. The observed and expected lung cancer deaths by Cr(VI) exposure 
    category are shown in Table VI-5. Ohio reference rates were used in 
    calculating the expected lung cancer deaths and cumulative exposures 
    were lagged five years.

Table VI-5

 

    
        The Crump et al. analysis used the same linear relative risk and 
    additive risk models as Environ on the individual data categorized into 
    the ten cumulative exposure groups (Ex. 35-58). Tests for systematic 
    departure from
    linearity were non-significant for both models (p>=0.11). The 
    cumulative dose coefficient determined by the maximum likelihood method 
    was 0.79 (95% CI: 0.47 to 1.19) per mg/m3-yr for the 
    relative risk model and 0.0016 (95% CI: 0.00098 to 0.0024) per mg/
    m3-person-yr for the additive risk model, respectively. The 
    authors noted that application of the linear models to five and seven 
    exposure groups resulted in no significant difference in dose 
    coefficients, although the results were not presented. The exposure 
    coefficients reported by Crump et al. were very similar to those 
    obtained by Environ above, although different exposure groups were used 
    and Crump et al. used a five-year lag for the cumulative exposure 
    calculation. The authors noted that the linear models did not fit the 
    exposure data grouped into ten categories very well (goodness-of-fit 
    p< =0.01) but fit the data much better with seven exposure groups 
    (p>0.3), replacing the many lower exposure categories where there were 
    few observed and expected cancers with more stable exposure groupings 
    with greater numbers of cancers. The reduction in number of exposure 
    groups did not substantially change the fitted exposure coefficients.
        The maximum likelihood estimate for the cumulative exposure 
    coefficient using the linear Cox regression model C2 was 0.66 (90% CI: 
    0.11 to 1.21), which was similar to the linear [Poisson regression] 
    relative risk model. When the Cox analysis was restricted to the 197 
    workers with known smoking status and a smoking variable in the model, 
    the dose coefficient for Cr(VI) was nearly identical to the estimate 
    without controlling for smoking. This led the authors to conclude that 
    "the available smoking data did not suggest that exposure to Cr(VI) 
    was confounded with smoking in this cohort, or that failure to control 
    for smoking had an appreciable effect upon the estimated carcinogenic 
    potency of Cr(VI)" (Ex. 35-58, p. 1156).
        Given the similarity in results, OSHA believes it is reasonable to 
    use the exposure coefficients reported by Crump et al. based on their 
    groupings of the individual cumulative exposure data to estimate excess 
    lifetime risk from the Luippold cohort. Table VI-6 presents the excess 
    risk for a working lifetime exposure to various TWA Cr(VI) levels as 
    predicted by Crump et al.'s relative and additive risk models using a 
    lifetable analysis with 2000 U.S. rates for all causes and lung cancer 
    mortality. The resulting maximum likelihood estimates indicate that 
    working lifetime exposures to the previous Cr(VI) PEL would result in 
    excess lifetime lung cancer risks around 100 per 1000 (95% C.I. approx. 
    60-150). The risk estimates based on the Luippold cohort are lower than 
    the risk estimates based on the Gibb cohort, as discussed further in 
    section VI.F.
    BILLING CODE 4510-26-P

Table VI-6

 

    
    BILLING CODE 4510-26-C
    
    E. Quantitative Risk Assessments Based on the Mancuso, Hayes, Gerin, 
    and Alexander Cohorts
    
        In addition to the preferred data sets analyzed above, there are 
    four other cohorts with available data sets for estimation of 
    additional lifetime risk of lung cancer. These are the Mancuso cohort, 
    the Hayes cohort, the Gerin cohort, and the Alexander cohort. Environ 
    did exposure-response analysis for all but the Hayes cohort (Ex. 33-
    15). Several years earlier, the K.S. Crump Division did quantitative 
    assessments on data from the Mancuso and Hayes cohort, under contract 
    with OSHA (Ex.13-5). The U.S. EPA developed quantitative risk 
    assessments from the Mancuso cohort data for its Integrated Risk 
    Information System (Exs. 19-1; 35-52). The California EPA (Ex. 35-54), 
    Public Citizen Health Research Group (Ex. 1), and the U.S. Air Force 
    Armstrong Laboratory (AFAL) for the Department of Defense (Ex. 35-51) 
    performed assessments from the Mancuso data using the 1984 U.S. EPA 
    risk estimates as their starting point. The U.S. EPA also published a 
    risk assessment based on the Hayes cohort data (Ex. 7-102). Until the 
    cohort studies of Gibb et al. and Luippold et al. became available, 
    these earlier assessments provided the most current projected cancer 
    risks from airborne exposure to Cr(VI). The previous risk assessments 
    were extensively described in the NPRM sections VI.E.1 and VI.E.2 (69 
    FR at 59375-59378). While the risk estimates from Mancuso, Hayes, 
    Gerin, and Alexander data sets are associated with a greater degree of 
    uncertainty, it is nevertheless valuable to compare them to the risk 
    estimates from the higher quality Gibb and Luippold data sets in order 
    to determine if serious discrepancies exist between them. OSHA believes 
    evaluating consistency in risk among several worker cohorts adds to the 
    overall quality of the assessment.
        The Mancuso and Luippold cohorts each worked at the Painesville 
    plant but the worker populations did not overlap due to different 
    selection criteria. Exposure estimates were also based on different 
    industrial hygiene surveys. The Hayes and Gibb cohorts both worked at 
    the Baltimore plant. Even though Cr(VI) exposures were reconstructed 
    from monitoring data measured at different facilities resulting in 
    significantly different exposure-response functions (see section VI.F), 
    there was some overlap in the two study populations. As a result, the 
    projected risks from these data sets can not strictly be viewed as 
    independent estimates. The Gerin and Alexander cohorts were not 
    chromate production workers and are completely independent from the 
    Gibb and Luippold data sets. The quantitative assessment of the four 
    data sets and comparison with the risk assessments based on the Gibb 
    and Luippold cohorts are discussed below.
    1. Mancuso Cohort
        As described in subsection VII.B.3, the Mancuso cohort was 
    initially defined in 1975 and updated in 1997. The cohort members were 
    hired between 1931 and 1937 and worked at the same Painesville facility 
    as the Luippold cohort workers. However, there was no overlap between 
    the two cohorts since all Luippold cohort workers were hired after 
    1939. The quantitative risk assessment by Environ used data reported in 
    the 1997 update (Ex. 23, Table XII) in which lung cancer deaths and 
    person-years of follow-up were classified into four groups of 
    cumulative exposure to soluble chromium, assumed to represent Cr(VI) 
    (Ex. 33-15). The mortality data and person-years were further broken 
    down by age of death in five year increments starting with age interval 
    40 to 44 years and going up to >75 years. No expected numbers of lung 
    cancers were computed, either for the cohort as a whole or for specific 
    groups of person-years. Environ applied an indirect method based on the 
    recorded median age and year of entry into the cohort to estimate age 
    information necessary to derive expected numbers of age- and calendar 
    year-adjusted lung cancers deaths required to complete the risk 
    assessment.
        Observed and expected lung cancer deaths by age and cumulative 
    exposure (mg/m\3\-yr) are presented in Table 3 of the 2002 Environ 
    report (Ex. 33-15, p. 39). The mean cumulative exposures to soluble 
    Cr(VI) were assumed to be equal to the midpoints of the tabulated 
    ranges. No lag was used for calculating the cumulative exposures. 
    Environ applied externally standardized risk models to these data, 
    similar to those described in section VI.C.1 but using an age-related 
    parameter, as discussed in the 2002 report (Ex. 33-15, p. 39). The 
    externally-standardized linear relative risk model with an age-
    dependent exposure term provided a superior fit over the other models.
        The predicted excess risk of lung cancer from a 45-year working 
    lifetime of exposure to Cr(VI) at the previous OSHA PEL using the best-
    fitting linear relative risk model is 293 per 1000 workers (95% C.I. 
    188 to 403). The maximum likelihood estimate from working lifetime 
    exposure to new PEL of 5.0 [mu]g/m\3\ Cr(VI) is 34 per 1000 workers 
    (95% C.I. 20 to 52 per 1000). These estimates are close to those 
    predicted from the Gibb cohort but are higher than predicted from the 
    Luippold cohort.
        There are uncertainties associated with both the exposure estimates 
    and the estimates of expected numbers of lung cancer deaths for the 
    1997 Mancuso data set. The estimates of exposure were derived from a 
    single set of measurements obtained in 1949 (Ex. 7-98). Although little 
    prior air monitoring data were available, it is thought that the 1949 
    air levels probably understate the Cr(VI) concentrations in the plant 
    during some of the 1930s and much of the 1940s when chromate production 
    was high to support the war. The sampling methodology used by Bourne 
    and Yee only measured soluble Cr(VI), but it is believed that the 
    chromate production process employed at the Painesville plant in these 
    early years yielded slightly soluble and insoluble Cr(VI) compounds 
    that would not be fully accounted for in the sampling results (Ex. 35-
    61). This would imply that risks would be overestimated by use of 
    concentration estimates that were biased low. However, it is possible 
    that the 1949 measurements did not underestimate the Cr(VI) air levels 
    in the early 1930s prior to the high production years. Some older 
    cohort members were also undoubtedly exposed to less Cr(VI) in the 
    1950s than measured in 1949 survey.
        Another uncertainty in the risk assessment for the Mancuso cohort 
    is associated with the post-hoc estimation of expected numbers of lung 
    cancer deaths. The expected lung cancers were derived based on 
    approximate summaries of the ages and assumed start times of the cohort 
    members. Several assumptions were dictated by reliance on the published 
    groupings of results (e.g., ages at entry, calendar year of entry, age 
    at end of follow-up, etc.) as well as by the particular choices for 
    reference mortality rates (e.g., U.S. rates, in particular years close 
    to the approximated time at which the person-years were accrued). Since 
    the validity of these assumptions could not be tested, the estimates of 
    expected numbers of lung cancer deaths are uncertain.
        There is also a potential healthy worker survivor effect in the 
    Mancuso cohort. The cohort was identified as workers first hired in the 
    1930s based on employment records surveyed in the late 1940s (Ex. 2-
    16). The historical company files in this time period were
    believed to be sparse and more likely to only identify employees still 
    working at the plant in the 1940s (Ex. 33-10). If there was a sizable 
    number of unidentified short-term workers who were hired but left the 
    plant in the 1930s or who died before 1940 (i.e. prior to systematic 
    death registration), then there may have been a selection bias (i.e., 
    healthy worker survivor effect) toward longer-term, healthier 
    individuals (Ex. 35-60). Since the mortality of these long-term 
    "survivors" is often more strongly represented in the higher 
    cumulative exposures, it can negatively confound the exposure-response 
    and lead to an underestimation of risk, particularly to shorter-term 
    workers (Ex. 35-63). This may be an issue with the Mancuso cohort, 
    although the magnitude of the potential underestimation is unclear.
        Earlier quantitative risk assessments by the K.S. Crump Division, 
    EPA, and others were done on cohort data presented in the 1975 Mancuso 
    report (Ex. 7-11). These assessments did not have access to the 20 
    additional years of follow-up nor did they have age-grouped lung cancer 
    mortality stratified by cumulative soluble chromium (presumed Cr(VI)) 
    exposure), which was presented later in the 1997 update. Instead, age-
    grouped lung cancer mortality was stratified by cumulative exposure to 
    total chromium that included not only carcinogenic Cr(VI) but 
    substantial amounts of non-carcinogenic Cr(III). OSHA believes that the 
    Environ quantitative risk assessment is the most credible analysis from 
    the Mancuso cohort. It relied on the updated cohort mortality data and 
    cumulative exposure estimates derived directly from air measurements of 
    soluble chromium.
    2. Hayes Cohort
        The K.S. Crump Division (Ex. 13-5) assessed risk based on the 
    exposure-response data reported in Table IV by Braver et al. (Ex. 7-17) 
    for the cohort studied by Hayes et al. (Ex. 7-14). The Hayes cohort 
    overlapped with the Gibb cohort. The Hayes cohort included 734 members, 
    not part of the Gibb cohort, who worked at an older facility from 1945 
    to 1950 but did not work at the newer production facility built in 
    August 1950. The Hayes cohort excluded 990 members of the Gibb cohort 
    who worked less than 90 days in the new production facility after 
    August 1950. As noted in section VI.B.4, Braver et al. derived a single 
    cumulative soluble Cr(VI) exposure estimate for each of four subcohorts 
    of chromate production workers categorized by duration of employment 
    and year of hire by Hayes et al. Thus, exposures were not determined 
    for individual workers using a more comprehensive job exposure matrix 
    procedure, as was done for the Gibb and Luippold cohorts. In addition, 
    the exposures were estimated from air monitoring conducted only during 
    the first five of the fifteen years the plant was in operation. Unlike 
    the Mancuso cohort, Hayes et al. did not stratify the observed lung 
    cancer deaths by age group. The expected number of lung cancer deaths 
    for each subcohort was based on the mortality statistics from 
    Baltimore.
        The K.S. Crump Division applied the externally standardized linear 
    relative risk approach to fit the exposure-response data (Ex. 13-5). 
    The maximum likelihood estimate for the dose coefficient (e.g., 
    projected linear slope of the Cr(VI) exposure-response curve) was 0.75 
    per mg Cr(VI)/m\3\-yr with a 90% confidence bound of between 0.45 and 
    1.1 per mg Cr(VI)/m\3\-yr. These confidence bounds are consistent with 
    the dose coefficient estimate obtained from modeling the Luippold 
    cohort data (0.83, 95% CI: 0.55 to 1.2) but lower than that from the 
    Gibb cohort data (3.5, 95% CI: 1.5 to 6.0). The linear relative risk 
    model fit the Hayes cohort data well (p=0.50). The K.S. Crump Division 
    predicted the excess risk from occupational exposure to Cr(VI) for a 45 
    year working lifetime at the previous OSHA PEL (52 [mu]g/m\3\) to be 88 
    lung cancer cases per 1000 workers (95% CI: 61 to 141). Predicted 
    excess risk at the new PEL of 5 [mu]g/m\3\ is about 9 excess lung 
    cancer deaths per 1000 (95% CI: 6.1 to 16) for the same duration of 
    occupational exposure. These estimates are somewhat lower than the 
    corresponding estimates based on the Gibb cohort data, probably because 
    of the rather high average soluble Cr(VI) level (218 [mu]g/m\3\) 
    assumed by Braver et al. for plant workers throughout the 1950s. If 
    these assumed air levels led to an overestimate of worker exposure, the 
    resulting risks would be underestimated.
    3. Gerin Cohort
        Environ (Ex. 33-15) did a quantitative assessment of the observed 
    and expected lung cancer deaths in stainless steel welders classified 
    into four cumulative Cr(VI) exposure groups reported in Tables 2 and 3 
    of Gerin et al. (Ex. 7-120). The lung cancer data came from a large 
    combined multi-center welding study in which a statistically 
    significant excess lung cancer risk was observed for the whole cohort 
    and non-statistically significant elevated lung cancer mortality was 
    found for the stainless steel welder subcohorts (Ex. 7-114). A positive 
    relationship with time since first exposure was also observed for the 
    stainless steel welders (the type of welding with the highest exposure 
    to Cr(VI)) but not with duration of employment.
        The exposure-response data from the Gerin study was only presented 
    for those stainless steel welders with at least five years employment. 
    Workers were divided into "ever stainless steel welders" and 
    "predominantly stainless steel welders" groups. The latter group were 
    persons known to have had extended time welding stainless steel only or 
    to have been employed by a company that predominantly worked stainless 
    steel. As stated in section VI.B.5, the cumulative exposure estimates 
    were not based on Cr(VI) air levels specifically measured in the cohort 
    workers, and therefore are subject to greater uncertainty than exposure 
    estimates from the chromate production cohort studies. Environ 
    restricted their analysis to the "ever stainless steel welders" since 
    that subcohort had the greater number of eligible subjects and person-
    years of follow-up, especially in the important lower cumulative 
    exposure ranges. The person-years, observed numbers of lung cancers, 
    and expected numbers of lung cancers were computed starting 20 years 
    after the start of employment. Gerin et al. provided exposure-response 
    data on welders with individual work histories (about two-thirds of the 
    workers) as well as the entire subcohort. Regardless of the subcohort 
    examined, there was no obvious indication of a Cr(VI) exposure-related 
    effect on lung cancer mortality. A plausible explanation for this 
    apparent lack of exposure-response is the potentially severe exposure 
    misclassification resulting from the use of exposure estimates based on 
    the welding literature (rather than exposure measurements at the plants 
    used in the study, which were not available to the authors).
        Environ used externally standardized models to fit the data (Ex. 
    33-15). They assumed that the cumulative Cr(VI) exposure for the 
    workers was at the midpoint of the reported range. A value of 2.5 mg/
    m\3\-yr was assumed for the highest exposure group (e.g., >0.5 mg/m\3\-
    yr), since Gerin et al. cited it as the mean value for the group, which 
    they noted to also include the "predominantly stainless steel 
    welders". All models fit the data adequately (p>0.28) with exposure 
    coefficients considerably lower than for the Gibb or Luippold cohorts 
    (Ex. 33-15, Table 6). In fact, the 95% confidence intervals for the 
    exposure coefficients overlapped 0, which would be expected when there 
    is no exposure-related trend.
        Based on the best fitting model, a linear relative risk model (Ex. 
    33-15, Table 9, p. 44), the projected excess risk of lung cancer from a 
    working lifetime exposure to Cr(VI) at the previous PEL was 46 (95% CI: 
    0 to 130) cases per 1000 workers. The 95 percent confidence interval 
    around the maximum likelihood estimate reflects the statistical 
    uncertainty associated with risk estimates from the Gerin cohort.
        Following the publication of the proposed rule, OSHA received 
    comments from Exponent (on behalf of a group of steel industry 
    representatives) stating that it is not appropriate to model exposure-
    response for this cohort because there was not a statistically 
    significant trend in lung cancer risk with estimated exposure, and risk 
    of lung cancer did not increase monotonically with estimated exposure 
    (Ex. 38-233-4, pp. 7-8). OSHA disagrees. Because the best-fitting model 
    tested by Environ fit the Gerin data adequately, OSHA believes that it 
    is reasonable to generate risk estimates based on this model for 
    comparison with the risk estimates based on the Gibb and Luippold 
    cohorts. This allows OSHA to quantitatively assess the consistency 
    between its preferred estimates and risk estimates derived from the 
    Gerin cohort.
        In post-hearing comments, Dr. Herman Gibb expressed support for 
    OSHA's approach. Dr. Gibb stated:
    
        The epidemiologic studies of welders * * * conducted to date 
    have been limited in their ability to evaluate a lung cancer risk. 
    It is conceivable that differences in exposure * * * between [this 
    industry] and the chromate production industry could lead to 
    differences in cancer risk. Because there aren't adequate data with 
    which to evaluate these differences, it is appropriate to compare 
    the upper bounds [on risk] derived from the Gerin et al. * * * 
    [study] with those predicted from the chromate production workers to 
    determine if they are consistent.
    
        OSHA agrees with Exponent that the results of the Gerin et al. 
    study were different from those of the Luippold (2003) and Gibb 
    cohorts, in that a statistically significant exposure-response 
    relationship and a monotonically increasing lung cancer risk with 
    exposure were not found in Gerin. Also, the maximum likelihood risk 
    estimates based on the Gerin cohort were somewhat lower than those 
    based on the Gibb and Luippold cohorts. However, OSHA believes the 
    lower risk estimates from the Gerin cohort may be explained by the 
    strong potential for bias due to Cr(VI) exposure misclassification and 
    possibly by the presence of co-exposures, as discussed in sections 
    VI.B.5 and VI.G.4. Part of the difference may also relate to 
    statistical uncertainty; note that the 95% confidence intervals (shown 
    in Table VI-7) overlap the lower end of OSHA's range based on the 
    preferred Gibb and Luippold (2003) studies.
    4. Alexander Cohort
        Environ (Ex. 33-15) did a quantitative assessment of the observed 
    and expected lung cancer incidence among aerospace workers exposed to 
    Cr(VI) classified into four cumulative chromate exposure groups, 
    reported in Table 4 of Alexander et al. (Ex. 31-16-3). The authors 
    stated that they derived "estimates of exposure to chromium [VI]" 
    based on the TWA measurements, but later on referred to "the index of 
    cumulative total chromate exposure (italics added) reported as [mu]g/
    m\3\ chromate TWA-years" (Ex. 31-16-3, p. 1254). Alexander et al. 
    grouped the lung cancer data by cumulative exposure with and without a 
    ten year lag period. They found no statistically significant elevation 
    in lung cancer incidence among the chromate-exposed workers or clear 
    trend with cumulative chromate exposure.
        For their analysis, Environ assumed that the cumulative exposures 
    were expressed in [mu]g/m\3\-yr of Cr(VI), rather than chromate 
    (CrO4-2) or chromic acid (CrO3). 
    Environ used an externally standardized linear relative risk model to 
    fit the unlagged data (Ex. 33-15). An additive risk model could not be 
    applied because person-years of observation were not reported by 
    Alexander et al. Environ assumed that workers were exposed to a 
    cumulative Cr(VI) exposure at the midpoint of the reported ranges. For 
    the open-ended high exposure category, Environ assumed a cumulative 
    exposure 1.5 times greater than the lower limit of 0.18 mg/m\3\-yr. The 
    model fit the data poorly (p=0.04) and the exposure coefficient was 
    considered to be 0 since positive values did not significantly improve 
    the fit. Given the lack of a positive trend between lung cancer 
    incidence and cumulative Cr(VI) exposure for this cohort, these results 
    are not surprising.
        Following the publication of the proposed rule, OSHA received 
    comments from Exponent (on behalf of the Aerospace Industries 
    Association) stating that the Agency should not apply a linear model to 
    the Alexander et al. study to derive risk estimates for comparison with 
    the estimates based on the Gibb and Luippold (2003) cohorts (Ex. 38-
    215-2, p. 10). Due to the poor fit of Environ's exposure-response model 
    to the Alexander cohort data, OSHA agrees with Exponent in this matter. 
    Risk estimates based on Alexander et al. are therefore not presented in 
    this risk assessment.
        OSHA believes that there are several possible reasons for the lack 
    of a positive association between Cr(VI) exposure and lung cancer 
    incidence in this cohort. First, follow-up time was extremely short, 
    averaging 8.9 years per cohort member. Long-term follow-up of cohort 
    members is particularly important for determining the risk of lung 
    cancer, which typically has an extended latency period of roughly 20 
    years or more. One would not necessarily expect to see excess lung 
    cancer or an exposure-response relationship among workers who had been 
    followed less than 20 years since their first exposure to Cr(VI), as 
    most exposure-related cancers would not yet have appeared. Other 
    possible reasons that an exposure-response relationship was not 
    observed in the Alexander cohort include the young age of the cohort 
    members (median 42 years at end of follow-up), which also suggests that 
    occupational lung cancers may not yet have appeared among many cohort 
    members. The estimation of cumulative Cr(VI) exposure was also 
    problematic, drawing on air measurement data that did not span the 
    entire employment period of the cohort (there were no data for 1940 to 
    1974) and were heavily grouped into a relatively small number of 
    "summary" TWA concentrations that did not capture individual 
    differences in workplace exposures to Cr(VI).
    
    F. Summary of Risk Estimates Based on Gibb, Luippold, and Additional 
    Cohorts
    
        OSHA believes that the best estimates of excess lifetime lung 
    cancer risks are derived from the Gibb and Luippold cohorts. Due to 
    their large size and long follow-up, these two cohorts accumulated a 
    substantial number of lung cancer deaths that were extensively examined 
    by several different analyses using a variety of statistical 
    approaches. Cohort exposures were reconstructed from air measurements 
    and job histories over three or four decades. The linear relative risk 
    model fit the Gibb and Luippold data sets well. It adequately fit 
    several epidemiological data sets used for comparative analysis. 
    Environ and NIOSH explored a variety of nonlinear dose-response forms, 
    but none provided a statistically significant improvement over the 
    linear relative risk model.
        The maximum likelihood estimates from a linear relative risk model 
    fit to the Gibb data are three- to five-fold higher than estimates 
    based on the Luippold data at equivalent cumulative
    Cr(VI) exposures and the confidence limits around the projected risks 
    from the two data sets do not overlap. This indicates that the maximum 
    likelihood estimates derived from one data set are unlikely to describe 
    the lung cancer mortality observed in the other data set. Despite this 
    statistical inconsistency between the risk estimates, the differences 
    between them are not unreasonably great given the potential 
    uncertainties involved in estimating cancer risk from the data (see 
    section VI.G). Since the analyses based on these two cohorts are each 
    of high quality and their projected risks are reasonably close (well 
    within an order of magnitude), OSHA believes the excess lifetime risk 
    of lung cancer from occupational exposure to Cr(VI) is best represented 
    by the range of risks that lie between maximum likelihood estimates of 
    the Gibb and Luippold data sets.

Table VI-7 Part 1

 

Table VI-7 Part 2

 

    
    BILLING CODE 4510-26-C
    
        OSHA's best estimates of excess lung cancer cases from a 45-year 
    working lifetime exposure to Cr(VI) are presented in Table VI-7. As 
    previously discussed, several acceptable assessments of the Gibb data 
    set were performed, with similar results. The 2003 Environ model E1, 
    applying the Baltimore City reference population and ten exposure 
    categories based on a roughly equal number of person-years per group, 
    was selected to represent the range of best risk estimates derived from 
    the Gibb cohort, in part because this assessment employed an approach 
    most consistent with the exposure grouping applied in the Luippold 
    analysis (see Table VI-6). To characterize the statistical uncertainty 
    of OSHA's risk estimates, Table VI-7 also presents the 95% confidence 
    limits associated with the maximum likelihood risk estimates from the 
    Gibb cohort and the Luippold cohort.
        OSHA finds that the most likely lifetime excess risk at the 
    previous PEL of 52 [mu]g/m\3\ Cr(VI) lies between 101 per 1000 and 351 
    per 1000, as shown in Table VI-7. That is, OSHA predicts that between 
    101 and 351 of 1000 workers occupationally exposed for 45 years at the 
    previous PEL would develop lung cancer as a result of their exposure. 
    The wider range of 62 per 1000 (lower 95% confidence bound, Luippold 
    cohort) to 493 per 1000 (upper 95% confidence bound, Gibb cohort) 
    illustrates the range of risks considered statistically plausible based 
    on these cohorts, and thus represents the statistical uncertainty in 
    the estimates of lung cancer risk. This range of risks decreases 
    roughly proportionally with exposure, as illustrated by the risk 
    estimates shown in Table VI-7 for working lifetime exposures at various 
    levels at and below the previous PEL.
        The risk estimates for the Mancuso, Hayes, and Gerin data sets are 
    also presented in Table VI-7. (As discussed previously, risk estimates 
    were not derived from the Alexander data set.) The exposure-response 
    data from these cohorts are not as strong as those from the two 
    featured cohorts. OSHA believes that the supplemental assessments for 
    the Mancuso and Hayes cohorts support the range of projected excess 
    lung cancer risks from the Gibb and Luippold cohorts. This is 
    illustrated by the maximum likelihood estimates and 95% confidence 
    intervals shown in Table VI-7. The risk estimates and 95% confidence 
    interval based on the Hayes cohort are similar to those based on the 
    Luippold cohort, while the estimates based on the Mancuso cohort are 
    more similar to those based on the Gibb cohort. Also, OSHA's range of 
    best risk estimates based on the two primary cohorts for a given 
    occupational Cr(VI) exposure overlap the 95 percent confidence limits 
    for the Mancuso, Hayes, and Gerin cohorts. This indicates that the 
    Agency's range of best estimates is statistically consistent with the 
    risks calculated by Environ from any of these data sets, including the 
    Gerin cohort where the lung cancers did not show a clear positive trend 
    with cumulative Cr(VI) exposure.
        Several commenters remarked on OSHA's use of both the Gibb cohort 
    and the Luippold cohort to define a preliminary range of risk estimates 
    associated with a working lifetime of exposure at the previous and 
    alternative PELs. Some suggested that OSHA should instead rely 
    exclusively on the Gibb study, due to its superior size, smoking data, 
    completeness of follow-up, and exposure information (Tr. 709-710, 769; 
    Exs. 40-18-1, pp. 2-3; 47-23, p. 3; 47-28, pp. 4-5). Others suggested 
    that OSHA should devise a weighting scheme to derive risk estimates 
    based on both studies but with greater weight assigned to the Gibb 
    cohort (Tr. 709-710, 769, Exs. 40-18-1, pp. 2-3; 47-23, p. 3), arguing 
    that "the use of the maximum likelihood estimate from the Luippold 
    study as the lower bound of OSHA's risk estimates * * * has the effect 
    of making a higher Permissible Exposure Limit (PEL) appear acceptable" 
    (Ex. 40-18-1, p. 3). OSHA disagrees with this line of reasoning. OSHA 
    believes that including all studies that provide a strong basis to 
    model the relationship between Cr(VI) and lung cancer, as the Luippold 
    study does, provides useful information and adds depth to the Agency's 
    risk assessment. OSHA agrees that in some cases derivation of risk 
    estimates based on a weighting scheme is an appropriate approach when 
    differences between the results of the two or more studies are believed 
    to primarily reflect sources of uncertainty or error in the underlying 
    studies. A weighting scheme might then be used to reflect the degree of 
    confidence in their respective results. However, the Gibb and Luippold 
    cohorts were known to be quite different populations, and the 
    difference between the risk estimates based on the two cohorts could 
    partly reflect variability in exposure-response. In this case, OSHA's 
    use of a range of risk defined by the two studies is appropriate for 
    the purpose of determining significance of risk at the previous PEL and 
    the alternative PELs that the Agency considered.
        Another commenter suggested that OSHA should derive a "single 
    'best' risk estimate [taking] into account all of the six quantitative 
    risk estimates" identified by OSHA as featured or supporting risk 
    assessments in the preamble to the proposed rule, consisting of the 
    Gibb and Luippold cohorts as well as studies by Mancuso (Ex. 7-11), 
    Hayes (Ex. 7-14), Gerin (Ex. 7-120), and Alexander (Ex. 31-16-3) (Ex. 
    38-265, p. 76). The commenter, Mr. Stuart Sessions of Environomics, 
    Inc., proposed that OSHA should use a weighted average of risk 
    estimates derived from all six studies, weighting the Gibb and Luippold studies 
    more heavily than the remaining four "admittedly weaker studies" (Ex. 
    38-265, p. 78). During the public hearing, however, he stated that OSHA 
    may reasonably choose not to include some studies in the development of 
    its quantitative risk model based on certain criteria or qualifications 
    related to the principles of sound epidemiology and risk assessment 
    (Tr. 2484-2485). Mr. Sessions agreed with OSHA that sufficient length 
    of follow-up (>=20 years) is a critical qualification for a cohort to 
    provide an adequate basis for lung cancer risk assessment, admitting 
    that "if we are dealing with [a] long latency sort of effect and if 
    you only follow them for a few years it wouldn't be showing up with 
    anywhere near the frequency that you would need to get a statistically 
    significant excess risk" (Tr. 2485). This criterion supports OSHA's 
    decision to exclude the Alexander study as a primary data set for risk 
    assessment, due in part to the inadequate length of follow-up on the 
    cohort (average 8.9 years).
        Mr. Sessions also agreed that the quality and comprehensiveness of 
    the exposure information for a study could be a deciding factor in 
    whether it should be used for OSHA's risk estimates (Tr. 2485-2487). As 
    discussed in the preamble to the proposed rule, significant uncertainty 
    in the exposure estimates for the Mancuso and Gerin studies was a 
    primary reason they were not used in the derivation of OSHA's 
    preliminary risk estimates (69 FR at 59362-3). Mancuso relied 
    exclusively on the air monitoring reported by Bourne and Yee (Ex. 7-98) 
    conducted over a single short period of time during 1949 to calculate 
    cumulative exposures for each cohort member, although the cohort 
    definition and follow-up period allowed inclusion of workers employed 
    as early as 1931 and as late as 1972. In the public hearing, Mr. 
    Sessions indicated that reliance on exposure data from a single year 
    would not necessarily "disqualify" a study from inclusion in the 
    weighted risk estimate he proposed, if "for some reason the exposure 
    hasn't changed much over the period of exposure" (Tr. 2486). However, 
    the Mancuso study provides no evidence that exposures in the 
    Painesville plant were stable over the period of exposure. To the 
    contrary, Mancuso stated that:
    
        The tremendous progressive increase in production in the 
    succeeding years from zero could have brought about a concomitant 
    increase in the dust concentrations to 1949 that could have exceeded 
    the level of the first years of operation. The company instituted 
    control measures after the 1949 study which markedly reduced the 
    exposure (Ex. 7-11, p. 4).
    
        In the Gerin et al. study, cohort members' Cr(VI) exposures were 
    estimated based on total fume levels and fume composition figures from 
    "occupational hygiene literature and and welding products 
    manufacturers' literature readily available at the time of the study", 
    supplemented by "[a] limited amount of industrial hygiene measurements 
    taken in the mid 1970s in eight of the [135] companies" from which the 
    cohort was drawn (Ex. 7-120, p. S24). Thus, cumulative exposure 
    estimates for workers in this cohort were generally not based on data 
    collected in their particular job or company. Gerin et al. explained 
    that the resulting "global average" exposure estimates "obscure a 
    number of between-plant and within-plant variations in specific factors 
    which affect exposure levels and would dilute a dose-response 
    relationship", including type of activity, * * * special processes, 
    arcing time, voltage and current characteristics, welder position, use 
    of special electrodes or rods, presence of primer paints and background 
    fumes coming from other activities (Ex. 7-120, p. S25).
        Commenting on the available welding epidemiology, NIOSH emphasized 
    that wide variation in exposure conditions across employers may exist, 
    and should be a consideration in multi-employer studies (Ex. 47-19, p. 
    6). Gerin et al. recommended refinement and validation of their 
    exposure estimates using "more complete and more recent quantitative 
    data" and accounting for variability within and between plants, but 
    did not report any such validation for their exposure-response 
    analysis. OSHA believes that the exposure misclassification in the 
    Gerin study could be substantial. It is therefore difficult to place a 
    high degree of confidence in its results, and it should not be used to 
    derive the Agency's quantitative risk estimates. Comments received from 
    Dr. Herman Gibb support OSHA's conclusion. He stated that epidemiologic 
    studies of welders conducted to date do not include adequate data with 
    which to evaluate lung cancer risk (Ex. 47-8, p. 2).
        Finally, Mr. Sessions agreed with OSHA that it is best to rely on 
    "independent studies on different cohorts of workers", rather than 
    including the results of two or more overlapping cohorts in the 
    weighted average he proposed (Tr. 2487). As discussed in the preamble 
    to the proposed rule, the Hayes et al. and Gibb et al. cohorts were 
    drawn from the same Baltimore chromate production plant (FR 69 at 
    59362). The workers in the subcohort of Hayes et al. analyzed by Braver 
    were first hired between 1945 and 1959; the Gibb cohort included 
    workers first hired between 1950 and 1974. Due to the substantial 
    overlap between the two cohorts, it is not appropriate to use the 
    results of the Hayes as well as the Gibb cohort in a weighted average 
    calculation (as proposed by Mr. Sessions).
        Having carefully reviewed the various comments discussed above, 
    OSHA finds that its selection of the Gibb and Luippold cohorts to 
    derive a range of quantitative risk estimates is the most appropriate 
    approach for the Cr(VI) risk assessment. Support for this approach was 
    expressed by NIOSH, which stated that "the strength is in looking at 
    [the Gibb and Luippold studies] together * * * appreciating the 
    strengths of each" (Tr. 313). Several commenters voiced general 
    agreement with OSHA's study selection, even while disagreeing with 
    OSHA's application of these studies' results to specific industries. 
    Said one commenter, "[w]e concur with the selection of the two focus 
    cohorts (Luippold et al. 2003 and Gibb et al. 2000) as the best data 
    available upon which to base an estimate of the exposure-response 
    relationship between occupational exposure to Cr(VI) and an increased 
    lung cancer risk" (38-8, p. 6); and another, "[i]t is clear that the 
    data from the two featured cohorts, Gibb et al. (2000) and Luippold et 
    al. (2003), offer the best information upon which to quantify the risk 
    due to Cr(VI) exposure and an increased risk of lung cancer" (Ex. 38-
    215-2, p. 16). Comments regarding the suitability of the Gibb and 
    Luippold cohorts as a basis for risk estimates in specific industries 
    will be addressed in later sections.
    
    G. Issues and Uncertainties
    
        The risk estimates presented in the previous sections include 
    confidence limits that reflect statistical uncertainty. This 
    statistical uncertainty concerns the limits of precision for 
    statistical inference, given assumptions about the input parameters and 
    risk models (e.g., exposure estimates, observed lung cancer cases, 
    expected lung cancer cases, linear dose-response). However, there are 
    uncertainties with regard to the above input and assumptions, not so 
    easily quantified, that may lead to underestimation or overestimation 
    of risk. Some of these uncertainties are discussed below.
    
    1. Uncertainty With Regard to Worker Exposure to Cr(VI)
        The uncertainty that may have the greatest impact on risk estimates 
    relates to the assessment of worker exposure. Even for the Gibb cohort, 
    whose exposures were estimated from roughly 70,000 air measurements 
    over a 35-year period, the calculation of cumulative exposure is 
    inherently uncertain. The methods used to measure airborne Cr(VI) did 
    not characterize particle size that determines deposition in the 
    respiratory tract (see section V.A). Workers typically differ from one 
    another with respect to working habits and they may have worked in 
    different areas in relation to where samples are taken. Inter-
    individual (and intra-facility) variability in cumulative exposure can 
    only be characterized to a limited degree, even with extensive 
    measurement. The impact of such variability is likely less for 
    estimates of long-term average exposures when there were more extensive 
    measurements in the Gibb and Luippold cohorts in the 1960s through 
    1980s, but could affect the reliability of estimates in the 1940s and 
    1950s when air monitoring was done less frequently. Exposure estimates 
    that rely on annual average air concentrations are also less likely to 
    reliably characterize the Cr(VI) exposure to workers who are employed 
    for short periods of time. This may be particularly true for the Gibb 
    cohort in which a sizable fraction of cohort members were employed for 
    only a few months.
        Like many retrospective cohort studies, the frequency and methods 
    used to monitor Cr(VI) concentrations may also be a source of 
    uncertainty in reconstructing past exposures to the Gibb and Luippold 
    cohorts. Exposures to the Gibb cohort in the Baltimore plant from 1950 
    until 1961 were determined based on periodic collection of samples of 
    airborne dust using high volume sampling pumps and impingers that were 
    held in the breathing zone of the worker for relatively short periods 
    of time (e.g., tens of minutes) (Ex. 31-22-11). The use of high volume 
    sampling with impingers to collect Cr(VI) samples may have 
    underestimated exposure since the accuracy of these devices depended on 
    an air flow low enough to ensure efficient Cr(VI) capture, the absence 
    of agents capable of reducing Cr(VI) to Cr(III), the proper storage of 
    the collected samples, and the ability of short-term collections to 
    accurately represent full-shift worker exposures. Further, impingers 
    would not adequately capture any insoluble forms of Cr(VI) present, 
    although other survey methods indicated minimal levels of insoluble 
    Cr(VI) were produced at the Baltimore facility (Ex. 13-18-14).
        In the 1960s, the Baltimore plant expanded its Cr(VI) air 
    monitoring program beyond periodic high volume sampling to include 
    extensive area monitoring in 27 exposure zones around the facility. 
    Multiple short-term samples were collected (e.g., twelve one-hour or 
    eight three-hour samples) on cellulose tape for an entire 24 hour 
    period and analyzed for Cr(VI). Studies have shown that Cr(VI) can be 
    reduced to Cr(III) on cellulose filters under certain circumstances so 
    there is potential for underestimation of Cr(VI) using this collection 
    method (Ex. 7-1, p. 370). Monitoring was conducted prior to 1971, but 
    the results were misplaced and were not accessible to Gibb et al. The 
    area monitoring was supplemented by routine full-shift personal 
    monitoring of workers starting in 1977. The 24-hour area sampling 
    supplemented with personal monitoring was continued until plant closure 
    in 1985.
        Some of the same uncertainties exist in reconstructing exposures 
    from the Luippold cohort. Exposure monitoring from operations at the 
    Painesville plant in the 1940s and early 1950s was sparse and consisted 
    of industrial hygiene surveys conducted by various groups (Ex. 35-61). 
    The United States Public Health Service (USPHS) conducted two 
    industrial hygiene surveys (1943 and 1951), as did the Metropolitan 
    Life Insurance Company (1945 and 1948). The Ohio Department of Health 
    (ODH) conducted surveys in 1949 and 1950. The most detailed exposure 
    information was available in annual surveys conducted by the Diamond 
    Alkali Company (DAC) from 1955 to 1971. Exponent chose not to consider 
    the ODH data in their analysis since the airborne Cr(VI) concentrations 
    reported in these surveys were considerably lower than values measured 
    at later dates by DAC. Excluding the ODH survey data in the exposure 
    reconstruction process may have led to higher worker exposure estimates 
    and lower predicted lung cancer risks.
        There were uncertainties associated with the early Cr(VI) exposure 
    estimates for the Painesville cohort. Like the monitoring in the 
    Baltimore plant, Cr(VI) exposure levels were determined from periodic 
    short-term, high volume sampling with impingers that may have 
    underestimated exposures (Ex. 35-61). Since the Painesville plant 
    employed a "high-lime" roasting process to produce soluble Cr(VI) 
    from chromite ore, a significant amount of slightly soluble and 
    insoluble Cr(VI) was formed. It was estimated that up to approximately 
    20 percent of the airborne Cr(VI) was in the less soluble form in some 
    areas of the plant prior to 1950 (Ex. 35-61). The impingers were 
    unlikely to have captured this less soluble Cr(VI) so some reported 
    Cr(VI) air concentrations may have been underestimated for this reason.
        The annual air monitoring program at the Painesville plant was 
    upgraded in 1966 in order to evaluate a full 24 hour period (Ex. 35-
    61). Unlike the continuous monitoring at the Baltimore plant, twelve 
    area air samples from sites throughout the plant were collected for 
    only 35 minutes every two hours using two in-series midget impingers 
    containing water. The more frequent monitoring using the in-series 
    impinger procedure may be an improvement over previous high-volume 
    sampling and is believed to be less susceptible to Cr(VI) reduction 
    than cellulose filters. While the impinger collection method at the 
    Painesville plant may have reduced one source of potential exposure 
    uncertainty, another source of potential uncertainty was introduced by 
    failure to collect air samples for more than 40 percent of the work 
    period. Also, personal monitoring of workers was not conducted at any 
    time.
        Concerns about the accuracy of the Gibb and Luippold exposure data 
    were expressed in comments following the publication of the proposed 
    rule. Several commenters suggested that exposures of workers in both 
    the Gibb and Luippold (2003) cohorts may have been underestimated, 
    resulting in systematic overestimation of risk in the analyses based on 
    these cohorts (Exs. 38-231, pp. 19-20; 38-233, p. 82; 39-74, p. 2; 47-
    27, p. 15; 47-27-3, p. 1). In particular, the possibility was raised 
    that exposure measurements taken with the RAC sampler commonly used in 
    the 1960s may have resulted in lower reported Cr(VI) levels as a result 
    of reduction of Cr(VI) on the sample strip. Concerns were also raised 
    that situations of exceptionally high exposure may not have been 
    captured by the sampling plans at the Baltimore and Painesville plants 
    and that Cr(VI) concentrations in workers' breathing zones would have 
    been generally higher than concentrations measured in general area 
    samples taken in the two plants (Exs. 38-231, p. 19; 40-12-1, p. 2). 
    One commenter noted that "the exposure values identified in both the 
    Painesville and Baltimore studies are consistently lower than those 
    reported for a similar time period by alternative sources (Braver et 
    al. 1985; PHS 1953)" (Exs. 38-231, p. 19; 40-12-1, p. 2). It was also 
    suggested that impinger samples used to estimate exposures in the 
    Painesville plant and the impinger and RAC samples used between 1950 and 1985 in 
    the Baltimore plant did not efficiently capture particles smaller than 
    1 [mu]m in diameter, which were believed to have constituted a 
    substantial fraction of particles generated during the chromite ore 
    roasting process, and thus led to an underestimate of exposures (Ex. 
    47-27-3, pp. 1-4).
        In his written testimony for the public hearing, Dr. Herman Gibb 
    addressed concerns about the type of samples on which the Gibb cohort 
    exposure estimates were based. Dr. Gibb stated, "[a] comparison of the 
    area and personal samples [collected during 1978-1985] found 
    essentially no difference for approximately two-thirds of the job 
    titles with a sufficient number of samples to make this comparison." 
    An adjustment was made for the remaining job titles, in which the area 
    samples were found to underestimate the breathing zone exposure, so 
    that the potential for underestimation of exposures based on general 
    area samples " * * * was accounted for and corrected * * * " in the 
    Gibb cohort exposure estimates (Ex. 44-4, pp. 5-6). Dr. Gibb also noted 
    that the publications claimed by commenters to have reported 
    consistently higher levels of exposure than those specified by the 
    authors of the Gibb et al. and Luippold et al. studies, in fact did not 
    report exposures in sufficient detail to provide a meaningful 
    comparison. In particular, Dr. Gibb said that the Public Health Service 
    (PHS) publication did not report plant-specific exposure levels, and 
    that Braver et al. did not report the locations or sampling strategies 
    used (Ex. 44-4, pp. 5-6).
        OSHA agrees with Dr. Gibb that the use of RAC general area samples 
    in the Baltimore plant are unlikely to have caused substantial error in 
    risk estimates based on the Gibb cohort. A similar comparison and 
    adjustment between area and personal samples could not be performed for 
    the Luippold et al. cohort, for which only area samples were available. 
    The fact that most general area samples were similar to personal 
    breathing zone samples in the Gibb cohort does not support the 
    contention that reduction on the RAC sample strip or small particle 
    capture issues would have caused substantial error in OSHA's risk 
    estimates. Speculation regarding unusually high exposures that may not 
    have been accounted for in sampling at the Baltimore and Painesville 
    plants raises an uncertainty common to many epidemiological studies and 
    quantitative risk analysis, but does not provide evidence that 
    occasional high exposures would have substantially affected the results 
    of this risk assessment.
        OSHA received comments from the Small Business Administration's 
    Office of Advocacy and others suggesting that, in addition to water-
    soluble sodium dichromate, sodium chromate, potassium dichromate, and 
    chromic acid, some members of the Gibb and Luippold cohorts may have 
    been exposed to less soluble compounds such as calcium chromate (Tr. 
    1825, Exs. 38-7, p. 4; 38-8, p. 12; 40-12-5, p. 5). These less soluble 
    compounds are believed to be more carcinogenic than Cr(VI) compounds 
    that are water-soluble or water-insoluble (e.g. lead chromate). The 
    Painesville plant used a high-lime process to roast chromite ore, which 
    is known to form calcium chromate and lesser amounts of other less 
    water-soluble Cr(VI) compounds (Ex. 35-61). The 1953 USPHS survey 
    estimated that approximately 20 percent of the total Cr(VI) in the 
    roasting residue at the Painesville plant consisted of the less water-
    soluble chromates (Ex. 2-14). The high lime roasting process is no 
    longer used in the production of chromate compounds.
        Proctor et al. estimated that a portion of the Luippold cohort 
    prior to 1950 were probably exposed to the less water-soluble Cr(VI) 
    compounds due to the use of a high-lime roasting process, but that it 
    would amount to less than 20 percent of their total Cr(VI) exposure 
    (Ex. 35-61). The Painesville plant subsequently reduced and eliminated 
    exposure to Cr(VI) roasting residue through improvements in the 
    production process. A small proportion of workers in the Special 
    Products Division of the Baltimore plant may have been exposed to less 
    water-soluble Cr(VI) compounds during the occasional production of 
    these compounds over the years. However, the high-lime process believed 
    to generate less soluble compounds at the Painesville plant was not 
    used at the Baltimore plant, and the 1953 USPHS survey detected minimal 
    levels of less soluble Cr(VI) at this facility (Braver et al. 1985, Ex. 
    7-17).
        OSHA agrees that some workers in the Luippold 2003 cohort 
    (Painesville plant) and perhaps in the Gibb cohort (Baltimore plant) 
    may have been exposed to minor amounts of calcium chromate and other 
    less-soluble Cr(VI) compounds. However, these exposures would have been 
    limited for most workers due to the nature of the production process 
    and controls that were instituted after the early production period at 
    the Painesville plant. The primary operation at the plants in 
    Painesville and Baltimore was the production of the water-soluble 
    sodium dichromate from which other primarily water-soluble chromates 
    such as sodium chromate, potassium dichromate, and chromic acid could 
    be made (Exs. 7-14; 35-61). Therefore, the Gibb and Luippold cohorts 
    were principally exposed to water-soluble Cr(VI). Risk of lung cancer 
    in these cohorts is therefore likely to reflect exposure to sodium 
    chromate and sodium dichromate, rather than calcium chromate.
        The results of the recent German post-change cohort showed that 
    excess lung cancer mortality occurred among chromate-exposed workers in 
    plants exclusively using a no-lime production process (Ex. 48-4). Like 
    the Gibb cohort, the German cohort was exposed to average full-shift 
    Cr(VI) exposures well below the previous PEL of 52 [mu]g/m\3\ but 
    without the possible contribution from the more carcinogenic calcium 
    chromate (Exs. 48-1-2; Ex. 7-91). OSHA believes the elevated lung 
    cancer mortality in these post-change workers are further evidence that 
    occupational exposure to the less carcinogenic water-soluble Cr(VI) 
    present a lung cancer risk.
        In their post-hearing brief, the Aerospace Industries Association 
    of America (AIA) stated:
    
        OSHA's quantitative risk estimates are based on exposure 
    estimates derived from impinger and RAC samplers in the Painesville 
    and Baltimore chromate production plants. It is likely that these 
    devices substantially underestimated airborne levels of Cr(VI), 
    especially considering that particles were typically < 1 [mu]m. If 
    exposure in these studies were underestimated, the risk per unit 
    exposure was overestimated, and the risk estimates provided in the 
    proposed rule overstate lung cancer risks (Ex. 47-29-2, p. 4).
    
    AIA supports its statements by citing a study by Spanne et al. (Ex. 48-
    2) that found very low collection efficiencies (e.g. < 20 percent) of 
    submicron particles (i.e. < 1 [mu]m) using midget impingers. OSHA does 
    not dispute that liquid impinger devices, primarily used to measure 
    Cr(VI) air levels at the Painesville plant, are less effective at 
    collecting small submicron particles. However, OSHA does not believe 
    AIA has adequately demonstrated that the majority of Cr(VI) particles 
    generated during soluble chromate production are submicron in size. 
    This issue is further discussed in preamble section VI.G.4.a. Briefly, 
    the AIA evidence is principally based on a particle size distribution 
    from two airborne dust samples collected at the Painesville plant by an 
    outdated sampling device under conditions that essentially excludes 
    particles >5 [mu]m (Ex. 47-29-2, Figure 4).
    OSHA believes it is more likely that Cr(VI) production workers in the 
    Gibb and Luippold cohorts were exposed to Cr(VI) mass as respirable 
    dust (i.e. < 10 [mu]m) mostly over 1 [mu]m in size. The Spanne et al. 
    study found that the impinger efficiency for particles greater than 2 
    [mu]m is above 80 percent. Cr(VI) exposure not only occurs during 
    roasting of chromite ore, where the smallest particles are probably 
    generated, but also during the leaching of water-soluble Cr(VI) and 
    packaging sodium dichromate crystals where particle sizes are likely 
    larger. Based on this information, OSHA does not have reason to believe 
    that the impinger device would substantially underestimate Cr(VI) 
    exposures during the chromate production process or lead to a serious 
    overprediction of risk.
        The RAC samplers employed at the Baltimore plant collected airborne 
    particles on filter media, not liquid media. AIA provided no data on 
    the submicron particle size efficiency of these devices. For reasons 
    explained earlier in this section, OSHA finds it unlikely that use of 
    the RAC samplers led to substantial error in worker exposure estimates 
    for the Gibb cohort.
        In summary, uncertainties associated with the exposure estimates 
    are a primary source of uncertainty in any assessment of risk. However, 
    the cumulative Cr(VI) exposure estimates derived from the Luippold 
    (2003) and Gibb cohorts are much more extensive than usually available 
    for a cancer cohort and are more than adequate as a basis for 
    quantitative risk assessment. OSHA does not believe the potential 
    inaccuracies in the exposure assessment for the Gibb and Luippold 
    (2003) cohorts are large enough to result in serious overprediction or 
    underprediction of risk.
    2. Model Uncertainty, Exposure Threshold, and Dose Rate Effects
        The models used to fit the observed data may also introduce 
    uncertainty into the quantitative predictions of risk. In the Preamble 
    to the Proposed Rule, OSHA solicited comments on whether the linear 
    relative risk model is the most appropriate approach on which to 
    estimate risk associated with occupational exposure to Cr(VI) (FR 69 at 
    59307). OSHA expressed particular interest in whether there is 
    convincing scientific evidence of a non-linear exposure-response 
    relationship and, if so, whether there are sufficient data to develop a 
    non-linear model that would provide more reliable risk estimates than 
    the linear approach that was used in the preliminary risk assessment.
        OSHA received a variety of comments regarding the uncertainties 
    associated with using the risk model based on the Gibb and Luippold 
    cohorts to predict risk to individuals exposed over a working lifetime 
    to low levels of Cr(VI). OSHA's model assumes that the risk associated 
    with a cumulative exposure resulting from long-term, low-level exposure 
    is similar to the risk associated with the same cumulative exposure 
    from briefer exposures to higher concentrations, and that a linear 
    relative risk model adequately describes the cumulative exposure-
    response relationship. These assumptions are common in cancer risk 
    assessment, and are based on scientifically accepted models of 
    genotoxic carcinogenesis. However, OSHA received comments from the 
    Small Business Administation's Office of Advocacy and others that 
    questioned the Agency's reliance on these assumptions in the case of 
    Cr(VI) (see e.g. Exs. 38-7, p. 2; 38-231, p. 18; 39-74, p. 2; 40-12-1, 
    p. 2; 38-106, p. 10, p. 23; 38-185, p. 4; 38-233, p. 87; 38-265-1, pp. 
    27-29; 43-2, pp. 2-3). Some comments suggested that a nonlinear or 
    threshold exposure-response model is an appropriate approach to 
    estimate lung cancer risk from Cr(VI) exposures. Evidence cited in 
    support of this approach rely on: (1) The lack of a statistically 
    significant increased lung cancer risk for workers exposed below a 
    cumulative Cr(VI) exposure of 1.0 mg/m\3\=yr (e.g., roughly equivalent 
    to 20 [mu]g/m\3\ TWA for a 45 year working lifetime) and below "a 
    highest reported eight hour average" Cr(VI) concentration of 52 [mu]g/
    m\3\; (2) the lack of observed lung tumors at lower dose levels in rats 
    chronically exposed to Cr(VI) by inhalation and repeated intratracheal 
    installations; and (3) the existence of physiological defense 
    mechanisms within the lung, such as extracellular reduction of Cr(VI) 
    to Cr(III) and repair of DNA damage. These commenters argue that the 
    evidence suggests a sublinear nonlinearity or threshold in exposure-
    response at exposures in the range of interest to OSHA.
        The Small Business Administration's Office of Advocacy and several 
    other commenters stated that OSHA's risk model may overestimate the 
    risk to individuals exposed for a working lifetime at "low" 
    concentrations (Exs. 38-7, p. 2; 38-231, p. 18; 39-74, p. 2; 40-12-1, 
    p. 2) or at concentrations as high as 20-23 [mu]g/m\3\ (Exs. 38-7, p. 
    6; 38-106, p. 10, p. 23; 38-185, p. 4; 38-233, p. 87; 38-265-1, pp. 27-
    29; 43-2, pp. 2-3), due to possible nonlinear features in the exposure-
    response relationship for Cr(VI). These comments cited various 
    published analyses of the Luippold and Gibb cohorts, including the 
    Luippold et al. 2003 publication (Exs. 38-106, p. 10, p. 22; 38-233-4, 
    p. 17), the Proctor et al. 2004 publication (Ex. 38-233-4, p. 17), the 
    Crump et al. 2003 publication (Exs. 38-106, p. 22; 38-265-1, p. 27), 
    and an analysis conducted by Exponent on behalf of chromium industry 
    representatives (Ex. 31-18-15-1). The following discussion considers 
    each of these analyses, as well as the overall weight of evidence with 
    respect to cancer risk from low exposure to Cr(VI).
    a. Linearity of the Relationship Between Lung Cancer Risk and 
    Cumulative Exposure
        In the Luippold et al. 2003 publication (Ex. 33-10) and the Proctor 
    et al. 2004 publication (Ex. 38-216-10), the authors reported observed 
    and expected lung cancer deaths for five categories of cumulative 
    exposure. Lung cancer mortality was significantly elevated in 
    categories above 1.05 mg/m3-yr Cr(VI) (p < 0.05), and was 
    non-significantly elevated in the category spanning 0.20-0.48 mg/
    m3-yr (8 observed lung cancer deaths vs. 4.4 expected), with 
    a slight deficit in lung cancer mortality for the first and third 
    categories (3 observed vs. 4.5 expected below 0.2 mg/m3-yr, 4 observed 
    vs. 4.4 expected at 0.48-1.04 mg/m3-yr) (Ex. 33-10, p. 455). 
    This analysis is cited by commenters who suggest that the lack of a 
    significantly elevated lung cancer risk in the range below 1.05 mg/
    m3-yr may reflect the existence of a threshold or other 
    nonlinearity in the exposure-response for Cr(VI), and that OSHA's use 
    of a linear relative risk model in the preliminary risk assessment may 
    not be appropriate (Exs. 38-106, pp. 10-11; 38-233-4, p. 18). OSHA 
    received similar comments citing the Crump et al. (2003) publication, 
    in which the authors found a "consistently significant" trend of 
    increasing risk with increasing cumulative exposure for categories of 
    exposure above 1 mg/m3-yr (Ex. 35-58, p. 1157). The Exponent 
    analysis of the Gibb et al. cohort was also cited, which found that 
    lung cancer SMRs were not significantly elevated for workers with 
    cumulative exposures below 0.42 mg/m3-yrs Cr(VI) when 
    Baltimore reference rates and a six-category exposure grouping were 
    used (Ex. 31-18-15-1, Table 6).
        Some commenters have interpreted these analyses to indicate 
    uncertainty about the exposure-response relationship at low exposure 
    levels. Others have asserted that "[c]redible health experts assessing 
    the same data as OSHA have concluded that 23 [mu]g/m3 is a protective 
    workplace standard (Ex. 38-185, p. 4) or that "[t]he Crump study 
    concluded that 23 [mu]g/m3 would be a standard that is 
    protective of workers health" (Ex. 47-35-1, p. 5). Contrary to these 
    assertions, it should be noted that the Gibb et al., Luippold et al., 
    and Crump et al. publications do not include any statements concluding 
    that 23 [mu]g/m3 or any other exposure level is protective 
    against occupational lung cancer. OSHA has reviewed these analyses to 
    determine whether they provide sufficient evidence to support the use 
    of a nonlinear or threshold-based exposure-response model for the 
    Cr(VI) risk assessment, and whether they support the assertion that a 
    PEL higher than that proposed would protect workers against a 
    significant risk of lung cancer.
        In discussing their results, Luippold et al. reported that 
    evaluation of a linear dose-response model using a chi-squared test 
    showed no significant departure from linearity and concluded that the 
    data are consistent with a linear dose-response model. They noted that 
    the results were also consistent with threshold or nonlinear effects at 
    low cumulative exposures, as they observed substantial increases in 
    cumulative exposure levels above approximately 1 mg/m3-yrs 
    (Ex. 33-10, p. 456). Ms. Deborah Proctor, lead author of the Proctor et 
    al. (2004) publication, confirmed these conclusions at the public 
    hearing, stating her belief that nonlinearities may exist but that the 
    data were also consistent with a linear dose response (Tr. 1845). The 
    authors of the Crump et al. 2003 publication (Ex. 35-58), in which 
    trend analyses were used to examine the exposure-response relationship 
    for cumulative exposure, stated that the data were " * * * neutral 
    with respect to these competing hypotheses" (Ex. 35-58, pp. 1159-
    1160). Crump et al. concluded that their study of the Luippold cohort 
    " * * * had limited power to detect increases [in lung cancer risk] at 
    these low exposure levels" (Ex. 35-58, p. 1147). OSHA agrees with 
    Crump et al.'s conclusion that their study could not detect the 
    relatively small increases in risk that would be expected at low 
    exposures. With approximately 3000 person-years of observation time and 
    4.5 expected lung cancers in each of the three cumulative exposure 
    categories lower than 0.19 mg/m3-yrs Cr(VI) (Ex. 33-10, p. 
    455), analyses of the Luippold cohort cannot effectively discriminate 
    between alternative risk models for cumulative exposures that a worker 
    would accrue from a 45-year working lifetime of occupational exposure 
    at relatively low exposures (e.g., 0.045-0.225 mg/m3-yrs 
    Cr(VI), corresponding to a working lifetime of exposure at 1-5 [mu]g 
    Cr(VI)/m3).
        The Exponent reanalysis of the Gibb cohort found that lung cancer 
    rates associated with exposures around 0.045 mg/m3-yrs 
    Cr(VI) and below were not significantly elevated in some analyses (Ex. 
    31-18-15-1, Table 6 p. 26). However, OSHA believes that this result is 
    likely due to the limited power of the study to detect small increases 
    in risk, rather than a threshold or nonlinearity in exposure-response. 
    In written testimony, Dr. Gibb explained that "[l]ack of a 
    statistically elevated lung cancer risk at lower exposures does not 
    imply that a threshold of response exists. As exposure decreases, so 
    does the statistical power of a given sample size to detect a 
    significantly elevated risk" (Ex. 44-4, p. 6). Exponent's analyses 
    found (non-significant) elevated risks for all exposure groups above 
    approximately 0.1 mg/m3-yrs, equivalent to 45 years of 
    occupational exposure at about 2.25 [mu]g/m3 Cr(VI) (Ex. 31-
    18-15-1, p. 20, Table 3). Furthermore, Gibb et al.'s SMR analysis based 
    on exposure quartiles found statistically significantly elevated lung 
    cancer risks among workers with cumulative exposures well below the 
    equivalent of 45 years at the proposed PEL of 1 [mu]g/m3. As 
    Dr. Gibb commented at the hearing, the proposed PEL " * * * is within 
    the range of observation [of the studies] * * * In a sense, you don't 
    even need risk models" to show that workers exposed to cumulative 
    exposures equivalent to a working lifetime of exposure at or above the 
    proposed PEL have excess risk of lung cancer as a result of their 
    occupational exposure to Cr(VI)" (Tr. 121-122).
        Furthermore, Robert Park of NIOSH reminded OSHA that "[a]nalysts 
    of both the Painesville and the Baltimore cohorts * * * did test for 
    deviation or departure from linearity in the exposure response and 
    found no significant effect. If there was a large threshold, you would 
    expect to see some deviance there" (Tr. 350-351). Post-hearing 
    comments from NIOSH indicated that further analysis of the Gibb data 
    provided no significant improvement in fit for nonlinear and threshold 
    models compared to the linear relative risk model (Ex. 47-19, p. 7). 
    Based on this evidence and on the previously discussed findings that 
    (1) linear relative risk models fit both the Gibb and Luippold data 
    sets adequately, and (2) the wide variety of nonlinear models tested by 
    various analysts failed to fit the available data better than the 
    linear model, OSHA believes that a linear risk model is appropriate and 
    that there is not convincing evidence to support the use of a threshold 
    or nonlinear exposure-response model, or to conclude that OSHA's risk 
    assessment has seriously overestimated risk at low exposures.
    b. The Cumulative Exposure Metric and Dose-Rate Effects on Risk
        The Small Business Administration's Office of Advocacy and several 
    other commenters questioned OSHA's reliance in the preliminary risk 
    assessment on models using cumulative exposure to estimate excess risk 
    of lung cancer, suggesting that cumulative exposures attained from 
    exposure to high concentrations of Cr(VI) for relatively short periods 
    of time, as for some individuals in the Gibb and Luippold cohorts, may 
    cause greater excess risk than equivalent cumulative exposures attained 
    from long-term exposure to low concentrations of Cr(VI) (Exs. 38-7, pp. 
    3-4, 38-215-2, pp. 17-18; 38-231, p. 18; 38-233, p. 82; 38-265-1, p. 
    27; 39-74, p. 2, 40-12-1, p. 2, 43-2, p. 2, 47-27, p. 14; 47-27-3, p. 
    1). This assertion implies that OSHA's risk assessment overestimates 
    risk from exposures at or near the proposed PEL due to a threshold or 
    dose-rate effect in exposure intensity. One commenter stated that 
    "[a]pplication of a linear model estimating lung cancer risk from 
    high-level expsoures . . . to very low-level exposure using the 
    exposure metric of cumulative dose will inevitably overestimate risk 
    estimates in the proposed PEL" (Ex. 47-27-3, p. 1). Comments on this 
    subject have cited analyses by Proctor et al. (2004) (Ex. 38-233-4, p. 
    17), Crump et al. (2003) (Exs. 38-106, p. 22; 38-265-1, p. 27), 
    Exponent (Ex. 31-18-15-1, pp. 31-34) and NIOSH (Ex. 47-19-1, p. 7); a 
    new study by Luippold et al. on workers exposed to relatively low 
    concentrations of Cr(VI) (Ex. 47-24-2); and mechanistic and animal 
    studies examining the potential for dose-rate effects in Cr(VI)-related 
    health effects (Exs. 31-18-7; 31-18-8; 11-7).
        Of the two featured cohorts in OSHA's preliminary risk assessment, 
    the Gibb cohort is better suited to assess risk from exposure 
    concentrations below the previous PEL of 52 [mu]g Cr(VI)/m\3\. Contrary 
    to some characterizations of the cohort's exposures as too high to 
    provide useful information about risk under modern workplace conditions 
    (See e.g. Exs. 38-106, p. 21; 38-233, p. 82; 38-265-1, p. 28), most 
    members of the Gibb cohort had relatively low exposures, with 
    42[percnt] of the cohort members having a median annual average exposure
    value below 10 [mu]g/m\3\ Cr(VI), 69[percnt] below 20 [mu]g/m\3\, and 91[percnt] below the 
    previous PEL (Ex. 35-295). In addition, Dr. Gibb indicated that 
    exposures in general were lower than suggested by some commenters (Tr. 
    1856, Ex. 38-215-2, p. 17). For example, about half of the total time 
    that workers were exposed was estimated to be below 14 [mu]g/m\3\ 
    Cr(VI) from 1960-1985 (Ex. 47-8, p. 1).
        Exponent calculated SMRs for six groups of workers in the Gibb 
    cohort, classified according to the level of their highest average 
    annual exposure estimates. They found that only the group of workers 
    whose highest exposure estimates were above approximately 95 [mu]g/m\3\ 
    Cr(VI) had statistically significantly elevated lung cancer risk when 
    Baltimore reference rates were used (Ex. 31-18-15-1, p. 33). Exponent's 
    results are presented in Table VI-8 below, adapted from Table 10 in 
    their report (Ex. 31-18-15-1, p. 33).
Table VI-8

 

        OSHA does not believe that Exponent's analysis of the Gibb data 
    provides convincing evidence of a threshold in exposure-response. While 
    the lower-exposure groups do not have statistically significantly 
    elevated lung cancer risk (p > 0.05) when compared with a Baltimore 
    reference population, the SMRs for all groups above 3.7 [mu]g/
    m3 are consistently elevated. Moreover, the increased risk 
    approaches statistical significance, especially for those subgroups 
    with higher power (Groups 2 and 3). This can be seen by the lower 95% 
    confidence bound on the SMR for these groups, which is only slightly 
    below 1. The analysis suggests a lack of power to detect excess risk in 
    Groups 2-5, rather than a lack of excess risk at these exposure levels.
        Analyses of the Luippold cohort by Crump et al. (Ex. 35-58) and 
    Proctor et al. (Ex. 38-216-10) used exposure estimates they called 
    "highest average monthly exposure" to explore the effects of exposure 
    intensity on lung cancer risk. They reported that lung cancer risk was 
    elevated only for individuals with exposure estimates higher than the 
    previous PEL of 52 [mu]g/m3 Cr(VI). Crump et al. 
    additionally found "statistically significant evidence of a dose-
    related increase in the relative risk of lung cancer mortality" only 
    for groups above four times the previous PEL, using a series of Poisson 
    regressions modeling the increase in risk across the first two 
    subgroups and with the successive addition of higher-exposed subgroups 
    (Ex. 35-58, p. 1154).
        As with the Gibb data, OSHA does not believe that the subgroup of 
    workers exposed at low levels is large enough to provide convincing 
    evidence of a threshold in exposure-response. In the Crump et al. and 
    Proctor et al. analyses, the groups for which no statistically 
    significant elevation or dose-related trends in lung cancer risk were 
    observed are quite small by the standards of cancer epidemiology (e.g., 
    the Luippold cohort had only about 100 workers below the previous PEL 
    and about 40 workers within 1-3 times the previous PEL). Crump et al. 
    emphasized that " * * * this study had limited power to detect 
    increases [in lung cancer risk] at these low exposure levels" (Ex. 35-
    58, p. 1147). The authors did not conclude that their results indicate 
    a threshold. They stated that their cancer potency estimates based on a 
    linear relative risk model using the cumulative exposure metric " * * 
    * are comparable to those developed by U.S. regulatory agencies and 
    should be useful for assessing the potential cancer hazard associated 
    with inhaled Cr(VI)" (Ex. 35-58, p. 1147).
        OSHA discussed the Exponent, Crump et al. and Luippold et al. SMR 
    analyses of the Gibb and Luippold cohorts in the preamble to the 
    proposed rule, stating that the lack of a statistically significant 
    result for a subset of the entire cohort should not be construed to 
    imply a threshold (69 FR at 59382). During the hearing, Robert Park of 
    NIOSH expressed agreement with OSHA's preliminary interpretation, 
    adding that:
    
        [W]e think that any interpretation of threshold in these studies 
    is basically a statistical artifact * * * It is important I think to 
    understand that any true linear or even just monotonic exposure 
    response that doesn't have a threshold will exhibit a threshold by 
    the methods that they used. If you stratify the exposure metric fine 
    enough and look at the lower levels, they will be statistically 
    insignificant in any finite study * * * telling you nothing about 
    whether or not in fact there is a threshold (Tr. 351).
    
        To further explore the effects of highly exposed individuals on 
    OSHA's risk model, The Chrome Coalition suggested that OSHA should base 
    its exposure-response model on a subcohort of workers excluding those 
    who were exposed to " * * * an extraordinary exposure level for some 
    extended period of time* * * ", e.g., estimated exposures greater than 
    the previous PEL for more than one year (Ex. 38-231, p. 21). The Chrome 
    Coalition stated,
    
        We are not aware of any study that has performed this type of 
    analysis but we believe that it should be a way of better estimating 
    the risk for exposures in the range that OSHA is considering for the 
    PEL (Ex. 38-231, p. 21).
    
    To gauge the potential utility of such an analysis, OSHA examined the 
    subset of the Gibb cohort that was exposed for more than 365 days and 
    had average annual exposure estimates above the previous PEL of 52 
    [mu]g/m3 Cr(VI). The Agency found that the subcohort 
    includes only 82 such individuals, of whom 37 were reported as deceased 
    at the end of follow-up and five had died of lung cancer. In a cohort 
    of 2357 workers with 122 lung cancers out of 855 deaths, it is unlikely that 
    exclusion of a group this size would impact the results of a regression 
    analysis significantly, especially as the proportion of mortality 
    attributable to lung cancer is similar in the highly-exposed subgroup 
    and the overall cohort (5/37 0.135, 122/855 [cong] 0.143). The great 
    majority of the Gibb cohort members did not have the 'extraordinary' 
    exposure levels implied by the Chrome Coalition. As discussed 
    previously, most had relatively low exposures averaging less than 20 
    [mu]g/m3.
        As discussed in their post-hearing comments, NIOSH performed 
    regression analyses designed to detect threshold or dose-rate effects 
    in the exposure-response relationship for the Gibb dataset (Ex. 47-19-
    1, p. 7). NIOSH reported that "[t]he best fitting models had no 
    threshold for exposure intensity and the study had sufficient power to 
    rule out thresholds as large as 30 [mu]g/m\3\ CrO3 (15.6 
    [mu]g/m\3\ Cr(VI) * * * " and that there was no statistically 
    significant departure from dose-rate linearity when powers of annual 
    average exposure values were used to predict lung cancer risk (Ex. 47-
    19-1, p. 7). This indicates that a threshold of approximately 20 [mu]g/
    m\3\ Cr(VI) suggested in some industry comments is not consistent with 
    the Gibb cohort data. Based on these and other analyses described in 
    their post-hearing comments, NIOSH concluded that:
    
        [E]xamination of non-linear features of the hexavalent chromium-
    lung cancer response supports the use of the traditional (lagged) 
    "cumulative exposure paradigm * * * ": that is, linear exposure-
    response with no threshold (Ex. 47-19-1, p. 7).
    
        OSHA recognizes that, like most epidemiologic studies, neither the 
    Luippold nor the Gibb cohort provides ideal information with which to 
    identify a threshold or detect nonlinearities in the relationship 
    between Cr(VI) exposure and lung cancer risk, and that it is important 
    to consider other sources of information about the exposure-response 
    relationship at very low levels of Cr(VI) exposure. The Agency agrees 
    with Dr. Gibb's belief that " * * * arguments for a 'threshold' should 
    not be based on statistical arguments but rather on a biological 
    understanding of the disease process" (Ex. 44-4, p. 7) and Crump et 
    al.'s statement that " * * * one needs to consider supporting data 
    from mechanistic and animal studies" in order to determine the 
    appropriateness of assuming that a threshold (or, presumably, other 
    nonlinearity) in exposure-response exists (Ex. 35-58, p. 1159). 
    Experimental and mechanistic evidence and related comments relevant to 
    the issue of threshold and dose-rate effects are reviewed in the 
    following discussion.
        c. Animal and Mechanistic Evidence Regarding Nonlinearities in 
    Cr(VI) Exposure-Response
        In the NPRM, OSHA analyzed several animal and mechanistic studies 
    and did not find convincing evidence of a threshold concentration in 
    the range of interest (i.e. 0.25 to 52 [mu]g/m\3\). However, the Agency 
    recognized that evidence of dose rate effects in an animal instillation 
    study and the existence of extracellular reduction, DNA repair, and 
    other molecular pathways within the lung that protect against Cr(VI)-
    induced respiratory tract carcinogenesis could potentially introduce 
    nonlinearities in Cr(VI) exposure-cancer response. OSHA solicited 
    comment on the scientific evidence for a non-linear exposure-response 
    relationship in the occupational exposure range of interest and whether 
    there was sufficient data to develop a non-linear model that would 
    provide more reliable risk estimates than the linear approach used in 
    the preliminary risk assessment (69 FR at 59307).
        Some commenters believed the scientific evidence from animal 
    intratracheal instillation and inhalation of Cr(VI) compounds showed 
    that a linear risk model based on lung cancers observed in the Gibb and 
    Luippold cohorts seriously overpredicts lung cancer risk to workers 
    exposed at the proposed PEL (Exs. 38-216-1; 38-233-4; 38-231). The 
    research cited in support of this presumed non-linear response was the 
    intratracheal instillation study of Steinhoff et al. and the inhalation 
    study of Glaser et al. (Exs. 11-7; 10-11). For example, Elementis 
    Chromium states that:
    
        Considering either the Steinhoff or Glaser studies, a calculated 
    risk based on the effect frequency at the highest daily exposure 
    would be considerably greater than that calculated from the next 
    lower daily exposure. We believe that the same effect occurs when 
    humans are exposed to Cr(VI) and consideration of this should be 
    taken when estimating risk at very low exposure levels based on 
    effects at much higher exposure levels (Ex. 38-216-1, p. 4).
    
        Despite the different mode of Cr(VI) administration and dosing 
    schemes, the Steinhoff and Glaser studies both feature dose levels at 
    which there was no observed incidence of lung tumors. The Steinhoff 
    study found no significant lung tumor incidence in rats intratracheally 
    administered highly soluble sodium dichromate at 87 [mu]g Cr(VI)/kg or 
    less regardless of whether the dose was received five times a week or 
    once a week for 30 months. However, rats administered a higher dose of 
    437 [mu]g Cr(VI)/kg of sodium dichromate or a similar amount of the 
    slightly soluble calcium chromate once a week developed significant 
    increases (about 17 percent incidence) in lung tumors. The study 
    documented a 'dose rate effect' since the same total dose administered 
    more frequently (i.e. five times weekly) at a five-fold lower dose 
    level (i.e. 87 [mu]g Cr(VI)/kg) did not increase lung tumor incidence 
    in the highly soluble sodium dichromate-treated rats. The Glaser 
    inhalation study reported no lung tumors in rats inhaling 50 [mu]g 
    Cr(VI)/m\3\ of sodium dichromate or lower Cr(VI) concentrations for 22 
    hours/day, 7 days a week. However, the next highest dose level of 100 
    [mu]g Cr(VI)/m\3\ produced a 15 percent lung tumor incidence (i.e. 3 of 
    19 rats). Both studies are more fully described in Section V.B.7.a.
        The apparent lack of lung tumors at lower Cr(VI) dose levels is 
    interpreted by the commenters to be evidence of a non-linear exposure-
    response relationship and, possibly, an exposure threshold below which 
    there is no risk of lung cancer.
        In written testimony, Dr. Harvey Clewell of ENVIRON Health Science 
    Institute addressed whether the Steinhoff, Glaser and other animal 
    studies provided evidence of a threshold for Cr(VI) induced lung 
    carcinogenicity (Ex. 44-5). He stated that the argument for the 
    existence of a threshold rests on two faulty premises:
    
        (1) Failure to detect an increased incidence of tumors from a 
    given exposure indicates there is no carcinogenic activity at that 
    exposure, and
        (2) Nonlinearities in dose response imply a threshold below 
    which there is no carcinogenic activity (Ex. 44-5, p. 13).
    
    In terms of the first premise, Dr. Clewell states:
    
        The ability to detect an effect depends on the power of the 
    study design. A statistically-based No Observed Adverse Effect Level 
    (NOAEL) in a toxicity study does not necessarily mean there is no 
    risk of adverse effect. For example, it has been estimated that a 
    typical animal study can actually be associated with the presence of 
    an effect in as many as 10% to 30% of the animals. Thus the failure 
    to observe a statistically significant increase in tumor incidence 
    at a particular exposure does not rule out the presence of a 
    substantial carcinogenic effect at that exposure (Ex. 44-5, p. 13-
    14).
    
    Dr. Clewell also addressed the second premise as it applies to the 
    Steinhoff instillation study as follows:
    
        It has been suggested, for example, that the results of the 
    Steinhoff study suggest that dose rate is an important factor in the 
    carcinogenic potency of chrome (VI), and therefore, there must be a 
    threshold. But these data, while they do provide an indication of a 
    dose rate effect * * * they don't provide information about where and 
    whether a threshold or even a non-linearity occurs, and to what extent 
    it does occur at lower concentrations (Tr. 158-159).
    
        OSHA agrees with Dr. Clewell that the absence of observed lung 
    tumor incidence at a given exposure (i.e. a NOAEL) in an animal study 
    should not be interpreted as evidence of a threshold effect. This is 
    especially true for clearly genotoxic carcinogens, such as Cr(VI), 
    where it is considered scientifically reasonable to expect some small, 
    but finite, probability that a very few molecules may damage DNA in a 
    single cell and eventally develop into a tumor. For this reason, it is 
    not appropriate to regard the lack of tumors in the Steinhoff or Glaser 
    studies as evidence for an exposure-response threshold.
        Exponent, in a technical memorandum prepared for an ad hoc group of 
    steel manufacturers, raises the possibility that the lung tumor 
    responses in the Steinhoff and Glaser studies were the result of damage 
    to lung tissue from excessive levels of Cr(VI). Exponent suggests that 
    lower Cr(VI) exposures that do not cause 'respiratory irritation' are 
    unlikely to lead an excess lung cancer risk (Ex. 38-233-4). Exponent 
    went on to summarize:
        In examining the weight of scientific evidence, for exposure 
    concentrations below the level which causes irritation, lung cancer 
    has not been reported. Not surprisingly, Cr(VI)-induced respiratory 
    irritation is an important characteristic of Cr(VI)-induced 
    carcinogenicity in both humans and animals * * * Based on the 
    information reviewed herein, it appears that the no effect level for 
    non-neoplastic respiratory irritation and lung cancer from 
    occupational exposure to Cr(VI) is approximately 20 [mu]g/m\3\. Thus 
    establishing a PEL of 1 [mu]g/m\3\ to protect against an excess lung 
    cancer risk is unnecessarily conservative (Ex. 38-233-4, p. 24).
    
        In support of the above hypothesis, Exponent points out that only 
    the highest Cr(VI) dose level (i.e. 437 [mu]g Cr(VI)/kg) of sodium 
    dichromate employed in the Steinhoff study resulted in significant lung 
    tumor incidence. Tracheal instillation of this dose once a week 
    severely damaged the lungs leading to emphysematous lesions and 
    pulmonary fibrosis in the Cr(VI)-exposed rats. Lower Cr(VI) dose levels 
    (i.e. 87 [mu]g Cr(VI)/kg or less) of the highly water-soluble sodium 
    dichromate that caused minimal lung damage did not result in 
    significant tumor incidence. However, the study also showed that a 
    relatively low dose (i.e. 81 [mu]g Cr(VI)/kg) of slightly soluble 
    calcium chromate repeatedly instilled (i.e. five times a week) in the 
    trachea of rats caused significant lung tumor incidence (about 7.5 
    percent) in the absence of lung tissue damage. This finding is 
    noteworthy because it indicates that tissue damage is not an essential 
    requirement for Cr(VI)-induced respiratory tract carcinogenesis. The 
    same instilled dose of the slightly soluble calcium chromate would be 
    expected to provide a more persistent and greater source of Cr(VI) in 
    proximity to target cells within the lung than would the highly water-
    soluble sodium dichromate. This suggests that the internal dose of 
    Cr(VI) at the tissue site, rather than degree of damage, may be the 
    critical factor determining lung cancer risk from low-level Cr(VI) 
    exposures.
        Exponent applies similar logic to the results of the Glaser 
    inhalation study of sodium dichromate in rats. Exponent states:
    
        In all experimental groups (i.e. 25, 50, and 100 [mu]g Cr(VI)/
    m\3\), inflammation effects were observed, but at 100 [mu]g Cr(VI)/
    m\3\ [the high dose group with significant lung tumor incidence], 
    effects were more severe, as expected (Ex. 38-233-4, p. 22).
    
    This assessment contrasts with that of the study authors who remarked:
    
        In this inhalation study, in which male Wistar rats were 
    continuously exposed for 18 months to both water soluble sodium 
    dichromate and slightly soluble chromium oxide mixture aerosols, no 
    clinical signs of irritation were obvious * * * For the whole time 
    of the study no significant effects were found from routine 
    hematology and clinico-chemical examinations in all rats exposed to 
    sodium dichromate aerosol (Ex. 10-11, p. 229).
    
    The rats in the Glaser carcinogenicity study developed a focalized form 
    of lung inflammation only evident from microscopic examination. This 
    mild response should not be considered equivalent to the widespread 
    bronchiolar fibrosis, collapsed/distorted alveolar spaces and severe 
    damage found upon macroscopic examination of rat lungs instilled with 
    the high dose (437 [mu]g Cr(VI)/kg) of sodium dichromate in the 
    Steinhoff study. The non-neoplastic lung pathology (e.g. accumulation 
    of pigmentized macrophages) described following inhalation of sodium 
    dichromate at all air concentrations of Cr(VI) in the Glaser study are 
    more in line with the non-neoplastic responses seen in the lungs of 
    rats intratracheally instilled with lower dose levels of sodium 
    dichromate (i.e. 87 [mu]g Cr(VI)/kg or less) that did not cause tumor 
    incidence in the Steinhoff study. OSHA finds no evidence that severe 
    pulmonary inflammation occurred following inhalation of 100 [mu]g 
    Cr(VI)/m\3\ in the Glaser carcinogenicity study or that the lung tumors 
    observed in these rats were the result of 'respiratory irritation'. Dr. 
    Clewell also testified that lung damage or chronic inflammation is not 
    a necessary and essential condition for C(VI) carcinogenesis in the 
    Glaser study:
    
        I didn't find any evidence that it [lung damage and chronic 
    inflammation] was necessary and essential. In particular, I think 
    the Glaser study was pretty good in demonstrating that there were 
    effects where they saw no evidence of irritation, or any clinical 
    signs of those kinds of processes (Tr. 192).
    
        Subsequent shorter 30-day and 90-day inhalation exposures with 
    sodium dichromate in rats were undertaken by the Glaser group to better 
    understand the non-neoplastic changes of the lung (Ex. 31-18-11). The 
    investigation found a transitory dose-related inflammatory response in 
    the lungs at exposures of 50 [mu]g Cr(VI)/m\3\ and above following the 
    30 day inhalation. This initial inflammatory response did not persist 
    during the 90 day exposure study except at the very highest dose levels 
    (i.e. 200 and 400 [mu]g Cr(VI)/m\3\). Significant increases in 
    biomarkers for lung tissue damage (such as albumin and lactate 
    dehydrogenase (LDH) in bronchioalveolar lavage fluid (BALF) as well as 
    bronchioalveolar hyperplasia) also persisted through 90 days at these 
    higher Cr(VI) air levels, especially 400 [mu]g Cr(VI)/m\3\. The study 
    authors considered the transient 30-day responses to represent 
    adaptive, rather than persistent pathological, responses to Cr(VI) 
    challenge. A dose-related elevation in lung weights due to 
    histiocytosis (i.e. accumulation of lung macrophages) was seen in all 
    Cr(VI)-administered rats at both time periods. The macrophage 
    accumulation is also likely to be an adaptive response that reflects 
    lung clearance of inhaled Cr(VI). These study results are more fully 
    described in section V.C.3.
        OSHA believes that Cr(VI)-induced carcinogenesis may be influenced 
    not only by the total Cr(VI) dose retained in the respiratory tract but 
    also by the rate at which the dose is administered. Exponent is correct 
    that one possible explanation for the dose rate effect observed in the 
    Steinhoff study may be the widespread, severe damage to the lung caused 
    by the immediate instillation of a high Cr(VI) dose to the respiratory 
    tract repeated weekly for 30 months. It is biologically plausible that 
    the prolonged cell proliferation in response to the tissue injury would 
    enhance tumor development and progression compared to the same total Cr(VI)
    instilled more frequently at smaller dose levels that do not cause widespread 
    damage to the respiratory tract. This is consistent with the opinion of Dr. Clewell 
    who testified that:
    
        I would not say that it [respiratory tract irritation, lung 
    damage, or chronic inflammation] is necessary and sufficient, but 
    rather it exacerbates an underlying process. If there is a 
    carcinogenic process, then increased cell proliferation secondary to 
    irritation is going to put mitogenic pressure on the cells, and this 
    will cause more likelihood of a transformation (Tr. 192).
    
        OSHA notes that increased lung tumor incidence was observed in 
    animals instilled with lower dose levels of calcium chromate in the 
    Steinhoff study and after inhalation of sodium dichromate in the Glaser 
    study. These Cr(VI) exposures did not trigger extensive lung damage and 
    OSHA believes it unlikely that the lung tumor response from these 
    treatments was secondary to 'respiratory irritation' as suggested by 
    Exponent. The more thorough investigation by the Glaser group did not 
    find substantive evidence of persistent tissue damage until rats 
    inhaled Cr(VI) at doses two- to four-fold higher than the Cr(VI) dose 
    found to elevate lung tumor incidence in the their animal cancer 
    bioassay.
        Exponent goes on to estimate a NOAEL (no observable adverse effect 
    level) for lung histopathology in the Steinhoff study. They chose the 
    lowest dose level (i.e. 3.8 [mu]g Cr(VI)/kg) in the study as their 
    NOAEL based on the minimal accumulation of macrophages found in the 
    lungs instilled with this dose of sodium dichromate five times weekly 
    (Ex. 38-233-4, p. 21). Exponent calculates that this lung dose is 
    roughly equivalent to the daily dose inhaled by a worker exposed to 27 
    [mu]g Cr(VI)/m\3\ using standard reference values (e.g. 70 kg human 
    inhaling 10 m\3\/day over a daily 8 hour work shift). Exponent 
    considers this calculated Cr(VI) air level as a threshold below which 
    no lung cancer risk is expected in exposed workers.
        However, Steinhoff et al. instilled Cr(VI) compounds directly on 
    the trachea rather than introducing the test compound by inhalation, 
    and was only able to characterize a significant dose rate effect at one 
    cumulative dose level. For these reasons, OSHA considers the data 
    inadequate to reliably determine the human exposures where this 
    potential dose transition might occur and to confidently predict the 
    magnitude of the resulting non-linearity. NIOSH presents a similar view 
    in their post-hearing comments:
    
        NIOSH disagrees with Dr. Barnhardt's analysis [Ex. 38-216-1] and 
    supports OSHA's view that the Steinhoff et al. [1986] rat study 
    found a dose-rate effect in rats under the specified experimental 
    conditions, that this effect may have implications for human 
    exposure and that the data are insufficient to use in a human risk 
    assessment for Cr(VI) * * * The study clearly demonstrates that, 
    within the constraints of the experimental design, a dose rate 
    effect was observed. This may be an important consideration for 
    humans exposed to high levels of Cr(VI). However, quantitative 
    extrapolation of that information to the human exposure scenario is 
    difficult (Ex. 47-19-1, p. 8).
    
        Exponent also relies on a case investigation of the benchmark dose 
    methodology applied to the pulmonary biomarker data measured in the 90-
    day Glaser study (Ex. 40-10-2-8). In this instance, the benchmark doses 
    represent the 95 percent lower confidence bound on the Cr(VI) air level 
    corresponding a 10 percent increase relative to unexposed controls for 
    a chosen biomarker (e.g. BALF total protein, albumin, or LDH). The 
    inhaled animal doses were adjusted to reflect human inhalation and 
    deposition in the respiratory tract as well as continuous environmental 
    exposure (e.g. 24 hours/day, 7 days/week) rather than an occupational 
    exposure pattern (e.g. 8 hours/day, 5 days/week). The benchmark doses 
    were reported to range from 34 to 140 [mu]g Cr(VI)/m\3\.
        Exponent concludes that "these [benchmark] values are akin to a 
    no-observed-adverse-effect level NOAEL in humans to which uncertainty 
    factors are added to calculate an RfC [i.e. Reference Concentration 
    below which adverse effects will not occur in most individuals]" and 
    "taken as a whole, the studies of Glaser et al. suggest that both non-
    neoplastic tissue damage and carcinogenicity are not observed among 
    rats exposed to Cr(VI) at exposure concentrations below 25 [mu]g/m\3\" 
    (Ex. 38-233-4, p. 22). Since the Exponent premise is that Cr(VI)-
    induced lung cancer only occurs as a secondary response to 
    histopathological changes in the respiratory tract, the suggested 25 
    [mu]g Cr(VI)/m\3\ is essentially being viewed as a threshold 
    concentration below which lung cancer is presumed not to occur.
        In his written testimony, Dr. Clewell indicated that the tumor data 
    from the Glaser cancer bioassay was more appropriately analyzed using 
    linear, no threshold exposure-response model rather than the benchmark 
    uncertainty factor approach that presumes the existence of threshold 
    exposure-response.
    
        The bioassay of Glaser et al. provides an example of a related 
    difficulty of interpreting data from carcinogenicity studies. The 
    tumor outcome appears to be nonlinear (0/18, 0/18, and 3/19 at 
    0.025, 0.05, and 0.1 mg Cr/m\3\). However, although the outcomes are 
    restricted to be whole numbers (of animals), they should not be 
    evaluated as such. Because the nature of cancer as a stochastic 
    process, each observed outcome represents a random draw from a 
    Poisson distribution. Statistical dose-response modeling, such as 
    the multistage model used by OSHA, is necessary to properly 
    interpret the cancer dose-response. In the case of Glaser et al. 
    (1986) study, such modeling would produce a maximum likelihood 
    estimate of the risk at the middle dose that was greater than zero. 
    In fact, the estimated risk at the middle dose would be on the order 
    of several percent, not zero. Therefore, suggesting a lack of lung 
    cancer risk at a similar human exposure would not be a health 
    protective position (Ex. 44-5, p. 14).
    
        The U.S. Environmental Protection Agency applied a linearized (no 
    threshold) multistage model to the Glaser data (Ex. 17-101). They 
    reported a maximum likelihood estimate for lifetime lung cancer risk of 
    6.3 per 1000 from continuous exposure to 1 [mu]g Cr(VI)/m\3\. This risk 
    would be somewhat less for an occupational exposure (e.g. 8 hours/day, 
    5 days/week) to the same air level and would be close to the excess 
    lifetime risk predicted by OSHA (i.e. 2-9 per 1000).
        In summary, OSHA does not believe the animal evidence demonstrates 
    that respiratory irritation is required for Cr(VI)-induced 
    carcinogenesis. Significant elevation in lung tumor incidence was 
    reported in rats that received Cr(VI) by instillation or inhalation at 
    dose levels that caused minimal lung damage. Consequently, OSHA 
    believes it inappropriate to consider a NOAEL (such as 25 [mu]g/m\3\) 
    where lung tumors were not observed in a limited number of animals to 
    be a threshold concentration below which there is no risk. Statistical 
    analysis of the animal inhalation data using a standard dose-response 
    model commonly employed for genotoxic carcinogens, such as Cr(VI), is 
    reported to predict risks similar to those estimated by OSHA from the 
    occupational cohorts of chromate production workers. While the rat 
    intratracheal instillation study indicates that a dose rate effect may 
    exist for Cr(VI)-induced carcinogenesis, it can not be reliably 
    determined from the data whether the effect would occur at the 
    occupational exposures of interest (e.g. working lifetime exposures at 
    0.25 to 52 [mu]g Cr(VI)/m\3\) without a better quantitative 
    understanding of Cr(VI) dosimetry within the lung. Therefore, OSHA does 
    not believe that the animal data show that cumulative Cr(VI)
    exposure is an inappropriate metric to estimate lung cancer risk.
        Exponent used the clinical findings from chromate production 
    workers in the Gibb and Luippold cohorts to support their contention 
    that 'respiratory irritation' was key to Cr(VI)-induced lung cancer 
    (Ex. 28-233-4, p. 18-19). They noted that over 90 percent of chromate 
    production workers employed at the Painesville plant during the 1930s 
    and 1940s, including some Luippold cohort members, were reported to 
    have damaged nasal septums. Based on this, Exponent concludes:
    
        Thus, it is possible that the increased incidence of lung cancer 
    in these workers (i.e. SMR of 365 from Luippold et al. cohort 
    exposed during the 1940s) is at least partially due to respiratory 
    system tissue damage resulting from high Cr(VI) concentrations to 
    which these workers were exposed. These exposures clearly exceed a 
    threshold for both carcinogenic and non-carcinogenic (i.e. 
    respiratory irritation) health effects (Ex. 38-233-4, p. 18).
    
    Exponent noted that about 60 percent of the Gibb cohort also suffered 
    ulcerated nasal septum tissue. The mean estimated annual Cr(VI) air 
    level at time of diagnosis was about 25 [mu]g Cr(VI)/m\3\. Ulcerated 
    nasal septum was found to be highly correlated with the average annual 
    Cr(VI) exposure of the workers as determined by a proportional hazards 
    model. These findings, again, led Exponent to suggest that:
    
        It may be reasonable to surmise that the high rates of lung 
    cancer risk observed among the featured cohorts (i.e. Gibb and 
    Luippold) was at least partially related to respiratory irritation 
    (Ex. 38-233-4, p. 19).
    
        In its explanations, Exponent assumes that the irritation and 
    damage to nasal septum tissue found in the exposed workers also occurs 
    elsewhere in the respiratory tract. Exponent provided no evidence that 
    Cr(VI) concentrations that damage tissue at the very front of the nose 
    will also damage tissue in the bronchoalveolar regions where lung 
    cancers are found. A national medical survey of U.S. chromate 
    production workers conducted by the U.S. Public Health Service in the 
    early 1950s found greater than half suffered nasal septum perforations 
    (Ex. 7-3). However, there was little evidence of non-cancerous lung 
    disease in the workers. The survey found only two percent of the 
    chromate workers had chronic bronchitis which was only slightly higher 
    than the prevalence in nonchromate workers at the same plants and less 
    than had been reported for ferrous foundry workers. Just over one 
    percent of the chromate production workers in the survey were found to 
    have chest X-ray evidence consistent with pulmonary fibrosis. This led 
    the U.S. Public Health Service to conclude "on the basis of X-ray data 
    we cannot confirm the presence of pneumoconiosis from chromate 
    exposure" (Ex. 7-3, p. 80). An earlier report noted fibrotic areas in 
    the autopsied lungs of three Painesville chromate production workers 
    employed during the 1940s who died of lung cancer (Ex. 7-12). The 
    authors attributed the fibrotic lesions to the large amounts of 
    chromite (a Cr(III) compound) ore found in the lungs.
        Exponent correctly noted that prevalence of nasal septum ulceration 
    in the Gibb cohort was "significantly associated with [average annual] 
    Cr(VI) exposure concentrations" using a proportional hazards model 
    (Ex. 38-233-4, p. 19). However, other related symptomatology, such as 
    nasal irritation and perforation, was not found to be correlated with 
    annual average Cr(VI) air levels. This led the authors to suggest that 
    nasal septum tissue damage was more likely related to short-term, 
    rather than annual, Cr(VI) air levels. Nasal septum ulceration was also 
    not a significant predictor of lung cancer when the confounding effects 
    of smoking and cumulative Cr(VI) exposure were accounted for in the 
    proportional hazards model (Ex. 31-22-11). The authors believed the 
    lack of correlation probably reflected cumulative Cr(VI) as the 
    dominant exposure metric related to the elevated lung cancer risk in 
    the workers, rather than the high, short-term Cr(VI) air levels thought 
    to be responsible for the high rate of nasal septum damage. The 
    modeling results are not consistent with nasal septum damage as a 
    predictor of Cr(VI)-induced lung cancer in chromate production workers. 
    Dr. Herman Gibb confirmed this in oral testimony:
    
        * * * I was curious to see if [respiratory] irritation might be 
    predictive of lung cancer. We did univariate analyses and found that 
    a number of them were [predictive]. But whenever you looked at, when 
    you put it into the regression model, none of them were. In other 
    words, [respiratory] irritation was not predictive of the lung 
    cancer response (Tr. 144).
    
        OSHA does not believe the evidence indicates that tissue damage in 
    the nasal septum of chromate production workers exposed to Cr(VI) air 
    levels around 20 [mu]g/m\3\ is responsible for the observed excess lung 
    cancers. The lung cancers are found in the bronchioalveolar region, far 
    removed from the nasal septum. Careful statistical analysis of the Gibb 
    cohort did not find a significant relationship between clinical 
    symptoms of nasal septum damage (e.g. ulceration, persistent bleeding, 
    perforation) and lung cancer mortality. A 1951 U.S. Public Health 
    Service medical survey found a high prevalence of nasal septum damage 
    with few cases of chronic non-neoplastic lung disease (e.g. chronic 
    bronchitis, pulmonary fibrosis). This suggests that the nasal septum 
    damage caused by high Cr(VI) air concentrations was not mirrored by 
    damage in lower regions of the respiratory tract where lung cancer 
    takes place. Given these findings, it seems unlikely that the lower 
    Cr(VI) air levels experienced by the Gibb cohort caused pervasive 
    bronchioalveolar tissue damage that would be responsible for the 
    clearly elevated lung cancer incidence in these workers. Therefore, the 
    Agency does not concur with Exponent that there is credible evidence 
    from occupational cohort studies that the high rates of lung cancer are 
    related to tissue damage in the respiratory tract or that occupational 
    exposure to 20 [mu]g Cr(VI)/m\3\ represents a 'no effect' level for 
    lung cancer.
        Some commenters felt that certain physiological defense mechanisms 
    that protect against the Cr(VI)-induced carcinogenic process introduce 
    a threshold or sublinear dose-response (Exs. 38-233-4; 38-215-2; 38-
    265). Some physiological defenses are thought to reduce the amount of 
    biologically active chromium (e.g. intracellular Cr(V), Cr(III), and 
    reactive oxygen species) able to interact with critical molecular 
    targets within the lung cell. A prime example is the extracellular 
    reduction of permeable Cr(VI) to the relatively impermeable Cr(III) 
    which reduces Cr(VI) uptake into cells. Other defense mechanisms, such 
    as DNA repair and apoptosis, can interfere with carcinogenic 
    transformation and progression. These defense mechanisms are presented 
    by commenters as highly effective at low levels of Cr(VI) but are 
    overwhelmed at high dose exposures and, thus, could "provide a 
    biological basis for a sublinear dose-response or a threshold below 
    which there is expected to be no increased lung cancer risk (Ex. 38-
    215-2, p. 29).
        One study, cited in support of an exposure-response threshold, 
    determined the amount of highly soluble Cr(VI) reduced to Cr(III) in 
    vitro by human bronchioalveolar fluid and pulmonary macrophage 
    fractions over a short period (Ex. 31-18-7). These specific activities 
    were used to estimate an "overall reducing capacity" of the lung. As 
    previously discussed, cell membranes are permeable to Cr(VI) but not 
    Cr(III), so only Cr(VI) enters cells to any appreciable extent. The 
    authors interpreted these data to mean that high
    levels of Cr(VI) would be required to "overwhelm" the reduction 
    capacity before significant amounts of Cr(VI) could enter lung cells 
    and damage DNA, thus creating a biological threshold to the exposure--
    response (Ex. 31-18-8).
        There are several problems with this threshold interpretation. The 
    in vitro reducing capacities were determined in the absence of cell 
    uptake. Cr(VI) uptake into lung cells happens concurrently and in 
    parallel with its extracellular reduction, so it cannot be concluded 
    from the study data that a threshold reduction capacity must be 
    exceeded before uptake occurs. The rate of Cr(VI) reduction to Cr(III) 
    is critically dependant on the presence of adequate amounts of 
    reductant, such as ascorbate or GSH (Ex. 35-65). It has not been 
    established that sufficient amounts of these reductants are present 
    throughout the thoracic and alveolar regions of the respiratory tract 
    to create a biological threshold. Moreover, the in vitro activity of 
    Cr(VI) reduction in epithelial lining fluid and alveolar macrophages 
    was shown to be highly variable among individuals (Ex. 31-18-7, p. 
    533). It is possible that Cr(VI) is not rapidly reduced to Cr(III) in 
    some workers or some areas of the lung. Finally, even if there was an 
    exposure threshold created by extracellular reduction, the study data 
    do not establish the dose range in which the putative threshold would 
    occur.
        Other commenters thought extracellular reduction and other 
    physiological defenses were unlikely to produce a biological threshold 
    (Exs. 44-5; 40-18-1). For example, Dr. Clewell remarked:
    
        Although studies attempted to estimate capacities of Cr(VI) (De 
    Flora et al., 1997) the extracellular reduction and cellular uptake 
    of Cr(VI) are parallel and competing kinetic processes. That is, 
    even at low concentrations where reductive capacity is undiminished, 
    a fraction of Cr(VI) will still be taken up into cells, as 
    determined by the relative rates of reduction and transport. For 
    this reason, reductive capacities should not be construed to imply 
    "thresholds" below which Cr(VI) will be completely reduced prior 
    to uptake. Rather, they indicate that there is possibly a "dose-
    dependent transition", i.e. a nonlinearity in concentration 
    dependence of the cellular exposure to Cr(VI). Evaluation of the 
    concentration-dependence of the cellular uptake of Cr(VI) would 
    require more data than is currently available on the relative 
    kinetics of dissolution, extracellular reduction, and cellular 
    uptake as well as on the homeostatic response to depletion of 
    reductive resources (e.g. reduction of glutathione reductase) (Ex. 
    44-5, p. 16)
    
        The same logic applies to other 'defense mechanisms' such as DNA 
    repair and apoptosis. Despite the ability of cells to repair DNA damage 
    or to undergo apoptosis (i.e. a form of programmed cell death) upon 
    exposure to low levels of Cr(VI), these protections are not absolute. 
    Since a single error in a critical gene may trigger neoplastic 
    transformation and DNA damage increases with intracellular 
    concentration of Cr(VI), it stands to reason that there may be some 
    risk of cancer even at low Cr(VI) levels. If the protective pathways 
    are saturable (e.g. protective capacity overwhelmed) then it might be 
    manifested as a dose transition or nonlinearity. However, as explained 
    above, an extensive amount of kinetic modeling data would be needed to 
    credibly predict the dose level at which a potential dose transition 
    occurs. OSHA agrees with Dr. Clewell that "in the absence of such a 
    biologically based [kinetic] dose-response model it is impossible to 
    determine either the air concentration of Cr(VI) at which the 
    nonlinearity might occur or the extent of the departure from a linear 
    dose-response that would result. Therefore, the assumption of a linear 
    dose-response is justified" (Ex. 44-5, p.17-18).
        In conclusion, OSHA believes that examination of the Gibb and 
    Luippold cohorts, the new U.S. cohorts analyzed in Luippold et al. 
    (2005), and the best available animal and mechanistic evidence does not 
    support a departure from the traditional linear, cumulative exposure-
    based approach to cancer risk assessment for hexavalent chromium. 
    OSHA's conclusion is supported by several commenters (see e.g. Tr. 121, 
    186, Exs. 40-10-2, p. 6; 44-7). For example, NIOSH stated:
    
        It is not appropriate to employ a threshold dose-response 
    approach to estimate cancer risk from a genotoxic carcinogen such as 
    Cr(VI) [Park et al. 2004]. The scientific evidence for a 
    carcinogenicity threshold for Cr(VI) described in the Preamble [to 
    the proposed rule] consists of the absence of an observed effect in 
    epidemiology studies and animal studies at low exposures, and in 
    vitro evidence of intracellular reduction. The epidemiologic and 
    animal studies lack the statistical power to detect a low-dose 
    threshold. In both the NIOSH and OSHA risk assessments, linear no-
    threshold risk models provided good fit to the observed cancer data. 
    The in vitro extracellular reduction studies which suggested a 
    theoretical basis for a non-linear reseponse to Cr(VI) exposure were 
    conducted under non-physiologic conditions. These results do not 
    demonstrate a threshold of response to Cr(VI) exposure (Ex. 40-10-2, 
    p. 6).
    
    OSHA's position is also supported by Dr. Herman Gibb's testimony at the 
    hearing that a linear, no-threshold model best characterizes the 
    relationship between Cr(VI) exposure and lung cancer risk in the Gibb 
    cohort (Tr. 121). Statements from Ms. Deborah Proctor and Crump et al. 
    (who conducted analyses utilizing the Luippold cohort) also indicated 
    that these data are consistent with the traditional linear model (Tr. 
    1845, Exs. 33-10, p. 456; 35-58, pp. 1159-1160). The significant excess 
    risk observed in the Gibb cohort, which was best suited to address risk 
    from low cumulative or average exposures, contradicts comments to the 
    effect that "[i]ncreased lung cancers have been demonstrated only at 
    workplace exposures significantly higher than the existing standard * * 
    * " (Ex. 38-185, p. 4) or that characterized OSHA's risk assessment 
    for the proposed PEL as "speculative" (Ex. 47-35-1, p. 4) or 
    "seriously flawed" (Ex. 38-106, p. 23). OSHA believes that the clear 
    excess risk among workers with cumulative exposures equivalent to those 
    accrued over a 45-year working lifetime of low-level exposure to 
    Cr(VI), combined with the good fit of linear exposure-response models 
    to the Gibb and Luippold (2003) datasets and the lack of demonstrable 
    nonlinearities or dose-rate effects, constitute strong evidence of risk 
    at low exposures in the range of interest to OSHA.
    3. Influence of Smoking, Race, and the Healthy Worker Survivor Effect
        A common confounder in estimating lung cancer risk to workers from 
    exposure to a specific agent such as Cr(VI) is the impact of cigarette 
    smoking. First, cigarette smoking is known to cause lung cancer. 
    Ideally, lung cancer risk attributable to smoking among the Cr(VI)-
    exposed cohorts should be controlled or adjusted for in characterizing 
    exposure-response. Secondly, cigarette smoking may interact with the 
    agent (i.e., Cr(VI)) or its biological target (i.e., susceptible lung 
    cells) in a manner that enhances or even reduces the risk of developing 
    Cr(VI)-induced lung cancer from occupational exposures, yet is not 
    accounted for in the risk model. The Small Business Administration's 
    Office of Advocacy commented that such an interactive effect may have 
    improperly increased OSHA's risk estimates (Ex. 38-7, p. 4).
        OSHA believes its risk estimates have adequately accounted for the 
    potential confounding effects of cigarette smoking in the underlying 
    exposure-lung cancer response data, particularly for the Gibb cohort. 
    One of the key issues in this regard is whether or not the reference 
    population utilized to derive the expected number of lung cancers 
    appropriately reflects the smoking behavior of the cohort members. The
    risk analyses of the Gibb cohort by NIOSH and Environ indicate that 
    cigarette smoking was properly controlled for in the exposure-response 
    modeling. NIOSH applied a smoking-specific correction factor that 
    included a cumulative smoking term for individual cohort members (Ex. 
    33-13). Environ applied a generic correction factor and used lung 
    cancer mortality rates from Baltimore City as a reference population 
    that was most similar to the cohort members with respect to smoking 
    behavior and other factors that might affect lung cancer rates (Ex. 33-
    12). Environ also used internally standardized models that did not 
    require use of a reference population and included a smoking-specific 
    (yes/no) variable. All these models predicted very similar estimates of 
    risk over a wide range of Cr(VI) exposures. There was less information 
    about smoking status for the Luippold cohort. However, regression 
    modeling that controlled for smoking indicated that it was not a 
    significant confounding factor when relating Cr(VI) exposure to the 
    lung cancer mortality (Ex. 35-58).
        Smoking has been shown to interact in a synergistic manner (i.e., 
    combined effect of two agents are greater than the sum of either agent 
    alone) with some lung carcinogens, most notably asbestos (Ex. 35-114). 
    NIOSH reported a slightly negative but nonsignficant interaction 
    between cumulative Cr(VI) exposure and smoking in a model that had 
    separate linear terms for both variables (Ex. 33-13). This means that, 
    at any age, the smoking and Cr(VI) contributions to the lung cancer 
    risk appeared to be additive, rather than synergistic, given the 
    smoking information in the Gibb cohort along with the cumulative 
    smoking assumptions of the analysis. In their final linear relative 
    risk model, NIOSH included smoking as a multiplicative term in the 
    background rate in order to estimate lifetime lung cancer risks 
    attributable to Cr(VI) independent of smoking. Although this linear 
    relative risk model makes no explicit assumptions with regard to an 
    interaction between smoking and Cr(VI) exposure, the model does assume 
    a multiplicative relationship between the background rate of lung 
    cancer in the reference population and Cr(VI) exposure. Therefore, to 
    the extent that smoking is a predominant influence on the background 
    lung cancer risk, the linear relative risk model implicitly assumes a 
    multiplicative (e.g., greater than additive and synergistic, in most 
    situations) relationship between cumulative Cr(VI) exposure and 
    smoking. Since current lung cancer rates reflect a mixture of smokers 
    and non-smokers, OSHA agrees with the Small Business Administration's 
    Office of Advocacy that the excess lung cancer risks from Cr(VI) 
    exposure predicted by the linear relative risk model may overestimate 
    the risks to non-smokers to some unknown extent. By the same token, the 
    model may underestimate the risk from Cr(VI) exposure to heavy smokers. 
    Because there were so few non-smokers in the study cohorts 
    (approximately 15 percent of the exposed workers and four lung cancer 
    deaths in the Gibb cohort), it was not possible to reliably estimate 
    risk for the nonsmoking subpopulation.
        Although OSHA is not aware of any convincing evidence of a specific 
    interaction between cigarette smoking and Cr(VI) exposure, prolonged 
    cigarette smoking does have profound effects on lung structure and 
    function that may indirectly influence lung cancer risk from Cr(VI) 
    exposure (Ex. 33-14). Cigarette smoke is known to cause chronic 
    irritation and inflammation of the respiratory tract. This leads to 
    decreases in airway diameter that could result in an increase in Cr(VI) 
    particulate deposition. It also leads to increased mucous volume and 
    decreased mucous flow, that could result in reduced Cr(VI) particulate 
    clearance. Increased deposition and reduced clearance would mean 
    greater residence time of Cr(VI) particulates in the respiratory tract 
    and a potentially greater probability of developing bronchogenic 
    cancer. Chronic cigarette smoking also leads to lung remodeling and 
    changes in the proliferative state of lung cells that could influence 
    susceptibility to neoplastic transformation. While the above effects 
    are plausible consequences of cigarette smoking on Cr(VI)-induced 
    carcinogenesis, the likelihood and magnitude of their occurrence have 
    not been firmly established and, thus, the impact on risk of lung 
    cancer in exposed workers is uncertain.
        Differences in lung cancer incidence with race may also introduce 
    uncertainty in risk estimates. Gibb et al. reported differing patterns 
    for the cumulative exposure-lung cancer mortality response between 
    whites and non-whites in their cohort of chromate production workers 
    (Ex. 31-22-11). In the assessment of risk from the Gibb cohort, NIOSH 
    reported a strong interaction between cumulative Cr(VI) exposure and 
    race, such that nonwhites had a higher cumulative exposure coefficient 
    (i.e., higher lung cancer risk) than whites based on a linear relative 
    risk model (Ex. 33-13). If valid, this might explain the slightly lower 
    risk estimates in the predominantly white Luippold cohort. However, 
    Environ found that including race as an explanatory variable in the Cox 
    proportional hazards model C1 did not significantly improve model fit 
    (p=0.15) once cumulative Cr(VI) exposure and smoking status had been 
    considered (Ex. 33-12).
        NIOSH suggested that exposure or smoking misclassification might 
    plausibly account for the Cr(VI) exposure-related differences in lung 
    cancer by race seen in the Gibb cohort (Ex. 33-13, p. 15). It is 
    possible that such misclassification might have occurred as a result of 
    systematic differences between whites and non-whites with respect to 
    job-specific Cr(VI) exposures at the Baltimore plant, unrecorded 
    exposure to Cr(VI) or other lung carcinogens when not working at the 
    plant, or in smoking behavior. Unknown differences in biological 
    processes critical to Cr(VI)-induced carcinogenesis could also 
    plausibly account for an exposure-race interaction. However, OSHA is 
    not aware of evidence that convincingly supports any of these possible 
    explanations.
        Another source of uncertainty that may impact the risk estimates is 
    the healthy worker survivor effect. Studies have consistently shown 
    that workers with long-term employment status have lower mortality 
    rates than short-term employed workers. This is possibly due to a 
    higher proportion of ill individuals and those with a less healthy 
    lifestyle in the short term group (Ex. 35-60). Similarly, worker 
    populations tend to be healthier than the general population, which 
    includes both employed and unemployed individuals. As a result, 
    exposure-response analyses based on mortality of long-term healthy 
    workers will tend to underestimate the risk to short-term workers and 
    vice versa, even when their cumulative exposure is similar. Also, an 
    increase in disease from occupational exposures in a working population 
    may not be detected when workers are compared to a reference population 
    that includes a greater proportion less healthy individuals.
        The healthy worker survivor effect is generally thought to be less 
    of a factor in diseases with a multifactorial causation and long onset, 
    such as cancer, than in diseases with a single cause or short onset. 
    However, there is evidence of a healthy worker effect in several 
    studies of workers exposed to Cr(VI), as discussed further in the next 
    section ("Suitability of Risk Estimates for Cr(VI) Exposures in Other 
    Industries"). In these studies, the healthy worker survivor effect may 
    mask increased lung cancer mortality due to occupational Cr(VI) exposure.
    4. Suitability of Risk Estimates for Cr(VI) Exposures in Other 
    Industries
        At issue is whether the excess lung cancer risks derived from 
    cohort studies of chromate production workers are representative of the 
    risks for other Cr(VI)-exposed workers (e.g., electroplaters, painters, 
    welders). Typically, OSHA has used epidemiologic studies from one 
    industry to estimate risk for other industries. For example, OSHA 
    relied on a cohort of cadmium smelter workers to estimate the excess 
    lung cancer risk in a wide range of affected industries for its cadmium 
    standard (57 FR at 42102, 9/14/1992). This approach is usually 
    acceptable because exposure to a common agent of concern is the primary 
    determinant of risk and not some other factor unique to the workplace. 
    However, in the case of Cr(VI), workers in different industries are 
    exposed to various Cr(VI) compounds that may differ in carcinogenic 
    potency depending to a large extent on water solubility. The chromate 
    production workers in the Gibb and Luippold cohorts were primarily 
    exposed to certain highly water-soluble chromates. As more fully 
    described in section V.B. of the Cancer Effects section, the scientific 
    evidence indicates that all Cr(VI) compounds are carcinogenic but that 
    the slightly soluble chromates (e.g. calcium chromate, strontium 
    chromate, and some zinc chromates) exhibit greater carcinogenicity than 
    the highly water soluble chromates (e.g. sodium chromate, sodium 
    dichromate, and chromic acid) or the water insoluble chromates (e.g. 
    lead chromates) provided the same dose is delivered and deposited in 
    the respiratory tract of the worker. It is not clear from the available 
    scientific evidence whether the carcinogenic potency of water-insoluble 
    Cr(VI) compounds would be expected to be more or less than highly 
    water-soluble Cr(VI) compounds. Therefore, OSHA finds it prudent to 
    regard both types of Cr(VI) compounds to be of similar carcinogenic 
    potency.
        The primary operation at the chromate production plants in 
    Painesville (Luippold cohort) and Baltimore (Gibb cohort) was the 
    production of the highly water-soluble sodium dichromate. Sodium 
    dichromate served as a starting material for the production of other 
    highly water-soluble chromates such as sodium chromate, potassium 
    dichromate, and chromic acid (Exs. 7-14; 35-61). As a result, the Gibb 
    and Luippold cohorts were principally exposed to water-soluble Cr(VI). 
    In the NPRM, OSHA requested comment on whether its risk estimates based 
    on the exposure-response data from these two cohorts of chromate 
    production workers were reasonably representative of the risks expected 
    from equivalent exposures to different Cr(VI) compounds encountered in 
    other industry sectors. Of particular interest was whether the 
    preliminary risk estimates from worker cohorts primarily engaged in the 
    production of the highly water soluble sodium chromate and sodium 
    dichromate would substantially overpredict lung cancer risk for workers 
    with the same level and duration of exposure to Cr(VI) but involving 
    different Cr(VI) compounds or different operations. These operations 
    include chromic acid aerosol in electroplating operations, the less 
    water soluble Cr(VI) particulates encountered during pigment production 
    and painting operations, and Cr(VI) released during welding, as well as 
    exposure in other applications.
        OSHA received comments on this issue from representatives of a wide 
    range of industries, including chromate producers, specialty steel 
    manufacturers, construction and electric power companies that engage in 
    stainless steel welding, the military and aerospace industry that use 
    anti-corrosive primers containing Cr(VI), the surface finishing 
    industry, color pigment manufacturers, and the Small Business 
    Administration's Office of Advocacy (Exs. 38-231, 38-233; 38-8; 47-5; 
    40-12-4; 38-215; 40-12-5; 38-106; 39-43; 38-7). Many industry 
    commenters expressed concerns about the appropriateness of the 
    underlying Gibb and Luippold data sets and the methodology (e.g. linear 
    instead of threshold model) used to generate the lung cancer risk 
    estimates. These issues have been addressed in other parts of section 
    VI. The color pigment manufacturers asserted that lead chromate 
    pigments, unlike other Cr(VI) compounds, lacked carcinogenic potential. 
    This issue was addressed in section V.B.9 of the Health Effects 
    section. In summary, OSHA finds lead chromate and other water-insoluble 
    Cr(VI) compounds to be carcinogenic. The Agency further concludes that 
    it is reasonable to regard water insoluble Cr(VI) compounds to be of 
    similar carcinogenic potency to highly soluble Cr(VI) compounds. Based 
    on this conclusion, OSHA no longer believes that its risk projections 
    will underestimate the lung cancer risk for workers exposed to 
    equivalent levels of water-insoluble Cr(VI), as suggested in the NPRM 
    (69 FR at 59384).
        Several commenters encouraged OSHA to rely on cohort studies that 
    examined the lung cancer mortality of workers in their particular 
    industry in lieu of the chromate production cohorts. Members of the 
    aircraft industry and their representatives commented that OSHA failed 
    to consider the results from several large cohort studies that showed 
    aerospace workers were not at increased risk of lung cancer (Exs. 38-
    106; 38-215-2; 44-33; 47-29-2). In addition, Boeing Corporation and the 
    Aeropspace Industries Association (AIA) provided data on the size 
    distribution of Cr(VI) aerosols generated during primer spraying 
    operations which showed most particles to be too large for deposition 
    in the region of the respiratory tract where lung cancer typically 
    occurs (Exs. 38-106-2; 38-215-2; 47-29-2). The Specialty Steel Industry 
    maintained that epidemiological data specific to alloy manufacturing 
    and experience within the their industry show that the lung cancer risk 
    estimated by OSHA is unreasonably high for steel workers exposed to the 
    proposed PEL of 1 [mu]g Cr(VI)/m\3\ (Ex. 38-233, p. 82). Several 
    comments argued that there was a lack of scientific evidence for a 
    quantifiable exposure-response relationship between Cr(VI) exposure 
    from stainless steel welding (Exs. 38-8; 38-233-4). The commenters went 
    on to suggest that the OSHA quantitative Cr(VI) exposure-lung cancer 
    response model derived from the chromate production cohorts should not 
    be used to characterize the risk to welders. The suitability of the 
    OSHA risk estimates for these particular industries is further 
    discussed below.
        a. Aerospace Manufacture and Maintenance. Most of the comments on 
    suitability of OSHA risk estimates were provided by AIA (Exs. 38-215; 
    47-29-2), Exponent on behalf of AIA (Exs. 38-215-2; 44-33), and the 
    Boeing Corporation (Exs. 38-106; 38-106-1). Cr(VI) is used as an anti-
    corrosive in primers and other coatings applied to the aluminum alloy 
    structural surfaces of aircraft. The principal exposures to Cr(VI) 
    occur during application of Cr(VI) primers and coatings and mechanical 
    sanding of the painted surfaces during aircraft maintenance. Cr(VI) 
    exposures are usually in the form of the slightly soluble strontium and 
    zinc chromates used in primers and chromic acid found in other 
    treatments and coatings designed to protect metal surfaces.
        Cohort Studies of Aerospace Workers. AIA commented that:
    
        OSHA has all but ignored a substantial body of evidence of 
    studies showing no increased risk of lung cancer in aerospace 
    workers * * *. While epidemiologic studies show a link between lung 
    cancer and chromium VI exposure in other industries [e.g. chromate 
    production], that relationship is not established in the aerospace 
    industry (Ex.38-106, p. 16).
    
    Aerospace commenters pointed to several cohort studies from aircraft 
    manufacturing and maintenance sites that did not find significantly 
    elevated lung cancer mortality in workers (Exs. 31-16-3; 31-16-4; 35-
    213; 35-210). However, OSHA believes that the vast majority of workers 
    in these cohorts were not routinely engaged in jobs involving potential 
    Cr(VI) exposures.
        Only two of the above studies (i.e., the Alexander and Boice 
    cohorts) specifically investigated the relationship between Cr(VI) 
    exposures and lung cancer mortality (Exs. 31-16-3; 31-16-4). The 
    Alexander cohort was evaluated as a supplemental data set for 
    quantitative risk assessment in sections VI.B.6 and VI.E.4. Briefly, 
    there were 15 observed lung cancer cases in the Alexander et al. study 
    with 19.5 expected (Ex. 31-16-3). There was no evidence of a positive 
    trend between cumulative Cr(VI) exposure and lung cancer incidence. The 
    lack of excess lung cancers was probably, in large part, due to the 
    short follow-up period (median nine years per member) and young age of 
    the cohort (median 42 years at the end of follow-up). Lung cancer 
    generally occurs 20 or more years after initial exposure to a 
    carcinogenic agent and mostly in persons aged 55 years and older. There 
    was no Cr(VI) air monitoring data for a significant portion of the 
    study period and reconstruction of worker exposure was reduced to a 
    limited number of 'summary time-weighted average exposure levels' based 
    on job category (Ex. 31-16-3). These limitations may have caused 
    inaccuracies in the worker exposure estimates that could lead to 
    potential misclassification of exposure, and, thus may also have 
    contributed to the lack of a positive Cr(VI) exposure--lung cancer 
    response.
        In the their technical comments on behalf of the AIA, Exponent 
    considered the Boice cohort to be "the largest, best defined, most 
    completely ascertained, and followed for the longest duration" of the 
    epidemiological studies examining lung cancer mortality and other 
    health outcomes of aerospace workers (Ex. 38-215-2, p. 10). The Boice 
    cohort (previously described in section V.B.6) consisted of 77,965 
    aerospace workers employed over a thirty-year period at a large 
    aircraft manufacturing plant in California (Ex. 31-16-4). The average 
    duration of employment was over ten years and thirty percent of the 
    cohort was deceased. Therefore, the Boice cohort was larger, older, and 
    had greater follow-up than the Alexander cohort. Unfortunately, Cr(VI) 
    air measurements were sparse in recent years and entirely absent during 
    early years of plant operation so, unlike the Alexander cohort, 
    quantitative Cr(VI) exposure reconstruction was not attempted. Instead, 
    all jobs were qualitatively categorized by the chemicals involved 
    (e.g., chromates, trichloroethylene, perchloroethylene, etc.) and their 
    frequency of chemical usage (routine, intermittent, or no exposure). 
    Duration of potential chemical exposure, including Cr(VI), was 
    determined for the cohort members based on work history (Ex. 47-19-15). 
    There were 3634 workers in the cohort believed to have routine 
    exposures to Cr(VI), mostly in painting/primer operations or operating 
    process equipment used for plating and corrosion protection. Another 
    3809 workers were thought to have potential 'intermittent exposure' to 
    chromates. Most workers with potential exposure to Cr(VI) also had 
    potential exposures to the chlorinated solvents tricholoroethylene 
    (TCE) and perchloroethylene (PCE). Because of an inadequate amount of 
    Cr(VI) exposure data, OSHA was unable to use the Boice study for 
    quantitative risk assessment.
        The Boice et al. study did not find excess lung cancer among the 
    45,323 aircraft factory workers when compared against the race-, age-, 
    calendar year-, and gender-adjusted rates for the general population of 
    the State of California (SMR=97). This is not a surprising result 
    considering more than 90 percent did not work in jobs that routinely 
    involve Cr(VI) exposure. Factory workers potentially exposed to Cr(VI) 
    also did not have significantly elevated lung cancer mortality 
    (SMR=102; 95% CI: 82-126) relative to the California general population 
    based on 87 observed lung cancer deaths. However, workers engaged in 
    spray painting/priming operations that likely had the highest potential 
    for Cr(VI) exposure did experience some excess lung cancer mortality 
    (SMR=111; 95% CI: 80-151) based on 41 deaths, but the increase was not 
    statistically significant.
        As commonly encountered in factory work, there was evidence of a 
    'healthy worker effect' in this aerospace cohort that became 
    increasingly pronounced in workers with long-term employment. The 
    healthy worker effect (HWE) refers to the lower rate of disease 
    relative to the general population sometimes observed in long-term 
    occupational cohorts. For example, the Boice cohort factory workers 
    employed for 20 years had statistically significant lower rates of 
    death than a standardized California reference population for all 
    causes (SMR=78; 95% CI: 75-81), lung cancer (SMR=70; 95% CI: 61-80), 
    heart disease (SMR=79; 95% CI: 74-83), cerebrovascular disease (SMR=67; 
    95% CI: 56-78), non-malignant respiratory disease (SMR=65; 95% CI: 57-
    74), and cirrhosis of the liver (SMR=67; 95% CI: 51-88) among other 
    specific causes (Ex. 31-16-4, Table 5). The study authors note that 
    "these reductions [in disease mortality] seem in part due to the 
    initial selection into the workforce and the continued employment of 
    healthy people [i.e. healthy worker effect] that is often found in 
    occupational studies" (Ex. 31-16-4, p. 592). If not properly accounted 
    for in mortality analysis, HWE can mask evidence of disease risk. Mr. 
    Robert Park, senior epidemiologist from NIOSH, confirmed this at the 
    public hearing when addressing implications of HWE for Cr(VI) lung 
    cancer risk in the Boice cohort.
    
        This [Boice cohort] is a population where you would expect to 
    see a very dramatic healthy worker effect * * * so just off the top, 
    I would say any [relative risk] estimates for lung cancer in the 
    Boice population based on SMRs, I would want to adjust upwards by 
    0.9, for example, if the real SMR ought to be around 0.9 due to the 
    healthy worker effect. So if you do that in their population, they 
    have classified some workers as [routinely] exposed to chromates, 
    about 8 percent of the population. They observe a SMR of 1.02 in 
    that group. If you look at some of the other groupings in that 
    study, for example, assembly has an SMR of 0.92, fabrication, which 
    is basically make all the parts, 0.92, maintenance, 0.79. So a lot 
    of evidence for healthy worker effect in general in that population. 
    So the chromate group actually is at least 10 or 12 percent higher 
    in their lung cancer SMR. Now again, the numbers are small, you'd 
    have to have a very huge study for an SMR of 1.1 or 1.15 to be 
    statistically significant. So it is not. But it is a hint (Tr. 345-
    347).
    
        OSHA agrees with Mr. Park that the relative risks for lung cancer 
    in the Boice cohort are likely understated due to HWE. This is also 
    illustrated in the study analysis of the lung cancer morality patterns 
    by exposure duration to specific chemicals using internal cohort 
    comparisons. The internal analysis presumably minimize any biases (e.g. 
    smoking, HWE) that might exist from comparisons to the general 
    population. The results for workers potentially exposed to Cr(VI), 
    trichloroethylene (TCE), and perchloroethylene (PCE) are presented in 
    Table VI-9.

Table VI-9

 

    
        As shown in the table, there was a statistically significant 
    decline in relative risk of lung cancer among factory workers with 
    duration of TCE exposure (p< 0.01) and PCE exposure (p=0.02). This 
    mirrors the decline with increasing employment duration seen in 
    comparison with the general California population and strongly suggests 
    the internal cohort analysis failed to adequately adjust for HWE.
        The table shows that, despite the downward influence of HWE on lung 
    cancer risk, there was a slight nonsignificant upward trend in excess 
    lung cancer mortality with duration of exposure to Cr(VI). The result 
    is that aircraft workers potentially exposed to chromate for five or 
    more years had 50 to 70 percent greater lung cancer mortality than 
    coworkers with a similar duration of potential exposure to the 
    chlorinated solvents. The relative excess is even more noteworthy given 
    that the subgroups had considerable overlap (e.g., many of the same 
    workers in the PCE and TCE groups were also in the chromate group). 
    This implies that a subset of Cr(VI) workers not exposed to chlorinated 
    solvents, possibly spray painters routinely applying Cr(VI) primers 
    over many years, may be at greater lung cancer risk than other Cr(VI)-
    exposed members of the cohort.
        The AIA and its technical representative, Exponent, objected to 
    OSHA reliance on the non-statistically significant upward trend in 
    excess lung cancers with increasing Cr(VI) exposure duration described 
    above (Exs. 38-215-2; 47-29-2). Exponent stated:
    
        Statistical tests for trend indicated there is no evidence for a 
    trend of increasing risk of lung cancer with increasing years 
    exposed to chromate (P< 0.20). OSHA seems to have 'eye-balled' the 
    estimates and felt confident accepting the slight and non-
    significant increases among risk estimates with overlapping 
    confidence intervals as evidence of a "slightly positive" trend. 
    However, OSHA's interpretation is an overstatement of the finding 
    and should be corrected in the final rule (Ex. 38-215-2, p. 13).
    
        OSHA does not agree with these comments and believes it has 
    objectively interpreted the trend data in a scientifically legitimate 
    fashion. The fact that an upward trend in lung cancer risk with Cr(VI) 
    exposure duration fails to meet a statistical confidence of 95 percent 
    does not mean the relationship does not exist. For example, a trend 
    with a p-value of 0.2 means random chance will not explain the 
    relationship 80 percent of the time. The positive trend is all the more 
    notable given that it occurs in spite of a significant downward trend 
    in lung cancer mortality with years of employment. In other words, 
    aerospace workers exposed to Cr(VI) experienced a slightly greater lung 
    cancer mortality with increasing number of years exposed even while 
    their co-workers exposed to other chemicals were experiencing a 
    substantially lower lung cancer mortality with increasing years 
    exposed.
        In its post-hearing comments, NIOSH calculated the observed excess 
    lung cancer risk to the Boice spray painters expected to have the 
    highest Cr(VI) exposures (SMR=1.11) to be 21 percent higher than the 
    minimally Cr(VI)-exposed assembly workers (SMR=0.92). NIOSH assumed the 
    painters were exposed to 15 [mu]g CrO3/m3 (i.e., 
    the arithmetic mean of Cr(VI) air sampling data in the plant between 
    1978 to 1991) for 10 years (i.e., the approximate average duration of 
    employment) to derive an excess risk per mg CrO3/
    m3 of 1.4 (Ex. 47-19-1). NIOSH noted that this was very 
    close to the excess risk per mg CrO3/m3 of 1.44 
    determined from their risk modeling of the Gibb cohort (Ex. 33-13). In 
    a related calculation, OSHA derived the expected excess risk ratio from 
    its linear relative risk model using a dose coefficient consistent with 
    the Gibb and Luippold data sets. Assuming the Boice spray painters were 
    exposed to 10 [mu]g Cr(VI)/m3 (90th percentile of plant air 
    sampling data converted from [mu]g CrO3 to [mu]g Cr(VI)) for 
    12 years (average employment duration of Boice factory workers), the 
    model predicts a risk ratio 1.20 which is also very close to the 
    observed excess risk ratio of 1.21 calculated from the observed SMR 
    data for spray painters above. These calculations suggest that the 
    excess lung cancer mortality observed in the Boice subcohort of Cr(VI)-
    exposed aerospace workers is consistent with excess risks predicted 
    from models based on the Gibb and Luippold cohort of chromate 
    production workers.
        The other cohort studies of aerospace workers cited by AIA were not 
    informative with regard to the association between Cr(VI) and lung 
    cancer. A cohort study by Garabrandt et al. of 14,067 persons employed 
    by an aircraft manufacturing company found significantly reduced excess 
    lung cancer mortality (SMR=80; 95% CI: 68-95) compared to adjusted 
    rates in the U.S. and San Diego County populations (Ex. 35-210). The 
    mean duration of follow-up was only 16 years and the study authors are 
    careful to state that the study can not rule out excess risk for 
    diseases, such as lung cancer, that have long latencies of 20 years or 
    more. The consistently low all-cause and cancer mortalities reported in 
    the study strongly suggest the presence of a healthy worker effect. 
    Another cohort study by Blair et al. of 14,457 aircraft maintenance 
    workers at Hill Air Force base in Utah did not find elevated lung 
    cancer mortality (SMR=90; 95% CI: 60-130) when compared to the general 
    population of Utah (Ex. 35-213). However, the study was exclusively 
    designed to investigate cancer incidence of chlorinated solvents (e.g. 
    TCE, PCE, methylene chloride) and makes no mention of Cr(VI). This was 
    also the case for a cohort study by Morgan et al. of 20,508 aerospace 
    workers employed at a Hughes Aircraft manufacturing
    plant, which found no excess lung cancer mortality (SMR=0.96; 95% CI: 
    87-106) compared to the general U.S. population. However, a detailed 
    investigation of jobs at a large aircraft manufacturing facility (i.e. 
    facility studied by Boice et al.) found that only about 8 percent of 
    employees had potential for routine Cr(VI) exposure (Ex. 47-19-15). If 
    this is representative of the workforce in the other studies cited 
    above, it is doubtful whether a Cr(VI)-related increase in lung cancer 
    from a small proportion of workers would be reflected in the mortality 
    experience of the entire cohort, most of whom would not have been 
    exposed to Cr(VI).
        In summary, OSHA does not find convincing evidence from the 
    aerospace cohort studies that the Agency's quantitative risk assessment 
    overstates the lung cancer risk to Cr(VI)-exposed workers. An 
    association between Cr(VI) exposure and lung cancer was never addressed 
    in most cohorts relied upon by the aerospace industry. Job analysis 
    shows that only a minor proportion of all aerospace workers are engaged 
    in workplace activities that routinely lead to Cr(VI) exposure. This 
    could explain the lack of excess lung cancer mortality found in studies 
    characterizing the mortality experience of all aerospace workers. 
    Alexander et al. identified a cohort of Cr(VI) exposed workers, made 
    individual worker estimates of cumulative Cr(VI) exposures, and found 
    no exposure-related trend with lung cancer incidence. However, the 
    absence of exposure-response could be the result of a number of study 
    limitations including the young age of the cohort (e.g. majority of 
    workers were under 50 years of age, when lung cancer incidence is 
    relatively uncommon), the inadequate follow-up period (e.g. majority of 
    workers followed <  10 years), and the potential for exposure 
    misclassification (e.g. Cr(VI) exposure levels prior to 1975 were not 
    monitored). Boice et al. also identified a subcohort of aerospace 
    workers with potential Cr(VI) exposure but lacked adequate air sampling 
    to investigate a quantitative relationship between Cr(VI) exposure and 
    lung cancer response. There was a significant decline in relative lung 
    cancer risk with length of employment among factory workers as well as 
    those exposed to chlorinated solvents, indicating a strong healthy 
    worker survivor effect among this pool of workers. The healthy worker 
    effect may have masked a significant trend in lung cancer with Cr(VI) 
    exposure duration. Risk projections based on the OSHA linear model were 
    found to be statistically consistent with the relative risk ratios 
    observed in the Boice cohort.
        Cr(VI) Particle Size Distribution During Aerospace Operations. 
    Differences in the size of Cr(VI) aerosols generated during chromate 
    production and aerospace operations is another reason representatives 
    of the aircraft industry believe the OSHA risk estimates overstate risk 
    to aerospace workers (Exs. 38-106; 38-106-1; 38-215-2; 39-43; 44-33; 
    47-29-2). The submitted particle size data indicated that spraying 
    Cr(VI) primers mostly generates large aerosol droplets (e.g.
    > 10 [mu]m) not expected to penetrate beyond the very upper portions of 
    the respiratory tract (e.g. nasal passages, larynx). Some aerospace 
    commenters also cited research showing that the few respirable primer 
    particulates that reach the lower regions of the lung contain less 
    Cr(VI) per particle mass than the larger non-respirable particles (Exs. 
    44-33; 38-106; 39-43). As a result, aerospace commenters contend that a 
    very small proportion of Cr(VI) aerosols generated by aircraft primer 
    operations deposit in the bronchioalveolar regions of the lung where 
    lung cancer occurs. OSHA agrees that the particle size studies 
    submitted to the record sufficiently demonstrate that a relatively 
    small proportion of Cr(VI) reaches the critical regions of the lung as 
    a result of these aircraft spraying operations. However, the Agency 
    believes the reduction in lung cancer risk from this lower Cr(VI) 
    particle burden is likely offset by the greater carcinogenic activity 
    of the slightly soluble strontium and zinc chromates inhaled during 
    spray primer application. Evaluation of the study data provided to the 
    record and the rationale behind the OSHA position are described below.
        The Agency reviewed the information provided by Boeing on the 
    particle size of paint aerosols from typical spraying equipment used in 
    aerospace applications. Boeing provided size characterization of paint 
    aerosol from their in-house testing of spray paint equipment (Ex. 38-
    106-1, p. 8-11). They measured droplet size distributions of non-
    chromated polyurethane enamels generated by high volume low pressure 
    (HVLP) and electrostatic air spray guns under typical settings. The 
    particle size was measured 10 to 12 inches from the nozzle of the gun 
    using laser diffraction techniques. Boeing found the median volumetric 
    droplet diameter (Dv50) of the paint particles to be in the range of 17 
    to 32 [mu]m under the test conditions. Less than 0.5 percent of 
    droplets in the spray were 5 [mu]m and smaller (e.g. typical of 
    particles that deposit in the bronchioalveolar region). Boeing 
    concluded:
    
        In typical operations and products, the best aerosol size is a 
    distribution with mass median diameter of about 30-40 microns, and a 
    relatively monodisperse distribution. As a result, the fraction of 
    the spray that is < 5 micron is about 1% or less; in overspray 
    perhaps [ap]2%. Therefore the deposited dose would be far less than 
    from exposure to an equal concentration of a smaller aerosol size, 
    and estimates of risk based on studies of other industry sectors are 
    not relevant to evaluation of risk in aerospace paint spraying (Ex. 
    38-106-1, p. 16).
    
    Although Boeing used a non-chromated enamel paint in their studies, 
    they contend that the results would be representative of the particle 
    size distribution for a Cr(VI) primer using the same equipment under 
    similar conditions.
        Boeing also submitted recent publications by the UCLA Center for 
    Occupational and Environmental Health measuring the Cr(VI) particle 
    size distribution during spray painting operations at an aerospace 
    manufacturing facility (Ex. 38-106-1). The UCLA group investigated 
    particle size distributions of Cr(VI) primers sprayed from HVLP 
    equipment in a lab bench-scale spray booth and in a field study of 
    spray booths at an aerospace facility (Ex. 38-106-1, attachment 6). The 
    tested primers contained the slightly soluble strontium chromate. The 
    study data are presented in two papers by Sabty-Daily et al. The 
    aerosol particles were collected at different locations several meters 
    from the spray gun in the bench-scale paint booth using a cascade 
    impactor. Full shift personal breathing zone samples from workers 
    spraying primer were also collected with a cascade impactor in the 
    field studies. The mass median aerodynamic diameter (MMAD) for Cr(VI) 
    particles in the field study was reported to be 8.5 [mu]m with a 
    geometric standard deviation of 2.2 [mu]m. On average, 62 percent of 
    the Cr(VI) mass was associated with non-respirable particles >10 [mu]m. 
    Taking into account deposition efficiency, it was estimated that less 
    than five percent of the Cr(VI) would potentially deposit in the lower 
    regions of the respiratory tract where lung cancer occurs. The bench 
    scale study gave particle distributions similar to the field studies. 
    It was shown that particle size decreases slightly as gun atomization 
    pressure increases. Particles in the direct spray were generally larger 
    than the overspray. Particle size was shown to decrease with distance 
    to the target surface due to evaporation of solvent.
        Both Sabty-Daily articles and the Boeing submission made reference 
    to another study that measured particle size distribution of a HVLP-
    generated paint aerosol in the breathing zone of the worker (Ex. 48-3). 
    Paint droplets were collected on polycarbonate filters with 0.2 [mu]m 
    pore size. Aerosol size was measured using a microscopic method that 
    minimizes bias from solvent evaporation. The breathing zone MMAD in the 
    overspray was reported to be 15 to 19 [mu]m with a GSD of 1.7 [mu]m. In 
    another study, LaPuma et al. investigated the Cr(VI) content of primer 
    particles from an HVLP spray gun using a cascade impactor (Ex. 31-2-2). 
    They reported that smaller particles (i.e. < 7 [mu]m) contained 
    disproportionately less Cr(VI) per mass of dry paint than larger 
    particles.
        Boeing concluded that "the particle size distribution reported by 
    Sabty-Daily et al. (2004a) significantly underestimate the size 
    distribution of paint aerosol" (Ex. 38-106-1, p. 14). They state that 
    "in typical [spraying] operations and products the best aerosol size 
    is a distribution with mass median diameter of about 30-45 microns" 
    (Ex. 38-106-1, p. 16). This particle size is larger than 15 to 20 [mu]m 
    reported in independent breathing zone measurements of spray paint 
    aerosol collected on conventional sampling media (i.e. polycarbonate 
    filters) (Carlton and Flynn, 1997).
        The Boeing rationale for dismissing the UCLA data was that the 
    cascade impactor had low collection efficiency for larger particles 
    relative to the Boeing laser diffraction method, which Boeing believes 
    is more accurate over the entire size distribution. OSHA notes, 
    however, that Boeing did not characterize aerosol particles in the 
    breathing zone of workers spraying Cr(VI) primer. Their study 
    characterized droplet size from an non-chromated enamel spray directly 
    out of the spray gun prior to contact with the target surface. While 
    collection efficiency accounts for some of the particle size 
    difference, other factors may also have contributed. These factors 
    include the composition of the spray paint, the sampling location, and 
    the degree of solvent evaporation. OSHA considers Cr(VI) primer 
    droplets with an average MMAD of 7 to 20 [mu]m, as measured in 
    breathing zone studies, to best represent the particle size inhaled by 
    a worker during spraying operations, since this range was measured in 
    breathing zone studies. The majority of these droplet particles would 
    not be expected to penetrate regions of the respiratory tract where 
    lung cancers occur.
        While aerosol particle size during spray application of Cr(VI) 
    primers has been measured, AIA acknowledged that the particle size 
    distribution during sanding procedures has not been well studied (Exs. 
    38-106; 47-29-2). However, they believe that most of the particles 
    released as a result of sanding and grinding operations to remove old 
    paint coatings from aircraft are non-respirable (e.g. >10 [mu]m). OSHA 
    is not aware of reliable data in the record to support or refute this 
    claim.
        The Cr(VI) particle size data from spray primer and sanding 
    applications in aerospace need to be evaluated against Cr(VI) particle 
    size during chromate production to determine its impact on OSHA risk 
    estimates. Boeing observed that the high temperature calcination 
    process that oxidizes chromite ore to sodium chromate would likely lead 
    to a high proportion of respirable fume (Ex. 38-106). During post-
    hearing comments, AIA provided a figure from the 1953 U.S. Public 
    Health Service survey report that indicated the geometric mean airborne 
    dust particle size in a chromate production plant was 0.3 to 0.4 m in 
    size (Ex. 47-29-2, p. 3). The data came from a thermal precipitator 
    analysis of one-hour dust samples collected from the roasting and 
    leaching areas of the plant (Ex. 7-3). An independent 1950 industrial 
    hygiene survey report of the Painesville plant from the Ohio Department 
    of Health indicates the median size of the in-plant dust was 1.7 
    microns and the median size of the mist generated during the leaching 
    operations was 3.8 microns (Ex. 7-98). The measurement method used to 
    determine this particle size was not clear from the survey report.
        The thermal precipitator used by the U.S. Public Health Service 
    survey is an older sampling device specifically used to characterize 
    particles smaller than 5 [mu]m. The thermal precipitator collection 
    efficiency for particles >5 [mu]m was considered suspect due to 
    gravitational and inertial effects caused by the very low air flow 
    rates (e.g. 6 ml/min) necessary to operate the device. The survey 
    figure shows that 95 percent of collected particles were smaller than 1 
    [mu]m. However, this is probably an inflated percentage given that the 
    thermal precipitator is unable to effectively collect particles outside 
    the fine and ultrafine range (e.g. greater than about 5 [mu]m).
        In their post-hearing brief, AIA introduced an Exponent microscopic 
    analysis of particles claimed to be landfilled 'roast residue' 
    generated as airborne dust from the Painesville plant 'decades' earlier 
    (Ex. 47-29-2). AIA stated that "the particle diameters ranged from 
    0.11 to 9.64 [mu]m and that 82 percent of the particles were less than 
    2.5 [mu]m (Ex. 47-29-2, p. 3). OSHA was unable to verify the nature of 
    the landfill dust or determine its relevance from the information 
    provided by AIA.
        In the same submission, AIA referenced several experimental and 
    animal studies as evidence that small particles less than 2.5 [mu]m in 
    diameter cause greater lung toxicity than larger particles (Ex. 47-29-
    2). AIA concluded that:
    
        It is important for OSHA to recognize in the quantitative risk 
    assessment that the particles to which the featured chromate 
    production workers were exposed were fine [particle diameters 0.1-
    2.5 [mu]m] and ultrafine particles [particle diameters < 0.1 [mu]m] 
    and that particles of this size range are known to be associated 
    with greater toxicity than larger particles. Thus, the quantitative 
    cancer risk estimates based on these studies are very conservative 
    and likely overestimate risks for Cr(VI) exposures in other 
    industries, most notably aerospace (Ex. 47-29-2, p. 7).
    
        The above studies showed that fine/ultrafine particles penetrate 
    into the alveolar region of the lung, are slowly cleared from 
    respiratory tract, and can lead to pulmonary inflammation and non-
    neoplastic respiratory disease. OSHA agrees that fine/ultrafine 
    particles can disrupt pulmonary clearance and cause chronic 
    inflammation if sufficient amounts are inhaled. However, AIA did not 
    provide data that demonstrated the Gibb and Luippold workers were 
    routinely exposed to levels of small particles that would trigger 
    serious lung toxicity.
        AIA also referred to a human epidemiological study that reported 
    the excess risk of lung cancer mortality from airborne fine/ultrafine 
    particles (i.e. 8 percent increase per 10 [mu]g/m\3\ in particles) to 
    be similar to the excess risk of cardiopulmonary disease (i.e. 6 
    percent increase with each 10 [mu]g/m\3\ in particles). AIA suggested 
    these results were evidence that the excess lung cancer mortality 
    attributed to Cr(VI) in chromate production cohorts were, in large 
    part, due to fine/ultrafine particles. However, the Luippold cohort had 
    an excess mortality from lung cancer (SMR=239) that was 10.6-fold 
    higher than the excess mortality of heart disease (SMR=113) (Ex. 33-
    10). The Gibb cohort had an excess mortality from lung cancer that was 
    5.7-fold higher than the excess mortality of arteriosclerotic heart 
    disease (SMR=114) (Ex. 33-11). These mortality patterns are not 
    consistent with the small particle study results above and strongly 
    indicate fine/ultrafine particles are not the primary cause of excess 
    lung cancer among the chromate production workers in the Luippold and 
    Gibb cohorts. Given the information provided, OSHA does not have reason 
    to expect that exposure to fine/ultrafine particles in the Luippold and 
    Gibb cohorts had a substantial quantitative impact on its estimates of 
    lung cancer risk from exposure to Cr(VI).
        Based on the evidence presented, OSHA believes the production of 
    sodium chromate and dichromate likely generated a greater proportion of 
    respirable Cr(VI) particles than the aerospace spray priming 
    operations. The roasting operation that oxidizes trivalent chromite ore 
    and soda ash to hexavalent sodium chromate salts would be expected to 
    generate a small particle fume based on information from other high 
    temperature calcination processes (e.g. beryllium oxide production). 
    This is supported by a small amount of particle size information from 
    the 1940s and 1950s (Ex. 7-98). However, there are insufficient data to 
    reliably determine the median diameter of Cr(VI) particles or otherwise 
    characterize the particle size distribution generated during sodium 
    chromate production in the breathing zone of the worker. It should also 
    be recognized that significant Cr(VI) exposures occurred during other 
    chromate production operations, such as leaching sodium chromate from 
    the roast, separating sodium dichromate crystals, and drying/bagging 
    the final purified sodium dichromate product. There is no information 
    on particle size for these operations, but it is reasonable to expect 
    greater proportions of larger particles than generated during the 
    roasting process. For these reasons, there is some degree of 
    uncertainty with regard to size distribution of Cr(VI) aerosols inhaled 
    by chromate production workers.
        OSHA agrees with the aerospace industry that the reduced proportion 
    of respirable particles from spray primer operations relative to 
    chromate production will tend to lower the lung cancer risk from 
    equivalent Cr(VI) exposures. This is because less Cr(VI) will reach the 
    bronchioalveolar regions of the respiratory tract where lung cancer 
    occurs. However, the chemical form of Cr(VI) must also be considered. 
    Spray primer and painting operations expose workers to the slightly 
    soluble strontium and zinc chromates while chromate production workers 
    are exposed primarily to highly soluble sodium chromate/dichromate.
        As explained earlier in section V.B.9 on carcinogenic effects, 
    animal and mechanistic evidence suggest that the slightly soluble 
    strontium and zinc chromates are more carcinogenic than the highly 
    soluble Cr(VI) compounds when equivalent doses are delivered to 
    critical regions of the respiratory tract. Slightly soluble Cr(VI) 
    compounds produced a higher incidence of bronchogenic tumors than 
    highly soluble Cr(VI) compounds (e.g. sodium dichromate, chromic acid) 
    when instilled in the respiratory tract of rats at similar dosing and 
    other experimental conditions (Ex. 11-2; 11-7). For example, 
    intrabronchial instillation of strontium chromate produced a 40 to 60-
    fold greater tumor incidence than instillation of sodium dichromate in 
    one study (Ex. 11-2). Unlike the highly soluble Cr(VI) compounds, the 
    less water soluble Cr(VI) compounds are better able to provide a 
    persistent source of high Cr(VI) concentration within the immediate 
    microenvironment of the lung epithelia facilitating cellular uptake of 
    chromate ion into target cells. The greater carcinogenicity of the 
    slightly soluble Cr(VI) compounds have led to ACGIH TLVs that are from 
    5-fold (i.e. zinc chromates) to 100-fold (i.e. strontium chromates) 
    lower than the TLV for highly water soluble Cr(VI) compounds.
        For these reasons, the risk reductions achieved from the lower 
    Cr(VI) particle burden that reaches the bronchioalveolar region of the 
    lung may, to a large extent, be offset by the greater carcinogenic 
    activity of the Cr(VI) compounds that are inhaled during aircraft spray 
    painting operations. Since significant lung cancer risk exists at 
    Cr(VI) air levels well below the new PEL (e.g. 0.5-2.5 [mu]g/m\3\) 
    based on chromate production cohorts, the risk would also likely be 
    significant even if the lung cancer risk from similar Cr(VI) exposures 
    in aerospace operations is slightly lower. Therefore, OSHA believes 
    that the risk models based on the Gibb and Luippold data sets will 
    provide reasonable estimates of lung cancer risk for aerospace workers 
    exposed to equivalent levels of Cr(VI). However, based on the lower 
    lung burden expected after considering the particle size distribution 
    evidence submitted to the record, OSHA no longer believes that its risk 
    projections will underestimate lung cancer risk for aerospace workers 
    exposed to strontium or zinc chromates, as suggested in the NPRM (69 FR 
    at 59384).
    b. Specialty Steel Industry and Stainless Steel Welding.
        Collier Shannon Scott submitted comments to OSHA on behalf of a 
    group of steel and superalloy industry trade associations and companies 
    including the Specialty Steel Industry of North America (SSINA), the 
    Steel Manufacturers Association (SMA), and the American Iron and Steel 
    Institute (AISI) as well as various individual companies. They 
    requested that OSHA "seriously consider" the results of the Arena et 
    al. (1998) study of workers employed in the high nickel alloys industry 
    (Tr. 661), as well as studies by Huvinen et al. (1996, 2002) and Moulin 
    et al. (1990) on stainless steel production workers (Exs. 38-233, p. 
    85; 47-5, p. 10) and by Danielsen et al. (1996) on Norweigen stainless 
    steel welders (Ex. 47-5, p. 10). On behalf of the SSINA, Ms. Joan 
    Fessler testified that the Arena et al. study (Ex. 38-233-2), also 
    referred to as the "Redmond Study", found no relationship between 
    Cr(VI) exposure and lung cancer, and in general " * * * no strong 
    epidemiological evidence causally associating occupational exposures 
    with excess risk" (Tr. 662). Ms. Fessler concluded that the study 
    results " * * * stand in stark contrast to the extrapolated estimates 
    of cancer risk OSHA has developed from the chromate worker cohorts to 
    develop the proposed rule" (Tr. 662) and "[show] that there is no 
    significant excess risk of lung cancer for workers in the steel 
    industry" (Ex. 40-12-4, p. 2). She cited studies conducted by Huvinen 
    et al. as additional evidence that workers in the stainless steel 
    production industry do not have excess risk of lung cancer from Cr(VI) 
    exposure (Tr. 663).
        OSHA reviewed the Arena et al. (1998) study, which examined 
    mortality in a cohort of 31,165 workers employed at 13 U.S. high nickel 
    alloy plants for at least one year between 1956 and 1967 (Ex. 38-233-2, 
    p. 908). The focus of the study is nickel exposure; it does not report 
    how many of the cohort members were exposed to Cr(VI) or the levels of 
    Cr(VI) exposure to which they may have been exposed. Therefore there 
    does not appear to be any basis for SSINA's conclusion that "[t]here 
    was no strong epidemiological evidence causally associating 
    occupational exposures with excess risk" in the study and that "[n]o 
    dose response relationship was demonstrated * * * " (Tr. 662). Ms. 
    Fessler stated, in response to a question by Dr. Lurie of Public 
    Citizen, that there is no information in the study on Cr(VI) exposures 
    with which to assess a dose-response relationship between occupational 
    exposure to Cr(VI) and excess lung cancer risk in the cohort (Tr. 685). 
    Without any information on the proportion of workers that were exposed 
    to Cr(VI) or the levels to which they were exposed, one cannot 
    determine that there is no carcinogenic effect of Cr(VI) exposure, or 
    that the results of the Arena study contradict OSHA's risk estimates.
        To more meaningfully compare the lung cancer risk predicted by 
    OSHA's risk model and that observed in the Arena et al. study, OSHA 
    estimated Cr(VI) exposures for the cohort members based in part on 
    exposures in the stainless steel industry. High-nickel alloys that 
    contain chromium are roughly comparable to stainless steel in terms of 
    chromium content and the temperatures at which they are melted. This 
    in turn determines the amount of trivalent chromium that converts to h
    exavalent chromium in the heating process. For example, cast stainless steels 
    with high nickel composition (e.g. Cast 18-38, Cast 12-60, Cast 15-65, 
    and Cast 15-35) have chromium content ranging from 10-21% and have 
    melting points between 2350 and 2450 degrees Fahrenheit. Other high-nickel 
    alloys with chromium content, such as Hastelloy alloys C and G, Incoloy, 
    Nimonic, and Inconel, range from 13 to 22% chromium (except Incoloy 804=29.7% Cr) 
    with melting points of 2300-2600 degrees Fahrenheit. Stainless steels, 
    in general, have 12-30% chromium content and melting points between 
    2350 and 2725 degrees Fahrenheit.
        For this analysis OSHA projected that the proportion of workers in 
    each production job category is approximately similar in stainless 
    steel and high-nickel alloy production. For example, OSHA assumed that 
    the percent of alloy production workers who are furnace operators is, 
    as in steel production, about 5%. Assuming that both the Cr(VI) 
    exposures typical of various production jobs and the proportion of 
    workers employed in each job are roughly similar, workers in the Arena 
    cohort producing high-nickel stainless steels and alloys containing 
    chromium are likely to have Cr(VI) exposures comparable to those 
    generally found in stainless steel production. Workers' exposures were 
    estimated using the exposure profile shown in Table III-62 of the Final 
    Economic Analysis section on steel mills (Ex. 49-1).
        Not all workers in the Arena et al. cohort had Cr(VI) exposures 
    comparable to those in stainless steel facilities. As discussed by Ms. 
    Fessler at the hearing, exposure to " * * * [c]hrome was not uniform 
    in all [industries included in the study] because some of those 
    industries * * * did only high nickel work or nickel mining or whatever 
    specific nickel work there was" (Tr. 683). OSHA assumed that Cr(VI) 
    exposures of workers producing high-nickel alloys without chromium 
    content, such as Duranickel, Permanickel, Hastelloy alloys B, D, and G, 
    and Monel alloys, are similar to those found in carbon steel mills and 
    other non-stainless facilities, which according to comments submitted 
    by Collier Shannon Scott:
    
        * * * may generate Cr(VI) due to trace levels of chromium in 
    feedstock materials or the inadvertent melting of stainless steel 
    scrap, as well as during various maintenance and welding operations 
    (Ex. 38-233, p. 10).
    
    Exposure levels for Arena cohort workers producing these alloys were 
    estimated using the carbon steel exposure profile shown in Table III-64 
    of the Final Economic Analysis section on steel mills (Ex. 49-1).
        Table VI-10 below shows the risk ratios (ratio of excess plus 
    background cancers to background only cancers) predicted by OSHA's 
    model for workers producing high-nickel alloys with and without 
    chromium content. The percentage of workers with 8-hour TWA exposures 
    in each range shown below are calculated for Ni-Cr alloys and non-Cr 
    alloys using profiles developed for the Final Economic Analysis 
    sections on stainless steel and carbon steel industries, respectively 
    (Ex. 49-1). An average exposure duration of 20 years was assumed. While 
    it was not clear how long workers were exposed on average, the reported 
    length of follow-up in the study indicates that the duration of 
    exposure was probably less than 20 years for most workers. Risk ratios 
    were calculated assuming that workers were followed through age 70. The 
    average age at end of follow-up was not clear from the Arena et al. 
    publication. Over half of the original cohort was under 30 as of 1978, 
    and follow-up ended in 1988 (Ex. 38-233-2, p. 908). Follow-up through 
    age 70 may therefore lead OSHA's model to overestimate risk in this 
    population, but would probably not lead to underestimation of risk.

Table VI-10

 

    
        The Arena et al. study reported lung cancer rates among white males 
    (who comprised the majority of the cohort) about 2%-13% higher than 
    background depending on the reference population used. The table above 
    illustrates that with reasonable assumptions about exposures in the 
    Arena cohort, OSHA's risk model predicts excess risks as low as those 
    reported by Arena et al. OSHA's model predicts the highest risks (1-6% 
    higher than background) among workers producing alloy mixtures similar 
    to stainless steel in chromium content. Unfortunately, it is not clear 
    from the Arena et al. publication how many of the workers were involved 
    in production of chromium-containing alloys. If an even split is 
    assumed between workers producing alloys with and without chromium 
    content in the Arena et al. cohort, OSHA's model predicts a lung cancer 
    rate between 0.8% and 3.8% higher than background.
        More precise information about the level or duration of cohort 
    members' exposures might increase or decrease OSHA's model predictions 
    somewhat. For example, some workers in the historical alloy industry 
    would have had higher exposures than their modern-day counterparts, so 
    that better exposure information may lead to somewhat higher model 
    predictions. On the other hand, better information on the duration of 
    exposure and workers' age at the end of follow-up would lower the model 
    predictions, because this analysis made assumptions likely to 
    overestimate both. The analysis presented here should be interpreted 
    cautiously in light of the considerable uncertainty about the actual 
    exposures to the Arena cohort members, and the fact that OSHA's model 
    predictions are based on a lifetable using year 2000 U.S. all-cause 
    mortality data (rather than data from the time period during which the 
    cohort was followed). This analysis is not intended to provide a 
    precise estimate of risk from exposure to Cr(VI) in the Arena cohort, 
    but rather to demonstrate that the relatively low excess risk seen in 
    the cohort is reasonably consistent with the excess risk that OSHA's 
    model would predict at low exposures. It illustrates that OSHA's risk 
    model does not predict far higher risk than was observed in this 
    cohort. Rather, the majority of workers in alloy production would be 
    predicted to have relatively low risk of occupational lung cancer based 
    on their relatively low exposure to Cr(VI).
        Regarding the Huvinen et al. (1996, 2002) studies, the comments 
    submitted by Collier Shannon Scott state that "there was not a 
    significant increase in the incidence of any disease, including lung 
    cancer, as compared to the control population" (Ex. 38-233, p. 85). 
    However, the authors also noted that risk of cancer could not be 
    excluded because the follow-up time was short and the exposed group was 
    young and small (Ex. 38-233-3, p. 747).
        In addition to the small size (109 workers) and young age (mean 
    43.3 years) of the Cr(VI)-exposed group in the Huvinen et al. study 
    population, the design of this study limits its relevance to the issue 
    of lung cancer risk among stainless steel workers. The subjects were 
    all employed by the company at the time of the study. Individuals with 
    lung cancer would be expected to leave active employment, and would not 
    have been surveyed in the study. The authors made only a limited 
    attempt to track former workers: Those who met the study criteria of 8 
    years' employment in a single production department were surveyed by 
    mailed questionnaire (Ex. 38-233-3, p. 743), and no follow-up on 
    nonrespondents was reported. A second study conducted on the original 
    study group five years later was again limited to employed workers, as 
    those who had left the company " * * * could not be contacted" (Ex. 
    38-233-3, p. 204). Due to the short follow-up period and the 
    restriction to living workers (still employed or survey respondents), 
    these studies are not well suited to identify lung cancer cases.
        Post-hearing comments stated that " * * * OSHA has failed to even 
    consider specific epidemiological studies performed on stainless steel 
    production workers and welders that would be far more relevant than the 
    chromate production studies OSHA relied upon for its analysis" (Ex. 
    47-5, p. 10). In particular, they suggest that OSHA should consider a 
    study by Danielsen et al. (1996) on Norweigian boiler welders and a 
    study by Moulin et al. (1990) on French stainless steel production 
    workers (Ex. 47-5, p. 10). However, the Moulin et al. study (Ex. 35-
    282), was discussed in the Preamble to the Proposed Rule (69 FR at 
    59339). OSHA concluded that the association between Cr(VI) and 
    respiratory tract cancer in this and similar studies is difficult to 
    assess because of co-exposures to other potential carcinogens such as 
    asbestos, polycyclic aromatic hydrocarbons, nickel, and the lack of 
    information on smoking (69 FR at 59339).
        The Danielsen et al. study was not evaluated in the NPRM, but is 
    similar to other studies of welders evaluated by OSHA in which excess 
    risk of lung cancer did not appear to be associated with stainless 
    steel welding. In Danielsen et al., as in most other welding studies, 
    no quantitative information on Cr(VI) exposure was available, there was 
    potential confounding by smoking and asbestos exposure, and there 
    appeared to be an overall healthy worker effect in the study (625 
    deaths vs. 659 expected). Therefore, OSHA does not believe that 
    Danielsen et al. contributes significant information beyond that in the 
    studies that are reviewed in Section V.B.4 of this preamble. OSHA's 
    interpretation and conclusions regarding the general findings of 
    welding cohort studies, discussed below in the context of comments 
    submitted by the Electric Power Research Institute, apply to the 
    results of Danielsen et al. as well.
        The Electric Power Research Institute (EPRI), Exponent, and others 
    submitted comments to OSHA that questioned whether the Agency's 
    exposure-response model, based on the Gibb and Luippold chromate 
    production industry cohorts, should be used to estimate lung cancer 
    risks to welders exposed to Cr(VI) (Exs. 38-8; 38-233-4; 39-25, pp. 2-
    3). EPRI stated that:
    
        OSHA's review of the toxicology, epidemiology, and mechanistic 
    data associated with health effects among welders was thorough and 
    accurate. We concur with the selection of the two focus cohorts 
    (Luippold et al. 2003 and Gibb et al. 2000) as the best data 
    available upon which to base an estimate of the exposure-response 
    relationship between occupational exposure to Cr(VI) and an 
    increased lung cancer risk"; however * * * it may be questionable 
    whether that relationship should be used for stainless steel welders 
    given that a positive relationship between exposure to Cr(VI) and 
    lung cancer risk was not observed in most studies of welder cohorts 
    (Ex. 38-8, pp. 6-7).
    
    EPRI's concerns, like other comments submitted to OSHA on risk to 
    welders, are based primarily on the results of the Gerin et al. (1993) 
    study and on several studies comparing stainless steel and mild steel 
    welders.
        As discussed above in Section V., Gerin et al. (1993) is the only 
    available study that attempts to relate estimated cumulative Cr(VI) 
    exposure and lung cancer risk among welders. While excess lung cancer 
    risks were found among stainless steel welders, there was no clear 
    relationship observed between the estimated amount of Cr(VI) exposure 
    and lung cancer (Ex. 38-8, p. 8). This led the authors to suggest that 
    the elevated risks might be " * * * related to other exposures such as 
    cigarette smoking, background asbestos exposure at work or other 
    occupational or environmental risks * * * " rather than to Cr(VI) 
    exposure. On the other hand, Gerin et al. stated that " * * * the 
    welding fume exposures in these populations may be too low to demonstrate 
    a gradient of risk", or misclassification of exposure might obscure the 
    dose-response relationship (Ex. 7-120, pp. S25-S26), a point with which EPRI 
    expressed agreement (Ex. 38-8, p. 8).
        OSHA agrees with Gerin et al. that co-exposures to carcinogens such 
    as nickel, asbestos, and cigarette smoke may have contributed to the 
    elevated lung cancer risks among welders. OSHA also agrees with the 
    authors that exposure misclassification may explain the absence of a 
    clear relationship between Cr(VI) and lung cancer in this study. Gerin 
    et al. derived their exposure data primarily from literature on welding 
    fume, as well as from a limited number of industrial hygiene 
    measurements taken in the mid 1970s in eight of the 135 companies 
    participating in the study (Ex. 7-120, p. S24, p. S27). Their exposure 
    estimates took account of the welding process used and the base metal 
    welded by individuals in the cohort, but they apparently had no 
    information on other important items, such as the size of the work 
    piece and weld time, which were identified by EPRI as factors affecting 
    the level of Cr(VI) exposure from welding (Ex. 38-8, p. 5).
        EPRI also identified ventilation as a particularly important 
    determinant of exposure (Ex. 38-8, p. 5). Gerin et al. did not appear 
    to have individual information on ventilation use for their exposure 
    estimates, relying instead on "information on the history of welding 
    practice * * * obtained from each company on the basis of an ad hoc 
    questionnaire" that described for each company the average percent of 
    time that welders used local ventilation, operated in confined or open 
    areas, and worked indoors or outdoors (Ex. 7-120, p. S23). The use of 
    local ventilation, time spent welding in confined areas, and time spent 
    welding outdoors may have varied considerably from worker to worker 
    within any single company. In this case exposure estimates based on 
    company average information would tend to overestimate exposure for 
    some workers and underestimate it for others, thus weakening the 
    appearance of an exposure-response relationship in the cohort.
        Gerin et al. also stated that the average exposure values they 
    estimated do not account for a number of factors which affect welders' 
    exposure levels, including " * * * type of activity (e.g. maintenance, 
    various types of production), special processes, arcing time, voltage 
    and current characteristics, welder position, use of special electrodes 
    or rods, presence of primer paints and background fumes coming from 
    other activities" (Ex. 7-120, p. S25). They noted that the resulting 
    difficulty in the construction of individual exposure estimates is 
    exacerbated by aggregation of data across small cohorts from many 
    different companies that may have different exposure conditions (Ex. 7-
    120, p. S25). According to Gerin et al., exposure misclassification of 
    this sort may have obscured a dose-response relationship in this cohort 
    (Ex. 7-120, p. S25). The authors suggest that their estimates should be 
    checked or corrected " * * * with data coming from well-documented 
    industrial hygiene studies or industrial hygiene data banks including 
    information on the major relevant factors" (Ex. 7-120, p. S26). OSHA 
    believes that there is insufficient information to determine why a 
    clear relationship between Cr(VI) exposure and lung cancer is not 
    observed in the Gerin et al. study, but agrees with the authors that 
    exposure misclassification and the influence of background exposures 
    may explain this result.
        EPRI noted the apparent lack of a relationship between exposure 
    duration and lung cancer risk in the Gerin et al. cohort (Ex. 38-8, p. 
    10). Duration of exposure is expected to show a relationship with 
    cancer risk if duration serves as a reasonable proxy for a measure of 
    exposure (e.g. cumulative exposure) that is related to risk. Since 
    cumulative exposure is equal to exposure duration multiplied by average 
    exposure level, duration of exposure may correlate reasonably well with 
    cumulative exposure if average exposure levels are similar across 
    workers, or if workers with longer employment tend to have higher 
    average exposure levels. In a cohort where exposure duration is 
    believed to correlate well with cumulative exposure, the absence of a 
    relationship between exposure duration and disease risk could be 
    interpreted as evidence against a relationship between cumulative 
    exposure and risk.
        High variation in average exposures among workers, unrelated to the 
    duration of their employment, would tend to reduce the correlation 
    between exposure duration and cumulative exposure. If, as EPRI states, 
    Cr(VI) exposure depends strongly on process, base metal, and other work 
    conditions that vary from workplace to workplace, then duration of 
    exposure may not correlate well with cumulative exposure across the 135 
    companies included in the Gerin et al. study. The lack of a positive 
    relationship between exposure duration and lung cancer in the Gerin et 
    al. cohort may therefore signify that duration of exposure is not a 
    good proxy for the amount of exposure accumulated by workers, and 
    should not be interpreted as evidence against an exposure-response 
    relationship.
        In post-hearing comments Mr. Robert Park of NIOSH discussed other 
    issues related to exposure duration in the Gerin et al. and other 
    welding cohorts:
    
        Several factors may impact the interpretation of [the Gerin et 
    al. (1993) and Simonato et al. (1991) welder cohort studies] and are 
    consistent with an underlying risk associated with duration * * *. 
    The healthy worker survivor effect is a form of confounding in which 
    workers with long employment durations systematically diverge from 
    the overall worker population on risk factors for mortality. For 
    example, because smoking is a risk factor for disease, disability 
    and death, long duration workers would tend to have a lower smoking 
    prevalence, and hence lower expected rates of diseases that are 
    smoking related, like lung cancer. Not taking this into account 
    among welders might result in long duration welders appearing to 
    have diminished excess risk when, in fact, excess risk continues to 
    increase with time (Ex. 47-19-1, p. 6).
    
    Mr. Park also emphasized the special importance of detailed information 
    for individual workers in multi-employer studies with exposure 
    conditions that vary widely across employers. He notes that high worker 
    turnover in highly exposed jobs " * * * could result in long duration 
    welding employment appearing to have lower risk than some shorter 
    duration [welding] employment when it does not" (Ex. 47-19-1, p. 6).
        EPRI compared the risk of lung cancer among a subset of workers in 
    the Gerin cohort exposed to high cumulative levels of Cr(VI) to the 
    risk found among chromate production workers in the Gibb et al. and 
    Luippold et al. studies. "Focusing on the highest exposure group, SMRs 
    for the cohorts of stainless steel workers studied by Gerin et al 
    (1993) * * * range from 133 to 148 for exposures >1.5 mg-yrs/m\3\ * * 
    *. By comparison, the SMR from the Luippold et al. (2003) cohort is 365 
    for cumulative exposures of 1.0 to 2.69 mg-yrs/m\3\", a difference 
    that EPRI argues " * * * draws into question whether the exposure-
    specific risk estimates from the chromate production industry can be 
    extrapolated to welders" (Ex. 38-8, p. 25). It is not clear why EPRI 
    chose to focus on the high exposure group, which had a minimum of 1.5 
    mg/m\3\-years cumulative Cr(VI) exposure, a mean of 2.5 mg/m\3\-years, 
    and no defined upper limit. Compared to the other exposure groups 
    described by Gerin et al., this group is likely to have had more 
    heterogenous exposure levels; may be expected to have a stronger
    healthy worker effect due to the association between high cumulative 
    exposure and long employment history; and is the least comparable to 
    either workers exposed for a working lifetime at the proposed PEL (1 
    [mu]g/m\3\ * 45 years = 0.045 mg/m\3\-years cumulative exposure) or 
    welders in modern-day working conditions, who according to an IARC 
    review cited in EPRI's comments typically have exposure levels less 
    than 10 [mu]g/m\3\ (<  0.45 mg/m\3\-years cumulative exposure over 45 
    years) (Ex. 38-8, p. 4). In addition, the majority of the observation 
    time in the Luippold et al. cohort and the vast majority in the Gibb et 
    al. cohort is associated with exposure estimates lower than 1.5 mg/
    m\3\-years Cr(VI) (Ex. 33-10, p. 455, Table 3; 25, p. 122, Table VI).
        It should be noted that the levels of excess lung cancer risk 
    observed among welders in the Gerin et al. cohort and chromate 
    production workers in the Gibb and Luippold cohorts are quite similar 
    at lower cumulative exposure ranges that are more typical of Cr(VI) 
    exposures experienced in the cohorts. For example, the group of welders 
    with estimated cumulative exposures ranging from 50 to 500 [mu]g-yrs/
    m\3\ has an SMR of 230. Chromate production workers from the Gibb and 
    Luippold cohorts with cumulative exposures within this range have 
    comparable SMRs, ranging from 184 to 234, as shown in Table VI-11 
    below. For reference, 45 years of occupational exposure at 
    approximately 1.1 [mu]g/m\3\ Cr(VI) would result in a cumulative 
    exposure of 50 [mu]g-yrs/m\3\; 45 years of occupational exposure at 
    approximately 11.1 [mu]g/m\3\ Cr(VI) would result in a cumulative 
    exposure of 500 [mu]g-yrs/m\3\.

Table VI-11

 

    
        OSHA performed an analysis comparing the risks predicted by OSHA's 
    models, based on the Gibb and Luippold data collected on chromate 
    production workers, with the lung cancer deaths reported for the 
    welders in the Gerin et al. study. Gerin et al. presented observed and 
    expected lung cancer deaths for four categories of cumulative exposure: 
    < 50 [mu]g-yrs/m\3\, 50-500 [mu]g-yrs/m\3\, 500-1500 [mu]g-yrs/m\3\, and 
    1500+ [mu]g-yrs/m\3\. The great majority of the Gerin et al. data on 
    stainless steel welders (98% of person-years) are in the highest three 
    categories, while the lowest category is extremely small (< 300 person-
    years of observation). OSHA's preferred risk models (based on the Gibb 
    and Luippold cohorts) were used to predict lung cancer risk for each of 
    the three larger exposure categories. The OSHA predictions were derived 
    using the mean values from each exposure range, except for the open-
    ended highest category, for which Gerin et al. reported a mean exposure 
    level of 2500 [mu]g-yrs/m\3\ (Ex. 7-120, p. S26). The ratio of 
    predicted to background lung cancer deaths, which approximately 
    characterizes the expected SMRs for these exposure groups, was 
    calculated for each group.
        The OSHA model predictions were calculated assuming that workers 
    were first exposed to Cr(VI) at age 29, the average age at the start of 
    employment reported by Gerin et al. (Ex. 7-120, p. S26). The SMRs 
    reported by Gerin et al. were calculated for welders with at least five 
    years of employment and at least 20 years of follow-up. However, the 
    average duration of employment and follow-up was not evident from the 
    publication. The OSHA model predictions were therefore calculated using 
    a range of reasonable assumptions about the duration of employment over 
    which workers were exposed (5, 10, 15, and 20 years) and the length of 
    follow-up (30, 40, and 50 years).
        Table VI-12 below presents the SMRs reported by Gerin et al. for 
    stainless steel welders in the three highest exposure categories, 
    together with the ratio of predicted to background lung cancer deaths 
    from OSHA's risk models. It should be noted that the ratio was 
    calculated using year 2000 U.S. lung cancer mortality rates, while the 
    SMRs reported by Gerin et al. were calculated using national lung 
    cancer mortality rates for the nine European countries represented in 
    the study (Ex. 7-114).

Table VI-12

 

    
        Table VI-12 shows that the range of risk ratios predicted by OSHA's 
    model is higher than the ratios reported for the highest exposure group 
    in the Gerin et al. cohort, consistent with EPRI's observations (Ex. 
    38-8, p. 25). However, the risk ratios predicted by OSHA's model are 
    consistent with the Gerin SMRs for the 500-1500 [mu]g-yrs/m\3\ 
    cumulative exposure range. For the 50-500 [mu]g-yrs/m\3\ cumulative 
    exposure range, the OSHA prediction falls slightly below the lung 
    cancer mortality ratio observed for the Gerin et al. cohort. The OSHA 
    predictions for each group overlap with the 95% confidence intervals of 
    the Gerin et al. SMRs, suggesting that sampling error may partly 
    account for the discrepancies between the observed and predicted risk 
    ratios in the lowest and highest exposure groups.
        As previously discussed, OSHA believes that the lack of a clear 
    exposure-response trend in the Gerin et al. study may be partly 
    explained by exposure misclassification. As shown in Table VI-12, the 
    highest exposure group has lower risk than might be expected based on 
    OSHA's preferred risk models, while the lowest exposure group appears 
    to have higher risk than OSHA's models would predict. This overall 
    pattern of generally elevated but non-increasing SMRs across the three 
    larger exposure groups in the Gerin study is consistent with 
    potentially severe exposure misclassification. The higher-than-
    predicted risks among welders in the lowest exposure group could 
    similarly reflect misclassification. However, it is not possible to 
    determine with certainty that exposure misclassification is the cause 
    of the differences between the risk predicted by OSHA's model and that 
    observed in the Gerin cohort.
        Finally, EPRI cites the generally similar relative risks found 
    among stainless steel and mild steel welders as further evidence that 
    exposure to Cr(VI) may not carry the same risk of lung cancer in 
    welding operations as it does in the chromate production industry. EPRI 
    states:
    
        [I]t is reasonable to expect that if Cr(VI) were a relevant risk 
    factor for welders in the development of lung cancer, and certain 
    types of welding involve Cr(VI) more than other types, then 
    subgroups of welders who are more exposed to Cr(VI) by virtue of the 
    type of welding they do should have higher rates of lung cancer than 
    welders not exposed to Cr(VI) in their welding occupation;
    
    in particular, " * * *stainless steel welders should have a higher 
    risk of lung cancer than welders of mild steel" (Ex. 38-8, p. 13). 
    OSHA believes that EPRI's point would be correct if the subgroups in 
    question are similar in terms of other important risk factors for lung 
    cancer, such as smoking, co-exposures, and overall population health. 
    However, no analysis comparing stainless steel welders with mild steel 
    welders has properly controlled for these factors, and in fact there 
    have been indications that mild steel welders may be at greater risk of 
    lung cancer than stainless steel welders from non-occupational causes. 
    As discussed by EPRI, "[r]esults from cohort studies of stainless 
    steel welders with SMRs much less than 100 support an argument that the 
    healthy worker effect might be more marked among stainless steel 
    workers compared to mild steel welders'; also " * * *stainless steel 
    welders are generally more qualified and paid more than other welders" 
    (Ex. 38-8, p. 16), a socioeconomic factor that suggests possible 
    differences in lung cancer risk due to smoking, community exposures, or 
    occupational exposures from employment other than welding.
        Comments submitted by Exponent (Ex. 38-233-4) and EPRI (Ex. 38-8) 
    compare the Cr(VI) compounds found in welding fumes and those found in 
    the chromate production environments of the Gibb and Luippold cohorts. 
    Exponent stated that "[t]he forms of Cr(VI) to which chromate 
    production workers were historically exposed are primarily the soluble 
    potassium and sodium chromates" found in stainless steel welding 
    fumes. Less soluble forms of Cr(VI) are also found in stainless steel 
    welding fumes in limited amounts, as discussed in the 1990 IARC 
    monograph on welding (Ex. 35-242, p. 460), and are believed to have 
    been present in limited amounts at the plants where the Gibb and 
    Luippold workers were employed (Ex. 38-233-4, p. 4). Exponent concludes 
    that, while it is difficult to compare the exposures of welders to 
    chromate production workers, " * * *there is no obvious difference * * 
    * in solubility * * * " that would lead to a significantly lesser risk 
    from Cr(VI) exposure in welding as compared to the Gibb and Luippold 
    cohort exposures (Ex. 38-233-4, p. 3, p. 11). OSHA believes that the 
    similarity in the solubility of Cr(VI) exposures to welders and 
    chromate production workers supports the Agency's use of its risk model 
    to describe Cr(VI)-related risks to welders.
        Exponent and others (Exs. 38-8; 39-25) commented on the possibility 
    that the bioavailability of Cr(VI) may nevertheless differ between 
    welders and chromate production workers, stating that " * * * 
    bioavailability of Cr(VI)-containing particles from welding fumes may 
    not be specifically related to solubility of the Cr(VI) chemical 
    species in the fume" (Ex. 38-233-4, p. 11). In this case, Exponent 
    argues,
    
    delivered doses of Cr(VI) to the lung could be quite dissimilar 
    among welders as compared to chromate production industry workers 
    exposed to the same Cr(VI) chemical species at the same Cr(VI) 
    airborne concentrations (Ex. 38-233-4, p. 11).
    
    However, Exponent provided no data or plausible rationale that would 
    support a Cr(VI) bioavailability difference between chromate production 
    and welding. The low proportion of respirable Cr(VI) particles that 
    apparently limits bioavailability of inhaled Cr(VI) during aircraft 
    spray priming operations described previously is not an issue with 
    welding. High temperature welding generates fumes of small
    respirable-size Cr(VI) particles able to penetrate the bronchoalveolar 
    region of the lung. OSHA finds no evidence indicating that Cr(VI) from 
    welding is less bioavailable than Cr(VI) from soluble chromate 
    production.
        In summary, OSHA agrees with EPRI and other commenters that 
    evidence of an exposure-response relationship is not as strong in 
    studies of Cr(VI)-exposed welders compared to studies of chromate 
    production workers. OSHA believes that the available welding studies 
    are less able to detect an exposure-response relationship, due to the 
    potentially severe exposure misclassification, occupational exposure to 
    other cancer causing agents, and the general lack of information with 
    which to control for any differences in background lung cancer risk 
    between Cr(VI)-exposed and unexposed welders. In contrast, the two 
    featured cohorts had sufficient information on workers' Cr(VI) 
    exposures and potential confounding exposures to support a reliable 
    exposure-response assessment. These are the primary factors that led 
    OSHA to determine (like EPRI and Exponent) that the Luippold and Gibb 
    cohorts are the best data available on which to base a model of 
    exposure-response between Cr(VI) and lung cancer (Exs. 38-8, p. 6; 38-
    233-4, p. 1). Moreover, EPRI admitted that examination of " * * * the 
    forms of Cr(VI) to which welders are exposed, exposure concentrations, 
    and other considerations such as particle size * * * " identified " * 
    * * no specific basis * * * " for a difference in Cr(VI)-related lung 
    cancer risk among welders and the Gibb and Luippold chromate production 
    cohorts (Ex. 38-8, p. 7). OSHA concludes that it is reasonable and 
    prudent to estimate welders' risk using the exposure-response model 
    developed on the basis of the Gibb et al. and Luippold et al. datasets.
    
    H. Conclusions
    
        OSHA believes that the best quantitative estimates of excess 
    lifetime lung cancer risks are those derived from the data sets 
    described by Gibb et al. and Luippold et al. Both data sets show a 
    significant positive trend in lung cancer mortality with increasing 
    cumulative Cr(VI) exposure. The exposure assessments for these two 
    cohorts were reconstructed from air measurements and job histories over 
    three or four decades and were superior to those of other worker 
    cohorts. The linear relative risk model generally provided the best fit 
    among a variety of different models applied to the Gibb et al. and 
    Luippold et al. data sets. It also provided an adequate fit to three 
    additional data sets (Mancuso, Hayes et al., and Gerin et al.). Thus, 
    OSHA believes the linear relative risk model is the most appropriate 
    model to estimate excess lifetime risk from occupational exposure to 
    Cr(VI). Using the Gibb et al. and Luippold et al. datasets and a linear 
    relative risk model, OSHA concludes that the lifetime lung cancer risk 
    is best expressed by the three-to five-fold range of risk projections 
    bounded by the maximum likelihood estimates from the two featured data 
    sets. This range of projected risks is within the 95 percent confidence 
    intervals from all five data sets.
        OSHA does not believe that it is appropriate to employ a threshold 
    dose-response approach to estimate cancer risk from a genotoxic 
    carcinogen, such as Cr(VI). Federal agencies, including OSHA, assume an 
    exposure threshold for cancer risk assessments to genotoxic agents only 
    when there is convincing evidence that such a threshold exists (see 
    e.g. EPA, Guidelines for Carcinogen Risk Assessment, March 2005, pp. 3-
    21). In addition, OSHA does not consider absence of a statistically 
    significant effect in an epidemiologic or animal study that lacks power 
    to detect such effects to be convincing evidence of a threshold or 
    other non-linearity. OSHA also does not consider theoretical reduction 
    capacities determined in vitro with preparations that do not fully 
    represent physiological conditions within the respiratory tract to be 
    convincing evidence of a threshold. While physiological defense 
    mechanisms (e.g. extracellular reduction, DNA repair, apoptosis) can 
    potentially introduce dose transitions, there is no evidence of a 
    significantly non-linear Cr(VI) dose-lung cancer response in the 
    exposures of interest to OSHA. Finally, as previously discussed, linear 
    no-threshold risk models adequately fit the existing exposure-response 
    data.
        The slightly soluble Cr(VI) compounds produced a higher incidence 
    of respiratory tract tumors than highly water soluble or highly water 
    insoluble Cr(VI) compounds in animal studies that tested Cr(VI) 
    compounds under similar experimental conditions. This likely reflects 
    the greater tendency for chromates of intermediate water solubility to 
    provide a persistent high local concentration of solubilized Cr(VI) in 
    close proximity to the target cell. Highly soluble chromates rapidly 
    dissolve and diffuse in the aqueous fluid lining the epithelia of the 
    lung and are more quickly cleared from the respiratory tract. Thus, 
    these chromates are less able to achieve the higher and more persistent 
    local concentrations within close proximity of the lung cell surface 
    than the slightly water soluble chromates. Water insoluble Cr(VI) 
    particulates are also able to come in close contact with the lung cell 
    surface but do not release readily absorbed chromate ions into the 
    biological environment as rapidly. OSHA concludes that slightly soluble 
    Cr(VI) compounds are likely to exhibit a greater degree of 
    carcinogenicity than highly water soluble or water insoluble Cr(VI) 
    when the same dose is delivered to critical target cells in the 
    respiratory tract of the exposed worker. OSHA also believes it 
    reasonable to regard water insoluble Cr(VI) to be of similar 
    carcinogenic potency to highly water soluble Cr(VI) compounds in the 
    absence of convincing scientific evidence to indicate otherwise.
        The Gibb and Luippold cohorts were predominantly exposed to highly 
    water-soluble chromates, particularly sodium chromate and dichromate. 
    After evaluating lung cancer rates in other occupational cohort studies 
    with respect to the forms of Cr(VI) in the workplace, reliability in 
    the Cr(VI) exposure data, and the presence of potentially confounding 
    influences (e.g. smoking) and bias (e.g. healthy worker survivor bias) 
    as well as information on solubility, particle size, cell uptake, and 
    other factors influencing delivery of Cr(VI) to lung cells, OSHA finds 
    the risks estimated from the Gibb and Luippold cohorts adequately 
    represent risks to workers exposed to equivalent levels of Cr(VI) 
    compounds in other industries.
        As with any risk assessment, there is some degree of uncertainty in 
    the projection of risks that results from the data, assumptions, and 
    methodology used in the analysis. The exposure estimates in the Gibb et 
    al. and Luippold et al. data sets relied, to some extent, on a paucity 
    of air measurements using less desirable sampling techniques to 
    reconstruct Cr(VI) exposures, particularly in the 1940s and 1950s. 
    Additional uncertainty is introduced when extrapolating from the cohort 
    exposures, which usually involved exposures to higher Cr(VI) levels for 
    shorter periods of time to an equivalent cumulative exposure involving 
    a lower level of exposure for a working lifetime. The study cohorts 
    consisted mostly of smokers, but detailed information on their smoking 
    behavior was unavailable. While the risk assessments make some 
    adjustments for the confounding effects of smoking, it is unknown 
    whether the assessments fully account for any interactive effects that 
    smoking and Cr(VI) exposure may have on
    carcinogenic action. In any case, OSHA does not have reason to believe 
    the above uncertainties would introduce errors that would result in 
    serious overprediction or underprediction of risk.
        OSHA's estimate of lung cancer risk from a 45 year occupational 
    exposure to Cr(VI) at the previous PEL of 52 [mu]g/m\3\ is 101 to 351 
    excess deaths per 1000 workers. This range, which is defined by maximum 
    likelihood estimates based on the Gibb and Luippold epidemiological 
    cohorts, is OSHA's best estimate of excess risk. It does not account 
    for statistical uncertainty, or for other potential sources of 
    uncertainty or bias. The wider range of 62 to 493 excess deaths per 
    1000 represents the statistical uncertainty associated with OSHA's 
    excess risk estimate at the previous PEL, based on lowest and highest 
    95% confidence bounds on the maximum likelihood estimates for the two 
    featured data sets. The excess lung cancer risks at alternative 8 hour 
    TWA PELs that were under consideration by the Agency were previously 
    shown in Table VI-7, together with the uncertainty bounds for the 
    primary and supplemental studies at these exposure concentrations. The 
    45-year exposure estimates satisfy the Agency's statutory obligation to 
    consider the risk of material impairment for an employee with regular 
    exposure to the hazardous agent for the period of his working life (29 
    U.S.C. 651 et seq.). Occupational risks from Cr(VI) exposure to less 
    than a full working lifetime are considered in Section VII on the 
    Significance of Risk and in Section VIII on the Benefits Analysis.
    
    VII. Significance of Risk
    
        In promulgating health standards, OSHA uses the best available 
    information to evaluate the risk associated with occupational 
    exposures, to determine whether this risk is severe enough to warrant 
    regulatory action, and to determine whether a new or revised rule will 
    substantially reduce this risk. OSHA makes these findings, referred to 
    as the "significant risk determination", based on the requirements of 
    the OSH Act and the Supreme Court's interpretation of the Act in the 
    "benzene" decision of 1980 (Industrial Union Department, AFL-CIO v. 
    American Petroleum Institute, 448 U.S. 607). The OSH Act directs the 
    Secretary of Labor to:
    
        set the standard which most adequately assures, to the extent 
    feasible, on the basis of the best available evidence, that no 
    employee will suffer material impairment of health or functional 
    capacity even if such employee has regular exposure to the hazard * 
    * * for the period of his working life [6(b)(5)].
    
    OSHA's authority to promulgate regulations to protect workers is 
    limited by the requirement that standards be "reasonably necessary and 
    appropriate to provide safe or healthful employment" [3(8)].
        In the benzene decision, the Supreme Court's interpretation of 
    Section 3(8) further defined OSHA's regulatory authority. The Court 
    stated:
    
        By empowering the Secretary to promulgate standards that are 
    "reasonably necessary or appropriate to provide safe or healthful 
    employment and places of employment," the Act implies that, before 
    promulgating any standard, the Secretary must make a finding that 
    the workplaces in question are not safe (IUD v. API 448 U.S. at 
    642).
    
        "But 'safe' is not the equivalent of 'risk-free' ", the Court 
    maintained. "[T]he Secretary is required to make a threshold finding 
    that a place of employment is unsafe-in the sense that significant 
    risks are present and can be eliminated or lessened by a change in 
    practices" (IUD v. API, 448 U.S. at 642). It has been Agency practice 
    in regulating health hazards to establish this finding by estimating 
    risk to workers using quantitative risk assessment, and determining the 
    significance of this risk based on judicial guidance, the language of 
    the OSH Act, and Agency policy considerations.
        The Agency has considerable latitude in defining significant risk 
    and in determining the significance of any particular risk. The Court 
    did not stipulate a means to distinguish significant from insignificant 
    risks, but rather instructed OSHA to develop a reasonable approach to 
    the significant risk determination. The Court stated that "it is the 
    Agency's responsibility to determine in the first instance what it 
    considers to be a 'significant' risk", and it did not express "any 
    opinion on the* * *difficult question of what factual determinations 
    would warrant a conclusion that significant risks are present which 
    make promulgation of a new standard reasonably necessary or 
    appropriate" (448 U.S. at 659). The Court also stated that, while 
    OSHA's significant risk determination must be supported by substantial 
    evidence, the Agency "is not required to support the finding that a 
    significant risk exists with anything approaching scientific 
    certainty" (448 U.S. at 656). Furthermore,
    
        A reviewing court [is] to give OSHA some leeway where its 
    findings must be made on the frontiers of scientific knowledge [and] 
    * * * the Agency is free to use conservative assumptions in 
    interpreting the data with respect to carcinogens, risking error on 
    the side of overprotection rather than underprotection [so long as 
    such assumptions are based on] a body of reputable scientific 
    thought (448 U.S. at 655, 656).
    
        To make the significance of risk determination for a new or 
    proposed standard, OSHA uses the best available scientific evidence to 
    identify material health impairments associated with potentially 
    hazardous occupational exposures, and, when possible, to provide a 
    quantitative assessment of exposed workers' risk of these impairments. 
    OSHA has reviewed extensive epidemiological and experimental research 
    pertaining to adverse health effects of occupational Cr(VI) exposure, 
    including lung cancer, and has established quantitative estimates of 
    the excess lung cancer risk associated with previously allowable Cr(VI) 
    exposure concentrations and the expected impact of the new PEL. OSHA 
    has determined that long-term exposure at the previous PEL would pose a 
    significant risk to workers' health, and that adoption of the new PEL 
    and other provisions of the final rule will substantially reduce this 
    risk.
    
    A. Material Impairment of Health
    
        As discussed in Section V of this preamble, there is convincing 
    evidence that exposure to Cr(VI) may cause a variety of adverse health 
    effects, including lung cancer, nasal tissue damage, asthma, and 
    dermatitis. OSHA considers these conditions to be material impairments 
    of health, as they are marked by significant discomfort and long-
    lasting adverse effects, can have adverse occupational and social 
    consequences, and may in some cases have permanent or potentially life-
    threatening consequences. Based on this finding and on the scientific 
    evidence linking occupational Cr(VI) to each of these effects, OSHA 
    concludes that exposure to Cr(VI) causes "material impairment of 
    health or functional capacity" within the meaning of the OSH Act.
    1. Lung Cancer
        OSHA considers lung cancer, an irreversible and frequently fatal 
    disease, to be a clear material impairment of health. OSHA's finding 
    that inhaled Cr(VI) causes lung cancer is based on the best available 
    epidemiological data, reflects substantial evidence from animal and 
    mechanistic research, and is consistent with the conclusions of other 
    government and public health organizations, including NIOSH, EPA,
    ACGIH, NTP, and IARC (Exs. 35-117; 35-52; 35-158; 17-9-D; 18-3, p. 
    213). The Agency's primary evidence comes from two epidemiological 
    studies that show significantly increased incidence of lung cancer 
    among workers in the chromate production industry (Exs. 25; 33-10). The 
    high quality of the data collected in these studies and the analyses 
    performed on them has been confirmed by OSHA and by independent peer 
    review. Supporting evidence of Cr(VI) carcinogenicity comes from 
    occupational cohort studies in chromate production, chromate pigment 
    production, and chromium plating, and by cell culture research into the 
    processes by which Cr(VI) disrupts normal gene expression and 
    replication. Studies demonstrating uptake, metabolism, and genotoxicity 
    of a variety of soluble and insoluble Cr(VI) compounds support the 
    Agency's position that all Cr(VI) compounds should be regulated as 
    occupational carcinogens (Exs. 35-148; 35-68; 35-67; 35-66; 12-5; 35-
    149; 35-134).
    2. Non-Cancer Impairments
        While OSHA has relied primarily on the association between Cr(VI) 
    inhalation and lung cancer to demonstrate the necessity of the 
    standard, the Agency has also determined that several other material 
    health impairments can result from exposure to airborne Cr(VI). As 
    shown in several cross-sectional and cohort studies, inhalation of 
    Cr(VI) can cause ulceration of the nasal passages and perforation of 
    the nasal septum (Exs. 35-1; 7-3; 9-126; 35-10; 9-18; 3-84; 7-50; 31-
    22-12). Nasal tissue ulcerations are often accompanied by swelling and 
    bleeding, heal slowly, and in some cases may progress to a permanent 
    perforation of the nasal septum that can only be repaired surgically. 
    Inhalation of Cr(VI) may also lead to asthma, a potentially life-
    threatening condition in which workers become allergic to Cr(VI) 
    compounds and experience symptoms such as coughing, wheezing, and 
    difficulty in breathing upon exposure to small amounts of airborne 
    Cr(VI). Several case reports have documented asthma from Cr(VI) 
    exposure in the workplace, supporting Cr(VI) as the sensitizing agent 
    by bronchial challenge (Exs. 35-7; 35-12; 35-16; 35-21).
        During the comment period, NIOSH requested that OSHA consider 
    allergic contact dermatitis (ACD) as a material impairment of health 
    due to occupational exposure to Cr(VI). NIOSH reasoned:
    
        Dermal exposure to Cr(VI) through skin contact * * * may lead to 
    sensitization or allergic contact dermatitis. This condition, while 
    not life-threatening, is debilitating and marked by significant 
    discomfort and long-lasting adverse effects; it can have adverse 
    occupational and social consequences and should be a material 
    impairment to the health of affected workers * * * Including 
    allergic contact dermatitis in OSHA's determination of material 
    impairment of health draws attention to the fact that Cr(VI) is both 
    a dermal exposure hazard and an inhalation hazard, and alerts 
    employers that they should seek to minimize exposure to both routes 
    (Ex. 40-10-2, p. 3)
    
        OSHA fully agrees with the NIOSH comment. There is strong evidence 
    that unprotected skin contact with Cr(VI)-containing materials and 
    solutions can cause ACD as well as irritant dermatitis and skin 
    ulceration (see section V.D). ACD is a delayed hypersensitivity 
    response. The worker initially becomes sensitized to Cr(VI) following 
    dermal exposure. Once a worker becomes sensitized, brief exposures to 
    small amounts of Cr(VI) can trigger symptoms such as redness, swelling, 
    itching, and scaling. ACD is characterized by the initial appearance of 
    small raised papules that can later develop into blisters and dry 
    thickened, cracked skin. The allergic condition is persistent, causing 
    some workers to leave their jobs (Ex. 35-320). Symptoms of ACD 
    frequently continue long after occupational exposure to Cr(VI) ends, 
    since sensitized individuals can react to contact with Cr(VI) in 
    consumer products and other non-occupational sources.
        Skin exposure to Cr(VI) compounds can also cause a non-allergic 
    form of dermatitis. This skin impairment results from direct contact 
    with Cr(VI) doses that damage or irritate the skin, but do not involve 
    immune sensitization. This form of dermatitis can range from mild 
    redness to severe burns and ulcers, known as "chrome holes", that 
    penetrate deep into tissues. Once the worker is removed from exposure, 
    the skin ulcers heal slowly, often with scarring.
    
    B. Risk Assessment
    
        When possible, epidemiological or experimental data and statistical 
    methods are used to characterize the risk of disease that workers may 
    experience under the currently allowable exposure conditions, as well 
    as the expected reduction in risk that would occur with implementation 
    of the new PEL. The Agency finds that the available epidemiological 
    data are sufficient to support quantitative risk assessment for lung 
    cancer among Cr(VI)-exposed workers. Using the best available studies, 
    OSHA has identified a range of expected risk from regular occupational 
    exposure at the previous PEL (101-351 excess lung cancer deaths per 
    1000 workers) and at the new PEL of 5 [mu]g/m\3\ (10-45 per 1000 
    workers), assuming a working lifetime of 45 years' exposure in each 
    case. These values represent the best estimates of multiple analysts 
    working with data from two extensively studied worker populations, and 
    are highly consistent across analyses using a variety of modeling 
    techniques and assumptions. While some attempts have been made to 
    assess the relationship between Cr(VI) exposure level and noncancer 
    adverse health effects, the Agency does not believe that a reliable 
    quantitative risk assessment can be performed for noncancer effects at 
    this time, and has therefore characterized noncancer risk 
    qualitatively.
        For estimates of lung cancer risk from Cr(VI) exposure, OSHA has 
    relied upon data from two cohorts of chromate production workers. The 
    Gibb cohort, which originates from a chromate production facility in 
    Baltimore, Maryland, includes 2357 workers who began work between 1950 
    and 1974 and were followed up through 1992 (Ex. 33-11). The extensive 
    exposure documentation available for this cohort, the high statistical 
    power afforded by the large cohort size, and the availability of 
    information on individual workers' race and smoking status provide a 
    strong basis for risk analysis. The Luippold cohort, from a facility in 
    Painesville, Ohio, includes 482 workers who began work between 1940 and 
    1972, worked for at least one year at the plant, and were followed up 
    through 1997 (Ex. 33-10). This cohort also provides a strong basis for 
    risk analysis, in that it has high-quality documentation of worker 
    Cr(VI) exposure and mortality, a long period of follow-up, and a large 
    proportion of relatively long-term employees (55% were employed for 
    longer than 5 years).
    1. Lung Cancer Risk Based on the Gibb Cohort
        Risk assessments were performed on the Gibb cohort data by Environ 
    International Corporation (Ex. 33-12), under contract with OSHA; Park 
    et al., as part of an ongoing effort by NIOSH (Ex. 33-13); and Exponent 
    on behalf of the Chrome Coalition (Ex. 31-18-15-1). A variety of 
    statistical models were considered, allowing OSHA to identify the most 
    appropriate models and assess the resulting risk estimates' sensitivity 
    to alternate modeling approaches. Models were tried with additive and 
    relative risk assumptions; various exposure groupings and lag times; 
    linear and nonlinear exposure-response functions; external and internal
    standardization; reference lung cancer rates from city-, state-, and 
    national-level data; inclusion and exclusion of short-term workers; and 
    a variety of ways to control for the effects of smoking. OSHA's 
    preferred approach, a relative risk model using Baltimore lung cancer 
    reference rates, and NIOSH's preferred approach, a relative risk model 
    using detailed smoking information and U.S. lung cancer reference 
    rates, are among several models that use reasonable assumptions and 
    provide good fits to the data. As discussed in section VI, the Environ, 
    Park et al., and linear Exponent models yield similar predictions of 
    excess risk from exposure at the previous PEL and the new PEL (see 
    Tables VI-2 and VI-3). OSHA's preferred models (from the Gibb data set) 
    predict about 300-350 excess lung cancers per 1000 workers exposed for 
    a working lifetime of 45 years at the previous PEL and about 35-45 
    excess lung cancers per 1000 workers at the new PEL of 5 [mu]g/m\3\.
        Environ and Crump et al. performed risk assessments on the Luippold 
    cohort, exploring additive and relative risk models, linear and 
    quadratic exposure-response functions, and several exposure groupings 
    (Exs. 35-59; 35-58). Additive and relative risk models by both analyst 
    groups fit the data adequately with linear exposure-response. All 
    linear models predicted similar excess risks, from which OSHA has 
    selected preferred estimates based on the Crump et al. analysis of 
    about 100 excess lung cancer deaths per 1000 workers exposed for 45 
    years at the previous PEL, and ten excess lung cancer deaths per 1000 
    workers at the new PEL.
    2. Lung Cancer Risk Based on the Luippold Cohort
        The risk assessments performed on the Luippold cohort yield 
    somewhat lower estimates of lung cancer risk than those performed on 
    the Gibb cohort. This discrepancy is probably not due to statistical 
    error in the risk estimates, as the confidence intervals for the 
    estimates do not overlap. The risk estimates based on the Gibb and 
    Luippold cohorts are nonetheless reasonably close. OSHA believes that 
    both cohorts support reasonable estimates of lung cancer risk, and 
    based on their results has selected a representative range of 101-351 
    per 1000 for 45 years' occupational exposure at the previous PEL and 
    10-45 per 1000 for 45 years' occupational exposure at the new PEL for 
    the significant risk determination. OSHA's confidence in these risk 
    estimates is further strengthened by the results of the independent 
    peer review to which the risk assessment was submitted, which supported 
    the Agency's approach and results. OSHA also received several comments 
    in support of its risk estimates (Exs. 44-7, 38-222; 39-73-1). A full 
    analysis of major comments on the results of OSHA's quantitative risk 
    assessment can be found in section VI.F.
    3. Risk of Non-Cancer Impairments
        Although nasal damage and asthma may be associated with 
    occupational exposure to airborne Cr(VI), OSHA has determined that 
    there are insufficient data to support a formal quantitative risk 
    assessment for these effects. Available occupational studies of Cr(VI)-
    induced nasal damage are either of cross-sectional study design, do not 
    provide adequate data on short-term airborne Cr(VI) exposure over an 
    entire employment period, or do not account for possible contribution 
    from hand-to-nose transfer of Cr(VI) (Exs. 31-22-12; 9-126; 35-10; 9-
    18). Occupational asthma caused by Cr(VI) has been documented in 
    clinical case reports but asthma occurrence has not been linked to 
    specific Cr(VI) exposures in a well-conducted epidemiological 
    investigation. The Agency has nonetheless made careful use of the best 
    available scientific information in its evaluation of noncancer health 
    risks from occupational Cr(VI) exposure. In lieu of a quantitative 
    analysis linking the risk of noncancer health effects, such as damage 
    to nasal tissue, with specific occupational exposure conditions, the 
    Agency has qualitatively considered information on the extent of these 
    effects and occupational factors affecting risk, as discussed below.
        Damage to the nasal mucosa and septum can occur from inhalation of 
    airborne Cr(VI) or transfer of Cr(VI) on workers' hands to the interior 
    of the nose. Epidemiological studies have found varying, but 
    substantial, prevalence of nasal damage among workers exposed to high 
    concentrations of airborne Cr(VI). In the cohort of 2357 chromate 
    production workers studied by Gibb et al., over 60% experienced nasal 
    tissue ulceration at some point during their employment, with half of 
    these workers' first ulcerations occurring within 22 days from the date 
    they were hired (Ex. 31-22-12). The authors found a statistically 
    significant relationship between nasal ulceration and workers' 
    contemporaneous exposures, with about half of the workers who developed 
    ulcerations first diagnosed while employed in a job with average 
    exposure concentrations greater than 20 [mu]g/m3. Nasal 
    septum perforations were reported among 17% of the Gibb cohort workers, 
    and developed over relatively long periods of exposure (median time 172 
    days from hire date to diagnosis).
        A high prevalence of nasal damage was also found in a study of 
    Swedish chrome platers (Ex. 9-126). Platers exposed to average 8-hour 
    Cr(VI) concentrations above 2 [mu]g/m3 with short-term 
    excursions above 20 [mu]g/m3 from work near the chrome bath 
    had a nearly 50 percent prevalence (i.e. 11 out of 24 workers) of nasal 
    ulcerations and septum perforations. These data, along with that from 
    the Gibb cohort, suggest a substantial and clearly significant risk of 
    nasal tissue damage from regular short-term exposures above 20 [mu]g/
    m3. More than half of the platers (i.e. 8 of 12 subjects) 
    with short-term excursions to somewhat lower Cr(VI) concentrations 
    between 2.5 and 11 [mu]g/m3 had atrophied nasal mucosa (i.e. 
    cellular deterioration of the nasal passages) but not ulcerations or 
    perforations. This high occurrence of nasal atrophy was substantially 
    greater than found among the workers with mean Cr(VI) levels less than 
    2 [mu]g/m3 (4 out of 19 subjects) and short-term Cr(VI) 
    exposures less than 1 [mu]g/m3 (1 of 10 subjects) or among 
    the office workers not exposed to Cr(VI) (0 of 19 subjects). This 
    result is consistent with a concentration-dependant gradation in 
    response from relatively mild nasal tissue atrophy to the more serious 
    nasal tissue ulceration with short-term exposures to Cr(VI) levels 
    above about 10 [mu]g/m3. For this reason, OSHA believes 
    short-term Cr(VI) exposures regularly exceeding about 10 [mu]g/
    m3 may still result in a considerable risk of nasal 
    impairment. However, the available data do not allow a precise 
    quantitative estimation of this risk.
        While dermal exposure to Cr(VI) can cause material impairment to 
    the skin, a credible quantitative assessment of the risk is not 
    possible because few occupational studies have measured the amounts of 
    Cr(VI) that contact the skin during job activities; studies rarely 
    distinguish dermatitis due to Cr(VI) from other occupational and non-
    occupational sources of dermatitis; and immune hypersensitivity 
    responses, such as ACD, have an exceedingly complex dose-response.
    
    C. Significance of Risk and Risk Reduction
    
        The Supreme Court's benzene decision of 1980 states that "before 
    he can promulgate any permanent health or safety standard, the 
    Secretary [of Labor] is required to make a threshold finding that a 
    place of employment is unsafe--in the sense that significant risks are
    present and can be eliminated or lessened by a change in practices" 
    (IUD v. API, 448 U.S. at 642). The Court broadly describes the range of 
    risks OSHA might determine to be significant:
    
        It is the Agency's responsibility to determine in the first 
    instance what it considers to be a "significant" risk. Some risks 
    are plainly acceptable and others are plainly unacceptable. If, for 
    example, the odds are one in a billion that a person will die from 
    cancer by taking a drink of chlorinated water, the risk clearly 
    could not be considered significant. On the other hand, if the odds 
    are one in a thousand that regular inhalation of gasoline vapors 
    that are 2 percent benzene will be fatal, a reasonable person might 
    well consider the risk significant and take the appropriate steps to 
    decrease or eliminate it. (IUD v. API, 448 U.S. at 655).
    
    The Court further stated, "The requirement that a "significant" risk 
    be identified is not a mathematical straitjacket * * *. Although the 
    Agency has no duty to calculate the exact probability of harm, it does 
    have an obligation to find that a significant risk is present before it 
    can characterize a place of employment as "unsafe"' and proceed to 
    promulgate a regulation (IUD v. API, 448 U.S. at 655).
        Table VII-1 presents the estimated excess risk of lung cancer 
    associated with various levels of Cr(VI) exposure allowed under the 
    current rule, based on OSHA's risk assessment and assuming either 20 
    years' or 45 years' occupational exposure to Cr(VI) as indicated. The 
    purpose of the OSH Act, as stated in Section 6(b), is to ensure "that 
    no employee will suffer material impairment of health or functional 
    capacity even if such employee has regular exposure to the hazard * * * 
    for the period of his working life." 29 U.S.C. 655(b)(5). Taking a 45-
    year working life from age 20 to age 65, as OSHA has always done in 
    significant risk determinations for previous standards, the Agency 
    finds an excess lung cancer risk of approximately 100 to 350 per 1000 
    workers exposed at the previous PEL of 52 [mu]g/m3 Cr(VI). 
    This risk is clearly significant, falling well above the level of risk 
    the Supreme Court indicated a reasonable person might consider 
    acceptable. Even assuming only a 20-year working life, the excess risk 
    of about 50 to 200 per 1000 workers is still clearly significant. The 
    new PEL of 5 [mu]g/m3 Cr(VI) is expected to reduce these 
    risks substantially, to below 50 excess lung cancers per 1000 workers. 
    However, even at the new PEL, the risk posed to workers with a lifetime 
    of regular exposure is still clearly significant.

Table VII-1

 

    
        Workers exposed to concentrations of Cr(VI) lower than the new PEL 
    and for shorter periods of time may also have significant excess cancer 
    risk. The Agency's risk estimates are roughly proportional to duration 
    for any given exposure concentration. The estimated risk to workers 
    exposed at any fixed concentration for 10 years is about one-half the 
    risk to workers exposed for 20 years; the risk for five years' exposure 
    is about one-fourth the risk for 20 years. For example, about 11 to 55 
    out of 1000 workers exposed at the previous PEL for five years are 
    expected to develop lung cancer as a result of their exposure. Those 
    exposed to 10 [mu]g/m3 Cr(VI) for 5 years have an estimated 
    excess risk of about 2-12 lung cancer deaths per 1000 workers. It is 
    thus not only workers exposed for many years at high levels who have 
    significant cancer risk under the old standard; even workers exposed 
    for shorter periods at levels below the previous PEL are at substantial 
    risk, and will benefit from implementation of the new PEL.
        To further demonstrate significant risk, OSHA compares the risk 
    from currently permissible Cr(VI) exposures to risks found across a 
    broad variety of occupations. The Agency has used similar occupational 
    risk comparisons in the significant risk determination for substance-
    specific standards promulgated since the benzene decision. This 
    approach is supported by evidence in the legislative record that 
    Congress intended the Agency to regulate unacceptably severe 
    occupational hazards, and not "to establish a utopia free from any 
    hazards"(116 Cong. Rec. 37614 (1970), Leg. Hist 480), or to address 
    risks comparable to those that exist in virtually any occupation or 
    workplace. It is also consistent with Section 6(g) of the OSH Act, 
    which states:
    
        In determining the priority for establishing standards under 
    this section, the Secretary shall give due regard to the urgency of 
    the need for mandatory safety and health standards for particular 
    industries, trades, crafts, occupations, businesses, workplaces or 
    work environments.
    
        Fatal injury rates for most U.S. industries and occupations may be 
    obtained from data collected by the Bureau of Labor Statistics. Table 
    VII-2 shows average annual fatality rates per 1000 employees for 
    several industries between 1992 and 2001, as well as projected 
    fatalities per 1000 employees for periods of 20 and 45 years based on 
    these annual rates (Ex. 35-305). While it is difficult to compare 
    aggregate fatality rates meaningfully to the risks estimated in the 
    quantitative risk assessment for Cr(VI), which target one specific 
    hazard (inhalation exposure to Cr(VI)) and health outcome (lung 
    cancer), these rates provide a useful frame of reference for 
    considering risk from Cr(VI) inhalation. Regular exposures at high 
    levels, including the previous PEL of 52 [mu]g/m3 Cr(VI), 
    are expected to cause substantially more deaths per 1000 workers from 
    lung cancer than result from occupational injuries in most private 
    industry. At the new PEL of 5 [mu]g/m3 Cr(VI) the Agency's 
    estimated range of excess lung cancer mortality overlaps the fatality 
    risk for mining and approaches that for construction, but still clearly exceeds 
    the risk in lower-risk industries such as manufacturing.

Table VII-2

 

    
        Because there is little available information on the incidence of 
    occupational cancer, risk from Cr(VI) exposure cannot be compared with 
    overall risk from other workplace carcinogens. However, OSHA's previous 
    risk assessments provide estimates of risk from exposure to certain 
    carcinogens. These risk assessments, like the current assessment for 
    Cr(VI), were based on animal or human data of reasonable or high 
    quality and used the best information then available. Table VII-3 shows 
    the Agency's best estimates of cancer risk from 45 years' occupational 
    exposure to several carcinogens, as published in the preambles to final 
    rules promulgated since the benzene decision in 1980.

Table VII-3

 

    
        The Cr(VI) risk estimate at the previous PEL is higher than many 
    risks the Agency has found to be significant in previous rules (Table 
    VII-3, "Risk at Previous PEL"). The estimated risk from lifetime 
    occupational exposure to Cr(VI) at the new PEL is 10-45 excess lung 
    cancer deaths per 1000 workers, a range which overlaps the estimated 
    risks from exposure at the current PELs for benzene and cadmium (Table 
    VII-3, "Risk at new PEL").
        Based on the results of the quantitative risk assessment, the 
    Supreme Court's guidance on acceptable risk, comparison with rates of 
    occupational fatality in various industries, and comparison with cancer 
    risk estimates developed in previous rules, OSHA finds that the risk of 
    lung cancer posed to workers under the previous permissible level of 
    occupational Cr(VI) exposure is significant. The new PEL of 5 is 
    expected to reduce risks to workers in Cr(VI)-exposed occupations 
    substantially (by about 8- to 10-fold). OSHA additionally finds that 
    nasal tissue ulceration and septum perforation can occur under exposure 
    conditions allowed by the previous PEL leading to an additional health 
    risk beyond the significant lung cancer risk present. The reduction of 
    the Cr(VI) PEL from 52 [mu]g/m3 to 5 [mu]g/m3 is 
    expected to substantially reduce workers' risk of nasal tissue damage. 
    With regard to dermal effects from Cr(VI) exposure, OSHA believes that 
    provision of appropriate protective clothing and adherence to 
    prescribed hygiene practices will serve to protect workers from the 
    risk of Cr(VI)-induced skin impairment.
    
    VIII. Summary of the Final Economic and Regulatory Flexibility Analysis
    
    A. Introduction
    
        OSHA's Final Economic and Regulatory Flexibility Analysis (FEA) 
    addresses issues related to the costs, benefits, technological and 
    economic feasibility, and economic impacts (including small business 
    impacts) of the Agency's Occupational Exposure to Hexavalent Chromium 
    rule. The full Final Economic and Regulatory Flexibility Analysis has 
    been placed in the docket as Ex. 49. The analysis also evaluates 
    alternatives that were considered by the agency before adopting the final 
    rule. This rule is an economically significant rule under Section 3(f)(1) 
    of Executive Order 12866 and has been reviewed by the Office of Information and 
    Regulatory Affairs in the Office of Management and Budget, as required 
    by executive order. The purpose of this Final Economic and Regulatory 
    Flexibility Analysis is to:
         Identify the establishments and industries potentially 
    affected by the final rule;
         Estimate current exposures and the technologically 
    feasible methods of controlling these exposures;
         Estimate the benefits of the rule in terms of the 
    reduction in lung cancer and dermatoses employers will achieve by 
    coming into compliance with the standard;
         Evaluate the costs and economic impacts that 
    establishments in the regulated community will incur to achieve 
    compliance with the final standard;
         Assess the economic feasibility of the rule for affected 
    industries; and
         Evaluate the principal regulatory alternatives to the 
    final rule that OSHA has considered.
        The full Final Economic Analysis contains the following chapters:
    
    Chapter I. Introduction
    Chapter II. Industrial Profile
    Chapter III. Technological Feasibility
    Chapter IV. Costs of Compliance
    Chapter V. Economic Impacts
    Chapter VI. Benefits and Net Benefits
    Chapter VII. Final Regulatory Flexibility Analysis
    Chapter VIII. Environmental Impacts
    Chapter IX. Assessing the Need for Regulation.
    
        These chapters are summarized in sections B to H of this Preamble 
    summary.
    
    B. Introduction and Industrial Profile (Chapters I and II)
    
        The final standard for occupational exposure to hexavalent chromium 
    was developed by OSHA in response to evidence that occupational 
    exposure to Cr(VI) poses a significant risk of lung cancer, nasal 
    septum ulcerations and perforations, and dermatoses. Exposure to Cr(VI) 
    may also lead to asthma. To protect exposed workers from these effects, 
    OSHA has set a Permissible Exposure Limit (PEL) of 5 [mu]g/m\3\ 
    measured as an 8-hour time weighted average. OSHA also examined 
    alternative PELs ranging from 20 [mu]g/m\3\ to 0.25 [mu]g/m\3\ measured 
    as 8-hour time weighted averages.
        OSHA's final standards for occupational exposure to Cr(VI) are 
    similar in format and content to other OSHA health standards 
    promulgated under Section 6(b)(5) of the Act. In addition to setting 
    PELs, the final rule requires employers to:
         Monitor the exposure of employees (though allowing a 
    performance-oriented approach to monitoring);
         Establish regulated areas when exposures may reasonably be 
    expected to exceed the PEL (except in shipyards and construction);
         Implement engineering and work practice controls to reduce 
    employee exposures to Cr(VI);
         Provide respiratory protection to supplement engineering 
    and work practice controls where those controls are not feasible, where 
    such controls are insufficient to meet the PEL, or in emergencies;
         Provide other protective clothing and equipment as 
    necessary for dermal protection;
         Make industrial hygiene facilities (hand washing stations) 
    available in some situations;
         Provide medical surveillance when employees are exposed 
    above the action level for 30 days or more;
         Train workers about the hazards of Cr(VI) (including 
    elements already required by OSHA's Hazard Communication Standard); and
         Keep records related to the standard.
        The contents of the standards, and the reasons for issuing separate 
    standards for general industry, construction and shipyard employment, 
    are more fully discussed in the Summary and Explanation section of this 
    Preamble.
        Chapter II of the full FEA describes the uses of Cr(VI) and the 
    industries in which such uses occur. Employee exposures are defined in 
    terms of "application groups," i.e., groups of firms where employees 
    are exposed to Cr(VI) when performing a particular function. This 
    methodology is appropriate to exposure to Cr(VI) where a widely used 
    chemical like chromium may lead to exposures in many kinds of firms in 
    many industries but the processes used, exposures generated, and 
    controls needed to achieve compliance may be the same. For example, 
    because a given type of welding produces Cr(VI) exposures that are 
    essentially the same regardless of whether the welding occurs in a 
    ship, on a construction site, as part of a manufacturing process, or as 
    part of a repair process, it is appropriate to analyze such processes 
    as a group. However, OSHA's analyses of costs and economic feasibility 
    reflect the fact that baseline controls, ease of implementing ancillary 
    provisions, and the economic situation of the employer may differ 
    within different industries in an application group.
        The most common sources of occupational exposure to Cr(VI), in 
    addition to the production and use of chromium metal and chromium metal 
    alloys, are chromium electroplating; welding of metals containing 
    chromium, particularly stainless steel or other high-chromium steels, 
    or with chromium coatings; and the production and use of Cr(VI)-
    containing compounds, particularly Cr(VI) pigments, but also Cr(VI) 
    catalysts, chromic acid, and the production of chromium-containing 
    pesticides.
        Some industries are seeing a sharp decline in chromium use. 
    However, many of the industries that are seeing a sharp decline have 
    either a small number of employees or have low exposure levels (e.g., 
    wood working, printing ink manufacturers, and printing). In the case of 
    lead chromate in pigment production, OSHA's sources indicate that there 
    is no longer domestic output containing lead chromates. Therefore, this 
    trend has been recognized in the FEA. Painting activities in general 
    industry primarily involve the application of strontium chromate 
    coatings to aerospace parts; these exposures are likely to continue 
    into the foreseeable future. Similarly, removal of lead chromate paints 
    in construction and maritime is likely to present occupational risks 
    for many years.
        In application groups where exposures are particularly significant, 
    both in terms of workforce size and exposure levels--notably in 
    electroplating and welding--OSHA anticipates very little decline in 
    exposures to hexavalent chromium due to the low potential for 
    substitution in the foreseeable future.
        OSHA has made a number of changes to the industrial profile of the 
    application groups as a result of comments on the proposed rule. Among 
    the most important are:
         Additions to the electroplating application group to 
    include such processes as chrome conversion, which were not considered 
    at the time of the proposal;
         Additions to the painting application group to cover 
    downstream users, particularly automobile repair shops and construction 
    traffic painting;
         Additions to glass manufacturing to cover fiberglass, flat 
    glass, and container glass industries;
         Addition of the forging industry;
         Addition of the ready mixed concrete industry;
         Additions to the welding application group to include 
    welding on low-chromium steel and increase the estimated number of 
    exposed workers in the maritime sector; and
         More careful division of the many different industries in 
    which electroplating, welding and painting may appear as applications.
        Table VIII-1 shows the application groups analyzed in OSHA's FEA, 
    as well as the industries in each application group, and for each 
    provides the number of establishments affected, the number of employees 
    working in those establishments, the number of entities (firms or 
    governments) fitting SBA's small business criteria for the industry, 
    and the number of employees in those firms. (The table shows data for 
    both establishments and entities--defined as firms or governments. An 
    entity may own more than one establishment.) The table also shows the 
    revenues of affected establishment and entities, updated to reflect 
    2002 data. (This table provides the latest available data at the time 
    this analysis was produced.) As shown in the table, there are a total 
    of 52,000 establishments affected by the final standard.
        Various types of welding applications account for the greatest 
    number of establishments and number of employees affected by the final 
    standard.
    BILLING CODE 4510-26-P

Table VIII-2 Part 1

 

Table VIII-2 Part 2

 

Table VIII-2 Part 3

 

Table VIII-2 Part 4

 

Table VIII-2 Part 5

 

Table VIII-2 Part 6

 

Table VIII-2 Part 7

 

Table VIII-2 Part 8

 

Table VIII-2 Part 9

 

Table VIII-2 Part 10

 

Table VIII-2 Part 11

 

Table VIII-2 Part 12

 

Table VIII-2 Part 13

 

Table VIII-2 Part 14

 

Table VIII-2 Part 15

 

Table VIII-2 Part 16

 

Table VIII-2 Part 17

 

    
    BILLING CODE 4510-26-C
        Table VIII-2 shows the current exposures to Cr(VI) by application 
    group. The exposure data relied on by OSHA in developing the exposure 
    profile and evaluating technological feasibility were compiled in a 
    database of exposures taken from OSHA compliance officers, site visits 
    by OSHA contractors and the National Institute for Occupational Safety 
    and Health (NIOSH), the U.S. Navy, published literature, commenters on 
    the proposed rule and other interested parties.
        It is also important to note that Table VIII-2 and OSHA's cost and 
    feasibility analyses reflect the full range of exposures occurring in 
    each application group, not the median exposures. Some commenters 
    (e.g., Ex. 47-27-1) misunderstood this and believed OSHA determined 
    that only employers with median exposures above the PEL would incur 
    costs for engineering and work practice controls. OSHA did not use 
    exposure medians to assign compliance costs in this rulemaking. OSHA 
    made limited use of exposure medians for only a few purposes. The first 
    was in the analysis of baseline controls, described in the 
    technological feasibility discussion below. Where both exposure data 
    and information on the controls in place were available, OSHA used the 
    median exposure level experienced in the presence of a specific type of 
    control to assign an effectiveness level to the control. Second, to 
    determine whether to assume baseline controls were already in place in 
    cases where OSHA only had exposure data available, it compared median 
    exposure levels to the median exposure levels previously assigned to 
    baseline controls.
    BILLING CODE 4510-26-P

Table VIII-2 Part 1

 

Table VIII-2 Part 2

 

Table VIII-2 Part 3

 

Table VIII-2 Part 4

 

Table VIII-2 Part 5

 

Table VIII-2 Part 6

 

Table VIII-2 Part 7

 

Table VIII-2 Part 8

 

Table VIII-2 Part 9

 

Table VIII-2 Part 10

 

    
    BILLING CODE 4510-26-C
    
        In all sectors OSHA has used the best available information to 
    determine baseline exposures and technological feasibility. Throughout 
    the rulemaking process OSHA requested industry-specific information. 
    These requests included site visits, discussions with industry experts 
    and trade associations, the 2002 Request for Information (RFI), and the 
    SBREFA process. These requests continued through the proposal and the 
    public hearing process where OSHA continued to request information. 
    OSHA reviewed all the data submitted to the record and where 
    appropriate updated the exposure profile. For exposure information to 
    be useful in the profile, only individual personal exposures 
    representing a full shift were used.
        As noted earlier, OSHA used a variety of sources to obtain 
    information about exposures in each application group. These sources 
    include: NIOSH Health Hazard Evaluations (HHEs), OSHA's Integrated 
    Management Information System (IMIS) exposure data, data from other 
    government agencies, published literature, OSHA/NIOSH site visits, 
    discussions with industry experts and trade associations, and data 
    submitted to the OSHA record. In some instances OSHA's contractor had 
    difficulty obtaining permission to perform site visits in a specific 
    application group. For instance, OSHA's contractor could obtain 
    permission to conduct a site visit only at a steel mill that used the 
    teeming and primary rolling method--in contrast to continuous casting, 
    now used in approximately 95 percent of steel mills. In these few 
    cases, OSHA acknowledged these potential problems and OSHA (or its 
    contractor) discussed its concerns with industry experts and used their 
    professional judgment to determine technological feasibility.
        In response to the exposure data submitted to the record OSHA has 
    made the following major changes to the exposure profile:
         Electroplating--Revised the exposure distribution for hard 
    chrome electroplating to use only the more-detailed exposure data from 
    site visits and other NIOSH reports.
         Welding--In construction, OSHA used exposure data from the 
    maritime sector for analogous operations to supplement the exposure 
    profile. Added additional exposure data to the profile as provided to 
    the record.
         Painting--Revised the exposure profile to reflect the 
    additional aerospace exposure data submitted to the record.
         Steel Mills--Revised the exposure profile to reflect 
    additional exposure data supplied to the record; welders were added 
    directly to this application group.
         Chromium Catalyst Users--Revised the exposure profile 
    based on additional exposure data from a NIOSH HHE.
         Wood working--Added information from the record.
         Construction--Revised the exposure profile to reflect the 
    additional exposure information submitted to the record.
        Detailed information on the changes made in the exposure profile 
    for each application group can be found in Chapter III of the Final 
    Economic Analysis.
        OSHA's analysis of technological feasibility examined employee 
    exposures at the operation or task level to the extent that such data 
    were available. There are approximately 558,000 workers exposed to 
    Cr(VI), of which 352,000 are exposed above 0.25 micrograms per cubic 
    meter and 68,000 above the PEL of 5 micrograms per cubic meter.
    
    C. Technological Feasibility
    
        In Chapter III of OSHA's FEA, OSHA assesses the current exposures 
    and the technological feasibility of the final standard in all affected 
    industry sectors. The analysis presented in this chapter is organized 
    by application group and analyzes employee exposures at the operation 
    or task level to the extent that such data are available. Accordingly, 
    OSHA collected exposure data at the operation or task level to identify 
    the Cr(VI)-exposed workers or job operations that need to improve their 
    process controls to achieve exposures at or below the PEL. In the few 
    instances where there were insufficient exposure data, OSHA used 
    analogous operations to characterize these operations.
        In general, OSHA considered the following kinds of controls that 
    could reduce employee exposures to Cr(VI): local exhaust ventilation 
    (LEV), which could include maintenance or upgrade of the current local 
    exhaust ventilation or installation of additional LEV; process 
    enclosures that would isolate the worker from the exposure; process 
    modifications that would reduce the generation of Cr(VI) dust or fume 
    in the work place; improved general dilution ventilation including 
    assuring that adequate make-up air is supplied to the work place; 
    improved housekeeping; improved work practices; and the supplemental 
    use of respiratory protection if engineering and work practice controls 
    were not sufficient to meet the PEL.
        The technologies used in this analysis are commonly known, readily 
    available and are currently used to some extent in the affected 
    industries and processes. OSHA's assessment of feasible controls and 
    the exposure levels they can achieve is based on information collected 
    by Shaw Environmental, Inc. (Ex. 50), a consultant to OSHA, on the 
    current exposure levels associated with existing controls, on the 
    availability of additional controls needed to reduce employee 
    exposures, and on other evidence presented in the docket.
        Through the above analysis, OSHA finds that a PEL of 5 [mu]g/m\3\ 
    is technologically feasible for most operations in all affected 
    industries through the use of engineering and work practice controls. 
    As discussed further below, the final rule requires that when painting 
    of aircraft or large aircraft parts is performed in the aerospace 
    industry, the employer is only required to use engineering and work 
    practice controls to reduce employee exposures to Cr(VI) to or below 25 
    [mu]g/m\3\. The employer must then use respiratory protection to 
    achieve the PEL. Apart from this limited exception, all other 
    industries can achieve the PEL with only minimal reliance on 
    respiratory protection. Table VIII-3 shows OSHA's estimate of 
    respirator use by industry for each of the PELs that OSHA considered. 
    At the final PEL of 5 [mu]g/m\3\, only 3.5 percent of exposed employees 
    will be required to use respirators.
        In only three sectors will respirator use be required for more than 
    5 percent of exposed employees. In two of these sectors, chromate 
    pigment producers and chromium dye producers, use of respirators will 
    be intermittent. The third sector, stainless steel welding, presents 
    technological challenges in certain environments such as confined 
    spaces. OSHA has concluded that, with a few limited exceptions which 
    are discussed below, employers will be able to reduce exposures to the 
    PEL through the use of engineering and work practice controls.
    BILLING CODE 4510-26-P

Table VIII-3 Part 1

 

Table VIII-3 Part 2

 

Table VIII-3 Part 3

 

    
    BILLING CODE 4510-26-C
    
        In determining technological feasibility OSHA has used the median 
    to describe the exposure data. Since the median is a statistical term 
    indicating the central point of a sequence of numbers (50 percent below 
    and 50 percent above) it best describes exposures for most people. The 
    median is also a good substitute for the geometric mean for a log 
    normal distribution which often describes exposure data. As described 
    by the Color Pigments Manufacturers Association, Inc. (CPMA) in an 
    economic impact study by IES Engineers:
    
        The exposure distribution (assuming it is log normal) can be 
    characterized by the geometric mean and standard deviation. The 
    median (not the average) is a reasonable estimate of the geometric 
    mean (Ex. 47-3, p. 54).
    
        In contrast, the use of an arithmetic mean (or average) may tend to 
    misrepresent the exposure of most people. For example, if there are a 
    few workers with very high exposures due to poor engineering or work 
    practice controls, the arithmetic mean will be artificially high, not 
    representing realistic exposures for the workers.
        The technological feasibility chapter of the FEA is broken down 
    into five main parts: Introduction, Exposure Profile, Baseline 
    Controls, Additional Controls and Substitution. The first part is an 
    introduction to the application group, which outlines the major changes 
    in the analysis between the Preliminary Economic Analysis and the Final 
    Economic Analysis and addresses comments specific to the application 
    group.
        The next part of the technological feasibility analysis is the 
    exposure profile. The exposure profile describes the prevailing 
    exposures in each application group on a job-by-job basis. The exposure 
    profile represents exposure situations that may be well controlled or 
    poorly controlled. The data used to determine the current exposures 
    were obtained from any of the following sources: OSHA site visits; the 
    OSHA compliance database, Integrated Management Information System 
    (IMIS); NIOSH site visits; NIOSH control technology or health hazard 
    evaluation reports (HHE); information from the U.S. Navy; published 
    literature; submissions by individual companies or associations; or, in 
    a few cases, by consideration of analogous operations. While the 
    exposure profile was developed from current exposures and is not 
    intended to demonstrate feasibility, there were a few instances where 
    the exposure profile was used as ancillary support for technological 
    feasibility if there were a significant number of facilities already 
    meeting the PEL. An example of this case can be seen in the production 
    of colored glass, where over 90 percent of the exposure data were below 
    0.25 [mu]g/m3.
        In the cases where analogous operations were used to determine 
    exposures, OSHA used data from industries or operations where materials 
    and exposure routes are similar. OSHA also tended to be conservative 
    (over-estimating exposures). For example, exposure data for the bagging 
    of pigments were used to estimate exposures for the bagging of plastic 
    colorants. In both cases the operation consists of bagging a pigmented 
    powder. However, exposures would tend to be higher for bagging pigments 
    due to the fact that in pigments there is a higher percentage of Cr(VI) 
    and the pigments tend to consist of finer particles than those in 
    plastic colorants where the Cr(VI) particles are diluted with other 
    ingredients. As Mr. Jeff Cox from Dominion Colour Corporation stated:
    
        Exposure of packers in the pigment industry, who are making a 
    fine powder, is very much higher than packers in the plastics 
    colorants industry, who are basically packing pellets of 
    encapsulated product which are a few millimeters in diameter (Tr. 
    1710).
    
        The use of operations that are more difficult to control to 
    estimate analogous operations would result in an overestimate of 
    exposures, subsequently resulting in an overestimate of the controls 
    needed to reduce the exposures to Cr(VI) in those analogous operations.
        The next section of OSHA's analysis of technological feasibility in 
    the FEA describes the baseline controls. OSHA determined controls to be 
    "baseline" if OSHA believed that such controls are commonly used in 
    the application group. This should not be interpreted to mean that OSHA 
    believes that all firms use these controls, but rather that the 
    controls are common and widely available in the industry. Information on 
    the controls used in each specific application group was obtained from 
    several different sources such as: site visits, NIOSH HHEs, industry 
    experts, industry associations, published literature, submissions to the 
    docket, and published reports from other federal agencies. OSHA used the 
    median to estimate the exposure level associated with the baseline controls. 
    For the majority of the operations, the median was calculated using the 
    exposures directly associated with the baseline controls. However, 
    there were a few cases where the median was calculated from the 
    exposure profile and OSHA determined these exposures reflected the 
    baseline controls (e.g., fiberglass production).
        The fourth section of the technological feasibility analysis 
    determined the need for additional controls. If the median exposure was 
    above the PEL with the use of baseline controls, OSHA would recommend 
    additional engineering or work practice controls that would reduce 
    exposures to or below the PEL. The final rule does not require an 
    employer to use these specific controls. The engineering controls or 
    work practices are, however, OSHA's suggestions for possible ways to 
    achieve the PEL. Through this process a few situations could arise when 
    the exposures with baseline exposures are above the PEL:
         Engineering and work practice controls alone: OSHA 
    determined that additional controls would reduce worker's exposure 
    below the PEL if: 1) the proposed additional controls were already in 
    use at other facilities in the same application group and exposures 
    there were below the PEL, or 2) the additional controls were used in 
    analogous industries or operations and they were effective.
         Respiratory protection required to meet the PEL: There 
    were a few instances where workers' exposures would remain above the 
    PEL even with the installation of additional controls. In these cases 
    OSHA indicated that the supplemental use of respirators may be needed 
    (e.g. enclosed spray-painting operations in aerospace).
         Intermittent respiratory protection: There were instances 
    where a worker performs specific job-related activities that could 
    result in higher exposures above the PEL for limited periods of time. 
    In these cases OSHA noted that the supplemental use of respirators 
    during these activities may be necessary. For example, an employee who 
    works in pigment production generally, may need to use a respirator 
    only when entering the enclosure where the bagging operations take 
    place because the enclosure is the engineering control in this 
    operation.
        The final component of the technological feasibility section in the 
    FEA is a discussion of substitution. Here, OSHA describes the options 
    available for eliminating or reducing the use of ingredients that 
    either contain or can produce Cr(VI) during processing. This is 
    primarily a discussion of the possibility of substitution. In some 
    cases there is no readily available substitute for either chromium 
    metal or Cr(VI) ingredients such as a non-Cr(VI) coating for corrosion 
    control in the aerospace industry. In other cases an application group 
    has been steadily reducing their use of Cr(VI), such as in the printing 
    industry. In some industries there are substitutes available for at 
    least some operations, such as the use of trivalent chromium in some 
    decorative electroplating operations. Finally, through hearing 
    testimony and docket submissions, OSHA received information regarding 
    new technologies that can be used to reduce some of the sources of 
    exposure to the workers.
        In most cases OSHA does not rely on material substitution for 
    reducing exposures to Cr(VI) to determine technological feasibility. 
    For example, in the case of some welding operations, OSHA has 
    determined that the use of an alternate welding process that reduces 
    fume generation, such as the switching from shielded metal arc welding 
    (SMAW) to gas metal arc welding (GMAW), could be effective in reducing 
    a worker's exposure to hexavalent chromium to a level at or below the 
    PEL. Alternatively, experiments have also shown that elimination or 
    reduction of sodium and potassium in the flux reduces the production of 
    Cr(VI) in the welding fume (Ex. 50). However, this technology has yet 
    to be commercialized due to potential weld quality problems. Thus, OSHA 
    ultimately determined that material substitution was currently not 
    feasible for SMAW welding operations.
        There were comments submitted to the record that did not agree with 
    certain aspects of OSHA's feasibility analysis. These comments 
    addressed:
         OSHA's use of median values to describe exposure data and 
    failure to address costs for exposures above the PEL where the median 
    was below the PEL;
         OSHA's use of the number of workers to determine the 
    number of facilities needing additional controls;
         The use/validity of OSHA's analytical method; and
         The lack of data/site visits to properly characterize an 
    application group.
        Several commenters objected to OSHA's use of the median in the 
    technological feasibility analysis. The National Coil Coating 
    association stated:
    
        It is inappropriate to use median exposure values to reach a 
    conclusion that no coil coating facility will be subject to 
    regulatory requirements associated with exceedances of the proposed 
    PEL. Of the 15 samples supplied, one sample exceeded the proposed 
    PEL and another one was equal to the proposed PEL (Ex. 39-72-1).
    
    Collier Shannon Scott, representing the Specialty Steel Industry of 
    North America, stated:
    
        OSHA conducted a technological feasibility analysis to determine 
    what engineering or administrative controls would be necessary to 
    achieve the proposed PEL only where the median exposure value for 
    any particular job category exceeded the proposed PEL. If correct, 
    this means that where the median exposure value fell below 1 ug/m3, 
    even though numerous of the exposure values for that job category 
    were above 1 ug/m3, OSHA's analysis does not recognize that controls 
    would have to be implemented for that job category at any facilities 
    where that job is conducted (Ex. 47-27-1).
    
        OSHA believes that these commenters misunderstood OSHA's use of the 
    median value and the term "additional controls." As stated earlier, 
    OSHA used the median value to describe either the overall exposures or 
    the effectiveness of various controls. However, to estimate the cost of 
    controls, OSHA used the entire exposure profile. Thus, if any exposures 
    were over the PEL, then costs for engineering controls would be 
    assigned. If for a job category the "baseline controls" have been 
    determined to reduce employee exposures to below the PEL, then OSHA 
    would include costs for "baseline controls" for the percentage of the 
    facilities that had exposures over the PEL. However, if the 
    "baseline" controls would not be sufficient to reduce worker 
    exposures to below the PEL then OSHA would cost the "additional 
    controls."
        Collier Shannon Scott, representing the Specialty Steel Industry of 
    North America also stated:
    
        OSHA wrongly uses percentage distribution by job category to 
    estimate the number of facilities that would be required to install 
    engineering controls. This is a logical error. There is no 
    connection between the number of facilities that must install 
    controls and the percentage of employees above a given exposure 
    level (Ex. 47-27-1).
    
        OSHA was also concerned about accurately using individual exposures 
    to represent the number of facilities that would need to implement either 
    baseline controls or additional controls. Thus, whenever exposure data 
    were associated with individual facilities, OSHA normalized the 
    exposure data by job category to the facility, with each facility 
    having a weighting factor of 1. However, if exposure data varied 
    significantly, OSHA accounted for this. For example, if fifty percent 
    of the exposure data for a job class in a facility was above the PEL 
    and fifty percent below the PEL, then OSHA counted this as representing 
    0.5 facilities above the PEL and 0.5 facilities below the PEL.
        The use of this weighting system ensured that each facility 
    received the same weight so that one facility that supplied a large 
    amount of data would not overwhelm the exposure profile and skew the 
    distribution in an application group. This is particularly important 
    when there is a wide range of sizes of facilities and a large facility 
    could outweigh a smaller facility. OSHA then used this weighting system 
    to determine the percentage of facilities affected, so that the costs 
    were based on a per-facility versus a per-employee basis. However, in a 
    few instances OSHA could not use the weighting factor system because 
    certain exposure data were presented to OSHA as representing the 
    industry. For examples, in maritime welding and aerospace painting the 
    exposure data could not be attributed to individual facilities but were 
    presented to OSHA as representing a group of facilities.
        There were comments about several different aspects of OSHA's 
    analytical method. The Policy Group, representing the Surface Finishing 
    Industry Council, was concerned about how OSHA interpreted the term 
    non-detect (ND):
    
        Appropriate assessment of ND qualitative value would require 
    that the sample specific quantitation limit be lower than any 
    targeted analytical value, such as the new proposed AL and PEL. 
    According to a leading OSHA/NIOSH contract laboratory (DataChem 
    Laboratories) in the field of IH analyses, laboratories only report 
    to the lowest calibration standard. Thus, the lowest standard value 
    in the curve is the quantitation limit or reporting limit. This 
    limit is the minimum value the labs generally report, regardless of 
    any theoretical LOD value (Ex. 47-17-8).
    
        OSHA agrees with The Policy Group's assessment and has updated the 
    exposure profiles to reflect non-detect samples as the Limit of 
    Quantification (LOQ) where the source of the data did not indicate the 
    limit of detection. This is discussed in more detail in the 
    electroplating section of the technological feasibility chapter in the 
    FEA.
        Several comments questioned whether OSHA's analytical method truly 
    represents a worker's exposure (Ex. 38-216-1). Several other sources 
    indicate that OSHA's analytical method ID 215 is appropriate and it 
    accurately represents a worker's exposure. In a Journal of 
    Environmental Monitoring article the authors conclude:
    
        * * * a field comparison of three recently developed or modified 
    CrVI sampling and analytical methods showed no statistically 
    significant differences among the means of the three methods based 
    on statistical analysis of variance. The overall performances of the 
    three CrVI methods were comparable in electroplating and spray 
    painting operations where soluble CrVI was present. Although the 
    findings reported herein are representative of workplace operations 
    utilizing soluble forms of CrVI, these analytical methods (using 
    identical sample preparation procedures) also have been shown to 
    quantitatively measure insoluble forms of CrVI in other occupational 
    settings. There were no significant differences observed among CrVI 
    concentrations measured by NIOSH 7605 and OSHA ID 215 (Ex. 40-10-5).
    
    In addition URS Corporation stated:
    
        The new OSHA method 215 was used to analyze samples collected 
    during the Site Visits for Company 1 and Company 18. This method is 
    far superior to the old OSHA method ID 103 and to other relative 
    older methods. The new method utilizes separations of the hexavalent 
    chromium from potential interferences prior to the analysis. It is 
    also designed to detect much lower CrVI concentrations levels and to 
    remove both positive and negative interferences at these lower 
    concentrations. Furthermore, this method has been fully validated in 
    the presence of interferences over a CrVI concentration range that 
    includes the proposed new AL and PEL values (Ex. 47-17-8).
    
    OSHA's analytical method ID 215 is a fully validated analytical method 
    that can analyze Cr(VI) well below the PEL within the accuracy of 
    measurement as specified in the final standard.
        Dr. Joel Barnhart, on behalf of the Chrome Coalition, questioned 
    how the samples were taken during the OSHA-sponsored site visits (Ex. 
    40-12-1). At all site visits conducted by OSHA's contractors, certified 
    industrial hygienists (CIHs) were responsible for either taking samples 
    or reviewing sampling data provided by the facility visited. All 
    samples were taken following procedures from either NIOSH or OSHA which 
    detail the type of sampler, filter and flow rates appropriate for the 
    analytical methods used. Full details about the samples, operations 
    they represent and engineering controls can be found in each site visit 
    report.
        Several commenters mentioned that OSHA relied solely on one site 
    visit for an entire application group (Exs. 38-218; 38-205). While the 
    OSHA/NIOSH site visits were important to OSHA's understanding of the 
    processes used in the different application groups, the site visits 
    were not the sole source of information. OSHA, as stated earlier, used 
    many different sources to properly characterize an application group. 
    These sources included: OSHA site visits, OSHA's compliance data base 
    (IMIS), NIOSH site visits, NIOSH engineering control technology reports 
    or health hazard evaluation reports, published literature, submissions 
    by individual companies, as well as detailed discussions with industry 
    experts. In addition, throughout the rulemaking process OSHA has 
    requested information regarding processes, exposures, engineering 
    controls, substitutes and other information pertinent to Cr(VI) 
    application groups. These requests came in many forms such as 
    stakeholder meetings, site visits, OSHA's 2002 Request for Information, 
    and the SBREFA review. OSHA continued to update the technological 
    feasibility analysis based on information submitted to the docket 
    during the hearings and during the pre- and post-hearing comment 
    periods.
        OSHA also received comments specific to application groups 
    regarding issues such as the number of employees potentially exposed, 
    additional exposure data, and the effectiveness of controls. Comments 
    that were application group-specific are addressed in the FEA in the 
    individual sections on those application groups.
        The major changes made to the technological feasibility analysis 
    for the Final Economic Analysis are listed below:
         Electroplating--The number of affected workers and 
    establishments was revised, the exposure distribution was revised for 
    hard chrome electroplating, and chromate conversion workers and 
    establishments were added.
         Welding--The number of maritime welders was increased, 
    mild steel welding was added, and control technology for reducing 
    worker exposure was revised.
         Painting--Auto body repair workers were added to general 
    industry and traffic painting was added to construction. Control 
    technology for reducing worker exposure was revised for aerospace spray 
    painting.
         Chromium Catalyst Production--Control technology for 
    reducing worker exposure was revised.
         Steel Mills--OSHA revised the distribution of steel 
    workers, carbon steel workers were added, and downstream users (e.g. 
    rolling mills and forging operations) were added to this application 
    group.
         Glass Production--Fiber, flat, and container glass 
    production were added.
         Producers of Pre-Cast Concrete Products--Ready mixed 
    concrete workers were added.
         Throughout the analysis the exposure profiles were updated 
    to reflect additional exposure data submitted to the docket.
        Technological Feasibility of the New PEL: There are over 558,000 
    workers exposed to Cr(VI). Table VIII-2 shows the current exposures to 
    Cr(VI) by application group. There are employers and some entire 
    application groups that already have nearly all exposures below the 
    PEL. However, many others will need to install or improve engineering 
    and work practice controls to achieve the PEL.
        OSHA has determined that the primary controls most likely to be 
    effective in reducing employee exposure to Cr(VI) are local exhaust 
    ventilation (LEV), process enclosure, process modification, and 
    improving general dilution ventilation. In some cases, a firm may not 
    need to upgrade its local exhaust system, but instead must ensure that 
    the exhaust system is working to design specification throughout the 
    process. In other cases, employers will need to upgrade or install new 
    LEV. This includes installing duct work, a type of hood and/or a 
    collection system. OSHA estimates that process enclosures may be 
    necessary for difficult-to-control operations such as dusty operations. 
    These enclosures would isolate the employees from high exposure 
    processes and reduce the need for respirators. Process modifications 
    can also be effective in reducing exposures in some industries to a 
    level at or below the PEL.
        Below are discussions of the types of engineering and work practice 
    controls that may be needed for the application groups where exposures 
    are more difficult to control.
        Electroplating: OSHA has determined that the PEL of 5 [mu]g/m\3\ is 
    technologically feasible for all job categories through the use of a 
    combination of engineering controls. For decorative plating and 
    anodizing the vast majority (over 80 percent) of workers are already 
    below 5 [mu]g/m\3\. For the workers above the PEL, there are several 
    control options to reduce exposures, such as properly maintained 
    ventilation and the use of fume suppressants. Some firms may not need 
    to upgrade their local exhaust systems, but must ensure that their 
    current exhaust systems are working according to design specification. 
    For example, in hard chrome electroplating (where Cr(VI) exposures are 
    highest) nearly 100 percent of hard chrome electroplating baths have 
    LEV at the tank; however, none of the systems inspected during site 
    visits and for NIOSH reports were operating at the designed 
    capabilities. Many had disconnected supply lines or holes in the hoods 
    and were working at 40 percent of their design capabilities. In such 
    cases, OSHA recommends that these facilities perform the proper 
    maintenance necessary to bring the system back to its initial 
    parameters. Even with these deficiencies in engineering controls, over 
    75 percent of workers are below 5 [mu]g/m\3\.
        In addition to improving LEV, the use of fume suppressants can 
    further reduce the volume of Cr(VI) fumes released from the plating 
    bath. However, OSHA was unable to conclude, based on the evidence in 
    the record, that the proposed PEL of 1 [mu]g/m\3\ would have been 
    technologically feasible for all hard chrome electroplating operations. 
    In particular, OSHA has significant concerns about the technological 
    feasibility of the proposed PEL for hard chrome electroplating 
    operations in which fume suppressants cannot be used to control 
    exposures to Cr(VI) because they would interfere with product 
    specifications and render the resulting product unusable.
        Welding: The welding operations OSHA expects to trigger 
    requirements under the new Cr(VI) rule are those performed on stainless 
    steel, as well as those performed on high-chrome-content carbon steel 
    and those performed on carbon steel in confined and enclosed spaces. At 
    the time of the proposal, OSHA believed that carbon steel contained 
    only trace amounts of chromium and therefore that welding on carbon 
    steel would not be affected by the standard. Comments and evidence 
    received during the rulemaking, however, led OSHA to conclude that 10 
    percent of carbon steel contains chromium in more than trace amounts; 
    OSHA adjusted its analysis accordingly. See Tr. 581-82.
        OSHA has determined that the PEL of 5 [mu]g/m\3\ is technologically 
    feasible for all affected welding job categories on carbon steel. OSHA 
    has concluded that no carbon steel welders are exposed to Cr(VI) above 
    5 [mu]g/m\3\, with the exception of a small portion of workers welding 
    on carbon steel in enclosed and confined spaces. Furthermore, OSHA has 
    determined that engineering and work practice controls are available to 
    permit the vast majority (over 95 percent) of welding operations on 
    carbon steel in enclosed and confined spaces to comply with a PEL of 5 
    [mu]g/m\3\.
        Although stainless steel welding generally results in higher 
    exposures than carbon steel welding, OSHA has determined that the PEL 
    of 5 [mu]g/m\3\ is also technologically feasible for all affected 
    welding job categories on stainless steel. Many welding processes, such 
    as tungsten-arc welding (TIG) and submerged arc welding (SAW), already 
    achieve Cr(VI) exposures below the PEL because they inherently generate 
    lower fume volumes. However, the two most common welding processes, 
    shielded metal arc welding (SMAW) and gas metal arc welding (GMAW), 
    generate greater exposures and may require the installation or 
    improvement of LEV (defined to include portable LEV systems such as 
    fume extraction guns (FEG)).
        OSHA has found process substitution to be the most effective method 
    of reducing Cr(VI) exposures. For example, the generation of Cr(VI) in 
    GMAW welding fume is approximately 4 percent of the total Cr content, 
    compared to upwards of 50 percent for SMAW. In the proposal, OSHA 
    estimated that all SMAW workers outside of confined spaces (over 90 
    percent of the welders) could switch welding processes. However, 
    hearing testimony and comments indicated that switching to GMAW is not 
    feasible to the extent that OSHA had originally estimated.
        Some comments indicated that this conversion has already taken 
    place where possible. For example, Atlantic Marine stated they have 
    already "greatly reduced the use of SMAW and replaced it with GMAW 
    over the last several years' (Ex. 39-60). Other comments indicated it 
    is still an ongoing process. For instance, General Dynamics stated, 
    "There are ongoing efforts to reduce the use of SMAW and replace it 
    with GMAW for both efficiency and health reasons" (Ex. 38-214). In 
    addition, some comments expressed concerns about the quality of the 
    weld if GMAW is used instead of SMAW. (Ex. 39-70).
        In view of these concerns OSHA has revised its estimate of the 
    percentage of SMAW welders that can switch to GMAW from 90 percent to 
    60 percent. This estimate is consistent with the estimate made by 
    Edison Welding Institute in a report for the Department of Defense on 
    Cr(VI) exposures which "identifies engineering controls that can be 
    effective in reducing worker exposure for many applications in the 
    shipbuilding and repair industry" (Ex. 35-410).
        For those stainless steel SMAW operations that cannot switch to 
    GMAW, and even for some GMAW operations, the installation or 
    improvement of LEV may be needed and can be used to reduce exposures. 
    OSHA has found that LEV would permit most SMAW and GMAW operations to 
    comply with a PEL of 5 [mu]g/m\3\. OSHA recognizes that the 
    supplemental use of respirators may still be necessary in some 
    situations. A significant portion of the welders who may need 
    supplemental respiratory protection are working in confined spaces or 
    other enclosed areas, where the use of engineering controls may be 
    limited due to space constraints. However, respirator use in those 
    circumstances will not be extensive and does not undermine OSHA's 
    finding that the PEL of 5 [mu]g/m\3\ is technologically feasible.
        For a more detailed explanation of OSHA's technological feasibility 
    analysis for all welding operations, see Chapter III of the FEA.
        Aerospace: OSHA has determined that most operations in the 
    aerospace industry can achieve a PEL of 5 [mu]g/m\3\. These operations 
    include sanding Cr(VI) coated parts, assembly, and two-thirds of the 
    spray painting operations. Field studies have shown that use of LEV at 
    the sanding source can reduce exposures by close to 90 percent, with 
    workers exposures well below the final PEL of 5 [mu]g/m\3\. Exposure 
    data provided to the docket show that the spray painting operations in 
    paint booths or paint rooms using optimum engineering controls can 
    achieve worker exposures below the final PEL of 5 [mu]g/m\3\ (excluding 
    large parts, whole planes, or the interior of the fuselage)
        OSHA recognizes that there are certain instances where the 
    supplemental use of respirators may be necessary because engineering 
    and work practice controls are not sufficient to reduce exposures below 
    the PEL. For example, when spray painting large parts or entire planes 
    in hangars, engineering controls become less effective because of the 
    large area needing ventilation and the constantly changing position of 
    workers in relationship to these controls. As a result, OSHA estimates 
    that engineering and work practice controls can limit exposures to 
    approximately 25 [mu]g/m\3\ under the conditions described above and 
    supplemental use of respirators will be needed to achieve the PEL of 5 
    [mu]g/m\3\. Accordingly, OSHA has adopted a provision for the painting 
    of whole aircrafts (interior or exterior) and large aircraft parts that 
    requires employers to reduce exposures to 25 [mu]g/m\3\ with 
    engineering and work practice controls and supplement these controls 
    with the use of respiratory protection to achieve the PEL. For a more 
    detailed explanation of OSHA's technological feasibility analysis for 
    aerospace painting, see Chapter III of the FEA.
        Other Industries: Other application groups that generate fine dusts 
    such as chromate pigment production, chromium catalyst production, and 
    chromium dye production may require new or improved ventilation to 
    achieve the PEL of 5 [mu]g/m\3\. Housekeeping measures are also 
    important for controlling Cr(VI) exposures in these industries. General 
    housekeeping and the use of HEPA vacuums instead of dry sweeping will 
    minimize background exposures for most job categories. For a more 
    detailed explanation of OSHA's technological feasibility analysis for 
    chromate pigment producers, chromium catalyst producers, and chromium 
    dye producers, see Chapter III of the FEA.
        Apart from the aerospace painting operations discussed above, OSHA 
    recognizes that there are a few limited operations where the 
    supplemental use of respirators may be necessary to achieve the PEL of 
    5 [mu]g/m\3\. However, OSHA believes that the final PEL can be achieved 
    in most operations most of the time with engineering and work practice 
    controls. As noted previously, Table VIII-3 shows OSHA's estimate of 
    respirator use by industry for each of the PELs that OSHA considered.
        Technological Feasibility of the Proposed PEL: As discussed more 
    thoroughly in paragraph (c) of the Summary and Explanation of the 
    Standard and in Chapter III of the FEA, OSHA has determined that the 
    proposed PEL of 1 [mu]g/m\3\ is not feasible across all industries 
    because it cannot be achieved using engineering and work practice 
    controls in a substantial number of industries and operations employing 
    a large number of workers covered by the standard (in particular, see 
    "Technological Feasibility of the Proposed 1 [mu]g/m\3\ 8-Hour TWA 
    PEL" in Chapter III of the FEA). Specifically, OSHA has determined 
    that a PEL of 1 [mu]g/m\3\ is not feasible for welding, which affects 
    the largest number of establishments and employees.
        A PEL of 1 [mu]g/m\3\ is also technologically infeasible for 
    aerospace painting, where two-thirds of all spray painting operations 
    cannot reduce exposures to at or below 1 [mu]g/m\3\ using engineering 
    and work practice controls. Finally, OSHA was unable to conclude that 
    the proposed PEL was technologically feasible for existing facilities 
    in several other industries or operations, such as pigment production, 
    catalyst production, and some hard chrome electroplating operations, 
    where a PEL of 1 [mu]g/m\3\ would significantly increase the number of 
    workers requiring respiratory protection.
    
    D. Costs
    
        The costs employers are expected to incur to comply with the final 
    standard are $282 million per year. In addition, OSHA estimates that 
    employers will incur $110 million per year to comply with the personal 
    protective equipment and hygiene requirements already present in 
    existing generic standards. The final requirements to provide 
    protective clothing and equipment and hygiene areas are closely aligned 
    with the requirements of OSHA's current generic PPE and sanitation 
    standards (e.g., 1910.132 and 1926.95 for PPE and 1910.142 and 1926.51 
    for the hygiene requirements). Therefore, OSHA estimates that the 
    marginal cost of complying with the new PPE and sanitation requirements 
    of the Cr(VI) standard was lower for firms currently subject to and in 
    compliance with existing generic standards. OSHA's research on these 
    current standards, however, uncovered some noncompliance. The baseline 
    chosen for the Cr(VI) regulatory impact analysis reflects this non-
    compliance with current requirements. Although OSHA estimates that 
    employers would need to spend an additional $110 million per year to 
    bring themselves into compliance with the personal protective equipment 
    and hygiene requirements already prescribed in existing generic 
    standards, this additional expenditure is not attributable to the 
    Cr(VI) rulemaking. However, the rule does require employers to pay for 
    PPE. In some cases where employers do not now pay for PPE, employers 
    will incur costs they did not previously have. However, because these 
    costs were previously borne by employees, this change does not 
    represent a net cost to the country. OSHA estimates that employers 
    would be essentially transferring a benefit to employees of $6 million 
    per year, the value of the portion of the total expense now paid by 
    employees.
        All costs are measured in 2003 dollars. Any one-time costs are 
    annualized over a ten-year period, and all costs are annualized at a 
    discount rate of 7 percent. (A sensitivity analysis using a discount 
    rate of 3 percent is presented in the discussion of net benefits.) The 
    derivation of these costs is presented in Chapter IV of the full FEA. 
    Table VIII-4 provides the annualized costs by provision and by 
    industry. Engineering control costs represent 41 percent of the costs 
    of the new provisions of the final standard, and respiratory protection costs 
    represent 25 percent of the costs of the new provisions of the final 
    standard. Costs for the new provisions for general industry are $192 
    million per year, costs for constructions are $67 million per year, and 
    costs for the shipyard sector are $23 million per year. In developing 
    the costs for construction, OSHA assumed that all work by construction 
    firms would be covered by the construction standard. However, in 
    practice some work by construction firms takes the form of maintenance 
    operations that would be covered by the general industry standard. 
    (OSHA sought comment on this issue but received none.)
    BILLING CODE 4510-26-P

Table VIII-4 Part 1

 

Table VIII-4 Part 2

 

Table VIII-4 Part 3

 

    
    BILLING CODE 4510-26-C
        Table VIII-4 also shows the costs by application group. The various 
    types of welding represent the most expensive application group, 
    accounting for 51 percent of the total costs.
        Table VIII-5 presents OSHA's final total annualized costs by cost 
    category for each of the alternative PELs considered by OSHA in the 
    proposed rule. At a discount rate of 7 percent, total costs range from 
    $112 million for a PEL of 20 [mu]g/m\3\ to $1.8 billion for a PEL of 
    0.25 [mu]g/m\3\.
        OSHA also presents, in Table VIII-6, the distribution of compliance 
    costs at the time they are imposed. Because firms will have the choice 
    of whether to finance expenditures in a single year, or spread them out 
    over four years, OSHA considers it unlikely that a firm would be 
    impacted in an amount equal to the entire startup cost in the year that 
    the initial requirements are imposed. On the other hand, capital 
    markets are not perfectly liquid and particular firms may face 
    additional lending constraints, therefore OSHA believes that 
    identifying startup costs, in addition to the annualized costs, is 
    relevant when exploring the question of economic feasibility and the 
    overall impact of this rulemaking.
    BILLING CODE 4510-26-P

Table VIII-5 Part 1

 

Table VIII-5 Part 2

 

    
    BILLING CODE 4510-26-C
    
    E. Economic Impacts
    
        To determine whether the final rule's projected costs of compliance 
    would raise issues of economic feasibility for employers in affected 
    industries, i.e., would adversely alter the competitive structure of 
    the industry, OSHA first compared compliance costs to industry revenues 
    and profits. OSHA then examined specific factors affecting individual 
    industries where compliance costs represent a significant share of 
    revenue, or where the record contains other evidence that the standard 
    could have significant impact on the competitive structure of the 
    industry.
        OSHA compared the baseline financial data with total annualized 
    incremental costs of compliance by computing compliance costs as a 
    percentage of revenues and profits. This impact assessment for all 
    firms is presented in Table VIII-7. This table is considered a 
    screening analysis and is the first step in OSHA's analysis of whether 
    the compliance costs potentially associated with the standard would 
    lead to significant impacts on establishments in the affected 
    industries. The actual impact of the standard on the viability of 
    establishments in a given industry, in a static world, depends, to a 
    significant degree, on the price elasticity of demand for the services 
    sold by establishments in that industry.
    BILLING CODE 4510-26-P

Table VIII-7 Part 1

 

Table VIII-7 Part 2

 

Table VIII-7 Part 3

 

Table VIII-7 Part 4

 

Table VIII-7 Part 5

 

Table VIII-7 Part 6

 

Table VIII-7 Part 7

 

Table VIII-7 Part 8

 

Table VIII-7 Part 9

 

    
    BILLING CODE 4510-26-C
        Price elasticity refers to the relationship between the price 
    charged for a service and the demand for that service; that is, the 
    more elastic the relationship, the less able is an establishment to 
    pass the costs of compliance through to its customers in the form of a 
    price increase and the more it will have to absorb the costs of 
    compliance from its profits. When demand is inelastic, establishments 
    can recover most of the costs of compliance by raising the prices they 
    charge for that service; under this scenario, profit rates are largely 
    unchanged and the industry remains largely unaffected. Any impacts are 
    primarily on those using the relevant services. On the other hand, when 
    demand is elastic, establishments cannot recover all the costs simply 
    by passing the cost increase through in the form of a price increase; 
    instead, they must absorb some of the increase from their profits. 
    Commonly, this will mean both reductions in the quantity of goods and 
    services produced and in total profits, though the profit rate may 
    remain unchanged. In general, "when an industry is subject to a higher 
    cost, it does not simply swallow it, it raises its price and reduces 
    its output, and in this way shifts a part of the cost to its consumers 
    and a part to its suppliers," in the words of the court in American 
    Dental Association v. Secretary of Labor (984 F.2d 823, 829 (7th Cir. 
    1993)).
        The Court's summary is in accordance with micro-economic theory. In 
    the long run, firms can only remain in business if their profits are 
    adequate to provide a return on investment that assures that investment 
    in the industry will continue. Over time, because of rising real 
    incomes and productivity, firms in most industries are able to assure 
    an adequate profit. As technology and costs change, however, the long 
    run demand for some products naturally increases and the long run 
    demand for other products naturally decreases. In the face of rising 
    external costs, firms that otherwise have a profitable line of business 
    may have to increase prices to stay viable. Commonly, increases in 
    prices result in reduced demand, but rarely eliminate all demand for 
    the product. Whether this decrease in the total production of the 
    product results in smaller production for each establishment within the 
    industry, or the closure of some plants within the industry, or a 
    combination of the two, is dependent on the cost and profit structure 
    of individual firms within the industry.
        If demand is completely inelastic (i.e., price elasticity is 0), 
    then the impact of compliance costs that are 1 percent of revenues for 
    each firm in the industry would result in a 1 percent increase in the 
    price of the product or service, with no decline in quantity demanded. 
    Such a situation represents an extreme case, but might be correct in 
    situations in which there are few if any substitutes for the product or 
    service in question, or if the products or services of the affected 
    sector account for only a very small portion of the income of its 
    consumers.
        If the demand is perfectly elastic (i.e., the price elasticity is 
    infinitely large), then no increase in price is possible and before-tax 
    profits would be reduced by an amount equal to the costs of compliance 
    (minus any savings resulting from improved employee health and/or 
    reduced insurance costs) if the industry attempted to keep producing 
    the same amount of goods and services as previously. Under this 
    scenario, if the costs of compliance are such a large percentage of 
    profits that some or all plants in the industry can no longer invest in 
    the industry with hope of an adequate return on investment, then some 
    or all of the firms in the industry will close. This scenario is highly 
    unlikely to occur, however, because it can only arise when there are 
    other goods and services that are, in the eyes of the consumer, perfect 
    substitutes for the goods and services the affected establishments 
    produce.
        A common intermediate case would be a price elasticity of one. In 
    this situation, if the costs of compliance amount to 1 percent of 
    revenues, then production would decline by 1 percent and prices would 
    rise by 1 percent. In this case, the industry revenues would stay the 
    same, with somewhat lower production, but similar profit rates (in most 
    situations where the marginal costs of production net of regulatory 
    costs would fall as well). Consumers would, however, get less of the 
    product or the service for their expenditures, and producers would 
    collect lower total profits; this, as the court described in ADA v. 
    Secretary of Labor, is the more typical case.
        If there is a price elasticity of one, the question of economic 
    feasibility is complicated. On the one hand, the industry will 
    certainly not be "eliminated" with the level of costs found in this 
    rulemaking, since under these assumptions the change in total profits 
    is somewhat less than the costs imposed by the regulation. But there is 
    still the question of whether the industry's competitive structure will 
    be significantly altered. For example, given a 20 percent increase in 
    costs, and an elasticity of one, the industry will not be eliminated. 
    However, if the increase in costs is such that all small firms in an 
    industry will have to close, this could reasonably be concluded to have 
    altered its competitive structure. For this reason, when costs are a 
    significant percentage of revenues, OSHA examines the differential 
    costs by size of firm, and other classifications that may be important.
        Some commenters (Ex. 38-265; Ex. 38-202; Ex. 40-12) questioned the 
    screening analysis approach for several reasons: (1) It fails to 
    provide for a facility-by-facility analysis; (2) it fails to consider 
    that, in some plants, there may be product lines that do not involve 
    hexavalent chromium; and (3) the concept of cost pass-through is 
    largely negated by foreign competition. It should be noted that almost 
    all commenters arguing for the inadequacy of screening analysis also 
    argued for much higher costs than those estimated by OSHA (criticisms 
    of costs were examined in Chapter 4). No one in the record presented an 
    argument as to why costs representing less than one percent of revenues 
    would be economically infeasible.
        First, some commenters (Ex. 38-265; Ex. 40-12; Ex. 47-5) argued 
    that industry ratios of costs to profits or costs to revenues cannot 
    adequately determine economic feasibility--instead the analysis must be 
    conducted on a facility-by-facility basis. OSHA rejects this argument 
    for two reasons. First, the judicial definition of economic feasibility 
    notes that a regulation may be economically feasible and yet cause some 
    marginal facilities to close. (American Textile Mfrs. Institute, Inc. 
    v. Donovan 452 U.S. 490, 530-532 (1981))
        OSHA's obligation is not to determine whether any plants will 
    close, or whether some marginal plants may close earlier than they 
    otherwise might have, but whether the regulation will eliminate or 
    alter the competitive structure of an industry. OSHA has an obligation 
    to examine industries, and to consider its industry definitions 
    carefully, so that they compare like with like. However, OSHA does not 
    have an obligation to conduct facility-by-facility analysis of the 
    thousands of facilities in the dozens of industries covered by a major 
    standard. OSHA criteria can be examined through examination of industry 
    ratios, particularly when the costs represent a very small percentage 
    of revenues. Again, it must be noted that almost all commenters arguing 
    for the inadequacy of screening analysis also argued for much higher 
    costs than those estimated by OSHA, and while not agreeing with the 
    need for facility-by-facility analysis, OSHA agrees that as costs 
    become high as a percentage of revenues, something more than industry 
    ratio analysis may be needed.
        Second, some commenters argued that some facilities and industries 
    have some lines of production involving hexavalent chromium, and some 
    that do not, and, in such cases, OSHA should analyze only the revenues 
    and profits associated with the lines using hexavalent chromium. Even 
    if this were desirable, the data for such an analysis is simply not 
    publicly available. No
    government data source collects data in a way that could be used for 
    this purpose, and there is little privately collected data that could 
    be used for this purpose. Even if such data were available, there are 
    reasons to produce a product line even if it has profits lower than 
    other product lines, and the data to examine this issue is even more 
    unavailable. Further, OSHA's mandates, as interpreted by the courts, 
    focus on the effect of a standard on industries, not on product lines 
    within those industries. (American Iron & Steel Institute v. OSHA, 939 
    F.2d 975, 986 (D.C. Cir, 1991))
        Finally, some commenters (SFIC, Ex. 38-265; SSINA, Ex. 40-12, Ex. 
    47-5; Engelhard, Ex. 38-202) questioned the above analysis by bringing 
    up the issue of foreign competition, and some presented the argument 
    that foreign competition made price increases impossible.
        While foreign competition is an important issue to consider in 
    analyzing economic feasibility, the presence of foreign competition 
    does not mean that price increases are impossible. In economic terms, 
    the case that foreign competition makes price increases impossible 
    would be an argument that foreign competition puts all firms into the 
    situation of having infinite elasticity of domestic demand, because 
    foreign firms are not subject to the regulation, and, as a result can 
    underprice American firms and drive them out of business.
        Is this the case? Both theory and history suggest that it is not. 
    From a theoretical viewpoint, the ability to sell to a consumer is 
    determined by the price at the site, plus the cost of transportation, 
    plus or minus intangible factors (such as quality or timeliness). Under 
    these circumstances, a specific establishment can be competitive even 
    if its cost of production is greater than that of foreign competitors--
    if the U.S. producer has other advantages.
        From a practical viewpoint, econometric studies typically talk 
    about the elasticity of domestic production with respect to foreign 
    prices. No one assumes that a lower foreign price simply and totally 
    assures that the domestic industry will be eliminated. Foreign 
    competition has been a fact for decades--this does not mean that any 
    domestic regulation assures that the domestic industry will be 
    eliminated.
        However, foreign competition does mean the elasticity of demand for 
    domestic production will be greater than the total elasticity of demand 
    for the product in question. Thus foreign competition is a factor that 
    can result in greater elasticity of demand for domestic firms, and that 
    needs to be considered in the context of the overall feasibility 
    analysis, just as other factors such as the presence or absence of good 
    substitutes need to be considered in the analysis.
        A different problem with the formulation in terms of demand 
    elasticity given above is that it ignores other things besides the 
    regulatory costs that may act to shift either the costs of the 
    production or demand for a product or service. In the normal course of 
    events, neither demand nor supply is static. Costs of inputs needed 
    commonly increase (at least in nominal terms). Productivity may 
    increase or decrease as technology changes. Increases in income or GDP 
    normally serve to increase demand for a good or service from year to 
    year (for the majority of goods with positive income elasticity). In a 
    typical year for most manufacturing industries, some costs will rise, 
    productivity will also improve, and increases in GDP will increase 
    demand. Adjusting to cost increases is thus a part of the normal 
    economic scene. Even a real cost increase brought about by a regulation 
    may be partially offset by productivity improvement. Finally, even real 
    price increases may not decrease the quantities sold (and thus force 
    employers to close) if the price increases are offset by income-driven 
    increased demand for the good or service. A real price increase caused 
    by the costs of a regulation will mean that the quantity sold will be 
    lower than it otherwise would have been, but does not imply that actual 
    quantity sold for the product will decline as compared to past years.
        Table VIII-7 provides costs as percentage of revenues and profits 
    for all affected establishments. OSHA believes that this is the best 
    starting point for fulfilling its statutory responsibility to determine 
    whether the standard affects the viability of an industry as a whole.
        Table VIII-8 shows costs as a percentage of profits and revenues 
    for firms classified as small by the Small Business Administration and 
    Table VIII-9 shows costs as a percentage of revenues and profits for 
    establishments with fewer than 20 employees. (These tables use costs 
    with a discount rate of 7 percent.) These small-business tables show 
    greater potential impacts, especially for small electroplating 
    establishments. Based on these results, OSHA has prepared a Final 
    Regulatory Flexibility Analysis (see Chapter VII of the FEA) to examine 
    the impacts on small businesses and how they can be alleviated. (Tables 
    V-5, V-6, and V-7 in the FEA show the same information using a discount 
    rate of 3 percent.)
    BILLING CODE 4510-26-P

Table VIII-8 Part 1

 

Table VIII-8 Part 2

 

Table VIII-8 Part 3

 

Table VIII-8 Part 4

 

Table VIII-8 Part 5

 

Table VIII-8 Part 6

 

Table VIII-8 Part 7

 

Table VIII-8 Part 8

 

Table VIII-9 Part 1

 

Table VIII-9 Part 2

 

Table VIII-9 Part 3

 

Table VIII-9 Part 4

 

Table VIII-9 Part 5

 

Table VIII-9 Part 6

 

Table VIII-9 Part 7

 

Table VIII-9 Part 8

 

Table VIII-9 Part 9

 

    
    BILLING CODE 4510-26-C
    
    Economic Feasibility for Many Industries With Low Potential Impacts
    
        To determine whether a rule is economically feasible, OSHA 
    evaluates evidence from a number of sources. And while there is no hard 
    and fast rule, in the absence of evidence to the contrary OSHA 
    generally considers a standard economically feasible when the costs of 
    compliance are less than one percent of revenues. Common-sense considerations 
    indicate that potential impacts of such a small magnitude are unlikely to 
    eliminate an industry or significantly alter its competitive structure 
    particularly since most industries have at least some ability to raise 
    prices to reflect increased costs. Of course, OSHA recognizes that even 
    when costs are within this range, there could be unusual circumstances 
    requiring further analysis. In addition, as a second check, OSHA also 
    looks to see whether even such low costs may represent more than ten 
    percent of the profit in a particular industry. If either of these 
    factors is present, or if there is other evidence of industry demise or 
    potential disruption in an industry's competitive structure because of 
    the standard, OSHA examines the effect of the rule on that industry 
    more closely. Finally, OSHA reviews the record for any other unusual 
    circumstances, such as excellent substitutes of equal cost that might 
    make an industry particularly sensitive to price change. In this case, 
    the only argument of this kind that OSHA noted was an argument by one 
    commenter that trivalent chromium plating might be substituted in some 
    applications for hexavalent chromium. However, even if this is the case 
    (some in the record did not agree), a plating operation could switch to 
    trivalent plating with minimal capital investment and thus remain in 
    business.
        OSHA believes that a potential one percent revenue effect is an 
    appropriate way to begin the analysis in light of the fact that the 
    United States has a dynamic and constantly changing economy. There is 
    an enormous variety of year-to-year events that could cause a one 
    percent increase in a business's costs, e.g., increasing fuel costs, an 
    unusual one-time expense, changes in costs of materials, increased 
    rents, increased taxes, etc. Table V-8, which shows year to year 
    changes in prices for a number of industries affected by the standard, 
    reflects this phenomenon.
        Changes in profits are also subject to the dynamics of the economy. 
    A recession, or a downturn in a particular industry, will typically 
    cause profit declines in excess of ten percent for several years in 
    succession. Table V-9, which shows annual profits for several years in 
    succession, illustrates this phenomenon. While a permanent loss of 
    profits presents a greater problem than a temporary loss, these year-
    to-year variations do serve to show that small changes in profits are 
    quite normal without affecting the viability of industries.
        The potential impacts of this regulation on the affected employers, 
    for the most part, are within the range of normal year-to-year 
    variation that firms and industries expect and survive. Table V-8 in 
    the FEA shows year-to-year price variations for selected industries 
    with hexavalent chromium exposure, and Table V-9 (in the FEA) shows 
    year-to-year profit variations for selected industries with hexavalent 
    chromium exposures. Table V-8 serves the purpose of showing that, for 
    many industries, annual price changes of one percent or more are 
    commonplace without affecting the viability of the industry. Table V-9 
    serves to show that temporary profit swings of significantly more than 
    ten percent are also well within the boundaries of normal year-to-year 
    change.
        Because a permanent decrease in profits is much more significant 
    than a temporary swing of the same magnitude, OSHA has also used the 
    fact that a very large short term decline can be compared in effect to 
    a smaller long-term decrease in profits to calculate the extent to 
    which the temporary changes shown in Table V-9 may demonstrate an 
    industry's ability to withstand a long-term change. For example, using 
    a 7 percent discount rate, and the assumption that profits return to 
    the long term average following a temporary decline, the following 
    short term declines are approximately equivalent to a 10 percent long-
    term decline:
    
    50 percent decline for one year;
    30 percent decline for two years;
    20 percent decline for three years.
    
        Looking at profits of the average corporation for the period of 
    1990 to 2002, events of one of the above magnitudes have occurred twice 
    in that 12-year period without threatening industrial viability. (Based 
    on corporate profit rate data from IRS, Statistics of Income: Corporate 
    Income Tax Returns, as Reported in U.S. Department of Commerce, U.S. 
    Statistical Abstract 2006). And since, as discussed below, demand is 
    not perfectly elastic in any of the affected industries, it is unlikely 
    that the actual effect on profits will be as high as indicated in Table 
    VIII-7.
        The record does not contain evidence that any of the affected 
    industries for which OSHA found that the costs of complying with the 
    standard will be less than both one percent of prior revenue and ten 
    percent of prior profits will in fact be threatened by the standard. 
    Although some industry representatives asserted that compliance would 
    threaten their existence, these assertions (with one exception, 
    discussed below) were not supported by empirical evidence that even the 
    proposed PEL of 1 would be economically infeasible. As noted above, 
    cost changes of less than one percent are routinely passed on and 
    impacts that are less than 10 percent of profits have not been shown to 
    be likely to affect the viability or competitive structure of any of 
    the industries affected by this standard.
    
    Economic Feasibility for Industries With Higher Potential Impacts
    
        In Table VIII-7, OSHA found that there were 9 industries in three 
    application groups in which costs were greater than 1 percent of 
    revenues, and an additional 22 industries in six application groups in 
    which costs were greater than 10 percent of profits.
        However, this number of industries is somewhat misleading. Seven of 
    the industries in which costs exceed one percent of revenues, and an 
    additional twelve of those in which costs exceeded 10 percent of 
    profits (without exceeding 1 percent of revenues) are industries in the 
    plating and welding application groups in which plating or welding are 
    exceedingly rare, such as electroplating in the performing arts, 
    spectator sports and related industries (NAICS 711) and welding in 
    religious, governmental, civil, and professional organizations (NAICS 
    813). In both cases, only one establishment in the entire industry 
    reported engaging in either welding or plating. It is difficult to 
    determine whether reports of welding or plating in such industries 
    represent an extremely unusual situation or, perhaps, simply someone 
    inadvertently checking the wrong box on a survey. In either case, OSHA 
    concludes that if such establishments do indeed engage in welding or 
    plating, they could maintain their primary line of business, as almost 
    everyone else in their industries does, by dropping welding or plating 
    operations if such operations represented any threat whatsoever to the 
    viability of their businesses.
        The same is true of the other industries that are in the general 
    category of extremely rare and unusual users of plating operations: 
    Specialty trade contractors (NAICS 238); wholesale trade and durable 
    goods (NAICS 423); motor vehicle and parts dealers (NAICS 441); 
    furniture and home furnishing stores (NAICS 442); electronics and 
    appliance stores (NAICS 443); building materials and garden equipment 
    dealers (NAICS 444); health and personal care stores (NAICS 446); 
    miscellaneous store retailers (NAICS 453); nonstore retailers (NAICS 
    454); information services and data processing service (NAICS 519); 
    rental and leasing services (NAICS 532); professional, scientific and 
    technical services (NAICS 541); performing arts, spectator sports and 
    related industries (NAICS 711); and personal and laundry services 
    (NAICS 812). In the welding application groups, the industries in this 
    category are: gasoline stations (NAICS 447); nursing and residential 
    care (NAICS 623); social assistance (NAICS 624); food services and 
    drinking places (NAICS 722); and religious, governmental, civil, and 
    professional organizations (NAICS 813).
        The remainder of this section examines those industries with higher 
    potential impacts where their businesses may be dependent on Cr (VI) 
    applications.
        Electroplating Job Shops: Electroplating job shops (NAICS 332813: 
    electroplating, plating, polishing anodizing and coloring services) are 
    a service industry for the manufacturing sector, and, to a lesser 
    extent, to those maintaining, restoring, or customizing objects with 
    metal parts. At a PEL of 5, job shops have costs as a percentage of 
    profits of 30 percent and costs as a percentage of revenues of 1.24 
    percent. These firms sell a service rather than a product. (Firms that 
    directly sell the products they plate end up in other NAICS codes.) As 
    a result, plating firms are primarily affected by foreign competition 
    through the loss of other manufacturing in the United States, rather 
    than through their customers sending products or their component parts 
    abroad for electroplating. However, some commenters noted that there 
    may be cases of sending products abroad for the sole purpose of 
    electroplating. This seems unlikely to be commonplace however, because 
    of the shipping times and costs for a process that normally represents 
    a very small part of the value added for the ultimate product. In 
    addition, because electroplating is essential to the manufacture of 
    most plated products, the ultimate demand for plating services is 
    unlikely to decrease significantly.
        Finally, independent electroplating shops have been subject to 
    annual profit changes larger in magnitude than those associated with 
    this standard. Table V-9 in the FEA shows that, over the past ten 
    years, profits in this industry have risen and fallen as much as 49 
    percent in one year without affecting the viability of the industry. 
    Although these kinds of temporary changes would not have the effect of 
    permanent decline of profits by 30 percent, OSHA believes that all of 
    the factors discussed above indicate that there is sufficient price 
    elasticity and other flexibility in this industry to absorb these 
    costs.
        The price increase of 1.24 percent required to fully restore 
    profits at a PEL of five is significantly less than the average annual 
    increase in price of electroplating services, as shown by Table V-8 in 
    the FEA. Further, during the period shown in Table V-8, the industry 
    successfully survived, without any real price increase, the regulatory 
    costs imposed by EPA's Chrome MACT standard. The costs of that standard 
    are somewhat uncertain. Some commenters argued that that standard could 
    be quite expensive. One commenter suggested that one facility had 
    incurred costs of $80,000 per year to meet that standard, and that such 
    high costs were not atypical. (Tr. 2003) Another commenter noted, 
    however, that "the effect of the MACT Standard was minimized when 
    people realized that the combination of a mist suppressant and the 
    development of a mist suppressant that would work in a hard chrome 
    installation along with the use of mesh pads puts you below the MACT 
    standard." (Tr. 2203) The commenter apparently felt that, in the 
    latter case, the costs would not have been significant. Nevertheless, 
    in either event, probably due to productivity improvement in other 
    aspects of the industry, there was no real price increase or massive 
    dislocation in the industry.
        SFIC (Ex. 38-265) also argued that it was difficult to pass on 
    costs in electroplating based on an EPA study that estimated a cost 
    pass through elasticity of 0.58. This study was based on pre-1996 data, 
    and found a statistical relationship between nominal price increases 
    and increases in a nominal cost index. Whatever the difficulties in 
    passing increased costs to its customers the industry might have had 
    before 1996, since that time nominal prices have increased in ways that 
    did not have the effects on profit predicted by the EPA study.
        Even in the event of a real price increase, we believe that demand 
    for electroplating services is relatively inelastic. For most products 
    that are plated, plating is basically essential to the function of the 
    product. The EPA study for the MACT standard found that products 
    incorporating electroplating had relatively inelastic demand, on the 
    order of less than 0.5, and the cost of plating represented a very 
    small percentage of the total costs of the products in question. In 
    this situation, the chief danger associated with a real cost increase 
    of less than 1 percent is that there would be some increased foreign 
    penetration of U.S. markets. However, the small size of the change, and 
    the difficulty of sending products abroad solely for plating services, 
    assures that the price change in question would not eliminate the 
    industry, and is unlikely to alter the competitive structure of the 
    industry.
        However, OSHA is concerned about the economic feasibility of the 
    standard for electroplating at a PEL of 1. At this lower PEL, costs of 
    the standard represent 2.7 percent of revenues and 65 percent of 
    profits. In almost all OSHA health standards in which this figure was 
    developed, the costs for the most affected industry have been less than 
    2 percent of revenues. (The major exception was brass and bronze 
    foundries, where the lead standard PEL was found economically 
    infeasible with the use of engineering controls.) Further, in standards 
    where the costs might have been in excess of 2 percent of revenues, 
    OSHA has sought ways to lower the cost through long term phase-ins of 
    engineering controls. OSHA examined this possibility for job-shop 
    electroplaters, and found that even allowing the use of respirators 
    rather than engineering controls would not significantly lower the 
    costs as percentage of revenues. OSHA also examined the issue of 
    whether there were particular types of platers that might have 
    unusually high or low costs, and found that even quite different 
    plating shop configurations with respect to the type of plating done 
    would have approximately equal average costs.
        Given the high level of costs as a percentage of revenues and 
    profits, and the inability to alleviate those impacts without a higher 
    PEL, OSHA further examined the economic feasibility of the standard at 
    a PEL of 1. It seems unlikely that a price increase of 2.7 percent, 
    although significantly larger than the average nominal price increases 
    in recent years, would eliminate the industry entirely. OSHA has 
    concluded, however, that the costs associated with such a PEL could 
    alter the competitive structure of the industry. OSHA has concluded 
    this because these costs substantially exceed the average nominal price 
    increases in the industry, and the reasons for these nominal price 
    increases--increases in the cost of labor and energy, for example--will 
    continue. Thus a price increase that would assure continued 
    profitability for the entire industry would require almost tripling the 
    annual nominal price increase. (The long term average price increase 
    for plating, as shown in Table V-9, is 1.6 percent per year. Assuming 
    this continues to be needed, an increase that would leave profits 
    unchanged would require a cost increase of 4.2 percent (1.6 plus 2.6), 
    almost three times as much.) That would represent a significant real 
    price increase that might not be passed forward, particularly by older 
    and less profitable segments of the industry.
        Welding (Stainless Steel) in Construction: OSHA calculated that the 
    costs of the standard could equal 22.3 percent of profits in this 
    industry, but only 0.92 percent of revenues. The maximum price 
    increases required to fully restore profits (0.92 percent) is unlikely 
    to significantly alter the demand for construction welding services 
    which are essential for many projects and not subject to foreign 
    competition. Further, costs of using stainless steel (the chief source 
    of welding exposure) already vary significantly from year to year, and 
    often from month to month. Table V-10 shows the producer price index 
    for steel prices. Prices of steel have changed by more than 10 percent 
    within a single year a number of times in the past ten years without 
    affecting the viability of the use of stainless steel in construction.
        Welding in General Industry: There are a significant number of 
    establishments engaged in welding in repair and maintenance (NAICS 811) 
    and in personal and laundry services (NAICS 812). For repair and 
    maintenance services, the costs as a percentage of revenues are 0.40 
    percent and the costs as a percentage of profits are 10.5 percent. For 
    personal and laundry services the costs as a percentage of revenues are 
    0.67 percent and costs as a percentage of profits are 13 percent. (All 
    costs include the costs of any respirators welders will need to use.) 
    These two sectors conduct maintenance and repair welding. Even if costs 
    cannot be passed on, the resulting declines in profits are unlikely to 
    affect the viability of an otherwise viable employer. Further, 
    businesses of this kind are more likely to be able to increase costs 
    because of the absence of foreign competition. While some loss of 
    revenue is possible with a price increase, it is unlikely that the 
    quantity of routine repairs would be significantly affected by price 
    increases of this magnitude.
        Painting and Corrosion Protection: Four sectors in the painting 
    application groups have costs as a percentage of revenues in excess of 
    one percent or costs as a percentage of profits in excess of 10 
    percent. These are motor vehicle body and trailer manufacturing (NAICS 
    3362) with costs of 0.51 percent and 20 percent; military armored 
    vehicle and tank manufacturers (NAICS 336992) with costs of 0.25 
    percent and 10 percent; used car dealers (NAICS 44112) with costs of 
    0.41 percent and 34 percent; and automotive body, paint and interior 
    repair (NAICS 81121) with costs of 1.5 percent and 39 percent. These 
    costs are incurred in part for the use of hexavalent chromium pigments, 
    but largely for using hexavalent chromium coating (applied like paint) 
    as undercoats for corrosion protection. In the case of the first two 
    NAICS codes, these are part of manufacturing processes. For both of 
    these manufacturing industries, while the costs of hexavalent chromium 
    coatings may be significant in the establishments where they are 
    applied, the costs of Hexavalent chromium coatings represent an 
    insignificant percentage of the costs of a car or a tank. While 
    manufacturers may seek substitutes for hexavalent chromium coatings, 
    additional expenses for such coatings are unlikely to affect the 
    ultimate demand for cars or tanks. The latter two affected industries 
    involve repair and refurbishing of existing automobiles. The cost 
    analysis assumes all firms who currently use hexavalent chromium in 
    these industries will continue to do so. In each case, there are 
    choices that would avoid the costs in question. One choice would be to 
    use non-hexavalent chromium pigments or non-hexavalent chromium 
    corrosion protection. A variety of substitutes have been developed, and 
    the use of hexavalent chromium based coatings for these purposes is 
    already banned in California. (Tr. 1913) Although these substitutes 
    have not yet been subject to long term use and their protectiveness is 
    currently less certain than that of hexavalent chromium, it is likely 
    that products that are equivalent to hexavalent chromium will be 
    developed, particularly if demand for such products increases as a 
    result of the standard. In addition, applying hexavalent chromium 
    coatings represents a very small portion of the business of either auto 
    body repair shops or used car dealers. A firm whose viability was 
    seriously threatened as a result of this standard could retain most of 
    its core businesses without continuing to use hexavalent chromium.
        In addition, it is also reasonable to suppose that both used cars 
    and auto body repair do not have highly elastic demand, such that a 
    small change in prices would result in a very large drop in the number 
    of cars repaired. As a result, the required increases in price can be 
    accommodated without such significant losses as to alter the 
    competitive structure of the industries.
        Chromium Catalyst Producers (0.8 percent; 27 percent) and Service 
    Companies (0.44 percent; 12 percent): Chromium catalyst production and 
    service companies are also unlikely to be affected by costs of the 
    relative magnitude found here. Most companies are locked into the use 
    of specific catalysts without major new investments. As a result, while 
    there may be some small long-term shift away from the use of chromium 
    catalysts, a price change of one percent is unlikely to immediately 
    prompt such a change. This also means that the market for chrome 
    catalyst services is likely to be maintained. Further, faced with a new 
    regulation, companies are more rather than less likely to turn to a 
    service company to handle chromium products. Based on these 
    considerations, OSHA determined that the standard is economically 
    feasible in these sectors.
        Iron and Steel Foundries: Iron and steel foundries (NAICS 3315) 
    have costs that are 0.42 percent of revenues and 15 percent of profits. 
    An oddity of the estimated costs for this industry is that 44 percent 
    of the costs are associated with monitoring costs. In this cost 
    estimate, OSHA assumes that iron and steel foundries will use scheduled 
    periodic monitoring rather than adopting the option of performance-
    based monitoring. Adopting a performance-based monitoring approach 
    rather than scheduled monitoring might well reduce costs as a 
    percentage of profits to less than 10 percent of profits. As noted 
    above, cost changes of less than one percent are routinely passed on 
    and impacts that are less than 10 percent of profits have not been 
    shown to be likely to affect the viability or competitive structure of 
    any of the industries affected by this standard.
        Even if costs are not reduced, the industry has demonstrated its 
    ability to survive real cost increases by remaining viable in the face 
    of a 32 percent increase in the price of its basic input, steel, over 
    the last two years. Based on these considerations, OSHA concludes the 
    standard is feasible for this sector.
    
    F. Benefits and Net Benefits
    
        OSHA estimated the benefits associated with alternative PELs for 
    Cr(VI) by applying the dose-response relationship developed in the risk 
    assessment to current exposure levels. OSHA determined current exposure 
    levels by first developing an exposure profile for industries with 
    Cr(VI) exposures using OSHA inspection and site visit data, and then 
    applying this profile to the total current worker population. The 
    industry-by-industry exposure profile was given in Table VIII-2 above.
        By applying the dose-response relationship to estimates of current 
    exposure levels across industries, it is possible to project the number 
    of lung cancers expected to occur in the worker
    population given current exposures (the "baseline"), and the number 
    of these cases that would be avoided under alternative, lower PELs. 
    OSHA assumed that exposures below the limit of detection (LOD) are 
    equivalent to no exposure to Cr(VI), thus assigning no baseline or 
    avoided lung cancers (and hence, no benefits) to these exposures. For 
    exposures above the current PEL and for purposes of determining the 
    benefit of reducing the PEL, OSHA assumed exposure at exactly the PEL.
        Consequently, the benefits computed below are attributable only to 
    a change in the PEL. No benefits are assigned to the effect of a new 
    standard increasing compliance with the current PEL. OSHA estimates 
    that between 3,167 and 12,514 lung cancers attributable to Cr(VI) 
    exposure will occur during the working lifetime of the current worker 
    population. Table VIII-10 shows the number of avoided lung cancers by 
    PEL. At the final PEL of 5 [mu]g/m3, an estimated 1,782 to 
    6,546 lung cancers would be prevented over the working lifetime of the 
    current worker population.
        Note that the Agency based these estimates on a worker who is 
    employed in a Cr(VI)-exposed occupation for his entire working life, 
    from age 20 to 65. The calculation also does not allow workers to enter 
    or exit Cr(VI) jobs, nor switch to other exposure groups during their 
    working lives. While the assumptions of 45 years of exposure and no 
    mobility among exposure groups may seem restrictive, these assumptions 
    actually are likely to yield somewhat conservative (lower) estimates of 
    the number of avoided cancers, given the nature of the risk assessment 
    model.
    BILLING CODE 4510-26-P

Table VIII-10

 

    
    BILLING CODE 4510-26-C
        For example, consider the case of job covered by five workers, each 
    working nine years rather than one worker for 45 years. The former 
    situation will likely yield a slightly higher rate of lung cancers, 
    since more workers are exposed to the carcinogen (albeit for a shorter 
    period of time) and the average age of the workers exposed is likely to 
    decrease. This is due to: (1) The linearity of the estimated dose-
    response relationship, and (2) once an individual accumulates a dose, the 
    increase in relative risk persists for the remainder of his lifetime. 
    For example, a worker exposed from age 20 to 30 will have a constant 
    increased relative risk for about 50 or so years (from age 30 on, 
    assuming no lag between exposure and increased risk and death at age 
    80), whereas a person exposed from age 40 to 50 will have only about 30 
    years of increased risk (again assuming no lag and death at age 80). 
    The persistence of the increased relative risk for a lifetime follows 
    directly from the risk assessment and is typical of life table 
    analysis.
        For informational purposes only, OSHA has estimated the monetary 
    value of the benefits associated with the final rule. These estimates 
    are informational because OSHA cannot use benefit-cost analysis as a 
    basis for determining the PEL for a health standard. In order to 
    estimate monetary values for the benefits associated with the final 
    rule, OSHA reviewed the approaches taken by other regulatory agencies 
    for similar regulatory actions. OSHA found that occupational illnesses 
    are analogous to the types of illnesses targeted by EPA regulations and 
    has thus used them in this analysis.
        OSHA is adopting EPA's approach, applying a value of $6.8 million 
    to each premature fatality avoided. The $6.8 million value represents 
    individuals' willingness-to-pay (WTP) to reduce the risk of premature 
    death.
        Nonfatal cases of lung cancer can be valued using a cost of illness 
    (COI) approach, using data on associated medical costs. The EPA Cost of 
    Illness Handbook (Ex.35-333) reports that the medical costs for a 
    nonfatal case of lung cancer are, on average, $136,460. Updating the 
    EPA figure to 2003 dollars yields the value of $160,030. Including 
    values for lost productivity, the total COI which is applied to the 
    OSHA estimate of nonfatal cases of lung cancer is $188,502.
        An important limitation of the COI approach is that it does not 
    measure individuals' WTP to avoid the risk of contracting nonfatal 
    cancers or illnesses. As an alternative approach, nonfatal cancer 
    benefits may be estimated by adjusting the value of lives saved 
    estimates. In its Stage 2 Disinfection and Disinfection Byproducts 
    water rule, EPA used studies on the WTP to avoid nonfatal lymphoma and 
    chronic bronchitis as a basis for valuing nonfatal cancers. In sum, EPA 
    valued nonfatal cancers at 58.3 percent of the value of a fatal cancer. 
    Using WTP information would yield a higher estimate of the benefits 
    associated with the reduction in nonfatal lung cancers, as the nonfatal 
    cancers would be valued at $4 million rather than $188,502 per case. 
    These values represent the upper and lower bound values for nonfatal 
    cases of lung cancer avoided.
        Using these assumptions, latency periods of 15, 20, 25, and 30 
    years--and adjustments to the value of statistical life to today--OSHA 
    estimated the total annual benefits of the standard at various PELS in 
    Table VIII-11, considering the benefits from preventing both fatal and 
    non-fatal cases of lung cancer.
        Occupational exposure to Cr(VI) has also been linked to a multitude 
    of other health effects, including irritated and perforated nasal 
    septum, skin ulceration, asthma, and dermatitis. Current data on Cr(VI) 
    exposure and health effects are insufficient to quantify the precise 
    extent to which many of these ailments occur. However, it is possible 
    to provide an upper bound estimate of the number of cases of dermatitis 
    that occur annually and an upper estimate of the number that will be 
    prevented by a standard. This estimate is an upper bound because it 
    uses data on incidence of dermatitis among cement workers, where 
    dermatitis is more common than it would be for other exposures to 
    Cr(VI). It is important to note that if OSHA were able to quantify all 
    Cr(VI)-related health effects, the quantified benefits would be 
    somewhat higher than the benefits presented in this analysis.
    BILLING CODE 4510-26-P

Table VIII-11

 

    
    BILLING CODE 4510-26-C
    
        Using National Institute for Occupational Safety and Health (NIOSH) 
    data, Ruttenberg and Associates (Ex. 35-332) estimate that the 
    incidence of dermatitis among concrete workers is between 0.2 and 1 
    percent. Applying the 0.2 percent-1 percent incidence rate indicates 
    that there are presently 418-2,089 cases of dermatitis occurring 
    annually. This approach represents an overestimate for cases of 
    dermatitis in other application groups, since some dermatitis among 
    cement workers is caused by other known factors, such as the high 
    alkalinity of cement. If the measures in this final standard are 50 
    percent effective in preventing dermatitis, then there would be an 
    estimated 209-1,045 cases of Cr(VI) dermatitis avoided annually.
        To assign values to the cases of avoided dermatitis OSHA applied 
    the COI approach. Ruttenberg and Associates computed that, on average, 
    the medical costs associated with a case of dermatitis are $119 (in 
    2003 dollars) and the indirect and lost productivity costs are $1,239 
    (Ex. 35-332). These estimates were based on an analysis of BLS data on 
    lost time associated with cases of dermatitis, updated to current 
    dollars. Based on the Ruttenberg values, OSHA estimates that a Cr(VI) 
    standard will yield $0.3 million to $1.4 million in annual benefits due 
    to reduced incidence of dermatitis.
        Occupational exposure to Cr(VI) can lead to nasal septum 
    ulcerations and nasal septum perforations. As with cases of dermatitis, 
    the data were insufficient to conduct a formal quantitative risk 
    assessment to relate exposures and incidence. However, previous studies 
    provide a basis for developing an approximate estimate of the number of 
    nasal perforations expected under the current PEL as well as PELs of 
    0.25 [mu]g/m3, 0.5 [mu]g/m3, 1.0 [mu]g/
    m3, 5.0 [mu]g/m3, 10.0 [mu]g/m3 and 
    20.0 [mu]g/m3. Cases of nasal perforations were computed 
    only for workers in electroplating and chrome production. The 
    percentage of workers with nasal tissue damage is expected to be over 
    50 percent for those regularly exposed above approximately 20 [mu]g/
    m3. Less than 25 percent of workers could reasonably be 
    expected to experience nasal tissue damage if Cr(VI) exposure was kept 
    below an 8-hour TWA of 5 [mu]g/m3 and regular short-term 
    exposures (e.g. an hour or so) were below 10 [mu]g/m3. Less 
    than 10 percent of workers could reasonably be expected to experience 
    nasal tissue damage at a TWA Cr(VI) below 2 [mu]g/m3 [and 
    short-term exposures below 10 [mu]g/m3]. It appears likely 
    that nasal damage might be avoided completely if all Cr(VI) exposures 
    were kept below 1 [mu]g/m3.
        OSHA estimates that 1,728 nasal perforations/ulcerations occur 
    annually under current exposure levels. OSHA estimates that 1,140 of 
    these would be prevented under the final PEL of 5 [mu]g/m3. 
    Due to insufficient data, it was not possible to monetize the benefits. 
    Thus, the benefits associated with a reduction in nasal perforations/
    ulcerations are excluded from the net benefits analysis presented 
    below.
        Finally, for informational purposes, OSHA examined the net benefits 
    of the standard, based on the benefits and costs presented above, and 
    the costs per case of cancer avoided, as shown in Table VIII-12.
        As noted above, the OSH Act requires OSHA to set standards based on 
    eliminating significant risk to the extent feasible. That criterion or 
    a criterion of maximizing net (monetary) benefits may result in very 
    different regulatory outcomes. Thus, these analyses of net benefits 
    cannot be used as the basis for a decision concerning the choice of a 
    PEL for a Cr(VI) standard.
    BILLING CODE 4510-26-P
    
Table VIII-12

 

    
    BILLING CODE 4510-26-C
        Nevertheless, the Agency agrees that additional information 
    concerning the circumstances in which monetary benefits exceed costs 
    would be a useful addition to the above table. OSHA found the following 
    conditions key to determining whether benefits exceed costs:
         If the risk is at the lowest end of the range considered, 
    then benefits do not exceed costs no matter what other variables are 
    used.
         If the risk is at the high end of the range, and a 
    discount rate of 7 percent is used, then benefits exceed costs for PELs 
    of 1 and 20 if the latency period is less than 20 years, and for PELs 
    of 5 and 10 if the latency period is less than 25 years.
         If the risk is at the high end of the range, and a 
    discount rate of 3 percent is used, then benefits exceed costs for a 
    PEL of 0.5 if the latency period is twenty years or less, and benefits 
    exceed costs for all latency periods for all higher PELs.
        Incremental costs and benefits are those that are associated with 
    increasing stringency of the standard. Comparison of incremental 
    benefits and costs provides an indication of the relative efficiency of 
    the various PELs. OSHA cannot use this information in selecting a PEL, 
    but it has conducted these calculations for informational purposes. 
    Incremental costs, benefits, net benefits and cost per cancer avoided 
    are presented in Table VIII-13.
        In addition to examining alternative PELs, OSHA also examined 
    alternatives to other provisions of the standard. These alternatives 
    are discussed in the summary of the Final Regulatory Flexibility 
    Analysis in the next section.

Table VIII-13

 

    
    G. Summary of the Final Regulatory Flexibility Analysis
    
        The full final regulatory flexibility analysis is presented in 
    Chapter VII of the FEA. Many of the topics discussed there, such as the 
    legal authority for the rule; the reasons OSHA is going forward with 
    the rule; and economic impacts on small business have been presented in 
    detail elsewhere in the Preamble. As a result, this section focuses on 
    two issues: duplicative, overlapping, or conflicting rules; and 
    alternatives OSHA considered.
    
    Federal Rules That May Duplicate, Overlap, or Conflict With the Final 
    Rules
    
        OSHA's SBREFA panel for this rule suggested that OSHA address a 
    number of possible overlapping or conflicting rules: EPA's Maximum 
    Achievable Control Technology (MACT) standard for chromium 
    electroplaters; EPA's standards under the Federal Insecticide, 
    Fungicide, and Rodenticide Act (FIFRA) for Chromium Copper Arsenate 
    (CCA) applicators; and state use of OSHA PELs for setting fence line 
    air quality standards. The Panel was also concerned that, in some 
    cases, other OSHA standards might overlap and be sufficient to assure 
    that a new final standard would not be needed, or that some of the 
    final standard's provisions might not be needed.
        OSHA has thoroughly studied the provisions of EPA's MACT standard 
    and has also consulted with EPA. The standards are neither duplicative 
    nor conflicting. The rules are not duplicative because they have 
    different goals--environmental protection and protection against 
    occupation exposure. It is quite possible, as many electroplaters are 
    now doing, to achieve environmental protection goals without achieving 
    occupational protection goals. The regulations are not conflicting 
    because there exist controls that can achieve both goals without 
    interfering with one another. However, it is possible that meeting the 
    final OSHA standard would cause someone to incur additional costs for 
    the MACT standard. If an employer has to make major changes to install 
    LEV, this could result in significant expenses to meet EPA requirements 
    not accounted for in OSHA's cost analysis. In its final cost estimates, 
    OSHA has included costs for additional MACT testing in cases where it 
    may be needed. OSHA has also allowed all facilities four years to 
    install engineering controls, with the result that electroplaters can 
    better coordinate their EPA and OSHA requirements and avoid the need 
    for extra testing.
        OSHA examined the potential problem of overlapping jurisdiction for 
    CCA applicators, and found that there would indeed be overlapping 
    jurisdiction. As a result, OSHA had excluded CCA applicators from the 
    scope of the coverage of the rule. OSHA has been unable to find a case 
    where a state, as a matter of law, bases fence line standards on OSHA 
    PELs. OSHA notes that the OSHA PEL is designed to address the risks 
    associated with life long occupational exposure only.
        OSHA has also examined other OSHA standards, and where standards 
    are overlapping, referred to them by reference in the final standard in 
    order to eliminate the possibility of overlapping, duplicative or conflicting 
    standards. Existing OSHA standards that may duplicate the final provisions 
    in some respect include the standards addressing respiratory protection (29 CFR 
    1910.134); hazard communication (29 CFR 1910.1200); access to medical 
    and exposure records (29 CFR 1910.1020); general requirements for 
    personal protective equipment in general industry (29 CFR 1910.132), 
    construction (29 CFR 1926.95), and shipyards (29 CFR 1915.152); and 
    sanitation in general industry (29 CFR 1910.141), construction (29 CFR 
    1926.51), and shipyards (29 CFR 1915.97).
    
    Regulatory Alternatives
    
        This section discusses various alternatives to the final standard 
    that OSHA considered, with an emphasis on those suggested by the SBREFA 
    Panel as potentially alleviating impacts on small firms. (A discussion 
    on the costs of some of these alternatives to OSHA's final regulatory 
    requirements for the hexavalent chromium standard can be found in 
    Section III.3 Costs of Regulatory Alternatives in the final report by 
    OSHA's contractor, Shaw (Shaw, 2006). In the Shaw report, costs are 
    analyzed by regulatory alternative and major industry sector at 
    discount rates of 7 percent and 3 percent.)
        Scope: The proposed standard covered exposure to all types of 
    Cr(VI) compounds in general industry, construction, and shipyard. 
    Cement work in construction was excluded.
        OSHA considered the Panel recommendation that sectors where there 
    is little or no known exposure to Cr(VI) be excluded from the scope of 
    the standard. OSHA decided against this option. The costs for such 
    sectors are relatively small--probably even smaller than OSHA has 
    estimated because OSHA did not assume that any industry would use 
    objective data to demonstrate that initial assessment was not needed. 
    However, it is possible that changes in technology and production 
    processes could change the exposure of employees in what are currently 
    low exposure industries. If this happens, OSHA would need to issue a 
    new standard to address the situation. As a result, OSHA is reluctant 
    to exempt industries from the scope of the standard.
        However, OSHA has rewritten the scope of the standard for the final 
    rule so that it exempts from the scope of the standard any employer who 
    can demonstrate that a material containing Cr(VI) or a specific 
    process, operation, or activity involving Cr(VI) will not result in 
    concentrations at or above 0.5 [mu]g/m\3\ under any condition of use. 
    As a result, industries are exempted from all provisions of the 
    standard and all costs if the industry can demonstrate that exposure is 
    always at relatively low levels. This approach seems the best way to 
    minimize the costs for the standard for industries where exposure is 
    currently minimal, but could change in the future.
        As stated above, the final standard does not cover exposures to 
    hexavalent chromium resulting solely from exposure to portland cement. 
    OSHA's assessment of the data indicates that the primary exposure to 
    cement workers is dermal contact that can lead to irritant or contact 
    allergic dermatitis. Current information indicates that the exposures 
    in cement work are well below 0.25 [mu]g/m\3\. Moreover, unlike other 
    exposures in construction, general industry or shipyards, exposures 
    from cement are most likely to be solely from dermal contact. There is 
    little potential for airborne exposures and unlikely to be any in the 
    future, as Cr(VI) appears in cement in only minute quantities 
    naturally. Given these factors, the final standard excludes cement from 
    the scope of the standard. OSHA has determined that addressing the 
    dermal hazards from these exposures to Cr(VI) through guidance 
    materials and enforcement of existing personal protective equipment and 
    hygiene standards may be a more effective approach. Such guidance 
    materials would include recommendations for specific work practices and 
    personal protective equipment for cement work in construction.
        OSHA's analysis suggests that there are 2,093 to 10,463 cases of 
    dermatitis among cement workers annually. Using a cost of illness (COI) 
    approach, avoiding 95 percent of these dermatoses would be valued at 
    $2.5 million to $12.6 million annually, and avoiding 50 percent of 
    these dermatoses would be valued $1.3 million to $6.6 million annually.
        The costs of including cement would depend on what requirements 
    were applied to wet cement workers. OSHA estimates that the costs 
    associated with existing standards (e.g., requirements for PPE and 
    hygiene practices) could range from $80 million to $300 million per 
    year. Placing wet cement within the scope of the standard would cost an 
    additional $33 million per year for compliance with such provisions as 
    initial monitoring; those costs would be incurred even if the employer 
    has no airborne exposures.
        PELS: Section F of this preamble summary presented data on the 
    costs and benefits of alternative PELS for all industries. The full FEA 
    contains detailed data on the impacts on small firms at each PEL.
        The SBREFA Panel also suggested alternatives to a uniform PEL 
    across all industries and exposures. The Panel recommended that OSHA 
    consider alternative approaches to industries that are intermittent 
    users of Cr(VI). OSHA has adopted the concept of permitting employers 
    with intermittent exposures to meet the requirements of the standard 
    using respirators rather than engineering controls. This approach has 
    been used in other standards and does not require workers to routinely 
    wear respirators.
        The SBREFA Panel also recommended considering Separate Engineering 
    Control Airborne Limits (SECALs). OSHA has adopted this approach for 
    applications in the aerospace industry. OSHA considered a SECAL for 
    electroplating when the Agency was considering setting PELs lower than 
    5, but found a SECAL would not significantly lower costs because 
    respirator use would be almost as expensive as using engineering 
    controls. The expense of respirator use would also be a problem with 
    SECALs for this sector at any PEL. OSHA's reasons for not using the 
    SECAL approach in other sectors are provided in the Summary and 
    Explanation. The SBREFA Panel also suggested that OSHA consider 
    different PELs for different Cr(VI) compounds leading to exposure to 
    Cr(VI). This issue is fully discussed in VI. Quantitative Risk 
    Assessment. Here, it will only be noted that this would result in lower 
    PELs than OSHA is setting in at least some industries, and thus 
    potentially increase impacts on some small businesses.
        Special Approaches to the Shipyard and Construction Industries: The 
    SBREFA Panel was concerned that changing work conditions in the 
    shipyard and construction industry would make it difficult to apply 
    some of the provisions that OSHA suggested at the time of the Panel. 
    OSHA has decided to change its approach in these sectors. OSHA is 
    proposing three separate standards, one for general industry, one for 
    construction, and one for shipyards. OSHA initially proposed that, in 
    shipyards and construction, medical surveillance would be required only 
    for persons with signs and symptoms, and regulated areas would not be 
    required. In the final standard, OSHA has provided for the same medical 
    surveillance standard in all sectors. The reasons for doing this are 
    discussed in the Summary and Explanation section of the Preamble. 
    However, employers must still meet the PEL with engineering controls 
    and work practices where feasible. OSHA's proposed rule did not require 
    exposure monitoring in the construction and maritime sectors. In light 
    of comments, OSHA has shifted from this approach to requiring all sectors 
    to conduct exposure monitoring, but allowing a performance-oriented option 
    to exposure monitoring.
        Timing of the Standard: The SBREFA Panel also recommended 
    considering a multi-year phase-in of the standard. OSHA has solicited 
    comment and examined the comments on this issue. OSHA has decided to 
    allow employers four years (rather than two years) to comply with the 
    engineering control provisions of the standard. This expanded phase-in 
    of engineering controls has several advantages from a viewpoint of 
    impacts on small businesses. First, it reduces the one-time initial 
    costs of the standard by spreading them out over time. This would be 
    particularly useful for small businesses that have trouble borrowing 
    large amounts of capital in a single year. A phase-in is also useful in 
    the electroplating sector by allowing employers to coordinate their 
    environmental and occupational safety and health control strategies to 
    minimize potential costs. See the Summary and Explanation section of 
    this Preamble for further discussion of this issue.
    
    SBREFA Panel
    
        Table VIII-14 lists all of the SBREFA Panel recommendations and 
    notes OSHA responses to these recommendations.

Table VIII-14 Part 1

 

Table VIII-14 Part 2

 

Table VIII-14 Part 3

 

Table VIII-14 Part 4

 

Table VIII-14 Part 5

 

Table VIII-14 Part 6

 

Table VIII-14 Part 7

 

Table VIII-14 Part 8

 

Table VIII-14 Part 9

 

Table VIII-14 Part 10

 

Table VIII-14 Part 11

 

Table VIII-14 Part 12

 

Table VIII-14 Part 13

 

Table VIII-14 Part 14

 

Table VIII-14 Part 15

 

    
    BILLING CODE 5410-26-C
    
    H. Need for Regulation
    
        Employees in work environments addressed by the final standards are 
    exposed to a variety of significant hazards that can and do cause 
    serious injury and death. The risks to employees are excessively large 
    due to the existence of market failures, and existing and alternative 
    methods of alleviating these negative consequences have been shown to 
    be insufficient. After carefully weighing the various potential 
    advantages and disadvantages of using a regulatory approach to improve 
    upon the current situation, OSHA concludes that in this case the final 
    mandatory standards represent the best choice for reducing the risks to 
    employees. In addition, rulemaking is necessary in this case in order 
    to replace older existing standards with updated, clear, and consistent 
    health standards.
    
    IX. OMB Review Under the Paperwork Reduction Act of 1995
    
        The final Cr(VI) rule contains collection of information 
    (paperwork) requirements that are subject to review by the Office of 
    Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
    (PRA-95), 44 U.S.C. 3501 et seq., and OMB's regulations at 5 CFR part 
    1320. The Paperwork Reduction Act defines "collection of information" 
    as "the obtaining, causing to be obtained, soliciting, or requiring 
    the disclosure to third parties or the public of facts or opinions by 
    or for an agency regardless of form or format * * * " (44 U.S.C. 
    3502(3)(A)). The collection of information requirements (paperwork) 
    associated with the proposed Cr(VI) rule were submitted to OMB on 
    October 1, 2004. On November 30, 2004 OMB did not approve the Cr(VI) 
    paperwork requirements, and instructed OSHA to examine "public comment 
    in response to the NPRM, including paperwork requirements," and 
    address any public comments on the paperwork in the preamble. OMB 
    assigned the control number 1218-0252 for the Agency to use in future 
    submissions.
        The major information collection requirements in the Standard 
    include conducting employee exposure assessment (Sec. Sec.  1910.1026 
    (d)(1)-(3), 1915.1026 (d)(1)-(3), and 1926.1126 (d)(1)-(3)), notifying 
    employees of their Cr(VI)exposures when employee exposures exceed the 
    PEL (Sec. Sec.  1910.1026 (d)(4), 1915.1026 (d)(4), and 1926.1126 
    (d)(4)), providing respiratory protection (Sec. Sec.  1910.1026 (g), 
    1915.1026 (f), and 1926.1126 (f)), labeling bags or containers of 
    contaminated protective clothing or equipment (Sec. Sec.  1910.1026 
    (h)(2), 1915.1026 (g)(2), and 1926.1126 (g)(2)), informing persons who 
    launder or cleans protective clothing or equipment contaminated with 
    Cr(VI) of the potential harmful effects (Sec. Sec.  1910.1026 (h)(3), 
    1915.1026 (g)(3), and 1926.1126 (g)(3)), implementing medical-
    surveillance of employees (Sec. Sec.  1910.1026 (k), 1915.1026 (i), and 
    1926.1126 (i)), providing physician or other licensed health care 
    professional (PLHCP) with information (Sec. Sec.  1910.1026 (k)(4), 
    1915.1026 (i)(4), and 1926.1126 (i)(4)), ensuring that employees 
    receive a copy of their medical-surveillance results (Sec. Sec.  
    1910.1026 (k)(5), 1915.1026 (i)(5), and 1926.1126 (i)(5)), maintaining 
    employees' exposure-monitoring and medical-surveillance records for 
    specific periods, and maintaining historical monitoring and objective 
    data (Sec. Sec.  1910.1026 (m), 1915.1026 (k), and 1926.1126 (k)). The 
    collection of information requirements in the rule are needed to assist 
    employers in identifying and controlling exposures to Cr(VI) in the 
    workplace, and to address Cr(VI)-related adverse health effects. OSHA 
    will also use records developed in response to this standard to 
    determine compliance.
        The final rule imposes new information collection requirements for 
    purposes of the PRA. In response to comments on the proposed rule, OSHA 
    has revised provisions of the final rule that affect collection of 
    information requirements. These revisions include:
         The final rule exempts exposures to portland cement in 
    general industry and shipyards;
         An exemption is included in the final rule where the 
    employer can demonstrate that Cr(VI) exposures will not exceed 0.5 
    [mu]g/m\3\ under any expected conditions;
         The final PEL of 5 [mu]g/m\3\ has been revised from the 
    proposed 1 [mu]g/m\3\;
         Requirements for exposure determination have been added to 
    the construction and shipyard standards, and a performance-oriented 
    option for exposure determination is included in the standards for each 
    sector (general industry, construction, and shipyards);
         Medical surveillance must be provided to employees exposed 
    to Cr(VI) above the action level (rather than the PEL) for 30 or more 
    days per year in general industry, construction, and shipyards;
         Requirements to maintain records used for exposure 
    determination have been added to the construction and shipyard 
    standards, while requirements for training records have been removed 
    for all sectors.
        OSHA has revised the paperwork package to reflect these changes, 
    and estimates the total burden hours associated with the collection of 
    information to be approximately 940,000 and estimates the cost for 
    maintenance and operation to be approximately $126 million.
        Potential respondents are not required to comply with the 
    information collection requirements until they have been approved by 
    OMB. OMB is currently reviewing OSHA's request for approval of the 
    final rule's paperwork requirements. OSHA will publish a subsequent 
    Federal Register document when OMB takes further action on the 
    information collection requirements in the Cr(VI) rule.
    
    X. Federalism
    
        The Agency reviewed the final Cr(VI) standard according to the most 
    recent Executive Order on Federalism (Executive Order 13132, 64 FR 
    43225, August 10, 1999). This Executive Order requires that federal 
    agencies, to the extent possible, refrain from limiting state policy 
    options, consult with states before taking actions that restrict their 
    policy options, and take such actions only when clear constitutional 
    authority exists and the problem is of national scope. The Executive 
    Order allows federal agencies to preempt state law only with the 
    expressed consent of Congress; in such cases, federal agencies must 
    limit preemption of state law to the extent possible. Under section 18 
    of the Occupational Safety and Health Act (the "Act" or "OSH Act"), 
    Congress expressly provides that OSHA preempt state occupational safety 
    and health standards to the extent that the Agency promulgates a 
    federal standard under section 6 of the Act. Accordingly, under section 
    18 of the Act OSHA preempts state promulgation and enforcement of 
    requirements dealing with occupational safety and health issues covered 
    by OSHA standards unless the state has an OSHA approved occupational 
    safety and health plan (i.e., is a state-plan state) [see Gade v. 
    National Solid Wastes Management Association, 112 S. Ct. 2374 (1992)]. 
    Therefore, with respect to states that do not have OSHA-approved plans, 
    the Agency concludes that this final rule falls under the preemption 
    provisions of the Act. Additionally, section 18 of the Act prohibits 
    states without approved plans from issuing citations for violations of 
    OSHA standards; the Agency finds that this final rulemaking does not 
    expand this limitation. OSHA has authority under Executive Order 13132 
    to promulgate a Cr(VI) standard because the problems addressed by these 
    requirements are national in scope.
        As explained in section VII of this preamble, employees face a 
    significant risk from exposure to Cr(VI) in the workplace. These 
    employees are exposed to Cr(VI) in general industry, construction, and 
    shipyards. Accordingly, the final rule would establish requirements for 
    employers in every state to protect their employees from the risks of 
    exposure to Cr(VI). However, section 18(c)(2) of the Act permits state-
    plan states to develop their own requirements to deal with any special 
    workplace problems or conditions, provided these requirements are at 
    least as effective as the requirements in this final rule.
    
    XI. State Plans
    
        The 26 states and territories with their own OSHA-approved 
    occupational safety and health plans must adopt comparable provisions 
    within six months of the publication date of the final hexavalent 
    chromium standard. These states and territories are: Alaska, Arizona, 
    California, Hawaii, Indiana, Iowa, Kentucky, Maryland, Michigan, 
    Minnesota, Nevada, New Mexico, North Carolina, Oregon, Puerto Rico, 
    South Carolina, Tennessee, Utah, Vermont, Virginia, Virgin Islands, 
    Washington, and Wyoming. Connecticut, New Jersey and New York have OSHA 
    approved State Plans that apply to state and local government employees 
    only. Until a state-plan state promulgates its own comparable 
    provisions, Federal OSHA will provide the state with interim 
    enforcement assistance, as appropriate.
    
    XII. Unfunded Mandates
    
        The Agency reviewed the final Cr(VI) standard according to the 
    Unfunded Mandates Reform Act of 1995 (UMRA) (2 U.S.C. 1501 et seq.) and 
    Executive Order 12875. As discussed in section VIII of this preamble, 
    OSHA estimates that compliance with this final rule would require 
    private-sector employers to expend about $288 million each year. 
    However, while this final rule establishes a federal mandate in the 
    private sector, it is not a significant regulatory action within the 
    meaning of section 202 of the UMRA (2 U.S.C. 1532). OSHA standards do 
    not apply to state and local governments, except in states that have 
    voluntarily elected to adopt an OSHA-approved state occupational safety 
    and health plan. Consequently, the provisions of the final rule do not 
    meet the definition of a "Federal intergovernmental mandate" [see 
    section 421(5) of the UMRA (2 U.S.C. 658(5))]. Therefore, based on a 
    review of the rulemaking record, the Agency believes that few, if any, 
    of the employers affected by the final rule are state, local, or tribal 
    governments. Therefore, the Cr(VI) requirements promulgated herein do 
    not impose unfunded mandates on state, local, or tribal governments.
    
    XIII. Protecting Children From Environmental Health and Safety Risks
    
        Executive Order 13045 requires that Federal agencies submitting 
    covered regulatory actions to OMB's Office of Information and 
    Regulatory Affairs (OIRA) for review pursuant to Executive Order 12866 
    must provide OIRA with (1) an evaluation of the environmental health or 
    safety effects that the planned regulation may have on children, and 
    (2) an explanation of why the planned regulation is preferable to other 
    potentially effective and reasonably feasible alternatives considered 
    by the agency. Executive Order 13045 defines "covered regulatory 
    actions" as rules that may (1) be economically significant under 
    Executive Order 12866 (i.e., a rulemaking that has an annual effect on 
    the economy of $100 million or more, or would adversely affect in a 
    material way the economy, a sector of the economy, productivity, 
    competition, jobs, the environment, public health or safety, or state, 
    local, or tribal governments or communities, and (2) concern an 
    environmental health risk or safety risk that an agency has reason to 
    believe may disproportionately affect children. In this context, the 
    term "environmental health risks and safety risks" means risks to 
    health or safety that are attributable to products or substances that 
    children are likely to come in contact with or ingest (e.g., through 
    air, food, water, soil, product use). The final Cr(VI) standard is 
    economically significant under Executive Order 12866 (see section VIII 
    of this preamble). However, after reviewing the final
    Cr(VI) standard, OSHA has determined that the standard would not impose 
    environmental health or safety risks to children as set forth in 
    Executive Order 13045. The final standard requires employers to limit 
    employee exposure to Cr(VI) and take other precautions to protect 
    employees from adverse health effects associated with exposure to 
    Cr(VI). To the best of OSHA's knowledge, no employees under 18 years of 
    age work under conditions that involve exposure to Cr(VI). However, if 
    such conditions exist, children who are exposed to Cr(VI) in the 
    workplace would be better protected from exposure to Cr(VI) under the 
    final rule than they are currently. Based on this determination, OSHA 
    believes that the final Cr(VI) standard does not constitute a covered 
    regulatory action as defined by Executive Order 13045.
    
    XIV. Environmental Impacts
    
        The Agency reviewed the final Cr(VI) standard according to the 
    National Environmental Policy Act (NEPA) of 1969 (42 U.S.C. 4321 et 
    seq.), the regulations of the Council on Environmental Quality (40 CFR 
    part 1500), and the Department of Labor's NEPA procedures (29 CFR part 
    11).
        As a result of this review, OSHA has made a final determination 
    that the final Cr(VI) standard will have no impact on air, water, or 
    soil quality; plant or animal life; the use of land or aspects of the 
    external environment. Therefore, OSHA concludes that the final Cr(VI) 
    standard will have no significant environmental impacts.
    
    XV. Summary and Explanation of the Standards
    
    (a) Scope
        OSHA is issuing separate standards addressing hexavalent chromium 
    (also referred to as chromium (VI) or Cr(VI)) exposure in general 
    industry, construction, and shipyards. The standard for shipyards also 
    applies to marine terminals and longshoring. The standards for 
    construction and shipyards are very similar to each other, but differ 
    in some respects from the standard for general industry. OSHA believes 
    that certain conditions in these two sectors warrant requirements that 
    are somewhat different than those that apply to general industry. This 
    summary and explanation will describe the final rule for general 
    industry and will note differences between it and the standards for 
    construction and shipyards.
        Commenters were generally supportive of OSHA's decision to propose 
    separate standards for general industry, construction, and shipyards 
    (e.g., Exs. 38-199-1; 38-212; 38-214; 38-220-1; 38-236; 38-244; 39-19), 
    although one commenter believed that a single standard should apply to 
    all sectors (Ex. 39-51). Where concerns were expressed about the 
    establishment of separate standards, they focused on the provisions of 
    the standards and their application, rather than the concept of 
    establishing separate standards. Some commenters argued that certain 
    activities or industries should be covered by the construction standard 
    rather than the general industry standard (e.g., Exs. 38-203; 38-228-1, 
    p. 18; 39-52-2; 39-56); others considered the proposed construction and 
    shipyard standards to be less protective than the proposed general 
    industry standard (Exs. 38-222; 39-71; 47-23, pp. 16-17; 47-28).
        OSHA has long recognized a distinction between the construction and 
    general industry sectors, and has issued standards specifically 
    applicable to construction work under 29 CFR Part 1926. The Agency has 
    provided a definition of the term "construction work" at 29 CFR 
    1910.12(b), has explained the terms used in that definition at 29 CFR 
    1926.13, and has issued numerous interpretations over the years 
    explaining the classification of activities as either general industry 
    or construction. OSHA recognizes that in some circumstances, general 
    industry activities and conditions in workplaces where general industry 
    tasks are performed may be comparable to those found in construction. 
    However, the Agency believes the longstanding delineation between 
    sectors is appropriate. The distinction between sectors is generally 
    well understood by both OSHA enforcement personnel and the regulated 
    community, and any attempt to create exceptions or to provide different 
    criteria in this final rule would not improve upon the current criteria 
    but would rather cause confusion.
        OSHA is issuing the construction and shipyard standards to account 
    for the particular conditions found in those sectors. The Agency 
    intends to ensure that Cr(VI)-exposed workers in construction and 
    shipyards are provided protection that, to the extent feasible, is 
    comparable to the protection afforded workers in general industry. OSHA 
    believes that concerns raised about differences between the Cr(VI) 
    proposed standard for general industry and the proposed standards for 
    construction and shipyards will be lessened because the final standards 
    are more consistent with one another than as originally proposed. 
    Specifically, OSHA proposed explicit exposure assessment requirements 
    for general industry, but not for construction and shipyard workplaces. 
    The requirements of the final rule for exposure determination are 
    nearly identical for all sectors (see discussion of exposure 
    determination under paragraph (d) of this section). In addition, OSHA 
    proposed a requirement for periodic medical examinations in general 
    industry, but not in construction and shipyards. The final rule 
    includes requirements for periodic medical examinations in all sectors 
    (see discussion of medical surveillance requirements under paragraph 
    (k) of this section). The final standards for construction and 
    shipyards provide the most adequate protection within the constraints 
    of feasibility.
        The final rule applies to occupational exposures to Cr(VI), that 
    is, any chromium species with a valence of positive six, regardless of 
    form or compound. Examples of Cr(VI) compounds include chromium oxide 
    (CrO2), ammonium dichromate 
    ((NH4)2Cr2O7), calcium 
    chromate (CaCrO4), chromium trioxide (CrO3), lead 
    chromate (PbCrO4), potassium chromate 
    (K2CrO4), potassium dichromate 
    (K2Cr2O7), sodium chromate 
    (Na2CrO4), strontium chromate 
    (SrCrO4), and zinc chromate (ZnCrO4).
        Some commenters supported the proposal to include all chromium 
    compounds within the scope of the new rule. (See, e.g., Exs. 38-214; 
    39-60). Other commenters, however, contended that specific Cr(VI) 
    compounds should be excluded from the scope of the final rule. Notably, 
    the Color Pigments Manufacturers Association and Dominion Colour 
    Corporation argued that differences in the bioavailability and toxicity 
    of lead chromate pigments when compared to other Cr(VI) compounds 
    warrant unique treatment (Exs. 38-201; 38-205). The Boeing Company also 
    argued that OSHA should consider the bioavailability of different 
    Cr(VI) compounds (Ex. 38-106). Boeing indicated that exposures to 
    strontium chromate and zinc chromate used in aerospace manufacturing 
    are not equivalent to Cr(VI) exposures in other industries.
        OSHA considers all Cr(VI) compounds to be carcinogenic. This 
    conclusion is based upon careful consideration of the epidemiological, 
    animal, and mechanistic evidence in the rulemaking record, and is 
    discussed in section V, "Health Effects," of this preamble. OSHA's 
    conclusion that all Cr(VI) compounds are carcinogenic is consistent 
    with the findings of IARC, NTP, and NIOSH. These organizations have 
    each found Cr(VI) compounds to be carcinogenic, without exception. 
    OSHA therefore sees no reason to exempt any Cr(VI) compounds from the final rule.
        Several commenters argued that existing standards provide adequate 
    protection for employees exposed to Cr(VI), citing in particular OSHA's 
    current welding and lead standards (Exs. 38-203; 38-254; 38-124; 39-19; 
    39-47; 39-48; 39-52, p. 22; 39-54; 39-56). However, none of these 
    standards provide the full range of protections afforded by the Cr(VI) 
    rule. For example, OSHA's welding requirements (29 CFR Subpart Q for 
    general industry; 1926 Subpart J for construction; 1915 Subpart D for 
    shipyards) include provisions for ventilation, but do not address other 
    aspects of worker protection included in the Cr(VI) rule such as 
    exposure determination or medical surveillance. OSHA's lead standards 
    (29 CFR 1910.1025 for general industry; 29 CFR 1926.62 for 
    construction) have a PEL of 50 [mu]g/m\3\, which effectively limits 
    Cr(VI) exposure from lead chromate to 12.5 [mu]g/m\3\; however, this 
    value is more than double the PEL in the Cr(VI) rule. Other standards 
    therefore do not provide protection equivalent to the final Cr(VI) 
    rule. Moreover, even though other requirements may affect Cr(VI) 
    occupational exposure, Cr(VI) exposure in the current workplace still 
    results in a significant risk that can be substantially reduced in a 
    feasible manner by the requirements of this final rule.
    
    Portland Cement
    
        The final rule does not cover exposure to Cr(VI) in portland 
    cement. OSHA proposed to exclude exposure to portland cement in 
    construction; the final rule extends this exclusion to all sectors. In 
    the proposal, OSHA identified two general industry application groups 
    where all employee exposure to Cr(VI) is from portland cement: Portland 
    Cement Producers and Precast Concrete Products. (A third application 
    group, Ready-Mixed Concrete, was later identified.) OSHA proposed to 
    cover exposures to portland cement in general industry because the 
    Agency's preliminary exposure profile indicated that some employees in 
    these application groups were exposed to Cr(VI) levels associated with 
    a significant risk of lung cancer. However, evidence in the record 
    indicating the low Cr(VI) content of portland cement has led OSHA to 
    conclude that the current PEL for portland cement effectively limits 
    inhalation exposures from work with portland cement.
        Cement ingredients (clay, gypsum, and chalk), chrome steel grinders 
    used to crush ingredients, refractory bricks lining the cement kiln, 
    and ash may serve as sources of chromium that may be converted to 
    Cr(VI) during kiln heating, leaving trace amounts of Cr(VI) in the 
    finished product (Ex. 35-317, p. 148). The amount of Cr(VI) in American 
    portland cement is generally less than 20 g Cr(VI)/g cement (Exs. 9-57; 
    9-22; 35-417). Because the Cr(VI) concentration in portland cement is 
    so low, OSHA's current PEL for portland cement (15 mg/m\3\ for total 
    dust, 29 CFR 1910.1000) effectively limits the Cr(VI) inhalation 
    exposure from cement to levels below the new Cr(VI) PEL and Action 
    Level (i.e., if an employee is exposed at the PEL for portland cement 
    and the Cr(VI) concentration in that cement is below 20 [mu]g/g, the 
    employee's exposure to Cr(VI) will be below 0.3 [mu]g/m\3\ ). Because 
    the evidence in the record demonstrates that current requirements for 
    portland cement are as protective as the new PEL with regard to Cr(VI) 
    inhalation exposures, OSHA considers it reasonable to exclude portland 
    cement from the scope of the final rule. This position was supported by 
    a number of commenters (e.g., Exs. 38-127; 38-217; 38-227; 38-229; 38-
    235).
        A number of other commenters, including over 200 laborers, 
    requested that portland cement be covered under the scope of the final 
    rule (e.g., Exs. 38-10; 38-35; 38-50; 38-110; 38-222). These comments 
    generally, but not exclusively, focused on dermal hazards associated 
    with exposure to portland cement. For example, the Building and 
    Construction Trades Department, AFL-CIO (BCTD) stated:
    
        To provide construction employees with protection from 
    predictable exposures to hexavalent chromium, the construction 
    standard must include portland cement within its scope. Portland 
    cement represents both a dermal and inhalation hazard in 
    construction, and reduction of exposures would greatly benefit 
    construction employees (Ex. 38-219).
    
        Commenters favoring coverage of portland cement in the final rule 
    argued that a number of the proposal's provisions would serve to 
    protect cement workers, such as requirements for appropriate protective 
    clothing (Exs. 47-26, pp. 26-27; 35-332, pp. 22-23; 40-4-2, p. 20), 
    hygiene facilities (particularly washing facilities)(Exs. 38-219-1, p. 
    14; 47-26, pp. 26-27; 35-332, p. 19; 40-4-2, p. 19), and training and 
    education (Exs. 47-26, pp. 26-27; 35-332, p. 19; 40-4-2, p. 19). Some 
    commenters also favored medical surveillance requirements for workers 
    exposed to portland cement (38-219-1, p. 18; 47-26, pp. 26-27) and 
    requirements to reduce the Cr(VI) content of portland cement through 
    the addition of ferrous sulfate (Exs. 38-199-1, p. 43; 38-219-1, p. 14-
    15; 38-222; 35-332, p. 23-24). Some noted that OSHA's Advisory 
    Committee on Construction Safety and Health had recommended that the 
    Agency apply certain provisions of the Cr(VI) rule to portland cement 
    exposures in construction (Ex. 38-199-1, p. 30).
        The primary intent of this rule is to protect workers from lung 
    cancer resulting from inhalation of Cr(VI). The Agency has established 
    that exposure to Cr(VI) at the previous PEL results in a significant 
    risk of lung cancer among exposed workers, and compliance with the new 
    PEL will substantially reduce that risk. As indicated previously, the 
    existing PEL for portland cement protects employees against inhalation 
    of Cr(VI) that is present in portland cement as a trace contaminant. 
    Therefore, OSHA does not believe further requirements addressing 
    inhalation exposure to Cr(VI) in portland cement are warranted.
        The Agency does recognize, however, that in addition to respiratory 
    effects resulting from Cr(VI) inhalation, Cr(VI) is also capable of 
    causing serious dermal effects (see discussion in section V of this 
    preamble). In previous chemical-specific health standards, OSHA 
    typically has addressed serious health effects associated with exposure 
    to a chemical, even if those effects are not the focus of the rule. For 
    example, OSHA issued a standard for cadmium primarily based on lung 
    cancer and kidney damage associated with inhalation exposures to 
    cadmium; however, contact with cadmium can also cause irritation of the 
    skin and OSHA included a provision in the final cadmium rule addressing 
    protective clothing and equipment to prevent skin irritation. OSHA has 
    followed a similar approach in the Cr(VI) rule, incorporating 
    provisions for protective clothing and equipment that will address 
    potential dermal hazards, and including consideration of dermal effects 
    in medical surveillance requirements. The Agency believes this is a 
    reasonable approach to protecting workers when a chemical causes a 
    variety of adverse health effects.
        The dermal hazards from contact with portland cement, however, are 
    not related solely to the Cr(VI) content of cement. Portland cement is 
    alkaline, abrasive, and hygroscopic (water-absorbing). Cement 
    dermatitis may be irritant contact dermatitis induced by these 
    properties, allergic contact dermatitis elicited by an immunological 
    reaction to Cr(VI), or a combination of the two (Exs. 35-317; 46-74). 
    Although reports vary, the weight of the evidence indicates that the vast 
    majority of cement dermatitis cases do not involve Cr(VI) sensitization 
    (Ex. 46-74). Dermatitis associated with exposure to portland cement is 
    thus substantially, perhaps even primarily, related to factors other 
    than Cr(VI) exposure.
        Moreover, OSHA believes that appropriate requirements are already 
    in place elsewhere in OSHA standards, to protect workers from dermal 
    effects associated with exposure to portland cement. The Agency has 
    existing requirements for the provision and use of personal protective 
    equipment (PPE) (29 CFR 1910.132 for general industry; 29 CFR 1915.152 
    for shipyards; 29 CFR 1926.95 for construction). These requirements are 
    essentially equivalent to the requirements of the final Cr(VI) rule 
    with respect to provision of protective clothing and equipment.
        OSHA also has existing requirements for washing facilities that are 
    comparable to those found in the final Cr(VI) rule (29 CFR 1910.141(d) 
    for general industry and shipyards; 29 CFR 1926.51(f) for 
    construction). For example, in operations where contaminants may be 
    harmful to employees, the Sanitation standard for construction requires 
    employers to provide adequate washing facilities in near proximity to 
    the worksite. With only limited exceptions for mobile crews and 
    normally unattended worksites, lavatories with running water, hand soap 
    or similar cleansing agents, and towels or warm air blowers must be 
    made available in all places of employment covered by the standard. The 
    Sanitation requirements that apply to general industry and shipyards 
    provide equivalent protections.
        OSHA's Hazard Communication standard (29 CFR 1910.1200) requires 
    training for all employees potentially exposed to hazardous chemicals, 
    including mixtures such as portland cement. This training must cover 
    the physical and health hazards of the chemicals and measures employees 
    can take to protect themselves from these hazards, such as appropriate 
    work practices, emergency procedures, and personal protective equipment 
    to be used.
        Concerns raised in the record with regard to protective clothing, 
    washing facilities, and training on cement dermatitis hazards appear to 
    relate to lack of compliance with these existing requirements, rather 
    than any inadequacy in the requirements themselves. For example, BCTD 
    representatives indicated that in spite of current requirements, 
    washing facilities are rarely provided on construction sites (Tr. 1464, 
    1470-1471, 1474, 1479-1480). By covering portland cement in the final 
    Cr(VI) rule, BCTD argued that compliance would improve (Tr. 1519-1522).
        OSHA recognizes that reiterating the requirements of generic rules 
    such as the Sanitation standard in a chemical-specific standard like 
    the Cr(VI) rule can be useful in some instances by providing employers 
    with a comprehensive reference of applicable requirements. However, the 
    Agency does not consider the Code of Federal Regulations to be the best 
    tool for raising awareness about existing standards. Rather, OSHA 
    believes guidance documents, compliance assistance efforts, and 
    enforcement of existing requirements are the best mechanisms for 
    accomplishing this objective.
        Some commenters argued that requirements not included in the 
    generic standards were needed to protect employees working with 
    portland cement. The International Brotherhood of Teamsters (IBT) 
    stated that absent coverage under the standard, portland cement workers 
    would be responsible for purchasing and maintaining their own PPE. If 
    there is no requirement for an employer to purchase and provide 
    required PPE, IBT argued, most employees would elect not to purchase it 
    (Ex. 38-199-1, p. 30). Of course many employers choose to pay for the 
    PPE so that they can be sure of its effectiveness. The important 
    factors are that the PPE must be suitable for the job and must be used 
    correctly. Moreover, even when employees provide their own protective 
    equipment, OSHA's PPE standards specify that the employer is 
    responsible for ensuring its adequacy, including proper maintenance and 
    sanitation (see 29 CFR 1910.132(b); 29 CFR 1926.95(b)).
        Other commenters believed that medical surveillance was needed for 
    employees exposed to portland cement (Exs. 38-219-1, p. 18; 47-26, pp. 
    26-27). However, irritant contact dermatitis and allergic contact 
    dermatitis present the same clinical appearance, and it is difficult to 
    determine if an employee with dermatitis is sensitized to Cr(VI). 
    Because cement dermatitis is often related to the irritant properties 
    of cement rather than Cr(VI), medical surveillance requirements for 
    portland cement would necessarily involve covering health effects not 
    solely, or even primarily, attributable to Cr(VI) exposure. OSHA 
    therefore does not consider a requirement for medical surveillance for 
    portland cement workers to be appropriate within the context of the 
    Cr(VI) rule.
    
    Ferrous Sulfate
    
        Finally, some commenters suggested it would be appropriate to 
    require the addition of ferrous sulfate to portland cement (Exs. 38-
    199-1, p. 43; 38-219-1, pp. 14-15; 38-222; 35-332, pp. 23-24; 47-26, p. 
    8). Cr(VI) concentrations in portland cement can be lowered by the 
    addition of ferrous sulfate, which reduces Cr(VI) to Cr(III). Residual 
    Cr(VI) concentrations of less than 2 ppm are typical. As discussed in 
    section V of this preamble, reports from two researchers suggest that 
    the addition of ferrous sulfate to cement in Scandinavian countries 
    reduces the incidence of Cr(VI)-related allergic contact dermatitis in 
    cement workers (Exs. 9-131; 48-8).
        It is reasonable to believe that a reduction in the Cr(VI) 
    concentration of portland cement would reduce the potential for Cr(VI)-
    induced allergic contact dermatitis. However, the lack of available 
    information regarding a dose-response relationship between Cr(VI) 
    exposure and allergic contact dermatitis makes it impossible to 
    estimate how substantial that reduction might be. For instance, a 
    portion of cement samples already have relatively low Cr(VI) 
    concentrations. Analyses of 42 samples of American portland cement 
    reported by Perone et al. indicated that 33 of the samples had Cr(VI) 
    concentrations below 2 ppm (Ex. 9-57); the benefit of adding ferrous 
    sulfate to cement with already low Cr(VI) concentrations is unclear.
        Moreover, it is not clear that the addition of ferrous sulfate to 
    cement would be successful in reducing Cr(VI) to Cr(III) under 
    conditions found in the U.S. Attempts in the U.S. to reduce Cr(VI) in 
    cement to Cr(III) with ferrous sulfate have been unsuccessful, due to 
    oxidation of the ferrous sulfate in the production process (Ex. 35-
    417). Methods used to handle and store cement have also been shown to 
    influence the effectiveness of ferrous sulfate in reducing Cr(VI). When 
    cement is exposed to moisture during storage, the ferrous sulfate in it 
    is likely to be oxidized, and as a result, the Cr(VI) will not be 
    reduced to Cr(III) when the cement is mixed with water (Ex. 9-91). 
    Handling and storage of cement in silos can have this effect (Tr. 
    1363). Because a substantial amount of cement in the U.S. is produced 
    in winter and stored for use during warmer weather, ferrous sulfate 
    added to the cement at the time of production could be oxidized during 
    that time, rendering it ineffective (Tr. 1363).
        Considering this evidence, OSHA does not believe the record 
    demonstrates that the addition of ferrous sulfate to portland cement in 
    the U.S. would necessarily result in a reduction in the incidence of 
    Cr(VI)-induced allergic contact dermatitis. Therefore, OSHA does not 
    believe that requiring the addition of ferrous sulfate to cement is warranted.
        In any event, even if ferrous sulfate was completely effective in 
    eliminating the potential for Cr(VI)-induced allergic contact 
    dermatitis from portland cement, the potential for portland cement to 
    induce irritant contact dermatitis would not be affected. (See section 
    V(D) of this preamble for additional discussion.) Therefore, 
    appropriate protective clothing, good hygiene practices, and training 
    on hazards and control methods would still be necessary and these are 
    adequately covered by OSHA's generic standards.
    
    Pesticides
    
        The final rule does not cover exposures to Cr(VI) that occur in the 
    application of pesticides. Some Cr(VI)-containing chemicals, such as 
    chromated copper arsenate (CCA) and acid copper chromate (ACC), are 
    used for wood treatment and are regulated by EPA as pesticides. Section 
    4(b)(1) of the OSH Act precludes OSHA from regulating working 
    conditions of employees where other Federal agencies exercise statutory 
    authority to prescribe or enforce standards or regulations affecting 
    occupational safety or health. Therefore, OSHA specifically excludes 
    those exposures to Cr(VI) resulting from the application of a pesticide 
    regulated by EPA from coverage under the final rule.
        The exception for exposures that occur in the application of 
    pesticides was limited to the proposed standard for general industry. 
    At the time, OSHA was not aware of exposures to Cr(VI) from application 
    of pesticides in other sectors. Exposures to Cr(VI) from pesticide 
    application outside of general industry were brought to OSHA's 
    attention during the public comment period (Exs. 39-47, p. 9; 39-48, p. 
    4; 39-52). This provision excluding coverage or exposures occurring in 
    the application of pesticides has therefore been added to the standards 
    for construction and shipyards as well.
        The exemption pertains to the application of pesticides only. The 
    manufacture of pesticides containing Cr(VI) is not considered pesticide 
    application, and is covered under the final rule. The use of wood 
    treated with pesticides containing Cr(VI) is also covered. In this 
    respect, the Cr(VI) standard differs from OSHA's Inorganic Arsenic 
    standard (29 CFR 1910.1018). The Inorganic Arsenic standard explicitly 
    exempts the use of wood treated with arsenic. When the Inorganic 
    Arsenic standard was issued in 1978, OSHA found that the evidence in 
    the record indicated "the arsenic in the preserved wood is bound 
    tightly to the wood sugars, exhibits substantial chemical differences 
    from other pentavalent arsenicals after reaction, and appears not to 
    leach out in substantial amounts" (43 FR 19584, 19613 (5/5/78)). Based 
    on the record in that rulemaking, OSHA did not consider it appropriate 
    to regulate the use of preserved wood. A number of commenters argued 
    that a similar exception should be included in the final rule for use 
    of wood preserved with Cr(VI) compounds (Exs. 38-208; 38-231; 38-244; 
    43-28). However, OSHA's exposure profile indicates that work with wood 
    treated with pesticides containing Cr(VI) can involve Cr(VI) exposures 
    above the new PEL (see FEA, Chapter III). OSHA therefore considers a 
    blanket exception from the scope of the final rule for use of wood 
    treated with Cr(VI) to be unjustified.
    
    Other Requested Exemptions
    
        In addition to those who maintained that Cr(VI)-treated wood should 
    be exempted from the final rule, a number of commenters requested 
    exemptions from the final rule for other operations or industries 
    (e.g., welding, electric utilities, Cr(VI) pigment production, 
    residential construction, and telecommunications (Exs. 38-124; 38-203; 
    38-205; 38-211; 38-230; 38-244; 38-254; 39-14; 39-15; 39-47; 47-25; 47-
    37). OSHA does not believe that the evidence in the record supports a 
    blanket exception from the final rule for these operations and 
    industries. In no case have commenters submitted data demonstrating 
    that the operations or industries for which an exception was requested 
    do not involve exposures to Cr(VI) that present significant risk to the 
    health of employees. Rather, the data presented in Chapter III of the 
    FEA indicate that exposures in these sectors can and do involve 
    exposures at levels that entail significant risk to workers, and may 
    exceed the new PEL. OSHA therefore has not included exceptions for 
    these operations or industries in the final rule.
        One commenter argued that the provisions of the standard, including 
    the new PEL, should apply only where Cr(VI) exposures occur on more 
    than 30 days per year (Ex. 38-233, pp. 43-44). However, exposures of 30 
    or fewer days per year may involve cumulative exposures associated with 
    significant risk of lung cancer. For example, if an employee was 
    exposed to 50 [mu]g/m3 Cr(VI) for 30 days during a year, 
    that employee s cumulative exposure for the year would exceed that of 
    an employee exposed at the new PEL of 5 [mu]g/m3 working 
    five days a week through the entire year. Therefore, OSHA does not 
    believe such an exemption is appropriate because it would deny workers 
    exposed to relatively high levels of Cr(VI) for 30 or fewer days per 
    year the protections afforded by the Cr(VI) rule. The Agency does 
    include exceptions from certain requirements of the rule for exposures 
    occurring on fewer than 30 days per year (e.g., with regard to 
    requirements for engineering controls and periodic medical 
    surveillance). However, these exceptions are related to the practical 
    aspects of implementing protective measures, and not to an absence of 
    risk for exposures occurring on fewer than 30 days per year.
        Other commenters suggested that materials or substances containing 
    trace amounts of Cr(VI) (e.g., less than 0.1% or 1%) be exempted from 
    the final rule (Exs. 38-203; 38-254; 39-19; 39-47; 39-48; 39-52; 39-54; 
    39-56). In particular, some utilities argued that fly ash produced by 
    the incineration of coal contains trace amounts of Cr(VI) that are so 
    low as to be insignificant, and that an exclusion from the final rule 
    for coal ash was warranted (Ex. 39-40). Edison Electric Institute 
    supported this argument by submitting sampling data and material safety 
    data sheets that indicated the Cr(VI) concentrations in ash by-products 
    of the coal combustion process (Exs. 47-25-1; 47-25-2; 47-25-3; 47-25-
    4; 47-25-5; 47-25-6; 47-25-7).
        OSHA does not believe that it would be appropriate to establish a 
    threshold Cr(VI) concentration for coverage of substances under the 
    scope of this final rule. The evidence in the rulemaking record is not 
    sufficient to lead OSHA to conclude that the suggested concentration 
    thresholds would be protective of employee health. While OSHA has 
    recognized that the Cr(VI) content of portland cement is sufficiently 
    low to warrant an exception from the standard, a threshold 
    concentration of 0.1% for Cr(VI) would be more than 50-fold higher than 
    Cr(VI) levels typically found in portland cement (< 0.002%). See above 
    discussion of the extremely low Cr(VI) concentration in portland cement 
    (< 20 [mu]g/g).
        Although evidence submitted to the record indicates that Cr(VI) 
    levels in coal ash may be comparable to levels in portland cement, OSHA 
    does not believe that the evidence is sufficient to establish that all 
    coal ash from allsources will necessarily have comparable Cr(VI) content.
        A threshold concentration is also not reasonable because many 
    operations where Cr(VI) exposures occur are the result of work with 
    materials that do not contain any Cr(VI). Welders, who represent nearly 
    half of the workers covered by this final rule, do not ordinarily work 
    with materials that contain Cr(VI). Rather, the high temperatures 
    created by welding oxidize chromium in steel to the hexavalent state. 
    An exception based on a specified Cr(VI) concentration could be 
    interpreted to exclude these workers from the scope of the standard. 
    This would be particularly inappropriate in view of the fact that data 
    in the record show that many welders have significant Cr(VI) exposures.
        OSHA does, however, appreciate the concerns of commenters regarding 
    situations where they believe exposures are minimal and represent very 
    little threat to the health of workers. The Agency believes that a 
    reasonable approach is to have an exception based on Cr(VI) exposure 
    level. OSHA is therefore including in the final rule an exception for 
    those circumstances where the employer has objective data demonstrating 
    that a material containing chromium or a specific process, operation, 
    or activity involving chromium cannot release dusts, fumes, or mists of 
    chromium (VI) in concentrations at or above 0.5 [mu]g/m3 as 
    an 8-hour TWA under any expected conditions of use.
        OSHA believes this approach is sensible because it provides an 
    exception for situations where airborne exposures are not likely to 
    present significant risk and thus allows employers to focus resources 
    on the exposures of greatest occupational health concern. The Agency 
    has added a definition for "objective data" (discussed with regard to 
    paragraph (b) of the final rule) to clarify what information and data 
    can be used to satisfy the obligation to demonstrate that Cr(VI) 
    exposures will be below 0.5 [mu]g/m3.
        Other standards which have included similar exceptions (e.g., 
    Acryolitrile, 29 CFR 1019.1045; Ethylene Oxide, 29 CFR 1910.1047; 1,3-
    Butadiene, 29 CFR 1910.1051) have generally relied upon the action 
    level as an exposure threshold. A threshold lower than the action level 
    has been selected for the Cr(VI) rule because OSHA believes this to be 
    more protective of worker health given the existing significant risk at 
    the action level. Although OSHA understands the difficulties of 
    developing objective data to demonstrate that exposures will be below a 
    given level, the Agency believes that the 0.5 [mu]g/m3 
    coverage threshold represents an exposure level where it is still 
    reasonably possible to develop objective data to take advantage of this 
    exception if Cr(VI) exposure levels are minimal. For instance, 
    variation in exposures even in well controlled workplaces requires that 
    typical exposures be below 0.25 [mu]g/m3 in order for an 
    employer to be reasonably sure that exposures will consistently be 
    below 0.5 [mu]g/m3 (see Exs. 46-79; 46-80; 46-81). Where 
    typical exposures are below 0.25 [mu]g/m3, an industry 
    survey might be used to show that exposures for a given operation would 
    be below 0.5 [mu]g/m3 under any expected conditions of use.
        When using the phrase "any expected conditions of use" OSHA is 
    referring to situations that can reasonably be foreseen. The criteria 
    are not intended to be so circumscribed that it is impossible to meet 
    them. OSHA acknowledges that a constellation of unforeseen 
    circumstances can occur that might lead to exposures above 0.5 [mu]g/
    m3 even when the objective data demonstration has been 
    correctly made, but believes that such occurrences will be extremely 
    rare.
    (b) Definitions
        "Action level" is defined as an airborne concentration of Cr(VI) 
    of 2.5 micrograms per cubic meter of air (2.5 [mu]g/m3) 
    calculated as an eight-hour time-weighted average (TWA). The action 
    level triggers requirements for exposure monitoring and medical 
    surveillance.
        Because employee exposures to airborne concentrations of Cr(VI) are 
    variable, workers may sometimes be exposed above the PEL even if 
    exposure samples (which are not conducted on a daily basis) are 
    generally below the PEL. Maintaining exposures below the action level 
    provides increased assurance that employees will not be exposed to 
    Cr(VI) at levels above the PEL on days when no exposure measurements 
    are made in the workplace. Periodic exposure measurements made when the 
    action level is exceeded provide the employer with a degree of 
    confidence in the results of the exposure monitoring. The importance of 
    the action level is explained in greater detail in the exposure 
    determination and medical surveillance discussions of this section 
    (paragraphs (d) and (k) respectively).
        As in other standards, the action level has been set at one-half of 
    the PEL. The Agency has had successful experience with an action level 
    of one-half the PEL in other standards, including those for inorganic 
    arsenic (29 CFR 1910.1018), ethylene oxide (29 CFR 1910.1047), benzene 
    (29 CFR 1910.1028), and methylene chloride (29 CFR 1910.1052).
        Following the publication of the proposed rule, which included a 
    proposed action level of 0.5 [mu]g/m3 (\1/2\ the proposed 
    PEL of 1 [mu]g/m3), OSHA received several comments 
    pertaining to the definition of the action level. Commenters such as 
    the International Brotherhood of Teamsters (IBT) supported OSHA s 
    preliminary determination that the action level should be set at one-
    half the permissible exposure limit (Exs. 38-199-1, p. 9; 38-219, p. 
    16-17; 38-228-1; 40-10-2). The IBT stated that the action level set at 
    one-half the PEL has been successful historically in OSHA's standards 
    such as inorganic arsenic, cadmium, benzene, ethylene oxide, 
    methylenedianiline, and methylene chloride (Ex. 38-199-1, pp. 9, 44). 
    NIOSH also supported OSHA's approach, stating that the action level of 
    one-half the PEL is the appropriate level to indicate sufficient 
    probability that an employee's exposure does not exceed the PEL on 
    other days (Ex. 40-10-2, p. 17). The North American Insulation 
    Manufacturer's Association (NAIMA) agreed that an action level of one-
    half the PEL is appropriate (in conjunction with a higher PEL than that 
    proposed) (Ex. 38-228-1, pp. 23-24).
        Previous standards have recognized a statistical basis for using an 
    action level of one-half the PEL (see, e.g., acrylonitrile, 29 CFR 
    1910.1045; ethylene oxide, 29 CFR 1910.1047). In brief, OSHA previously 
    determined (based in part on research conducted by Leidel et al.) that 
    where exposure measurements are above one-half the PEL, the employer 
    cannot be reasonably confident that the employee is not exposed above 
    the PEL on days when no measurements are taken (Ex. 46-80).
        Following the publication of the proposed rule, the United 
    Automobile, Aerospace, and Agricultural Implement Workers of America 
    (UAW) requested an action level of one-tenth of the permissible 
    exposure limit (PEL) (Tr. 791; Exs. 39-73; 39-73-2, pp. 3, 10; 40-19-
    1). The UAW argued that the lower action level is appropriate because 
    variability in exposures is greater than was previously believed in 
    some occupational settings. While OSHA previously assumed a geometric 
    standard deviation (GSD) of 1.4, the UAW stated that a GSD of 2 should 
    be assumed as a matter of policy. They concluded that this GSD implies 
    an action level of one-tenth the PEL to minimize the frequency of 
    exposures above the PEL on days when measurements are not taken (Ex. 
    39-73-2, p. 12).
        If the variability of workplace exposures is typically as high as 
    the UAW suggests, an action level less than one-half the PEL would be 
    required to give employers a high degree of confidence that employees' 
    exposures are below the PEL on most workdays. Leidel et al., calculated 
    that for exposures with a GSD of 2.0, an action level of 0.115 times 
    the PEL would be required to limit to 5% the probability that 5% or 
    more of an employee's unmeasured daily exposure averages will exceed 
    the PEL (Ex. 46-80, p. 29). However, the evidence in the record is 
    insufficient to permit OSHA to conclude that a GSD of 2.0 is typical of 
    workplace Cr(VI) exposures. Furthermore, while OSHA recognizes the 
    value of high (95%) confidence that exposures exceed the PEL very 
    infrequently (<  5%), the Agency believes that the action level should 
    be set at a value that effectively encourages employers to reduce 
    exposures below the action level while still providing reasonable 
    (though possibly <  95%) assurance that workers' exposures are typically 
    below the PEL. OSHA's experience with past rules and the comments and 
    testimony of NIOSH and other union representatives indicate that 
    reasonable assurance of day-to-day compliance with the PEL is achieved 
    with an action level of one-half the PEL (Exs. 40-10-2, p. 17; 199-1, 
    pp. 9, 44).
        The Agency's experience with previous standards also indicates that 
    an action limit of one-half the PEL effectively encourages employers, 
    where feasible, to reduce exposures below the action level to avoid the 
    added costs of required complian