[Federal Register Volume 82, Number 5 (Monday, January 9, 2017)]
[Rules and Regulations]
[Pages 2470-2757]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-30409]
Vol. 82
Monday,
No. 5
January 9, 2017
Part II
Department of Labor
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Occupational Safety and Health Administration
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29 CFR Parts 1910, 1915, and 1926
Occupational Exposure to Beryllium; Final Rule
Federal Register / Vol. 82 , No. 5 / Monday, January 9, 2017 / Rules
and Regulations
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DEPARTMENT OF LABOR
Occupational Safety and Health Administration
29 CFR Parts 1910, 1915, and 1926
[Docket No. OSHA-H005C-2006-0870]
RIN 1218-AB76
Occupational Exposure to Beryllium
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 its existing standards for occupational exposure to beryllium
and beryllium compounds. OSHA has determined that employees exposed to
beryllium at the previous permissible exposure limits face a
significant risk of material impairment to their health. The evidence
in the record for this rulemaking indicates that workers exposed to
beryllium are at increased risk of developing chronic beryllium disease
and lung cancer. This final rule establishes new permissible exposure
limits of 0.2 micrograms of beryllium per cubic meter of air (0.2
μg/m3\) as an 8-hour time-weighted average and 2.0 μg/m3\ as a
short-term exposure limit determined over a sampling period of 15
minutes. It also includes other provisions to protect employees, such
as requirements for exposure assessment, methods for controlling
exposure, respiratory protection, personal protective clothing and
equipment, housekeeping, medical surveillance, hazard communication,
and recordkeeping.
OSHA is issuing three separate standards--for general industry, for
shipyards, and for construction--in order to tailor requirements to the
circumstances found in these sectors.
DATES: Effective date: The final rule becomes effective on March 10,
2017.
Compliance dates: Compliance dates for specific provisions are set
in Sec. 1910.1024(o) for general industry, Sec. 1915.1024(o) for
shipyards, and Sec. 1926.1124(o) for construction. There are a number
of collections of information contained in this final rule (see Section
IX, OMB Review under the Paperwork Reduction Act of 1995).
Notwithstanding the general date of applicability that applies to all
other requirements contained in the final rule, affected parties do not
have to comply with the collections of information until the Department
of Labor publishes a separate document in the Federal Register
announcing the Office of Management and Budget has approved them under
the Paperwork Reduction Act.
ADDRESSES: In accordance with 28 U.S.C. 2112(a), the Agency designates
Ann Rosenthal, Associate Solicitor of Labor for Occupational Safety and
Health, Office of the Solicitor of Labor, Room S-4004, U.S. Department
of Labor, 200 Constitution Avenue NW., Washington, DC 20210, to receive
petitions for review of the final rule.
FOR FURTHER INFORMATION CONTACT: For general information and press
inquiries, contact Frank Meilinger, Director, Office of Communications,
Room N-3647, OSHA, U.S. Department of Labor, 200 Constitution Avenue
NW., Washington, DC 20210; telephone (202) 693-1999; email
meilinger.francis2@dol.gov.
For technical inquiries, contact William Perry or Maureen Ruskin,
Directorate of Standards and Guidance, Room N-3718, OSHA, U.S.
Department of Labor, 200 Constitution Avenue NW., Washington, DC 20210;
telephone (202) 693-1950.
SUPPLEMENTARY INFORMATION: The preamble to the rule on occupational
exposure to beryllium follows this outline:
I. Executive Summary
II. Pertinent Legal Authority
III. Events Leading to the Final Standards
IV. Chemical Properties and Industrial Uses
V. Health Effects
VI. Risk Assessment
VII. Significance of Risk
VIII. Summary of the Final Economic Analysis and Final Regulatory
Flexibility Analysis
IX. OMB Review Under the Paperwork Reduction Act of 1995
X. Federalism
XI. State-Plan States
XII. Unfunded Mandates Reform Act
XIII. Protecting Children From Environmental Health and Safety Risks
XIV. Environmental Impacts
XV. Consultation and Coordination With Indian Tribal Governments
XVI. Summary and Explanation of the Standards
Introduction
(a) Scope and Application
(b) Definitions
(c) Permissible Exposure Limits (PELs)
(d) Exposure Assessment
(e) Beryllium Work Areas and Regulated Areas (General Industry);
Regulated Areas (Maritime); and Competent Person (Construction)
(f) Methods of Compliance
(g) Respiratory Protection
(h) Personal Protective Clothing and Equipment
(i) Hygiene Areas and Practices
(j) Housekeeping
(k) Medical Surveillance
(l) Medical Removal
(m) Communication of Hazards
(n) Recordkeeping
(o) Dates
(p) Appendix A (General Industry)
Authority and Signature
Amendments to Standards
Citation Method
In the docket for the beryllium rulemaking, found at http://www.regulations.gov, every submission was assigned a document
identification (ID) number that consists of the docket number (OSHA-
H005C-2006-0870) followed by an additional four-digit number. For
example, the document ID number for OSHA's Preliminary Economic
Analysis and Initial Regulatory Flexibility Analysis is OSHA-H005C-
2006-0870-0426. Some document ID numbers include one or more
attachments, such as the National Institute for Occupational Safety and
Health (NIOSH) prehearing submission (see Document ID OSHA-H005C-2006-
0870-1671).
When citing exhibits in the docket, OSHA includes the term
"Document ID" followed by the last four digits of the document ID
number, the attachment number or other attachment identifier, if
applicable, page numbers (designated "p." or "Tr." for pages from a
hearing transcript). In a citation that contains two or more document
ID numbers, the document ID numbers are separated by semi-colons. In
some sections, such as Section V, Health Effects, author names and year
of study publication are included before the document ID number in a
citation, for example: (Deubner et al., 2011, Document ID 0527). Where
multiple exhibits are listed with author names and year of study
publication, document ID numbers after the first are in parentheses,
for example: (Elder et al., 2005, Document ID 1537; Carter et al., 2006
(1556); Refsnes et al., 2006 (1428)).
I. Executive Summary
This final rule establishes new permissible exposure limits (PELs)
for beryllium of 0.2 micrograms of beryllium per cubic meter of air
(0.2 μg/m3\) as an 8-hour time-weighted average (TWA) and 2.0
μg/m3\ as a short-term exposure limit (STEL) determined over a
sampling period of 15 minutes. In addition to the PELs, the rule
includes provisions to protect employees such as requirements for
exposure assessment, methods for controlling exposure, respiratory
protection, personal protective clothing and equipment, housekeeping,
medical surveillance, hazard communication, and recordkeeping. OSHA is
issuing three separate standards--for general
industry, for shipyards, and for construction--in order to tailor
requirements to the circumstances found in these sectors. There are,
however, numerous common elements in the three standards.
The final rule is based on the requirements of the Occupational
Safety and Health Act (OSH Act) and court interpretations of the Act.
For health standards issued under section 6(b)(5) of the OSH Act, OSHA
is required to promulgate a standard that reduces significant risk to
the extent that it is technologically and economically feasible to do
so. See Section II, Pertinent Legal Authority, for a full discussion of
OSH Act legal requirements.
OSHA has conducted an extensive review of the literature on adverse
health effects associated with exposure to beryllium. OSHA has also
developed estimates of the risk of beryllium-related diseases, assuming
exposure over a working lifetime, at the preceding PELs as well as at
the revised PELs and action level. Comments received on OSHA's
preliminary analysis, and the Agency's final findings, are discussed in
Section V, Health Effects, Section VI, Risk Assessment, and Section
VII, Significance of Risk. OSHA finds that employees exposed to
beryllium at the preceding PELs are at an increased risk of developing
chronic beryllium disease (CBD) and lung cancer. As discussed in
Section VII, OSHA concludes that exposure to beryllium constitutes a
significant risk of material impairment to health and that the final
rule will substantially lower that risk. The Agency considers the level
of risk remaining at the new TWA PEL to still be significant. However,
OSHA did not adopt a lower TWA PEL because the Agency could not
demonstrate technological feasibility of a lower TWA PEL. The Agency
has adopted the STEL and ancillary provisions of the rule to further
reduce the remaining significant risk.
OSHA's examination of the technological and economic feasibility of
the rule is presented in the Final Economic Analysis and Regulatory
Flexibility Analysis (FEA), and is summarized in Section VIII of this
preamble. OSHA concludes that the final PELs are technologically
feasible for all affected industries and application groups. Thus, OSHA
concludes that engineering and work practice controls will be
sufficient to reduce and maintain beryllium exposures to the new PELs
or below in most operations most of the time in the affected
industries. For those few operations within an industry or application
group where compliance with the PELs cannot be achieved even when
employers implement all feasible engineering and work practice
controls, use of respirators will be required.
OSHA developed quantitative estimates of the compliance costs of
the rule for each of the affected industry sectors. The estimated
compliance costs were compared with industry revenues and profits to
provide a screening analysis of the economic feasibility of complying
with the rule and an evaluation of the economic impacts. Industries
with unusually high costs as a percentage of revenues or profits were
further analyzed for possible economic feasibility issues. After
performing these analyses, OSHA finds that compliance with the
requirements of the rule is economically feasible in every affected
industry sector.
The final rule includes several major changes from the proposed
rule as a result of OSHA's analysis of comments and evidence received
during the comment periods and public hearings. The major changes are
summarized below and are fully discussed in Section XVI, Summary and
Explanation of the Standards. OSHA also presented a number of
regulatory alternatives in the Notice of Proposed Rulemaking (80 FR
47566, 47729-47748 (8/7/2015). Where the Agency received substantive
comments on a regulatory alternative, those comments are also discussed
in Section XVI. A full discussion of all regulatory alternatives can be
found in Chapter VIII of the Final Economic Analysis (FEA).
Scope. OSHA proposed to cover occupational exposures to beryllium
in general industry, with an exemption for articles and an exemption
for materials containing less than 0.1% beryllium by weight. OSHA has
made a final determination to cover exposures to beryllium in general
industry, shipyards, and construction under the final rule, and to
issue separate standards for each sector. The final rule also provides
an exemption for materials containing less than 0.1% beryllium by
weight only where the employer has objective data demonstrating that
employee exposure to beryllium will remain below the action level of
0.1 μg/m3\ as an 8-hour TWA under any foreseeable conditions.
Exposure Assessment. The proposed rule would have required periodic
exposure monitoring annually where employee exposures are at or above
the action level but at or below the TWA PEL; no periodic monitoring
would have been required where employee exposures exceeded the TWA PEL.
The final rule specifies that exposure monitoring must be repeated
within six months where employee exposures are at or above the action
level but at or below the TWA PEL, and within three months where
employee exposures are above the TWA PEL or STEL. The final rule also
includes provisions allowing the employer to discontinue exposure
monitoring where employee exposures fall below the action level and
STEL. In addition, the final rule includes a new provision that allows
employers to assess employee exposures using any combination of air
monitoring data and objective data sufficient to accurately
characterize airborne exposure to beryllium (i.e., the "performance
option").
Beryllium Work Areas. The proposed rule would have required the
employer to establish and maintain a beryllium work area wherever
employees are, or can reasonably be expected to be, exposed to airborne
beryllium, regardless of the level of exposure. As discussed in the
Summary and Explanation section of this preamble, OSHA has narrowed the
definition of beryllium work area in the final rule from the proposal.
The final rule now limits the requirement to work areas containing a
process or operation that can release beryllium where employees are, or
can reasonably be expected to be, exposed to airborne beryllium at any
level. The final rule expands the exposure requirement to include work
areas containing a process or operation where there is potential dermal
contact with beryllium based on comments from public health experts
that relying solely on airborne exposure omits the potential
contribution of dermal exposure to total exposure. See the Summary and
Explanation section of this preamble for a full discussion of the
relevant comments and reasons for changes from the proposed standard.
Beryllium work areas are not required under the standards for shipyards
and construction.
Respiratory Protection. OSHA has added a provision in the final
rule requiring the employer to provide a powered air-purifying
respirator (PAPR) instead of a negative pressure respirator where
respiratory protection is required by the rule and the employee
requests a PAPR, provided that the PAPR provides adequate protection.
Personal Protective Clothing and Equipment. The proposed rule would
have required use of protective clothing and equipment where employee
exposure exceeds, or can reasonably be expected to exceed the TWA PEL
or STEL; where employees' clothing or skin may become visibly
contaminated with beryllium; and where employees'
skin can reasonably be expected to be exposed to soluble beryllium
compounds. The final rule requires use of protective clothing and
equipment where employee exposure exceeds, or can reasonably be
expected to exceed the TWA PEL or STEL; or where there is a reasonable
expectation of dermal contact with beryllium.
Medical Surveillance. The exposure trigger for medical examinations
has been revised from the proposal. The proposed rule would have
required that medical examinations be offered to each employee who has
worked in a regulated area (i.e., an area where an employee's exposure
exceeds, or can reasonably be expected to exceed, the TWA PEL or STEL)
for more than 30 days in the last 12 months. The final rule requires
that medical examinations be offered to each employee who is or is
reasonably expected to be exposed at or above the action level for more
than 30 days per year. A trigger to offer periodic medical surveillance
when recommended by the most recent written medical opinion was also
added the final rule. Under the final rule, the licensed physician
recommends continued periodic medical surveillance for employees who
are confirmed positive for sensitization or diagnosed with CBD. The
proposed rule also would have required that medical examinations be
offered annually; the final rule requires that medical examinations be
offered at least every two years.
The final medical surveillance provisions have been revised to
provide enhanced privacy for employees. The rule requires the employer
to obtain a written medical opinion from a licensed physician for
medical examinations provided under the rule but limits the information
provided to the employer to the date of the examination, a statement
that the examination has met the requirements of the standard, any
recommended limitations on the employee's use of respirators,
protective clothing, and equipment, and a statement that the results of
the exam have been explained to the employee. The proposed rule would
have required that such opinions contain additional information,
without requiring employee authorization, such as the physician's
opinion as to whether the employee has any detected medical condition
that would place the employee at increased risk of CBD from further
exposure, and any recommended limitations upon the employee's exposure
to beryllium. In the final rule, the written opinion provided to the
employer will only include recommended limitations on the employee's
exposure to beryllium, referral to a CBD diagnostic center, a
recommendation for continued periodic medical surveillance, or a
recommendation for medical removal if the employee provides written
authorization. The final rule requires a separate written medical
report provided to the employee to include this additional information,
as well as detailed information related to the employee's health.
The proposed rule would have required that the licensed physician
provide the employer with a written medical opinion within 30 days of
the examination. The final rule requires that the licensed physician
provide the employee with a written medical report and the employer
with a written medical opinion within 45 days of the examination,
including any follow-up beryllium lymphocyte proliferation test
(BeLPTs).
The final rule also adds requirements for the employer to provide
the CBD diagnostic center with the same information provided to the
physician or other licensed health care professional who administers
the medical examination, and for the CBD diagnostic center to provide
the employee with a written medical report and the employer with a
written medical opinion. Under the final standard, employees referred
to a CBD diagnostic center can choose to have future evaluations
performed there. A requirement that laboratories performing BeLPTs be
certified was also added to the final rule.
The proposed rule would have required that employers provide low
dose computed tomography (LDCT) scans to employees who met certain
exposure criteria. The final rule requires LDCT scans when recommended
by the physician or other licensed healthcare professional
administering the medical exam, after considering the employee's
history of exposure to beryllium along with other risk factors.
Dates. OSHA proposed an effective date 60 days after publication of
the rule; a date for compliance with all provisions except change rooms
and engineering controls of 90 days after the effective date; a date
for compliance with change room requirements, which was one year after
the effective date; and a date for compliance with engineering control
requirements of two years after the effective date.
OSHA has revised the proposed compliance dates. The final rule is
effective 60 days after publication. All obligations for compliance
commence one year after the effective date, with two exceptions: The
obligation for change rooms and showers commences two years after the
effective date; and the obligation for engineering controls commences
three years after the effective date.1
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1 Note that the main analysis of costs and benefits presented
in this FEA does not take into account the lag in effective dates
but, instead, assumes that the rule takes effect in Year 1. To
account for the lag in effective dates, OSHA has provided in the
sensitivity analysis in Chapter VII of the FEA an estimate of its
separate effects on costs and benefits relative to the main
analysis. This analysis, which appears in Table VII-16 of the FEA,
indicates that if employers delayed implementation of all provisions
until legally required, and no benefits occurred until all
provisions went into effect, this would decrease the estimated costs
by 3.9 percent; the estimated benefits by 8.5 percent, and the
estimated net benefits of the standard by 9.2 percent (to $442
million).
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Under the OSH Act's legal standard directing OSHA to set health
standards based on findings of significant risk of material impairment
and technological and economic feasibility, OSHA does not use cost-
benefit analysis to determine the PEL or other aspects of the rule. It
does, however, determine and analyze costs and benefits for its own
informational purposes and to meet certain Executive Order
requirements, as discussed in Section VIII, Summary of the Final
Economic Analysis and Final Regulatory Flexibility Analysis and in the
FEA. Table I-1--which is derived from material presented in Section
VIII of this preamble--provides a summary of OSHA's best estimate of
the costs and benefits of the rule using a discount rate of 3 percent.
As shown, the rule is estimated to prevent 90 fatalities and 46 new
cases of CBD annually once the full effects are realized, and the
estimated cost of the rule is $73.9 million annually. Also as shown in
Table I-1, the discounted monetized benefits of the rule are estimated
to be $560.9 annually, and the rule is estimated to generate net
benefits of approximately $487 annually; however, there is a great deal
of uncertainty in those benefits due to assumptions made about dental
workers' exposures and reductions; see Section VIII of this preamble.
As that section shows, benefits significantly exceed costs regardless
of how dental workers' exposures are treated.
Table I-1--Annualized Benefits, Costs and Net Benefits of OSHA's Final
Beryllium Standard
[3 Percent discount rate, 2015 dollars]
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Annualized Costs:
Control Costs......................................... $12,269,190
Rule Familiarization.................................. 180,158
Exposure Assessment................................... 13,748,676
Regulated Areas....................................... 884,106
Beryllium Work Areas.................................. 129,648
Medical Surveillance.................................. 7,390,958
Medical Removal....................................... 1,151,058
Written Exposure Control Plan......................... 2,339,058
Protective Work Clothing & Equipment.................. 1,985,782
Hygiene Areas and Practices........................... 2,420,584
Housekeeping.......................................... 22,763,595
Training.............................................. 8,284,531
Respirators........................................... 320,885
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Total Annualized Costs (Point Estimate)........... $73,868,230
Annual Benefits: Number of Cases Prevented:
Fatal Lung Cancers (Midpoint Estimate)................ 4
Fatal Chronic Beryllium Disease....................... 86
Beryllium-Related Mortality........................... 90
Beryllium Morbidity................................... 46
Monetized Annual Benefits (Midpoint Estimate)......... $560,873,424
Net Benefits:
Net Benefits.......................................... $487,005,194
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Sources: US DOL, OSHA, Directorate of Standards and Guidance, Office of
Regulatory Analysis.
II. Pertinent Legal Authority
The purpose of the Occupational Safety and Health Act (29 U.S.C.
651 et seq.) ("the Act" or "the OSH 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 set mandatory occupational safety and
health standards applicable to businesses affecting interstate
commerce" (29 U.S.C. 651(b)(3); see 29 U.S.C. 654(a) (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 primary statutory provision relied upon by the Agency in
promulgating health standards is section 6(b)(5) of the Act; other
sections of the OSH Act, however, authorize the Occupational Safety and
Health Administration ("OSHA") to require labeling and other
appropriate forms of warning, exposure assessment, medical
examinations, and recordkeeping in its standards (29 U.S.C. 655(b)(5),
655(b)(7), 657(c)).
The Act provides that in promulgating standards dealing with toxic
materials or harmful physical agents, such as beryllium, 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. 655(b)(5)).
Thus, "[w]hen Congress passed the Occupational Safety and Health Act
in 1970, it chose to place pre-eminent value on assuring employees a
safe and healthful working environment, limited only by the feasibility
of achieving such an environment" (American Textile Mfrs. Institute,
Inc. v. Donovan, 452 US 490, 541 (1981) ("Cotton Dust")).
OSHA proposed this new standard for beryllium and beryllium
compounds and conducted its rulemaking pursuant to section 6(b)(5) of
the Act ((29 U.S.C. 655(b)(5)). The preceding beryllium standard,
however, was adopted under the Secretary's authority in section 6(a) of
the OSH Act (29 U.S.C. 655(a)), to adopt national consensus and
established Federal standards within two years of the Act's enactment
(see 29 CFR 1910.1000 Table Z-1). Any rule that "differs substantially
from an existing national consensus standard" must "better effectuate
the purposes of this Act than the national consensus standard" (29
U.S.C. 655(b)(8)). Several additional legal requirements arise from the
statutory language in sections 3(8) and 6(b)(5) of the Act (29 U.S.C.
652(8), 655(b)(5)). The remainder of this section discusses these
requirements, which OSHA must consider and meet before it may
promulgate this occupational health standard regulating exposure to
beryllium and beryllium compounds.
Material Impairment of Health
Subject to the limitations discussed below, when setting standards
regulating exposure to toxic materials or harmful physical agents, the
Secretary is required to set health standards that ensure that "no
employee will suffer material impairment of health or functional
capacity. . ." (29 U.S.C. 655(b)(5)). "OSHA is not required to state
with scientific certainty or precision the exact point at which each
type of [harm] becomes a material impairment" (AFL-CIO v. OSHA, 965
F.2d 962, 975 (11th Cir. 1992)). Courts have also noted that OSHA
should consider all forms and degrees of material impairment--not just
death or serious physical harm (AFL-CIO, 965 F.2d at 975). Thus the
Agency has taken the position that "subclinical" health effects,
which may be precursors to more serious disease, can be material
impairments of health that OSHA should address when feasible (43 FR
52952, 52954 (11/14/78) (Lead Preamble)).
Significant Risk
Section 3(8) of the Act requires that workplace safety and health
standards be "reasonably necessary or appropriate to provide safe or
healthful employment" (29 U.S.C. 652(8)). The Supreme Court, in its
decision on OSHA's benzene standard, interpreted section 3(8) to mean
that before promulgating any standard, the Secretary must evaluate
whether "significant risk[ ]" exists under current conditions and to
then determine whether that risk can be "eliminated or lessened"
through regulation (Indus. Union Dep't, AFL-CIO v. Am. Petroleum Inst.,
448 U.S. 607, 642 (1980) (plurality opinion) ("Benzene")). The
Court's holding is consistent with evidence in the legislative record,
with regard to section 6(b)(5) of the Act (29 U.S.C. 655(b)(5)), that
Congress intended the Agency to regulate unacceptably severe
occupational hazards, and not "to establish a utopia free from any
hazards" or to address risks comparable to those that exist in
virtually any occupation or workplace (116 Cong. Rec. 37614 (1970),
Leg. Hist. 480-82). It is also consistent with Section 6(g) of the OSH
Act, which states that, in determining regulatory priorities, "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" (29 U.S.C. 655(g)).
The Supreme Court in Benzene clarified that "[i]t is the Agency's
responsibility to determine, in the first instance, what it considers
to be a `significant' risk" (Benzene, 448 U.S. at 655), and that it
was not the Court's responsibility to "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" (Benzene, 448
U.S. at 659). The Court stated, however, that the section 6(f) (29
U.S.C. 655(b)(f)) substantial evidence standard applicable to OSHA's
significant risk determination does not require the Agency "to support
its finding that a significant risk exists with anything approaching
scientific certainty" (Benzene, 448 U.S. at 656). Rather, OSHA may
rely on "a body of reputable scientific thought" to which
"conservative assumptions in interpreting the data . . . " may be
applied, "risking error on the side of
overprotection" (Benzene, 448 U.S. at 656; see also United
Steelworkers of Am., AFL-CIO-CLC v. Marshall, 647 F.2d 1189, 1248 (D.C.
Cir. 1980) ("Lead I") (noting the Benzene court's application of this
principle to carcinogens and applying it to the lead standard, which
was not based on carcinogenic effects)). OSHA may thus act with a
"pronounced bias towards worker safety" in making its risk
determinations (Bldg & Constr. Trades Dep't v. Brock, 838 F.2d 1258,
1266 (D.C. Cir. 1988) ("Asbestos II").
The Supreme Court further recognized that what constitutes
"significant risk" is "not a mathematical straitjacket" (Benzene,
448 U.S. at 655) and will be "based largely on policy considerations"
(Benzene, 448 U.S. at 655 n. 62). The Court gave the following example:
If . . . 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% benzene will be fatal, a reasonable person might well
consider the risk significant . . . (Benzene, 448 U.S. at 655).
Following Benzene, OSHA has, in many of its health standards,
considered the one-in-a-thousand metric when determining whether a
significant risk exists. Moreover, as "a prerequisite to more
stringent regulation" in all subsequent health standards, OSHA has,
consistent with the Benzene plurality decision, based each standard on
a finding of significant risk at the "then prevailing standard" of
exposure to the relevant hazardous substance (Asbestos II, 838 F.2d at
1263). The Agency's final risk assessment is derived from existing
scientific and enforcement data and its final conclusions are made only
after considering all evidence in the rulemaking record. Courts
reviewing the validity of these standards have uniformly held the
Secretary to the significant risk standard first articulated by the
Benzene plurality and have generally upheld the Secretary's significant
risk determinations as supported by substantial evidence and "a
reasoned explanation for his policy assumptions and conclusions"
(Asbestos II, 838 F.2d at 1266).
Once OSHA makes its significant risk finding, the "more stringent
regulation" (Asbestos II, 838 F.2d at 1263) it promulgates must be
"reasonably necessary or appropriate" to reduce or eliminate that
risk, within the meaning of section 3(8) of the Act (29 U.S.C. 652(8))
and Benzene (448 U.S. at 642) (see Asbestos II, 838 F.2d at 1269). The
courts have interpreted section 6(b)(5) of the OSH Act as requiring
OSHA to set the standard that eliminates or reduces risk to the lowest
feasible level; as discussed below, the limits of technological and
economic feasibility usually determine where the new standard is set
(see UAW v. Pendergrass, 878 F.2d 389, 390 (D.C. Cir. 1989)). In
choosing among regulatory alternatives, however, "[t]he determination
that [one standard] is appropriate, as opposed to a marginally [more or
less protective] standard, is a technical decision entrusted to the
expertise of the agency . . . " (Nat'l Mining Ass'n v. Mine Safety and
Health Admin., 116 F.3d 520, 528 (D.C. Cir. 1997)) (analyzing a Mine
Safety and Health Administration standard under the Benzene significant
risk standard). In making its choice, OSHA may incorporate a margin of
safety even if it theoretically regulates below the lower limit of
significant risk (Nat'l Mining Ass'n, 116 F.3d at 528 (citing American
Petroleum Inst. v. Costle, 665 F.2d 1176, 1186 (D.C. Cir. 1982))).
Working Life Assumption
The OSH Act requires OSHA to set the standard that most adequately
protects employees against harmful workplace exposures for the period
of their "working life" (29 U.S.C. 655(b)(5)). OSHA's longstanding
policy is to define "working life" as constituting 45 years; thus, it
assumes 45 years of exposure when evaluating the risk of material
impairment to health caused by a toxic or hazardous substance. This
policy is not based on empirical data that most employees are exposed
to a particular hazard for 45 years. Instead, OSHA has adopted the
practice to be consistent with the statutory directive that "no
employee" suffer material impairment of health "even if" such
employee is exposed to the hazard for the period of his or her working
life (see 74 FR 44796 (8/31/09)). OSHA's policy was given judicial
approval in a challenge to an OSHA standard that lowered the
permissible exposure limit (PEL) for asbestos (Asbestos II, 838 F.2d at
1264-1265). In that case, the petitioners claimed that the median
duration of employment in the affected industry sectors was only five
years. Therefore, according to petitioners, OSHA erred in assuming a
45-year working life in calculating the risk of health effects caused
by asbestos exposure. The D.C. Circuit disagreed, stating "[e]ven if
it is only the rare worker who stays with asbestos-related tasks for 45
years, that worker would face a 64/1000 excess risk of contracting
cancer; Congress clearly authorized OSHA to protect such a worker"
(Asbestos II, 838 F.2d at 1264-1265). OSHA might calculate the health
risks of exposure, and the related benefits of lowering the exposure
limit, based on an assumption of a shorter working life, such as 25
years, but such estimates are for informational purposes only.
Best Available Evidence
Section 6(b)(5) of the Act requires OSHA to set standards "on the
basis of the best available evidence" and to consider the "latest
available scientific data in the field" (29 U.S.C. 655(b)(5)). As
noted above, the Supreme Court, in its Benzene decision, explained that
OSHA must look to "a body of reputable scientific thought" in making
its material harm and significant risk determinations, while noting
that a reviewing court must "give OSHA some leeway where its findings
must be made on the frontiers of scientific knowledge" (Benzene, 448
U.S. at 656).
The courts of appeals have afforded OSHA similar latitude to issue
health standards in the face of scientific uncertainty. The Second
Circuit, in upholding the vinyl chloride standard, stated: "[T]he
ultimate facts here in dispute are `on the frontiers of scientific
knowledge', and, though the factual finger points, it does not
conclude. Under the command of OSHA, it remains the duty of the
Secretary to act to protect the workingman, and to act even in
circumstances where existing methodology or research is deficient"
(Society of the Plastics Industry, Inc. v. OSHA, 509 F.2d 1301, 1308
(2d Cir. 1975) (quoting Indus. Union Dep't, AFL-CIO v. Hodgson, 499
F.2d 467, 474 (D.C. Cir. 1974) ("Asbestos I"))). The D.C. Circuit, in
upholding the cotton dust standard, stated: "OSHA's mandate
necessarily requires it to act even if information is incomplete when
the best available evidence indicates a serious threat to the health of
workers" (Am. Fed'n of Labor & Cong. of Indus. Orgs. v. Marshall, 617
F.2d 636, 651 (D.C. Cir. 1979), aff'd in part and vacated in part on
other grounds, American Textile Mfrs. Inst., Inc. v. Donovan, 452 U.S.
490 (1981)). When there is disputed scientific evidence in the record,
OSHA must review the evidence on both sides and "reasonably resolve"
the dispute (Pub. Citizen Health Research Grp. v. Tyson, 796 F.2d 1479,
1500 (D.C. Cir. 1986)). The Court in Public Citizen further noted that,
where "OSHA has the expertise we lack and it has exercised that
expertise by carefully reviewing the scientific data," a dispute
within the scientific community is not occasion for the reviewing court
to take sides about which view is correct (Pub. Citizen Health Research
Grp., 796 F.2d
at 1500) or for OSHA or the courts to " `be paralyzed by debate
surrounding diverse medical opinions' " (Pub. Citizen Health Research
Grp., 796 F.2d at 1497 (quoting H.R. Rep. No. 91-1291, 91st Cong., 2d
Sess. 18 (1970), reprinted in Legislative History of the Occupational
Safety and Health Act of 1970 at 848 (1971))). Provided the Agency gave
adequate notice in the proposal's preamble discussion of potential
regulatory alternatives that the Secretary would be considering one or
more stated options for regulation, OSHA is not required to prefer the
option in the text of the proposal over a given regulatory alternative
that was addressed in the rulemaking if substantial evidence in the
record supports inclusion of the alternative in the final standard. See
Owner-Operator Independent Drivers Ass'n, Inc. v. Federal Motor Carrier
Safety Admin., 494 F.3d 188, 209 (D.C. Cir. 2007) (notice by agency
concerning modification of sleeper-berth requirements for truck drivers
was sufficient because proposal listed several options and asked a
question regarding the details of the one option that ultimately
appeared in final rule); Kooritzky v. Reich, 17 F.3d 1509, 1513 (D.C.
Cir. 1994) (noting that a final rule need not match a proposed rule, as
long as "the agency has alerted interested parties to the possibility
of the agency's adopting a rule different than the one proposed" and
holding that agency failed to comply with notice and comment
requirements when "preamble in July offered no clues of what was to
come in October").
Feasibility
The OSH Act requires that, in setting a standard, OSHA must
eliminate the risk of material health impairment "to the extent
feasible" (29 U.S.C. 655(b)(5)). The statutory mandate to consider the
feasibility of the standard encompasses both technological and economic
feasibility; these analyses have been done primarily on an industry-by-
industry basis (Lead I, 647 F.2d at 1264, 1301). The Agency has also
used application groups, defined by common tasks, as the structure for
its feasibility analyses (Pub. Citizen Health Research Grp. v. OSHA,
557 F.3d 165, 177-179 (3d Cir. 2009)). The Supreme Court has broadly
defined feasible as "capable of being done" (Cotton Dust, 452 U.S. at
509-510).
Although OSHA must set the most protective PEL that the Agency
finds to be technologically and economically feasible, it retains
discretion to set a uniform PEL even when the evidence demonstrates
that certain industries or operations could reasonably be expected to
meet a lower PEL. OSHA health standards generally set a single PEL for
all affected employers; OSHA exercised this discretion most recently in
its final rules on occupational exposure to Chromium (VI) (71 FR 10100,
10337-10338 (2/28/2006) and Respirable Crystalline Silica (81 FR 16285,
16576-16575 (3/25/2016); see also 62 FR 1494, 1575 (1/10/97) (methylene
chloride)). In its decision upholding the chromium (VI) standard,
including the uniform PEL, the Court of Appeals for the Third Circuit
addressed this issue as one of deference, stating "OSHA's decision to
select a uniform exposure limit is a legislative policy decision that
we will uphold as long as it was reasonably drawn from the record"
(Chromium (VI), 557 F.3d at 183 (3d Cir. 2009)); see also Am. Iron &
Steel Inst. v. OSHA, 577 F.2d 825, 833 (3d Cir. 1978)). OSHA's reasons
for choosing one chromium (VI) PEL, rather than imposing different PELs
on different application groups or industries, included: Multiple PELs
would create enforcement and compliance problems because many
workplaces, and even workers, were affected by multiple categories of
chromium (VI) exposure; discerning individual PELs for different groups
of establishments would impose a huge evidentiary burden on the Agency
and unnecessarily delay implementation of the standard; and a uniform
PEL would, by eliminating confusion and simplifying compliance, enhance
worker protection (Chromium (VI), 557 F.3d at 173, 183-184). The Court
held that OSHA's rationale for choosing a uniform PEL, despite evidence
that some application groups or industries could meet a lower PEL, was
reasonably drawn from the record and that the Agency's decision was
within its discretion and supported by past practice (Chromium (VI),
557 F.3d at 183-184).
Technological Feasibility
A standard is technologically feasible if the protective measures
it requires already exist, can be brought into existence with available
technology, or can be created with technology that can reasonably be
expected to be developed (Lead I, 647 F.2d at 1272; Amer. Iron & Steel
Inst. v. OSHA, 939 F.2d 975, 980 (D.C. Cir. 1991) ("Lead II")).
OSHA's standards may be "technology forcing," i.e., where the Agency
gives an industry a reasonable amount of time to develop new
technologies, OSHA is not bound by the "technological status quo"
(Lead I, 647 F.2d at 1264). While the test for technological
feasibility is normally articulated in terms of the ability of
employers to decrease exposures to the PEL, provisions such as exposure
measurement requirements must also be technologically feasible (see
Forging Indus. Ass'n v. Sec'y of Labor, 773 F.2d 1436, 1453 (4th Cir.
1985)).
In its Lead decisions, the D.C. Circuit described OSHA's obligation
to demonstrate the technological feasibility of reducing occupational
exposure to a hazardous substance.
[W]ithin the limits of the best available evidence . . . OSHA
must prove a reasonable possibility 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 . . . The effect of
such proof is to establish a presumption that industry can meet the
PEL without relying on respirators . . . Insufficient proof of
technological feasibility for a few isolated operations within an
industry, or even OSHA's concession that respirators will be
necessary in a few such operations, will not undermine this general
presumption in favor of feasibility. Rather, in such operations
firms will remain responsible for installing engineering and work
practice controls to the extent feasible, and for using them to
reduce . . . exposure as far as these controls can do so (Lead I,
647 F.2d at 1272).
Additionally, the D.C. Circuit explained that "[f]easibility of
compliance turns on whether exposure levels at or below [the PEL] can
be met in most operations most of the time . . ." (Lead II, 939 F.2d
at 990).
Courts have given OSHA significant deference in reviewing its
technological feasibility findings. "So long as we require OSHA to
show that any required means of compliance, even if it carries no
guarantee of meeting the PEL, will substantially lower . . . exposure,
we can uphold OSHA's determination that every firm must exploit all
possible means to meet the standard" (Lead I, 647 F.2d at 1273). Even
in the face of significant uncertainty about technological feasibility
in a given industry, OSHA has been granted broad discretion in making
its findings (Lead I, 647 F.2d at 1285). "OSHA cannot let workers
suffer while it awaits . . . scientific certainty. It can and must make
reasonable [technological feasibility] predictions on the basis of
`credible sources of information,' whether data from existing plants or
expert testimony" (Lead I, 647 F.2d at 1266 (quoting Am. Fed'n of
Labor & Cong. of Indus. Orgs., 617 F.2d at 658)). For example, in Lead
I, the D.C. Circuit allowed OSHA to use, as best available evidence,
information about new and expensive industrial smelting processes that
had not yet been adopted in the U.S. and would require the rebuilding
of plants (Lead I, 647 F.2d at 1283-1284). Even under circumstances
where
OSHA's feasibility findings were less certain and the Agency was
relying on its "legitimate policy of technology forcing," the D.C.
Circuit approved of OSHA's feasibility findings when the Agency granted
lengthy phase-in periods to allow particular industries time to comply
(Lead I, 647 F.2d at 1279-1281, 1285).
OSHA is permitted to adopt a standard that some employers will not
be able to meet some of the time, with employers limited to challenging
feasibility at the enforcement stage (Lead I, 647 F.2d at 1273 & n.
125; Asbestos II, 838 F.2d at 1268). Even when the Agency recognized
that it might have to balance its general feasibility findings with
flexible enforcement of the standard in individual cases, the courts of
appeals have generally upheld OSHA's technological feasibility findings
(Lead II, 939 F.2d at 980; see Lead I, 647 F.2d at 1266-1273; Asbestos
II, 838 F.2d at 1268). Flexible enforcement policies have been approved
where there is variability in measurement of the regulated hazardous
substance or where exposures can fluctuate uncontrollably (Asbestos II,
838 F.2d at 1267-1268; Lead II, 939 F.2d at 991). A common means of
dealing with the measurement variability inherent in sampling and
analysis is for the Agency to add the standard sampling error to its
exposure measurements before determining whether to issue a citation
(e.g., 51 FR 22612, 22654 (06/20/86) (Asbestos Preamble)).
Economic Feasibility
In addition to technological feasibility, OSHA is required to
demonstrate that its standards are economically feasible. A reviewing
court will 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 . . ." (Lead
I, 647 F.2d at 1265 (omitting citation)). As articulated by the D.C.
Circuit in Lead I, "OSHA must construct a reasonable estimate of
compliance costs and demonstrate a reasonable likelihood that these
costs will not threaten the existence or competitive structure of an
industry, even if it does portend disaster for some marginal firms"
(Lead I, 647 F.2d at 1272). A reasonable estimate entails assessing
"the likely range of costs and the likely effects of those costs on
the industry" (Lead I, 647 F.2d at 1266). As with OSHA's consideration
of scientific data and control technology, however, the estimates need
not be precise (Cotton Dust, 452 U.S. at 528-29 & n. 54) as long as
they are adequately explained. Thus, as the D.C. Circuit further
explained:
Standards may be economically feasible even though, from the
standpoint of employers, they are financially burdensome and affect
profit margins adversely. Nor does the concept of economic
feasibility necessarily guarantee the continued existence of
individual employers. It would appear to be consistent with the
purposes of the Act to envisage the economic demise of an employer
who has lagged behind the rest of the industry in protecting the
health and safety of employees and is consequently financially
unable to comply with new standards as quickly as other employers.
As the effect becomes more widespread within an industry, the
problem of economic feasibility becomes more pressing (Asbestos I,
499 F.2d. at 478).
OSHA standards therefore satisfy the economic feasibility criterion
even if they impose significant costs on regulated industries so long
as they do not cause massive economic dislocations within a particular
industry or imperil the very existence of the industry (Lead II, 939
F.2d at 980; Lead I, 647 F.2d at 1272; Asbestos I, 499 F.2d. at 478).
As with its other legal findings, OSHA "is not required to prove
economic feasibility with certainty, but is required to use the best
available evidence and to support its conclusions with substantial
evidence" ((Lead II, 939 F.2d at 980-981) (citing Lead I, 647 F.2d at
1267)).
Because section 6(b)(5) of the Act explicitly imposes the "to the
extent feasible" limitation on the setting of health standards, OSHA
is not permitted to use cost-benefit analysis to make its standards-
setting decisions (29 U.S.C. 655(b)(5)).
Congress itself defined the basic relationship between costs and
benefits, by placing the "benefit" of worker health above all
other considerations save those making attainment of this
"benefit" unachievable. Any standard based on a balancing of costs
and benefits by the Secretary that strikes a different balance than
that struck by Congress would be inconsistent with the command set
forth in Sec. 6(b)(5) (Cotton Dust, 452 U.S. at 509).
Thus, while OSHA estimates the costs and benefits of its proposed and
final rules, these calculations do not form the basis for the Agency's
regulatory decisions; rather, they are performed to ensure compliance
with requirements such as those in Executive Orders 12866 and 13563.
Structure of OSHA Health Standards
OSHA's health standards traditionally incorporate a comprehensive
approach to reducing occupational disease. OSHA substance-specific
health standards generally include the "hierarchy of controls,"
which, as a matter of OSHA's preferred policy, mandates that employers
install and implement all feasible engineering and work practice
controls before respirators may be used. The Agency's adherence to the
hierarchy of controls has been upheld by the courts (ASARCO, Inc. v.
OSHA, 746 F.2d 483, 496-498 (9th Cir. 1984); Am. Iron & Steel Inst. v.
OSHA, 182 F.3d 1261, 1271 (11th Cir. 1999)). In fact, courts view the
legal standard for proving technological feasibility as incorporating
the hierarchy: "OSHA must prove a reasonable possibility 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. . .
. The effect of such proof is to establish a presumption that industry
can meet the PEL without relying on respirators" (Lead I, 647 F.2d at
1272).
The reasons supporting OSHA's continued reliance on the hierarchy
of controls, as well as its reasons for limiting the use of
respirators, are numerous and grounded in good industrial hygiene
principles (see discussion in Section XVI. Summary and Explanation of
the Standards, Methods of Compliance). The hierarchy of controls
focuses on removing harmful airborne materials at their source "to
prevent atmospheric contamination" to which the employee would be
exposed, rather than relying on the proper functioning of a respirator
as the primary means of protecting the employee (see 29 CFR 1910.134,
1910.1000(e), 1926.55(b)).
In health standards such as this one, the hierarchy of controls is
augmented by ancillary provisions. These provisions work with the
hierarchy of controls and personal protective equipment requirements to
provide comprehensive protection to employees in affected workplaces.
Such provisions typically include exposure assessment, medical
surveillance, hazard communication, and recordkeeping.
The OSH Act compels OSHA to require all feasible measures for
reducing significant health risks (29 U.S.C. 655(b)(5); Pub. Citizen
Health Research Grp., 796 F.2d at 1505 ("if in fact a STEL [short-term
exposure limit] would further reduce a significant health risk and is
feasible to implement, then the OSH Act compels the agency to adopt it
(barring alternative avenues to the same result)"). When there is
significant risk below the PEL, the D.C. Circuit indicated that OSHA
should use its regulatory authority to impose additional requirements
on employers when those requirements will result in
a greater than de minimis incremental benefit to workers' health
(Asbestos II, 838 F.2d at 1274). The Supreme Court alluded to a similar
issue in Benzene, pointing out that "in setting a permissible exposure
level in reliance on less-than-perfect methods, OSHA would have the
benefit of a backstop in the form of monitoring and medical testing"
(Benzene, 448 U.S. at 657). OSHA concludes that the ancillary
provisions in this final standard provide significant benefits to
worker health by providing additional layers and types of protection to
employees exposed to beryllium and beryllium compounds.
III. Events Leading to the Final Standards
The first occupational exposure limit for beryllium was set in 1949
by the Atomic Energy Commission (AEC), which required that beryllium
exposure in the workplaces under its jurisdiction be limited to 2
µg/m3\ as an 8-hour time-weighted average (TWA), and 25
µg/m3\ as a peak exposure never to be exceeded (Document ID
1323). These exposure limits were adopted by all AEC installations
handling beryllium, and were binding on all AEC contractors involved in
the handling of beryllium.
In 1956, the American Industrial Hygiene Association (AIHA)
published a Hygienic Guide which supported the AEC exposure limits. In
1959, the American Conference of Governmental Industrial Hygienists
(ACGIH[supreg]) also adopted a Threshold Limit Value (TLV[supreg]) of 2
µg/m3\ as an 8-hour TWA (Borak, 2006). In 1970, ANSI issued a
national consensus standard for beryllium and beryllium compounds (ANSI
Z37.29-1970). The standard set a permissible exposure limit (PEL) for
beryllium and beryllium compounds at 2 µg/m3\ as an 8-hour TWA;
5 µg/m3\ as an acceptable ceiling concentration; and 25
µg/m3\ as an acceptable maximum peak above the acceptable
ceiling concentration for a maximum duration of 30 minutes in an 8-hour
shift (Document ID 1303).
In 1971, OSHA adopted, under Section 6(a) of the Occupational
Safety and Health Act of 1970, and made applicable to general industry,
the ANSI standard (Document ID 1303). Section 6(a) provided that in the
first two years after the effective date of the Act, OSHA was to
promulgate "start-up" standards, on an expedited basis and without
public hearing or comment, based on national consensus or established
Federal standards that improved employee safety or health. Pursuant to
that authority, in 1971, OSHA promulgated approximately 425 PELs for
air contaminants, including beryllium, derived principally from Federal
standards applicable to government contractors under the Walsh-Healey
Public Contracts Act, 41 U.S.C. 35, and the Contract Work Hours and
Safety Standards Act (commonly known as the Construction Safety Act),
40 U.S.C. 333. The Walsh-Healey Act and Construction Safety Act
standards, in turn, had been adopted primarily from ACGIH[supreg]'s
TLV[supreg]s as well as several from United States of America Standards
Institute (USASI) [later the American National Standards Institute
(ANSI)].
The National Institute for Occupational Safety and Health (NIOSH)
issued a document entitled Criteria for a Recommended Standard:
Occupational Exposure to Beryllium (Criteria Document) in June 1972
with Recommended Exposure Limits (RELs) of 2 µg/m3\ as an 8-hour
TWA and 25 µg/m3\ as an acceptable maximum peak above the
acceptable ceiling concentration for a maximum duration of 30 minutes
in an 8-hour shift. OSHA reviewed the findings and recommendations
contained in the Criteria Document along with the AEC control
requirements for beryllium exposure. OSHA also considered existing data
from animal and epidemiological studies, and studies of industrial
processes of beryllium extraction, refinement, fabrication, and
machining. In 1975, OSHA asked NIOSH to update the evaluation of the
existing data pertaining to the carcinogenic potential of beryllium. In
response to OSHA's request, the Director of NIOSH stated that, based on
animal data and through all possible routes of exposure including
inhalation, "beryllium in all likelihood represents a carcinogenic
risk to man."
In October 1975, OSHA proposed a new beryllium standard for all
industries based on information from studies finding that beryllium
caused cancer in animals (40 FR 48814 (10/17/75)). Adoption of this
proposal would have lowered the 8-hour TWA exposure limit from 2
µg/m3\ to 1 µg/m3\. In addition, the proposal included
ancillary provisions for such topics as exposure monitoring, hygiene
facilities, medical surveillance, and training related to the health
hazards from beryllium exposure. The rulemaking was never completed.
In 1977, NIOSH recommended an exposure limit of 0.5 µg/m3\
and identified beryllium as a potential occupational carcinogen. In
December 1998, ACGIH published a Notice of Intended Change for its
beryllium exposure limit. The notice proposed a lower TLV of 0.2
µg/m3\ over an 8-hour TWA based on evidence of CBD and
sensitization in exposed workers. Then in 2009, ACGIH adopted a revised
TLV for beryllium that lowered the TWA to 0.05 μg/m3\ (inhalable)
(see Document ID 1755, Tr. 136).
In 1999, the Department of Energy (DOE) issued a Chronic Beryllium
Disease Prevention Program (CBDPP) Final Rule for employees exposed to
beryllium in its facilities (Document ID 1323). The DOE rule set an
action level of 0.2 μg/m3\, and adopted OSHA's PEL of 2 μg/m3\
or any more stringent PEL OSHA might adopt in the future (10 CFR
850.22; 64 FR 68873 and 68906, Dec. 8, 1999).
Also in 1999, OSHA was petitioned by the Paper, Allied-Industrial,
Chemical and Energy Workers International Union (PACE) (Document ID
0069) and by Dr. Lee Newman and Ms. Margaret Mroz, from the National
Jewish Health (NJH) (Document ID 0069), to promulgate an Emergency
Temporary Standard (ETS) for beryllium in the workplace. In 2001, OSHA
was petitioned for an ETS by Public Citizen Health Research Group and
again by PACE (Document ID 0069). In order to promulgate an ETS, the
Secretary of Labor must prove (1) that employees are exposed to grave
danger from exposure to a hazard, and (2) that such an emergency
standard is necessary to protect employees from such danger (29 U.S.C.
655(c) [6(c)]). The burden of proof is on the Department and because of
the difficulty of meeting this burden, the Department usually proceeds
when appropriate with ordinary notice and comment [section 6(b)]
rulemaking rather than a 6(c) ETS. Thus, instead of granting the ETS
requests, OSHA instructed staff to further collect and analyze research
regarding the harmful effects of beryllium in preparation for possible
section 6(b) rulemaking.
On November 26, 2002, OSHA published a Request for Information
(RFI) for "Occupational Exposure to Beryllium" (Document ID 1242).
The RFI contained questions on employee exposure, health effects, risk
assessment, exposure assessment and monitoring methods, control
measures and technological feasibility, training, medical surveillance,
and impact on small business entities. In the RFI, OSHA expressed
concerns about health effects such as chronic beryllium disease (CBD),
lung cancer, and beryllium sensitization. OSHA pointed to studies
indicating that even short-term exposures below OSHA's PEL of 2
µg/m3\ could lead to CBD. The RFI also cited studies describing
the relationship between beryllium sensitization and CBD (67 FR at
70708). In addition,
OSHA stated that beryllium had been identified as a carcinogen by
organizations such as NIOSH, the International Agency for Research on
Cancer (IARC), and the Environmental Protection Agency (EPA); and
cancer had been evidenced in animal studies (67 FR at 70709).
On November 15, 2007, OSHA convened a Small Business Advocacy
Review Panel for a draft proposed standard for occupational exposure to
beryllium. OSHA convened this panel under Section 609(b) of the
Regulatory Flexibility Act (RFA), as amended by the Small Business
Regulatory Enforcement Fairness Act of 1996 (SBREFA) (5 U.S.C. 601 et
seq.).
The Panel included representatives from OSHA, the Solicitor's
Office of the Department of Labor, the Office of Advocacy within the
Small Business Administration, and the Office of Information and
Regulatory Affairs of the Office of Management and Budget. Small Entity
Representatives (SERs) made oral and written comments on the draft rule
and submitted them to the panel.
The SBREFA Panel issued a report on January 15, 2008 which included
the SERs' comments. SERs expressed concerns about the impact of the
ancillary requirements such as exposure monitoring and medical
surveillance. Their comments addressed potential costs associated with
compliance with the draft standard, and possible impacts of the
standard on market conditions, among other issues. In addition, many
SERs sought clarification of some of the ancillary requirements such as
the meaning of "routine" contact or "contaminated surfaces."
OSHA then developed a draft preliminary beryllium health effects
evaluation (Document ID 1271) and a draft preliminary beryllium risk
assessment (Document ID 1272), and in 2010, OSHA hired a contractor to
oversee an independent scientific peer review of these documents. The
contractor identified experts familiar with beryllium health effects
research and ensured that these experts had no conflict of interest or
apparent bias in performing the review. The contractor selected five
experts with expertise in such areas as pulmonary and occupational
medicine, CBD, beryllium sensitization, the Beryllium Lymphocyte
Proliferation Test (BeLPT), beryllium toxicity and carcinogenicity, and
medical surveillance. Other areas of expertise included animal
modeling, occupational epidemiology, biostatistics, risk and exposure
assessment, exposure-response modeling, beryllium exposure assessment,
industrial hygiene, and occupational/environmental health engineering.
Regarding the preliminary health effects evaluation, the peer
reviewers concluded that the health effect studies were described
accurately and in sufficient detail, and OSHA's conclusions based on
the studies were reasonable (Document ID 1210). The reviewers agreed
that the OSHA document covered the significant health endpoints related
to occupational beryllium exposure. Peer reviewers considered the
preliminary conclusions regarding beryllium sensitization and CBD to be
reasonable and well presented in the draft health evaluation section.
All reviewers agreed that the scientific evidence supports
sensitization as a necessary condition in the development of CBD. In
response to reviewers' comments, OSHA made revisions to more clearly
describe certain sections of the health effects evaluation. In
addition, OSHA expanded its discussion regarding the BeLPT.
Regarding the preliminary risk assessment, the peer reviewers were
highly supportive of the Agency's approach and major conclusions
(Document ID 1210). The peer reviewers stated that the key studies were
appropriate and their selection clearly explained in the document. They
regarded the preliminary analysis of these studies to be reasonable and
scientifically sound. The reviewers supported OSHA's conclusion that
substantial risk of sensitization and CBD were observed in facilities
where the highest exposure generating processes had median full-shift
exposures around 0.2 µg/m3\ or higher, and that the greatest
reduction in risk was achieved when exposures for all processes were
lowered to 0.1 µg/m3\ or below.
In February 2012, the Agency received for consideration a draft
recommended standard for beryllium (Materion and USW, 2012, Document ID
0754). This draft standard was the product of a joint effort between
two stakeholders: Materion Corporation, a leading producer of beryllium
and beryllium products in the United States, and the United
Steelworkers, an international labor union representing workers who
manufacture beryllium alloys and beryllium-containing products in a
number of industries. They sought to craft an OSHA-like model beryllium
standard that would have support from both labor and industry. OSHA has
considered this proposal along with other information submitted during
the development of the Notice of Proposed Rulemaking (NPRM) for
beryllium. As described in greater detail in the Introduction to the
Summary and Explanation of the final rule, there was substantial
agreement between the submitted joint standard and the OSHA proposed
standard.
On August 7, 2015, OSHA published its NPRM in the Federal Register
(80 FR 47565 (8/7/15)). In the NPRM, the Agency made a preliminary
determination that employees exposed to beryllium and beryllium
compounds at the preceding PEL face a significant risk to their health
and that promulgating the proposed standard would substantially reduce
that risk. The NPRM (Section XVIII) also responded to the SBREFA Panel
recommendations, which OSHA carefully considered, and clarified the
requirements about which SERs expressed confusion. OSHA also discussed
the regulatory alternatives recommended by the SBREFA Panel in NPRM,
Section XVIII, and in the PEA (Document ID 0426).
The NPRM invited interested stakeholders to submit comments on a
variety of issues and indicated that OSHA would schedule a public
hearing upon request. Commenters submitted information and suggestions
on a variety of topics. In addition, in response to a request from the
Non-Ferrous Founders' Society, OSHA scheduled an informal public
hearing on the proposed rule. The Agency invited interested persons to
participate by providing oral testimony and documentary evidence at the
hearing. OSHA also welcomed presentation of data and documentary
evidence that would provide the Agency with the best available evidence
to use in determining whether to develop a final rule.
The public hearing was held in Washington, DC on March 21 and 22,
2016. Administrative Law Judge William Colwell presided over the
hearing. The Agency heard testimony from several organizations, such as
public health groups, the Non-Ferrous Founders' Society, other industry
representatives, and labor unions. Following the hearing, participants
who had filed notices of intent to appear were allowed 30 days--until
April 21, 2016--to submit additional evidence and data, and an
additional 15 days--until May 6, 2016--to submit final briefs,
arguments, and summations (Document ID 1756, Tr. 326).
In 2016, in an action parallel to OSHA's rulemaking, DOE proposed
to update its action level to 0.05 μg/m3\ (81 FR 36704-36759, June
7, 2016). The DOE action level triggers workplace precautions and
control measures such as periodic monitoring, exposure
reduction or minimization, regulated areas, hygiene facilities and
practices, respiratory protection, protective clothing and equipment,
and warning signs (Document ID 1323; 10 CFR 850.23(b)). Unlike OSHA's
PEL, however, DOE's selection of an action level is not required to
meet statutory requirements of technological and economic feasibility.
In all, the OSHA rulemaking record contains over 1,900 documents,
including all the studies OSHA relied on in its preliminary health
effects and risk assessment analyses, the hearing transcript and
submitted testimonies, the joint Materion-USW draft proposed standard,
and the pre- and post-hearing comments and briefs. The final rule on
occupational exposure to beryllium and beryllium compounds is thus
based on consideration of the entire record of this rulemaking
proceeding, including materials discussed or relied upon in the
proposal, the record of the hearing, and all written comments and
exhibits timely received. Based on this comprehensive record, OSHA
concludes that employees exposed to beryllium and beryllium compounds
are at significant risk of material impairment of health, including
chronic beryllium disease and lung cancer. The Agency concludes that
the PEL of 0.2 μg/m3\ reduces the significant risks of material
impairments of health posed to workers by occupational exposure to
beryllium and beryllium compounds to the maximum extent that is
technologically and economically feasible. OSHA's substantive
determinations with regard to the comments, testimony, and other
information in the record, the legal standards governing the decision-
making process, and the Agency's analysis of the data resulting in its
assessments of risks, benefits, technological and economic feasibility,
and compliance costs are discussed elsewhere in this preamble. More
technical or complex issues are discussed in greater detail in the
background documents referenced in this preamble.
IV. Chemical Properties and Industrial Uses
Chemical and Physical Properties
Beryllium (Be; CAS Number 7440-41-7) is a silver-grey to greyish-
white, strong, lightweight, and brittle metal. It is a Group IIA
element with an atomic weight of 9.01, atomic number of 4, melting
point of 1,287 [deg]C, boiling point of 2,970 [deg]C, and a density of
1.85 at 20 [deg]C (Document ID 0389, p. 1). It occurs naturally in
rocks, soil, coal, and volcanic dust (Document ID 1567, p. 1).
Beryllium is insoluble in water and soluble in acids and alkalis. It
has two common oxidation states, Be(0) and Be(+2). There are several
beryllium compounds with unique CAS numbers and chemical and physical
properties. Table IV-1 describes the most common beryllium compounds.
Table IV-1--Properties of Beryllium and Beryllium Compounds
--------------------------------------------------------------------------------------------------------------------------------------------------------
Synonyms and Molecular Melting point
Chemical name CAS No. trade names weight ([deg]C) Description Density (g/cm3) Solubility
--------------------------------------------------------------------------------------------------------------------------------------------------------
Beryllium metal............... 7440-41-7 Beryllium; 9.0122 1287............. Grey, close- 1.85 (20 [deg]C). Soluble in most
beryllium-9, packed, dilute acids
beryllium hexagonal, and alkali;
element; brittle metal. decomposes in
beryllium hot water;
metallic. insoluble in
mercury and
cold water.
Beryllium chloride............ 7787-47-5 Beryllium 79.92 399.2............ Colorless to 1.899 (25 [deg]C) Soluble in
dichloride. slightly yellow; water, ethanol,
orthorhombic, diethyl ether
deliques-cent and pyridine;
crystal. slightly
soluble in
benzene, carbon
disulfide and
chloroform;
insoluble in
acetone,
ammonia, and
toluene.
Beryllium fluoride............ 7787-49-7 Beryllium 47.01 555.............. Colorless or 1.986............ Soluble in
(12323-05-6) difluoride. white, water, sulfuric
amorphous, acid, mixture
hygroscopic of ethanol and
solid. diethyl ether;
slightly
soluble in
ethanol;
insoluble in
hydrofluoric
acid.
Beryllium hydroxide........... 13327-32-7 Beryllium 43.3 138 (decomposes White, amorphous, 1.92............. Soluble in hot
(1304-49-0) dihydroxide. to beryllium amphoteric concentrated
oxide). powder. acids and
alkali;
slightly
soluble in
dilute alkali;
insoluble in
water.
Beryllium sulfate............. 13510-49-1 Sulfuric acid, 105.07 550-600 [deg]C Colorless crystal 2.443............ Forms soluble
beryllium salt (decomposes to tetrahydrate in
(1:1). beryllium oxide). hot water;
insoluble in
cold water.
Beryllium sulfate tetrhydrate. 7787-56-6 Sulfuric acid; 177.14 100 [deg]C....... Colorless, 1.713............ Soluble in
beryllium salt tetragonal water; slightly
(1:1), crystal. soluble in
tetrahydrate. concentrated
sulfuric acid;
insoluble in
ethanol.
Beryllium Oxide............... 1304-56-9 Beryllia; 25.01 2508-2547 [deg]C. Colorless to 3.01 (20 [deg]C). Soluble in
beryllium white, hexagonal concentrated
monoxide crystal or acids and
thermalox TM. amorphous, alkali;
amphoteric insoluble in
powder. water.
Beryllium carbonate........... 1319-43-3 Carbonic acid, 112.05 No data.......... White powder..... No data.......... Soluble in acids
beryllium salt, and alkali;
mixture with insoluble in
beryllium cold water;
hydroxide. decomposes in
hot water.
Beryllium nitrate trihydrate.. 7787-55-5 Nitric acid, 187.97 60............... White to faintly 1.56............. Very soluble in
beryllium salt, yellowish, water and
trihydrate. deliquescent ethanol.
mass.
Beryllium phosphate........... 13598-15-7 Phosphoric acid, 104.99 No data.......... Not reported..... Not reported..... Slightly soluble
beryllium salt in water.
(1:1).
--------------------------------------------------------------------------------------------------------------------------------------------------------
ATSDR, 2002.
The physical and chemical properties of beryllium were realized
early in the 20th century, and it has since gained commercial
importance in a wide range of industries. Beryllium is lightweight,
hard, spark resistant, non-magnetic, and has a high melting point. It
lends strength, electrical and thermal conductivity, and fatigue
resistance to alloys (Document ID 0389, p. 1). Beryllium also has a
high affinity for oxygen in air and water, which can cause a thin
surface film of beryllium oxide to form on the bare metal, making it
extremely resistant to corrosion. These properties make beryllium
alloys highly suitable for defense, nuclear, and aerospace applications
(Document ID 1342, pp. 45, 48).
There are approximately 45 mineralized forms of beryllium. In the
United States, the predominant mineral form mined commercially and
refined into pure beryllium and beryllium alloys is bertrandite.
Bertrandite, while containing less than 1% beryllium compared to 4% in
beryl, is easily and efficiently processed into beryllium hydroxide
(Document ID 1342, p. 48). Imported beryl is also converted into
beryllium hydroxide as the United States has very little beryl that can
be economically mined (Document ID 0616, p. 28).
Industrial Uses
Materion Corporation (Materion), formerly called Brush Wellman, is
the only producer of primary beryllium in the United States. Beryllium
is used in a variety of industries, including aerospace, defense,
telecommunications, automotive, electronic, and medical specialty
industries. Pure beryllium metal is used in a range of products such as
X-ray transmission windows, nuclear reactor neutron reflectors, nuclear
weapons, precision instruments, rocket propellants, mirrors, and
computers (Document ID 0389, p. 1). Beryllium oxide is used in
components such as ceramics, electrical insulators, microwave oven
components, military vehicle armor, laser structural components, and
automotive ignition systems (Document ID 1567, p. 147). Beryllium oxide
ceramics are used to produce sensitive electronic items such as lasers
and satellite heat sinks.
Beryllium alloys, typically beryllium/copper or beryllium/aluminum,
are manufactured as high beryllium content or low beryllium content
alloys. High content alloys contain greater than 30% beryllium. Low
content alloys are typically less than 3% beryllium. Beryllium alloys
are used in automotive electronics (e.g., electrical connectors and
relays and audio components), computer components, home appliance
parts, dental appliances (e.g., crowns), bicycle frames, golf clubs,
and other articles (Document ID 0389, p. 2; 1278, p. 182; 1280, pp. 1-
2; 1281, pp. 816, 818). Electrical components and conductors are
stamped and formed from beryllium alloys. Beryllium-copper alloys are
used to make switches in automobiles (Document ID 1280, p. 2; 1281, p.
818) and connectors, relays, and switches in computers, radar,
satellite, and telecommunications equipment (Document ID 1278, p. 183).
Beryllium-aluminum alloys are used in the construction of aircraft,
high resolution medical and industrial X-ray equipment, and mirrors to
measure weather patterns (Document ID 1278, p. 183). High content and
low content beryllium alloys are precision machined for military and
aerospace applications. Some welding consumables are also manufactured
using beryllium.
Beryllium is also found as a trace metal in materials such as
aluminum ore, abrasive blasting grit, and coal fly ash. Abrasive
blasting grits such as coal slag and copper slag contain varying
concentrations of beryllium, usually less than 0.1% by weight. The
burning of bituminous and sub-bituminous coal for power generation
causes the naturally occurring beryllium in coal to accumulate in the
coal fly ash byproduct. Scrap and waste metal for smelting and refining
may also contain beryllium. A detailed discussion of the industries and
job tasks using beryllium is included in the Preliminary Economic
Analysis (Document ID 0385, 0426).
Occupational exposure to beryllium can occur from inhalation of
dusts, fume, and mist. Beryllium dusts are created during operations
where beryllium is cut, machined, crushed, ground, or otherwise
mechanically sheared. Mists can also form during operations that use
machining fluids. Beryllium fume can form while welding with or on
beryllium components, and from hot processes such as those found in
metal foundries.
Occupational exposure to beryllium can also occur from skin, eye,
and mucous membrane contact with beryllium particulate or solutions.
V. Health Effects
Overview of Findings and Supportive Comments
As discussed in detail throughout this section (section V, Final
Health Effects) and in Section VI, Final Quantitative Risk Assessment
and Significance of Risk, OSHA finds, based upon the best available
evidence in the record, that exposure to soluble and poorly soluble
forms of beryllium are associated with several adverse health outcomes
including sensitization, chronic beryllium disease, acute beryllium
disease and lung cancer.
The findings and conclusions in this section are consistent with
those of the National Academies of Sciences (NAS), the World Health
Organization's International Agency for Research on Cancer (IARC), the
U.S. Department of Health and Human Services' (HHS) National Toxicology
Program (NTP), the National Institute for Occupational Safety and
Health (NIOSH), the Agency for Toxic Substance and Disease Registry
(ATSDR), the European Commission on Health, Safety and Hygiene at Work,
and many other organizations and individuals, as evidenced in the
rulemaking record and further discussed below. Other scientific
organizations and governments have recognized the strong body of
scientific evidence pointing to the health risks of exposure to
beryllium and have deemed it necessary to take action to reduce those
risks. In 1999, the Department of Energy (DOE) updated its airborne
beryllium concentration action level to 0.2 μg/m3\ (Document ID
1323). In 2009, the American Conference of Governmental Industrial
Hygienists (ACGIH), a professional society that has been recommending
workplace exposure limits for six decades, revised its Threshold Limit
Value (TLV) for beryllium and beryllium-containing compounds to 0.05
μg/m3\ (Document ID 1304).
In finalizing this Health Effects preamble section for the final
rule, OSHA updated the preliminary Health Effects section published in
the NPRM based on the stakeholder response received by the Agency
during the public comment period and public hearing. OSHA also
corrected several non-substantive errors that were published in the
NPRM as well as those identified by NIOSH and Materion including
several minor organizational changes made to sections V.D.3 and V.E.2.b
(Document ID 1671, pp. 10-11; 1662, pp. 3-5). A section titled "Dermal
Effects" was added to V.F.5 based on comments received by the American
Thoracic Society (ATS), National Jewish Health, and the National
Supplemental Screening Program (Document ID 1688, p. 2; 1664, p. 5;
1677, p. 3). Additionally, the Agency responded to relevant stakeholder
comments contained in specific sections.
In developing its review of the preliminary health effects from
beryllium exposure and assessment of risk for the NPRM, OSHA prepared a
pair of draft documents, entitled "Occupation Exposure to Beryllium:
Preliminary Health Effects Evaluation" (OSHA, 2010, Document ID 1271)
and "Preliminary Beryllium Risk Assessment" (OSHA, 2010, Document ID
1272), that underwent independent scientific peer review in accordance
with the Office of Management and Budget's (OMB) Information Quality
Bulletin for Peer Review. Eastern Research Group, Inc. (ERG), under
contract with OSHA, selected five highly qualified experts with
collective expertise in occupational epidemiology, occupational
medicine, toxicology, immunology, industrial hygiene, and risk
assessment methodology.2 The peer reviewers responded to 27 questions
that covered the accuracy, completeness, and understandability of key
studies and adverse health endpoints as well as questions regarding the
adequacy, clarity and reasonableness of the risk analysis (ERG, 2010;
Document ID 1270).
---------------------------------------------------------------------------
2 The five selected peer reviewers were John Balmes, MD,
University of California-San Francisco; Patrick Breysse, Ph.D.,
Johns Hopkins University, Bloomberg School of Public Health; Terry
Gordon, Ph.D., New York University School of Medicine; Milton
Rossman, MD, University of Pennsylvania School of Medicine; Kyle
Steenland, Ph.D., Emory University, Rollins School of Public Health.
---------------------------------------------------------------------------
Overall, the peer reviewers found that the OSHA draft health
effects evaluation described the studies in sufficient detail,
appropriately addressed their strengths and limitations, and drew
scientifically sound conclusions. The peer reviewers were also
supportive of the Agency's preliminary risk assessment approach and the
major conclusions. OSHA provided detailed responses to reviewer
comments in its publication of the NPRM (80 FR 47646-47652, 8/7/2015).
Revisions to the draft health effects evaluation and preliminary risk
assessment in response to the peer review comments were reflected in
sections V and VI of the same publication (80 FR 47581-47646, 8/7/
2015). OSHA received public comment and testimony on the Health Effects
and Preliminary Risk Assessment sections published in the NPRM, which
are discussed in this preamble.
The Agency received a wide variety of stakeholder comments and
testimony for this rulemaking on issues related to the health effects
and risk of beryllium exposure. Statements supportive of OSHA's Health
Effects section include comments from NIOSH, the National Safety
Council, the American Thoracic Society (ATS), Representative Robert C.
"Bobby" Scott, Ranking Member of Committee on Education and the
Workforce, the U.S. House of Representatives, national labor
organizations (American Federation of Labor--Congress of Industrial
Organizations (AFL-CIO), North American Building Trades Unions (NABTU),
United Steelworkers (USW), Public Citizen, ORCHSE, experts from
National Jewish Health (Lisa Maier, MD and Margaret Mroz, MSPH), the
American Association for Justice, and the National Council for
Occupational Safety and Health.
For example, NIOSH commented in its prepared written hearing
testimony:
OSHA has appropriately identified and documented all critical
health effects associated with occupational exposure to beryllium
and has appropriately focused its greatest attention on beryllium
sensitization (BeS), chronic beryllium disease (CBD) and lung cancer
. . .
NIOSH went on to say that sensitization was more than a test result
with little meaning. It relates to a condition in which the immune
system is able to recognize and adversely react to beryllium in a way
that increases the risk of developing CBD. NIOSH agrees with OSHA that
sensitization is a functional change that is necessary in order to
proceed along the pathogenesis to serious lung disease.
The National Safety Council, a congressionally chartered nonprofit
safety organization, also stated that "beryllium represents a serious
health threat resulting from acute or chronic exposures." (Document ID
1612, p. 5). Representative Robert C. "Bobby" Scott, Ranking Member
of Committee on Education and the Workforce, the U.S. House of
Representatives, submitted a statement recognizing that the evidence
strongly supports the conclusion that sensitization can occur from
exposure to soluble and poorly soluble forms of beryllium (Document ID
1672, p. 3).
OSHA also received supporting statements from ATS and ORCHSE on the
inclusion of beryllium sensitization, CBD, skin disease, and lung
cancer as major adverse health effects associated with beryllium
exposure (Document ID 1688, p. 7; 1691, p. 14). ATS specifically
stated:
. . . the ATS supports the inclusion of beryllium sensitization,
CBD, and skin disease as the major adverse health effects associated
with exposure to beryllium at or below 0.1 μg/m3\ and acute
beryllium disease at higher exposures based on the currently
available epidemiologic and experimental studies. (Document ID 1688,
p. 2)
In addition, OSHA received supporting comments from labor organizations
representing workers exposed to beryllium. The AFL-CIO, NABTU, and USW
submitted comments supporting the inclusion of beryllium sensitization,
CBD and lung cancer as health effects from beryllium exposure (Document
ID 1689, pp. 1, 3; 1679, p. 6; 1681, p. 19). AFL-CIO commented that
"[t]he proposal is based on extensive scientific and medical evidence
. . ." and "[b]eryllium exposure causes immunological sensitivity,
CBD and lung cancer. These health effects are debilitating, progressive
and irreversible. Workers are exposed to beryllium through respiratory,
dermal and gastrointestinal routes." (Document ID 1689, pp. 1, 3).
Comments submitted by USW state that "OSHA has correctly identified,
and comprehensively documented the material impairments of health
resulting from beryllium exposure." (Document ID 1681, p. 19).
Dr. Lisa Maier and Ms. Margaret Mroz of National Jewish Health
testified about the health effects of beryllium in support of the
beryllium standard:
We know that chronic beryllium disease often will not manifest
clinically until irreversible lung scarring has occurred, often
years after exposure, with a latency of 20 to 30 years as discussed
yesterday. Much too late to make changes in the work place. We need
to look for early markers of health effects, cast the net widely to
identify cases of sensitization and disease, and use screening
results in concert with exposure sampling to identify areas of
increased risk that can be modified in the work place. (Document ID
1756, Tr. 102; 1806).
American Association for Justice noted that:
Unlike many toxins, there is no threshold below which no worker
will become sensitized to beryllium. Worker sensitization to
beryllium is a precursor to CBD, but not cancer. The symptoms of
chronic beryllium disease (CBD) are part of a continuum of disease
that is progressive in nature. Early recognition of and treatment
for CBD may lead to a lessening of symptoms and may prevent the
disease from progressing further. Symptoms of CBD may occur at
exposure levels well below the proposed permissible exposure limit
of .2 µg/m3\ and even below the action level of .1 µg/
m3\. OSHA has clear authority to regulate health effects across the
entire continuum of disease to protect workers. We applaud OSHA for
proposing to do so. (Document ID 1683, pp. 1-2).
National Committee for Occupational Safety and Health support OSHA
findings of health effects due to beryllium exposure (1690, p. 1).
Comments from Public Citizen also support OSHA findings: "Beryllium is
toxic at extremely low levels and exposure can result in BeS, an immune
response that eventually can lead to an autoimmune granulomatous lung
disease known as CBD. BeS is a necessary prerequisite to the
development of CBD, with OSHA's
NPRM citing studies showing that 31-49 percent of all sensitized
workers were diagnosed with CBD after clinical evaluations. Beryllium
also is a recognized carcinogen that can cause lung cancer." (Document
ID 1670, p.2).
In addition to the comments above and those noted throughout this
Health Effects section, Materion submitted their correspondence to the
National Academies (NAS) regarding the company's assessment of the NAS
beryllium studies and their correspondence to NIOSH regarding the
Cummings 2009 study (Document 1662, Attachments) to OSHA. For the NAS
study, Materion included a series of comments regarding studies
included in the NAS report. OSHA has reviewed these comments and found
that the comments submitted to the NAS critiquing their review of the
health effects of beryllium were considered and incorporated where
appropriate. For the NIOSH study Materion included comments regarding 2
cases of acute beryllium disease evaluated in a study published by
Cummings et al., 2009. NIOSH also dealt with the comments from Materion
as they found appropriate. However, none of the changes recommended by
Materion to the NAS or NIOSH altered the overall findings or
conclusions from either study. OSHA has taken the Materion comments
into account in the review of these documents. OSHA found them not to
be sufficient to discount either the findings of the NAS or NIOSH.
Introduction
Beryllium-associated health effects, including acute beryllium
disease (ABD), beryllium sensitization (also referred to in this
preamble as "sensitization"), chronic beryllium disease (CBD), and
lung cancer, can lead to a number of highly debilitating and life-
altering conditions including pneumonitis, loss of lung capacity
(reduction in pulmonary function leading to pulmonary dysfunction),
loss of physical capacity associated with reduced lung capacity,
systemic effects related to pulmonary dysfunction, and decreased life
expectancy (NIOSH, 1972, Document ID 1324, 1325, 1326, 1327, 1328;
NIOSH, 2011 (0544)).
This Health Effects section presents information on beryllium and
its compounds, the fate of beryllium in the body, research that relates
to its toxic mechanisms of action, and the scientific literature on the
adverse health effects associated with beryllium exposure, including
ABD, sensitization, CBD, and lung cancer. OSHA considers CBD to be a
progressive illness with a continuous spectrum of symptoms ranging from
no symptomatology at its earliest stage following sensitization to mild
symptoms such as a slight almost imperceptible shortness of breath, to
loss of pulmonary function, debilitating lung disease, and, in many
cases, death. This section also discusses the nature of these
illnesses, the scientific evidence that they are causally associated
with occupational exposure to beryllium, and the probable mechanisms of
action with a more thorough review of the supporting studies.
A. Beryllium and Beryllium Compounds--Particle Characterization
1. Particle Physical/Chemical Properties
Beryllium has two oxidative states: Be(0) and Be(2\+\) (Agency for
Toxic Substance and Disease Registry (ATSDR) 2002, Document ID 1371).
It is likely that the Be(2\+\) state is the most biologically reactive
and able to form a bond with peptides leading to it becoming antigenic
(Snyder et al., 2003) as discussed in more detail in the Beryllium
Sensitization section below. Beryllium has a high charge-to-radius
ratio, forming various types of ionic bonds. In addition, beryllium has
a strong tendency for covalent bond formation (e.g., it can form
organometallic compounds such as Be(CH3)2 and
many other complexes) (ATSDR, 2002, Document ID 1371; Greene et al.,
1998 (1519)). However, it appears that few, if any, toxicity studies
exist for the organometallic compounds. Additional physical/chemical
properties, such as solubility, for beryllium compounds that may be
important in their biological response are summarized in Table 1 below.
Solubility (as discussed in biological fluids in Section V.A.2.A below)
is an important factor in evaluating the biological response to
beryllium. For comparative purposes, water solubility is used in Table
1. The International Chemical Safety Cards lists water solubility as a
way to standardize solubility values among particles and fibers. The
information contained within Table 1 was obtained from the
International Chemical Safety Cards (ICSC) for beryllium metal (ICSC
0226, Document ID 0438), beryllium oxide (ICSC 1325, Document ID 0444),
beryllium sulfate (ICSC 1351, Document ID 0443), beryllium nitrate
(ICSC 1352, Document ID 0442), beryllium carbonate (ICSC 1353, Document
ID 0441), beryllium chloride (ICSC 1354, Document ID 0440), beryllium
fluoride (ICSC 1355, Document ID 0439) and from the hazardous substance
data bank (HSDB) for beryllium hydroxide (CASRN: 13327-32-7), and
beryllium phosphate (CASRN: 13598-15-7, Document ID 0533). Additional
information on chemical and physical properties as well as industrial
uses for beryllium can be found in this preamble at Section IV,
Chemical Properties and Industrial Uses.
Table 1--Beryllium Characteristics and Properties
----------------------------------------------------------------------------------------------------------------
Solubility in
Compound name Chemical formula Molecular Acute physical water at 20
mass hazards [deg]C
----------------------------------------------------------------------------------------------------------------
Beryllium Metal.............. Be............................ 9.0 Combustible; Finely None.
dispersed
particles--Explosi
ve.
Beryllium Oxide.............. BeO........................... 25.0 Not combustible or Very sparingly
explosive. soluble.
Beryllium Carbonate.......... Be2CO3(OH)/Be2CO5 H2.......... 181.07 Not combustible or None.
explosive.
Beryllium Sulfate............ BeSO4......................... 105.1 Not combustible or Slightly
explosive. soluble.
Beryllium Nitrate............ BeN2O6/Be(NO3)2............... 133.0 Enhances combustion Very soluble
of other (1.66 x 106
substances. mg/L).
Beryllium Hydroxide.......... Be(OH)2....................... 43.0 Not reported....... Slightly
soluble 0.8 x
10\-4\ mol/L
(3.44 mg/L).
Beryllium Chloride........... BeCl2......................... 79.9 Not combustible or Soluble.
explosive.
Beryllium Fluoride........... BeF2.......................... 47.0 Not combustible or Very soluble.
explosive.
Beryllium Phosphate.......... Be3(PO4)2..................... 271.0 Not reported....... Soluble.
----------------------------------------------------------------------------------------------------------------
Beryllium shows a high affinity for oxygen in air and water,
resulting in a thin surface film of beryllium oxide on the bare metal.
If the surface film is disturbed, it may become airborne and cause
respiratory tract exposure or dermal exposure (also referred to as
dermal contact). The physical properties of solubility, particle
surface area, and particle size of some beryllium compounds are
examined in more detail below. These properties have been evaluated in
many toxicological studies. In particular, the properties related to
the calcination (firing temperatures) and differences in crystal size
and solubility are important aspects in their toxicological profile.
2. Factors Affecting Potency and Effect of Beryllium Exposure
The effect and potency of beryllium and its compounds, as for any
toxicant, immunogen, or immunotoxicant, may be dependent upon the
physical state in which they are presented to a host. For occupational
airborne materials and surface contaminants, it is especially critical
to understand those physical parameters in order to determine the
extent of exposure to the respiratory tract and skin since these are
generally the initial target organs for either route of exposure.
For example, solubility has an important part in determining the
toxicity and bioavailability of airborne materials as well. Respiratory
tract retention and skin penetration are directly influenced by the
solubility and reactivity of airborne material. Large particles may
have less of an effect in the lung than smaller particles due to
reduced potential to stay airborne, to be inhaled, or be deposited
along the respiratory tract. In addition, once inhalation occurs
particle size is critical in determining where the particle will
deposit along the respiratory tract.
These factors may be responsible, at least in part, for the process
by which beryllium sensitization progresses to CBD in exposed workers.
Other factors influencing beryllium-induced toxicity include the
surface area of beryllium particles and their persistence in the lung.
With respect to dermal contact or exposure, the physical
characteristics of the particle are also important since they can
influence skin absorption and bioavailability. This section addresses
certain physical characteristics (i.e., solubility, particle size,
particle surface area) that influence the toxicity of beryllium
materials in occupational settings.
a. Solubility
Solubility has been shown to be an important determinant of the
toxicity of airborne materials, influencing the deposition and
persistence of inhaled particles in the respiratory tract, their
bioavailability, and the likelihood of presentation to the immune
system. A number of chemical agents, including metals that contact and
penetrate the skin, are able to induce an immune response, such as
sensitization (Boeniger, 2003, Document ID 1560; Mandervelt et al.,
1997 (1451)). Similar to inhaled agents, the ability of materials to
penetrate the skin is also influenced by solubility because dermal
absorption may occur at a greater rate for soluble materials than
poorly soluble materials (Kimber et al., 2011, Document ID 0534). In
post-hearing comments, NIOSH explained:
In biological systems, solubility is used to describe the rate
at which a material will undergo chemical clearance and dissolve in
a fluid (airway lining, inside phagolysomes) relative to the rate of
mechanical clearance. For example, in the lung a "poorly soluble"
material is one that dissolves at a rate slower than the rate of
mechanical removal via the mucociliary escalator. Examples of poorly
soluble forms of beryllium are beryllium silicates, beryllium oxide,
and beryllium metal and alloys (Deubner et al. 2011; Huang et al.
2011; Duling et al. 2012; Stefaniak et al. 2006, 201la, 2012). A
highly soluble material is one that dissolves at a rate faster than
mechanical clearance. Examples of highly soluble forms of beryllium
are beryllium fluoride, beryllium sulfate, and beryllium chloride.
(Document ID 1660-A2, p. 9).
This section reviews the relevant information regarding solubility, its
importance in a biological matrix and its relevance to sensitization
and beryllium lung disease. The weight of evidence presented below
suggests that both soluble and poorly soluble forms of beryllium can
induce a sensitization response and result in progression of lung
disease.
Beryllium salts, including the chloride (BeCl2),
fluoride (BeF2), nitrate (Be(NO3)2),
phosphate (Be3 (PO4)2), and sulfate
(tetrahydrate) (BeSO4 [middot] 4H2O) salts, are
all water soluble. However, soluble beryllium salts can be converted to
less soluble forms in the lung (Reeves and Vorwald, 1967, Document ID
1309). According to an EPA report, aqueous solutions of the soluble
beryllium salts are acidic as a result of the formation of
Be(OH2)4 2\+\, the tetrahydrate, which will react
to form poorly soluble hydroxides or hydrated complexes within the
general physiological range of pH values (between 5 and 8) (EPA, 1998,
Document ID 1322). This may be an important factor in the development
of CBD since lower-soluble forms of beryllium have been shown to
persist in the lung for longer periods of time and persistence in the
lung may be needed in order for this disease to occur (NAS, 2008,
Document ID 1355).
Beryllium oxide (BeO), hydroxide (Be(OH)2), carbonate
(Be2 CO3 (OH)2), and sulfate
(anhydrous) (BeSO4) are either insoluble, slightly soluble,
or considered to be sparingly or poorly soluble (almost insoluble or
having an extremely slow rate of dissolution and most often referred to
as poorly soluble in more recent literature). The solubility of
beryllium oxide, which is prepared from beryllium hydroxide by
calcining (heating to a high temperature without fusing in order to
drive off volatile chemicals) at temperatures between 500 and 1,750
[deg]C, has an inverse relationship with calcination temperature.
Although the solubility of the low-fired crystals can be as much as 10
times that of the high-fired crystals, low-fired beryllium oxide is
still only sparingly soluble (Delic, 1992, Document 1547). In a study
that measured the dissolution kinetics (rate to dissolve) of beryllium
compounds calcined at different temperatures, Hoover et al., compared
beryllium metal to beryllium oxide particles and found them to have
similar solubilities. This was attributed to a fine layer of beryllium
oxide that coats the metal particles (Hoover et al., 1989, Document ID
1510). A study conducted by Deubner et al. (2011) determined ore
materials to be more soluble than beryllium oxide at pH 7.2 but similar
in solubility at pH 4.5. Beryllium hydroxide was more soluble than
beryllium oxide at both pHs (Deubner et al., 2011, Document ID 0527).
Investigators have also attempted to determine how biological
fluids can dissolve beryllium materials. In two studies, poorly soluble
beryllium, taken up by activated phagocytes, was shown to be ionized by
myeloperoxidases (Leonard and Lauwerys, 1987, Document ID 1293;
Lansdown, 1995 (1469)). The positive charge resulting from ionization
enabled the beryllium to bind to receptors on the surface of cells such
as lymphocytes or antigen-presenting cells which could make it more
biologically active (NAS, 2008, Document ID 1355). In a study utilizing
phagolysosomal-simulating fluid (PSF) with a pH of 4.5, both beryllium
metal and beryllium oxide dissolved at a greater rate than that
previously reported in water or SUF (simulant fluid) (Stefaniak et al.,
2006, Document ID 1398), and the rate of dissolution of the multi-
constituent (mixed) particles
was greater than that of the single-constituent beryllium oxide powder.
The authors speculated that copper in the particles rapidly dissolves,
exposing the small inclusions of beryllium oxide, which have higher
specific surface areas (SSA) and therefore dissolve at a higher rate. A
follow-up study by the same investigational team (Duling et al., 2012,
Document ID 0539) confirmed dissolution of beryllium oxide by PSF and
determined the release rate was biphasic (initial rapid diffusion
followed by a latter slower surface reaction-driven release). During
the latter phase, dissolution half-times were 1,400 to 2,000 days. The
authors speculated this indicated bertrandite was persistent in the
lung (Duling et al., 2012, Document ID 0539).
In a recent study investigating the dissolution and release of
beryllium ions for 17 beryllium-containing materials (ore, hydroxide,
metal, oxide, alloys, and processing intermediates) using artificial
human airway epithelial lining fluid, Stefaniak et al. (2011) found
release of beryllium ions within 7 days (beryl ore smelter dust). The
authors calculated dissolution half-times ranging from 30 days
(reduction furnace material) to 74,000 days (hydroxide). Stefaniak et
al. (2011) speculated that despite the rapid mechanical clearance,
billions of beryllium ions could be released in the respiratory tract
via dissolution in airway lining fluid (ALF). Under this scenario,
beryllium-containing particles depositing in the respiratory tract
dissolving in ALF could provide beryllium ions for absorption in the
lung and interact with immune cells in the respiratory tract (Stefaniak
et al., 2011, Document ID 0537).
Huang et al. (2011) investigated the effect of simulated lung fluid
(SLF) on dissolution and nanoparticle generation and beryllium-
containing materials. Bertrandite-containing ore, beryl-containing ore,
frit (a processing intermediate), beryllium hydroxide (a processing
intermediate) and silica (used as a control), were equilibrated in SLF
at two pH values (4.5 and 7.2) to reflect inter- and intra-cellular
environments in the lung tissue. Concentrations of beryllium, aluminum,
and silica ions increased linearly during the first 20 days in SLF, and
rose more slowly thereafter, reaching equilibrium over time. The study
also found nanoparticle formation (in the size range of 10-100 nm) for
all materials (Huang et al., 2011, Document ID 0531).
In an in vitro skin model, Sutton et al. (2003) demonstrated the
dissolution of beryllium compounds (poorly soluble beryllium hydroxide,
soluble beryllium phosphate) in a simulated sweat fluid (Document ID
1393). This model showed beryllium can be dissolved in biological
fluids and be available for cellular uptake in the skin. Duling et al.
(2012) confirmed dissolution and release of ions from bertrandite ore
in an artificial sweat model (pH 5.3 and pH 6.5) (Document ID 0539).
In summary, studies have shown that soluble forms of beryllium
readily dissolve into ionic components making them biologically
available for dermal penetration and activation of immune cells
(Stefaniak et al., 2011; Document ID 0537). Soluble forms can also be
converted to less soluble forms in the lung (Reeves and Vorwald, 1967,
Document ID 1309) making persistence in the lung a possibility and
increasing the potential for development of CBD (see section V.D.2).
Studies by Stefaniak et al. (2003, 2006, 2011, 2012) (Document ID 1347;
1398; 0537; 0469), Huang et al. (2011), Duling et al. (2012), and
Deubner et al. (2011) have demonstrated poorly soluble forms can be
readily dissolved in biological fluids such as sweat, lung fluid, and
cellular fluids. The dissolution of beryllium ions into biological
fluids increases the likelihood of beryllium presentation to immune
cells, thus increasing the potential for sensitization through dermal
contact or lung exposure (Document ID 0531; 0539; 0527) (see section
V.D.1).
OSHA received comments from the Non-Ferrous Founders' Society
(NFFS) contending that the scientific evidence does not support
insoluble beryllium as a causative agent for sensitization and CBD
(Document ID 1678, p. 6). The NFFS contends that insoluble beryllium is
not carcinogenic or a sensitizer to humans, and argues that based on
this information, OSHA should consider a bifurcated standard with
separate PELs for soluble and poorly soluble beryllium and beryllium
compounds and insoluble beryllium metallics (Document ID 1678, p. 7).
As evidence supporting its conclusion, the NFFS cited a 2010 statement
written by Dr. Christian Strupp commissioned by the beryllium industry
(Document ID 1785, 1814), which reviewed selected studies to evaluate
the toxic potential of beryllium metal and alloys (Document ID 1678,
pp. 7). The Strupp and Furnes statement (2010) cited by the NFFS is the
background material and basis of the Strupp (2011a and 2011b) studies
in the docket (Document ID 1794; 1795). In response to Strupp 2011 (a
and b), Aleks Stefaniak of NIOSH published a letter to the editor
refuting some of the evidence presented by Strupp (2011a and b,
Document ID 1794; 1795). The first study by Strupp (2011a) evaluated
selected animal studies and concluded that beryllium metal was not a
sensitizer. Stefaniak (2011) evaluated the validity of the Strupp
(2011a) study of beryllium toxicity and noted numerous deficiencies,
including deficiencies in the study design, improper administration of
beryllium test compounds, and lack of proper controls (Document ID
1793). In addition, Strupp (2011a) omitted numerous key animal and
epidemiological studies demonstrating the potential of poorly soluble
beryllium and beryllium metal as a sensitizing agent. One such study,
Tinkle et al. (2003), demonstrated that topical application of poorly
soluble beryllium induced skin sensitization in mice (Document ID
1483). Comments from NIOSH and National Jewish Medical Center state
that poorly soluble beryllium materials are capable of dissolving in
sweat (Document ID 1755; 1756). After evaluating the scientific
evidence from epidemiological and animal studies, OSHA finds, based on
the best available evidence, that soluble and poorly soluble forms of
beryllium and beryllium compounds are causative agents of sensitization
and CBD.
b. Particle Size
The toxicity of beryllium as exemplified by beryllium oxide is
dependent, in part, on the particle size, with smaller particles (less
than 10 μm in diameter) able to penetrate beyond the larynx
(Stefaniak et al., 2008, Document ID 1397). Most inhalation studies and
occupational exposures involve quite small (less than 1-2 μm in
diameter) beryllium oxide particles that can penetrate to the pulmonary
regions of the lung (Stefaniak et al., 2008, Document ID 1397). In
inhalation studies with beryllium ores, particle sizes are generally
much larger, with deposition occurring in several areas throughout the
respiratory tract for particles less than 10 μm in diameter.
The temperature at which beryllium oxide is calcined influences its
particle size, surface area, solubility, and ultimately its toxicity
(Delic, 1992, Document ID 1547). Low-fired (500 [deg]C) beryllium oxide
is predominantly made up of poorly crystallized small particles, while
higher firing temperatures (1000-1750 [deg]C) result in larger particle
sizes (Delic, 1992, Document ID 1547).
In order to determine the extent to which particle size plays a
role in the toxicity of beryllium in occupational settings, several key
studies are reviewed and detailed below. The findings on particle size
have been related, where possible, to work process
and biologically relevant toxicity endpoints of either sensitization or
CBD.
Numerous studies have been conducted evaluating the particle size
generated during basic industrial and machining operations. In a study
by Cohen et al. (1983), a multi-cyclone sampler was utilized to measure
the size mass distribution of the beryllium aerosol at a beryllium-
copper alloy casting operation (Document ID 0540). Briefly, Cohen et
al. (1983) found variable particle size generation based on the
operations being sampled with particle size ranging from 3 to 16 μm.
Hoover et al. (1990) also found variable particle sizes being generated
across different operations (Document ID 1314). In general, Hoover et
al. (1990) found that milling operations generated smaller particle
sizes than sawing operations. Hoover et al. (1990) also found that
beryllium metal generated higher concentrations than metal alloys.
Martyny et al. (2000) characterized generation of particle size during
precision beryllium machining processes (Document ID 1053). The study
found that more than 50 percent of the beryllium machining particles
collected in the breathing zone of machinists were less than 10 μm
in aerodynamic diameter with 30 percent of those smaller particles
being less than 0.6 μm. A study by Thorat et al. (2003) found
similar results with ore mixing, crushing, powder production and
machining ranging from 5.0 to 9.5 μm (Document ID 1389). Kent et al.
(2001) measured airborne beryllium using size-selective samplers in
five furnace areas at a beryllium processing facility (Document ID
1361). A statistically significant linear trend was reported between
the alveolar-deposited particle mass concentration and prevalence of
CBD and sensitization in the furnace production areas. The study
authors suggested that the concentration of alveolar-deposited
particles (e.g., <3.5 μm) may be a better predictor of sensitization
and CBD than the total mass concentration of airborne beryllium.
A recent study by Virji et al. (2011) evaluated particle size
distribution, chemistry, and solubility in areas with historically
elevated risk of sensitization and CBD at a beryllium metal powder,
beryllium oxide, and alloy production facility (Document ID 0465). The
investigators observed that historically, exposure-response
relationships have been inconsistent when using mass concentration to
identify process-related risk, possibly due to incomplete particle
characterization. Two separate exposure surveys were conducted in March
1999 and June-August 1999 using multi-stage personal impactor samplers
(to determine particle size distribution) and personal 37 mm closed
face cassette (CFC) samplers, both located in workers' breathing zones.
One hundred and ninety eight time-weighted-average (TWA) personal
impactor samples were analyzed for representative jobs and processes. A
total of 4,026 CFC samples were collected over the collection period
and analyzed for mass concentration, particle size, chemical content
and solubility and compared to process areas with high risk of
sensitization and CBD. The investigators found that total beryllium
concentration varied greatly between workers and among process areas.
Analysis of chemical form and solubility also revealed wide variability
among process areas, but high risk process areas had exposures to both
soluble and poorly soluble forms of beryllium. Analysis of particle
size revealed most process areas had particles ranging from 5 to 14
µm mass median aerodynamic diameter (MMAD). Rank order
correlating jobs to particle size showed high overall consistency
(Spearman r = 0.84) but moderate correlation (Pearson r = 0.43). The
investigators concluded that by considering more relevant aspects of
exposure such as particle size distribution, chemical form, and
solubility could potentially improve exposure assessments (Virji et
al., 2011, Document ID 0465).
To summarize, particle size influences deposition of beryllium
particles in the lung, thereby influencing toxicity. Studies by
Stefaniak et al. (2008) demonstrated that the majority of particles
generated by beryllium processing operations were in the respirable
range (less than 1-2 μm) (Document ID 1397). However, studies by
Virji et al. (2011) (Document ID 0465), Cohen et al. (1983) (Document
ID 0540) and Hoover et al. (1990) (Document ID 1314) showed that some
operations could generate particle sizes ranging from 3 to 16 μm.
c. Particle Surface Area
Particle surface area has been postulated as an important metric
for beryllium exposure. Several studies have demonstrated a
relationship between the inflammatory and tumorigenic potential of
ultrafine particles and their increased surface area (Driscoll, 1996,
Document ID 1539; Miller, 1995 (0523); Oberdorster et al., 1996
(1434)). While the exact mechanism explaining how particle surface area
influences its biological activity is not known, a greater particle
surface area has been shown to increase inflammation, cytokine
production, pro- and anti-oxidant defenses and apoptosis, which has
been shown to increase the tumorigenic potential of poorly-soluble
particles (Elder et al., 2005, Document ID 1537; Carter et al., 2006
(1556); Refsnes et al., 2006 (1428)).
Finch et al. (1988) found that beryllium oxide calcined at
500[deg]C had 3.3 times greater specific surface area (SSA) than
beryllium oxide calcined at 1000 [deg]C, although there was no
difference in size or structure of the particles as a function of
calcining temperature (Document ID 1317). The beryllium-metal aerosol
(airborne beryllium particles), although similar to the beryllium oxide
aerosols in aerodynamic size, had an SSA about 30 percent that of the
beryllium oxide calcined at 1000 [deg]C. As discussed above, a later
study by Delic (1992) found calcining temperatures had an effect on SSA
as well as particle size (Document ID 1547).
Several studies have investigated the lung toxicity of beryllium
oxide calcined at different temperatures and generally have found that
those calcined at lower temperatures have greater toxicity and effect
than materials calcined at higher temperatures. This may be because
beryllium oxide fired at the lower temperature has a loosely formed
crystalline structure with greater specific surface area than the fused
crystal structure of beryllium oxide fired at the higher temperature.
For example, beryllium oxide calcined at 500 [deg]C has been found to
have stronger pathogenic effects than material calcined at 1,000
[deg]C, as shown in several of the beagle dog, rat, mouse and guinea
pig studies discussed in the section on CBD pathogenesis that follows
(Finch et al., 1988, Document ID 1495; Pol[aacute]k et al., 1968
(1431); Haley et al., 1989 (1366); Haley et al., 1992 (1365); Hall et
al., 1950 (1494)). Finch et al. have also observed higher toxicity of
beryllium oxide calcined at 500 [deg]C, an observation they attribute
to the greater surface area of beryllium particles calcined at the
lower temperature (Finch et al., 1988, Document ID 1495). These authors
found that the in vitro cytotoxicity to Chinese hamster ovary (CHO)
cells and cultured lung epithelial cells of 500 [deg]C beryllium oxide
was greater than that of 1,000 [deg]C beryllium oxide, which in turn
was greater than that of beryllium metal. However, when toxicity was
expressed in terms of particle surface area, the cytotoxicity of all
three forms was similar. Similar results were observed in a study
comparing the cytotoxicity of beryllium metal particles of various
sizes to cultured rat alveolar macrophages, although specific surface
area did not entirely predict cytotoxicity (Finch et al., 1991,
Document ID 1535).
Stefaniak et al. (2003) investigated the particle structure and
surface area of beryllium metal, beryllium oxide, and copper-beryllium
alloy particles (Document ID 1347). Each of these samples was separated
by aerodynamic size, and their chemical compositions and structures
were determined with x-ray diffraction and transmission electron
microscopy, respectively. In summary, beryllium-metal powder varied
remarkably from beryllium oxide powder and alloy particles. The metal
powder consisted of compact particles, in which SSA decreases with
increasing surface diameter. In contrast, the alloys and oxides
consisted of small primary particles in clusters, in which the SSA
remains fairly constant with particle size. SSA for the metal powders
varied based on production and manufacturing process with variations
among samples as high as a factor of 37. Stefaniak et al. (2003) found
lesser variation in SSA for the alloys or oxides (Document ID 1347).
This is consistent with data from other studies summarized above
showing that process may affect particle size and surface area.
Particle size and/or surface area may explain differences in the rate
of beryllium sensitization and CBD observed in some epidemiological
studies. However, these properties have not been consistently
characterized in most studies.
B. Kinetics and Metabolism of Beryllium
Beryllium enters the body by inhalation, absorption through the
skin, or ingestion. For occupational exposure, the airways and the skin
are the primary routes of uptake.
1. Exposure Via the Respiratory System
The respiratory tract, especially the lung, is the primary target
of inhalation exposure in workers. Disposition (deposition and
clearance) of the particle or droplet along the respiratory tract
influences the biological response to the toxicant (Schlesinger et al.,
1997, Document ID 1290). Inhaled beryllium particles are deposited
along the respiratory tract in a size dependent manner as described by
the International Commission for radiological Protection (ICRP) model
(Figure 1). In general, particles larger than 10 μm tend to deposit
in the upper respiratory tract or nasal region and do not appreciably
penetrate lower in the tracheobronchial or pulmonary regions (Figure
1). Particles less than 10 μm increasingly penetrate and deposit in
the tracheobronchial and pulmonary regions with peak deposition in the
pulmonary region occurring below 5 μm in particle diameter. The CBD
pathology of concern is found in the pulmonary region. For particles
below 1 μm in particle diameter, regional deposition changes
dramatically. Ultrafine particles (generally considered to be 100 nm or
lower) have a higher rate of deposition along the entire respiratory
system (ICRP model, 1994). However, due to the hygroscopic nature of
soluble particles, deposition patterns may be slightly different with
an enhanced preference for the tracheobronchial or bronchial region of
the lung. Nonetheless, soluble particles are still capable of
depositing in the pulmonary region (Schlesinger et al., 1997, Document
ID 1290).
Particles depositing in the lung and along the entire respiratory
tract may encounter immunologic cells or may move into the vascular
system where they are free to leave the lung and can contribute to
systemic beryllium concentrations.
[GRAPHIC] [TIFF OMITTED] TR09JA17.000
Beryllium is removed from the respiratory tract by various
clearance mechanisms. Soluble beryllium is removed from the respiratory
tract via absorption or chemical clearance (Schlesinger, 1997, Document
ID 1290). Sparingly soluble or poorly soluble beryllium is removed via
mechanical mechanisms and may remain in the
lungs for many years after exposure, as has been observed in workers
(Schepers, 1962, Document ID 1414). Clearance mechanisms for sparingly
soluble or poorly soluble beryllium particles include: In the nasal
passage, sneezing, mucociliary transport to the throat, or dissolution;
in the tracheobronchial region, mucociliary transport, coughing,
phagocytosis, or dissolution; in the pulmonary or alveolar region,
phagocytosis, movement through the interstitium (translocation), or
dissolution (Schlesinger, 1997, Document ID 1290). Mechanical clearance
mechanisms may occur slowly in humans, which is consistent with some
animal and human studies. For example, subjects in the Beryllium Case
Registry (BCR), which identifies and tracks cases of acute and chronic
beryllium diseases, had elevated concentrations of beryllium in lung
tissue (e.g., 3.1 μg/g of dried lung tissue and 8.5 μg/g in a
mediastinal node) more than 20 years after termination of short-term
(generally between 2 and 5 years) occupational exposure to beryllium
(Sprince et al., 1976, Document ID 1405).
Due to physiological differences, clearance rates can vary between
humans and animal species (Schlesinger, 1997, Document ID 1290; Miller,
2000 (1831)). However, clearance rates are also dependent upon the
solubility, dose, and size of the inhaled beryllium compound. As
reviewed in a WHO Report (2001) (Document ID 1282), more soluble
beryllium compounds generally tend to be cleared from the respiratory
system and absorbed into the bloodstream more rapidly than less soluble
compounds (Van Cleave and Kaylor, 1955, Document ID 1287; Hart et al.,
1980 (1493); Finch et al., 1990 (1318)). Animal inhalation or
intratracheal instillation studies administering soluble beryllium
salts demonstrated significant absorption of approximately 20 percent
of the initial lung burden with rapid dissolution of soluble compounds
from the lung (Delic, 1992, Document ID 1547). Absorption of poorly
soluble compounds such as beryllium oxide administered via inhalation
or intratracheal instillation was slower and less significant (Delic,
1992, Document ID 1547). Additional animal studies have demonstrated
that clearance of poorly soluble beryllium compounds was biphasic: A
more rapid initial mucociliary transport phase of particles from the
tracheobronchial tree to the gastrointestinal tract, followed by a
slower phase via translocation to tracheobronchial lymph nodes,
alveolar macrophages uptake, and beryllium particles dissolution
(Camner et al., 1977, Document ID 1558; Sanders et al., 1978 (1485);
Delic, 1992 (1547); WHO, 2001 (1282)). Confirmatory studies in rats
have shown the half-time for the rapid phase to be between 1 and 60
days, while the slow phase ranged from 0.6 to 2.3 years. Studies have
also shown that this process was influenced by the solubility of the
beryllium compounds: Weeks/months for soluble compounds, months/years
for poorly soluble compounds (Reeves and Vorwald, 1967; Reeves et al.,
1967; Rhoads and Sanders, 1985). Studies in guinea pigs and rats
indicate that 40-50 percent of the inhaled soluble beryllium salts are
retained in the respiratory tract. Similar data could not be found for
the poorly soluble beryllium compounds or metal administered by this
exposure route. (WHO, 2001, Document ID 1282; ATSDR, 2002 (1371).)
Evidence from animal studies suggests that greater amounts of
beryllium deposited in the lung may result in slower clearance times.
Acute inhalation studies performed in rats and mice using a single dose
of inhaled aerosolized beryllium metal showed that exposure to
beryllium metal can slow particle clearance and induce lung damage in
rats and mice (Finch et al., 1998, Document ID 1317; Haley et al., 1990
(1314)). In another study, Finch et al. (1994) exposed male F344/N rats
to beryllium metal at concentrations resulting in beryllium lung
burdens of 1.8, 10, and 100 μg. These exposure levels resulted in an
estimated clearance half-life ranging from 250 to 380 days for the
three concentrations. For mice (Finch et al., 1998, Document ID 1317),
lung clearance half-lives were 91-150 days (for 1.7- and 2.6-μg lung
burden groups) or 360-400 days (for 12- and 34-μg lung burden
groups). While the lower exposure groups were quite different for rats
and mice, the highest groups were similar in clearance half-lives for
both species.
Beryllium absorbed from the respiratory system was shown to
distribute primarily to the tracheobronchial lymph nodes via the lymph
system, bloodstream, and skeleton (Stokinger et al., 1953, Document ID
1277; Clary et al., 1975 (1320); Sanders et al., 1975 (1486); Finch et
al., 1990 (1318)). Studies in rats demonstrated accumulation of
beryllium chloride in the skeletal system following intraperitoneal
injection (Crowley et al., 1949, Document ID 1551; Scott et al., 1950
(1413)) and accumulation of beryllium phosphate and beryllium sulfate
in both non-parenchymal and parenchymal cells of the liver after
intravenous administration in rats (Skilleter and Price, 1978, Document
ID 1408). Studies have also demonstrated intracellular accumulation of
beryllium oxide in bone marrow throughout the skeletal system after
intravenous administration to rabbits (Fodor, 1977, Document ID 1532;
WHO, 2001 (1282)). Trace amounts of beryllium have also been shown to
be distributed throughout the body (WHO, 2001, Document ID 1282).
Systemic distribution of the more soluble compounds was shown to be
greater than that of the poorly soluble compounds (Stokinger et al.,
1953, Document ID 1277). Distribution has also been shown to be dose
dependent in research using intravenous administration of beryllium in
rats; small doses were preferentially taken up in the skeleton, while
higher doses were initially distributed preferentially to the liver.
Beryllium was later mobilized from the liver and transferred to the
skeleton (IARC, 1993, Document ID 1342). A half-life of 450 days has
been estimated for beryllium in the human skeleton (ICRP, 1960,
Document ID 0248). This indicates the skeleton may serve as a
repository for beryllium that may later be reabsorbed by the
circulatory system, making beryllium available to the immunological
system (WHO, 2001, Document ID 1282). In a recent review of the
information, the American Conference of Governmental Industrial
Hygienists (ACGIH, 2010) was not able to confirm the association
between occupational inhalation and urinary excretion (Document ID
1662, p. 4). However, IARC (2012) noted that an accidental exposure of
25 people to beryllium dust reported in a study by Zorn et al. (1986)
resulted in a mean serum concentration of 3.5 μg/L one day after the
exposure, which decreased to 2.4 μg/L by day six. The IARC report
concluded that beryllium from beryllium metal was biologically
available for systemic distribution from the lung (IARC, 2012, Document
ID 0650).
Based on these studies, OSHA finds that the respiratory tract is a
primary pathway for beryllium exposure. While particle size and surface
area may contribute to the toxicity of beryllium, there is not
sufficient evidence for OSHA to regulate based on size and surface
area. However, the Agency finds that both soluble and poorly soluble
forms of beryllium and beryllium compounds can contribute to exposure
via the respiratory system and therefore can be causative agents of
sensitization and CBD.
2. Dermal Exposure
Beryllium compounds have been shown to cause skin irritation and
sensitization in humans and certain animal models (Van Ordstrand et
al., 1945, Document ID 1383; de Nardi et al., 1953 (1545); Nishimura,
1966 (1435); Epstein, 1991 (0526); Belman, 1969 (1562); Tinkle et al.,
2003 (1483); Delic, 1992 (1547)). The Agency for Toxic Substances and
Disease Registry (ATSDR) estimated that less than 0.1 percent of
beryllium compounds are absorbed through the skin (ATSDR, 2002,
Document ID 1371). However, even minute contact and absorption across
the skin may directly elicit an immunological response resulting in
sensitization (Deubner et al., 2001, Document ID 1543; Toledo et al.,
2011 (0522)). Studies by Tinkle et al. (2003) showed that penetration
of beryllium oxide particles was possible ex vivo for human intact skin
at particle sizes of less than or equal to 1μm in diameter, as
confirmed by scanning electron microscopy (Document ID 1483). Using
confocal microscopy, Tinkle et al. demonstrated that surrogate
fluorescent particles up to 1 μm in size could penetrate the mouse
epidermis and dermis layers in a model designed to mimic the flexing
and stretching of human skin in motion. Other poorly soluble particles,
such as titanium dioxide, have been shown to penetrate normal human
skin (Tan et al., 1996, Document ID 1391) suggesting the flexing and
stretching motion as a plausible mechanism for dermal penetration of
beryllium as well. As earlier summarized, poorly soluble forms of
beryllium can be solubilized in biological fluids (e.g., sweat) making
them available for absorption through intact skin (Sutton et al., 2003,
Document ID 1393; Stefaniak et al., 2011 (0537) and 2014 (0517); Duling
et al., 2012 (0539)).
Although its precise role remains to be elucidated, there is
evidence that dermal exposure can contribute to beryllium
sensitization. As early as the 1940s it was recognized that dermatitis
experienced by workers in primary beryllium production facilities was
linked to exposures to the soluble beryllium salts. Except in cases of
wound contamination, dermatitis was rare in workers whose exposures
were restricted to exposure to poorly soluble beryllium-containing
particles (Van Ordstrand et al., 1945, Document ID 1383). Further
investigation by McCord in 1951 (Document ID 1448) indicated that
direct skin contact with soluble beryllium compounds, but not beryllium
hydroxide or beryllium metal, caused dermal lesions (reddened,
elevated, or fluid-filled lesions on exposed body surfaces) in
susceptible persons. Curtis, in 1951, demonstrated skin sensitization
to beryllium with patch testing using soluble and poorly soluble forms
of beryllium in beryllium-na[iuml]ve subjects. These subjects later
developed granulomatous skin lesions with the classical delayed-type
contact dermatitis following repeat challenge (Curtis, 1951, Document
ID 1273). These lesions appeared after a latent period of 1-2 weeks,
suggesting a delayed allergic reaction. The dermal reaction occurred
more rapidly and in response to smaller amounts of beryllium in those
individuals previously sensitized (Van Ordstrand et al., 1945, Document
ID 1383). Contamination of cuts and scrapes with beryllium can result
in the beryllium becoming embedded within the skin causing an
ulcerating granuloma to develop in the skin (Epstein, 1991, Document ID
0526). Soluble and poorly soluble beryllium-compounds that penetrate
the skin as a result of abrasions or cuts have been shown to result in
chronic ulcerations and skin granulomas (Van Ordstrand et al., 1945,
Document ID 1383; Lederer and Savage, 1954 (1467)). Beryllium
absorption through bruises and cuts has been demonstrated as well
(Rossman et al., 1991, Document ID 1332).
In a study by Ivannikov et al. (1982) (as cited in Deubner et al.,
2001, Document ID 0023), beryllium chloride was applied directly to
three different types of wounded skin: abrasions (superficial skin
trauma), cuts (skin and superficial muscle trauma), and penetration
wounds (deep muscle trauma). According to Deubner et al. (2001) the
percentage of the applied dose systemically absorbed during a 24-hour
exposure was significant, ranging from 7.8 percent to 11.4 percent for
abrasions, from 18.3 percent to 22.9 percent for cuts, and from 34
percent to 38.8 percent for penetration wounds (Deubner et al., 2001,
Document ID 0023).
A study by Deubner et al. (2001) concluded that exposure across
damaged skin can contribute as much systemic loading of beryllium as
inhalation (Deubner et al., 2001, Document ID 1543). Deubner et al.
(2001) estimated dermal loading (amount of particles penetrating into
the skin) in workers as compared to inhalation exposure. Deubner's
calculations assumed a dermal loading rate for beryllium on skin of
0.43 μg/cm2, based on the studies of loading on skin after workers
cleaned up (Sanderson et al.., 1999, Document ID 0474), multiplied by a
factor of 10 to approximate the workplace concentrations and the very
low absorption rate of beryllium into skin of 0.001 percent (taken from
EPA estimates). As cited by Deubner et al. (2001), the EPA noted that
these calculations did not take into account absorption of soluble
beryllium salts that might occur across nasal mucus membranes, which
may result from contact between contaminated skin and the nose (Deubner
et al., 2001, Document ID 1543).
A study conducted by Day et al. (2007) evaluated the effectiveness
of a dermal protection program implemented in a beryllium alloy
facility in 2002 (Document ID 1548). The investigators evaluated levels
of beryllium in air, on workplace surfaces, on cotton gloves worn over
nitrile gloves, and on the necks and faces of workers over a six day
period. The investigators found a strong correlation between air
concentrations determined from sampling data and work surface
contamination at this facility. The investigators also found measurable
levels of beryllium on the skin of workers as a result of work
processes even from workplace areas promoted as "visually clean" by
the company housekeeping policy. Importantly, the investigators found
that the beryllium contamination could be transferred from body region
to body region (e.g., hand to face, neck to face) demonstrating the
importance of dermal protection measures since sensitization can occur
via dermal exposure as well as respiratory exposure. The investigators
demonstrated multiple pathways of exposure which could lead to
sensitization, increasing risk for developing CBD (Day et al., 2007,
Document ID 1548).
The same group of investigators extended their work on
investigating multiple exposure pathways contributing to sensitization
and CBD (Armstrong et al., 2014, Document ID 0502). The investigators
evaluated four different beryllium manufacturing and processing
facilities to assess the contribution of various exposure pathways on
worker exposure. Airborne, work surface and cotton glove beryllium
concentrations were evaluated. The investigators found strong
correlations between air and surface concentrations; glove and surface
concentrations; and air and glove concentrations at this facility. This
work supports findings from Day et al. (2007) (Document ID 1548)
demonstrating the importance of airborne beryllium concentrations to
surface contamination and dermal exposure even at exposures below the
preceding OSHA PEL (Armstrong et al., 2014, Document ID 0502).
OSHA received comments regarding the potential for dermal
penetration of poorly soluble particles. Materion contended there is no
supporting evidence to suggest that insoluble or poorly soluble
particles penetrate skin and stated:
. . . we were aware that, a hypothesis has been put forth which
suggests that being sensitized to beryllium either through a skin
wound or via penetration of small beryllium particles through intact
skin could result in sensitization to beryllium which upon receiving
a subsequent inhalation dose of airborne beryllium could result in
CBD. However, there are no studies that skin absorption of insoluble
beryllium results in a systemic effect. The study by Curtis, the
only human study looking for evidence of a beryllium sensitization
reaction occurring through intact human skin, found no sensitization
reaction using insoluble forms of beryllium. (Document ID 1661, p.
12).
OSHA disagrees with the assertion that no studies are available
indicating skin absorption of poorly soluble (insoluble) beryllium. In
addition to the study cited by Materion (Curtis, 1951, Document ID
1273), OSHA reviewed numerous studies on the effects of beryllium
solubility and dermal penetration (see section V. B. 2) including the
Tinkle et al. (2003) (Document ID 1483) study which demonstrated the
potential for poorly soluble beryllium particles to penetration skin
using an ex vivo human skin model. While OSHA believes that these
studies demonstrate poorly soluble beryllium can in fact penetrate
intact skin, penetration through intact skin is not the only means for
a person to become sensitized through skin contact with poorly soluble
beryllium. During the informal hearing proceedings, NIOSH was asked
about the role of poorly soluble beryllium in sensitizing workers to
beryllium. Aleks Stefaniak, Ph.D., NIOSH, stated that "intact skin
naturally has a barrier that prevents moisture from seeping out of the
body and things from getting into the body. Very few people actually
have fully intact skin, especially in an industrial environment. So the
skin barrier is often compromised, which would make penetration of
particles much easier." (Document ID 1755, Tr. 36).
As summarized above, poorly soluble beryllium particles have been
shown to solubilize in biological fluids (e.g., sweat) releasing
beryllium ions and making them available for absorption through intact
skin (Sutton et al., 2003, Document ID 1393; Stefaniak et al. 2014
(0517); Duling et al., 2012 (0539)). Epidemiological studies evaluating
the effectiveness of PPE in facilities working with beryllium (with
special emphasis on skin protection) have demonstrated a reduced rate
of beryllium sensitization after implementation of this type of control
(Day et al., 2007, Document ID 1548; Armstrong et al., 2014 (0502)).
Dr. Stefaniak confirmed these findings:
[T]he particles can actually dissolve when they're in contact
with liquids on the skin, like sweat. So we've actually done a
series of studies, using a simulant of sweat, but it had
characteristics that very closely matched human sweat. We see in
those studies that, in fact, beryllium particles, beryllium oxide,
beryllium metal, beryllium alloys, all these sort of what we call
insoluble forms actually do in fact dissolve very readily in analog
of human sweat. And once beryllium is in an ionic form on the skin,
it's actually very easy for it to cross the skin barrier. And that's
been shown many, many times in studies that beryllium ions can cross
the skin and induce sensitization. (Document ID 1755, Tr. 36-37).
Based on information from various studies demonstrating that poorly
soluble particles have the potential to penetrate skin, that skin as a
barrier is rarely intact (especially in industrial settings), and that
beryllium particles can readily dissolve in sweat and other biological
fluids, OSHA finds that dermal exposure to poorly soluble beryllium can
cause sensitization (Rossman, et al., 1991, Document ID 1332; Deubner
et al., 2001 (1542); Tinkle et al., 2003 (1483); Sutton et al., 2003
(1393); Stefaniak et al., 2011 (0537) and 2014 (0517); Duling et al.,
2012 (0539); Document ID 1755, Tr. 36-37).
3. Oral and Gastrointestinal Exposure
According to the WHO Report (2001), gastrointestinal absorption of
beryllium can occur by both the inhalation and oral routes of exposure
(Document ID 1282). In the case of inhalation, a portion of the inhaled
material is transported to the gastrointestinal tract by the
mucociliary escalator or by the swallowing of the poorly soluble
material deposited in the upper respiratory tract (Schlesinger, 1997,
Document ID 1290). Animal studies have shown oral administration of
beryllium compounds to result in very limited absorption and storage
(as reviewed by U.S. EPA, 1998, Document ID 0661). Oral studies
utilizing radio-labeled beryllium chloride in rats, mice, dogs, and
monkeys, found the majority of the beryllium was unabsorbed by the
gastrointestinal tract and was eliminated in the feces. In most
studies, less than 1 percent of the administered radioactivity was
absorbed into the bloodstream and subsequently excreted in the urine
(Crowley et al., 1949, Document ID 1551; Furchner et al., 1973 (1523);
LeFevre and Joel, 1986 (1464)). Research using soluble beryllium
sulfate has shown that as the compound passes into the intestine, which
has a higher pH than the stomach (approximate pH of 6 to 8 for the
intestine, pH of 1 or 2 for the stomach), the beryllium is precipitated
as the poorly soluble phosphate and is not absorbed (Reeves, 1965,
Document ID 1430; WHO, 2001 (1282)).
Further studies suggested that beryllium absorbed into the
bloodstream is primarily excreted via urine (Crowley et al., 1949,
Document ID 1551; Furchner et al., 1973 (1523); Scott et al., 1950
(1413); Stiefel et al., 1980 (1288)). Unabsorbed beryllium is primarily
excreted via the fecal route (Finch et al., 1990, Document ID 1318;
Hart et al., 1980 (1493)). Parenteral administration in a variety of
animal species demonstrated that beryllium was eliminated at much
higher percentages in the urine than in the feces (Crowley et al.,
1949, Document ID 1551; Furchner et al., 1973 (1523); Scott et al.,
1950 (1413)). A study using percutaneous administration of soluble
beryllium nitrate in rats demonstrated that more than 90 percent of the
beryllium in the bloodstream was eliminated via urine (WHO, 2001,
Document ID 1282). Greater than 99 percent of ingested beryllium
chloride was excreted in the feces (Mullen et al., 1972, Document ID
1442). A study of mice, rats, monkeys, and dogs given intravenously
dosed with beryllium chloride determined elimination half-times to be
between 890 to 1,770 days (2.4 to 4.8 years) (Furchner et al., 1973,
Document ID 1523). In a comparison study, baboons and rats were
instilled intratracheally with beryllium metal. Mean daily excretion
rates were calculated as 4.6 x 10-5 percent of the dose
administered in baboons and 3.1 x 10-5 percent in rats
(Andre et al., 1987, Document ID 0351).
In summary, animal studies evaluating the absorption, distribution
and excretion of beryllium compounds found that, in general, poorly
soluble beryllium compounds were not readily absorbed in the
gastrointestinal tract and was mostly excreted via feces (Hart et al.,
1980, Document ID 1493; Finch et al., 1990 (1318); Mullen et al., 1972
(1442)). Soluble beryllium compounds orally administered were partially
cleared via urine; however, some soluble forms are precipitated in the
gastrointestinal tract due to different pH values between the intestine
and the stomach (Reeves, 1965, Document ID 1430). Intravenous
administration of
poorly soluble beryllium compounds were distributed systemically
through the lymphatics and stored in the skeleton for potential later
release (Furchner et al., 1973, Document ID 1523). Therefore, while
intravenous administration can lead to uptake, OSHA does not consider
oral and gastrointestinal exposure to be a major route for the uptake
of beryllium because poorly soluble beryllium is not readily absorbed
in the gastrointestinal tract.
4. Metabolism
Beryllium and its compounds may not be metabolized or
biotransformed, but soluble beryllium salts may be converted to less
soluble forms in the lung (Reeves and Vorwald, 1967, Document ID 1309).
As stated earlier, solubility is an important factor for persistence of
beryllium in the lung. Poorly soluble phagocytized beryllium particles
can be dissolved into an ionic form by an acidic cellular environment
and by myeloperoxidases or macrophage phagolysomal fluids (Leonard and
Lauwerys, 1987, Document ID 1293; Lansdown, 1995 (1469); WHO, 2001
(1282); Stefaniak et al., 2006 (1398)). The positive charge of the
beryllium ion could potentially make it more biologically reactive
because it may allow the beryllium to bind to a peptide or protein and
be presented to the T cell receptor or antigen-presenting cell
(Fontenot, 2000, Document ID 1531).
5. Conclusion For Particle Characterization and Kinetics and Metabolism
of Beryllium
The forms and concentrations of beryllium across the workplace vary
substantially based upon location, process, production and work task.
Many factors may influence the potency of beryllium including
concentration, composition, structure, size, solubility and surface
area of the particle.
Studies have demonstrated that beryllium sensitization can occur
via the skin or inhalation from soluble or poorly soluble beryllium
particles. Beryllium must be presented to a cell in a soluble form for
activation of the immune system (NAS, 2008, Document ID 1355), and this
will be discussed in more detail in the section to follow. Poorly
soluble beryllium can be solubilized via intracellular fluid, lung
fluid and sweat to release beryllium ions (Sutton et al., 2003,
Document ID 1393; Stefaniak et al., 2011(0537) and 2014(0517)). For
beryllium to persist in the lung it needs to be poorly soluble.
However, soluble beryllium has been shown to precipitate in the lung to
form poorly soluble beryllium (Reeves and Vorwald, 1967, Document ID
1309).
Some animal and epidemiological studies suggest that the form of
beryllium may affect the rate of development of BeS and CBD. Beryllium
in an inhalable form (either as soluble or poorly soluble particles or
mist) can deposit in the respiratory tract and interact with immune
cells located along the entire respiratory tract (Scheslinger, 1997,
Document ID 1290). Interaction and presentation of beryllium (either in
ionic or particulate form) is discussed further in Section V.D.1.
C. Acute Beryllium Diseases
Acute beryllium disease (ABD) is a relatively rapid onset
inflammatory reaction resulting from breathing high airborne
concentrations of beryllium. It was first reported in workers
extracting beryllium oxide (Van Ordstrand et al., 1943, Document ID
1383) and later reported by Eisenbud (1948) and Aub (1949) (as cited in
Document ID 1662, p. 2). Since the Atomic Energy Commission's adoption
of a maximum permissible peak occupational exposure limit of 25 μg/
m3\ for beryllium beginning in 1949, cases of ABD have been much
rarer. According to the World Health Organization (2001), ABD is
generally associated with exposure to beryllium levels at or above 100
μg/m3\ and may be fatal in 10 percent of cases (Document ID 1282).
However, cases of ABD have been reported with beryllium exposures below
100 µg/m3\ (Cummings et al., 2009, Document ID 1550). The
Cummings et al. (2009) study examined two cases of workers exposed to
soluble and poorly soluble beryllium below 100 µg/m3\ using data
obtained from company records. Cummings et al. (2009) also examined the
possibility that an immune-mediated mechanism may exist for ABD as well
as CBD and that ABD and CBD are on a pathological continuum since some
patients would later develop CBD after recovering from ABD (ACCP, 1965,
Document ID 1286; Hall, 1950 (1494); Cummings et al., 2009 (1550)).
ABD involves an inflammatory or immune-mediated reaction that may
include the entire respiratory tract, involving the nasal passages,
pharynx, bronchial airways and alveoli. Other tissues including skin
and conjunctivae may be affected as well. The clinical features of ABD
include a nonproductive cough, chest pain, cyanosis, shortness of
breath, low-grade fever and a sharp drop in functional parameters of
the lungs. Pathological features of ABD include edematous distension,
round cell infiltration of the septa, proteinaceous materials, and
desquamated alveolar cells in the lung. Monocytes, lymphocytes and
plasma cells within the alveoli are also characteristic of the acute
disease process (Freiman and Hardy, 1970, Document ID 1527).
Two types of acute beryllium disease have been characterized in the
literature: A rapid and severe course of acute fulminating pneumonitis
generally developing within 48 to 72 hours of a massive exposure, and a
second form that takes several days to develop from exposure to lower
concentrations of beryllium (still above the levels set by regulatory
and guidance agencies) (Hall, 1950, Document ID 1494; DeNardi et al.,
1953 (1545); Newman and Kreiss, 1992 (1440)). Evidence of a dose-
response relationship to the concentration of beryllium is limited
(Eisenbud et al., 1948, Document ID 0490; Stokinger, 1950 (1484);
Sterner and Eisenbud, 1951 (1396)). Recovery from either type of ABD is
generally complete after a period of several weeks or months (DeNardi
et al., 1953, Document ID 1545). However, deaths have been reported in
more severe cases (Freiman and Hardy, 1970, Document ID 1527).
According to the BCR, in the United States, approximately 17 percent of
ABD patients developed CBD (BCR, 2010). The majority of ABD cases
occurred between 1932 and 1970 (Eisenbud, 1982, Document ID 1254;
Middleton, 1998 (1445)). ABD is extremely rare in the workplace today
due to more stringent exposure controls implemented following
occupational and environmental standards set in 1970-1971 (ACGIH, 1971,
Document ID 0543; ANSI, 1970 (1303); OSHA, 1971, see 39 FR 23513; EPA,
1973 (38 FR 8820)).
Materion submitted post-hearing comments regarding ABD (Document ID
1662, p. 2; Attachment A, p. 1). Materion contended that only soluble
forms of beryllium have been demonstrated to produce ABD at exposures
above 100 µg/m3\ because cases of ABD were only found in workers
exposed to beryllium during beryllium extraction processes which always
contain soluble beryllium (Document ID 1662, pp. 2, 3). Citing
communications between Marc Kolanz (Materion) and Dr. Eisenbud,
Materion noted that when Mr. Kolanz asked Dr. Eisenbud if he ever
"observed an acute reaction to beryllium that did not involve the
beryllium extraction process and exposure to soluble salts of
beryllium," Dr. Eisenbud responded that "he did not know of a case
that was not either directly associated with
exposure to soluble compounds or where the work task or operation would
have been free from exposure to soluble beryllium compounds from
adjacent operations." (Document ID 1662, p. 3). OSHA acknowledges that
workers with ABD may have been exposed to a combination of soluble and
poorly soluble beryllium. This alone, however, cannot completely
exclude poorly soluble beryllium as a causative or contributing agent
of ABD. The WHO (2001) has concluded that both ABD and CBD results from
exposure to both soluble and insoluble forms of beryllium. In addition,
the European Commission has classified poorly soluble beryllium and
beryllium oxide as acute toxicity categories 2 and 3 (Document ID 1669,
p. 2).
Additional comments from Materion regarding ABD criticized the
study by Cummings et al. (2009), stating that it "incompletely
explained the source of the workers exposures, which resulted in the
use of a misleading statement that, `None of the measured air samples
exceeded 100 μg/m3\ and most were less than 10 μg/m3\.' "
(Document ID 1662, p. 3). Materion argues that the Cummings et al.
study is not valid because workers in that study "had been involved
with high exposures to soluble beryllium salts caused by upsets during
the chemical extraction of beryllium." (Document ID 1662, pp. 3-4). In
response, NIOSH written testimony explained that the measurements in
the study "were collected in areas most likely to be sources of high
beryllium exposures in processes, but were not personal breathing zone
measurements in the usual sense." (Document ID 1725, p. 3). "Cummings
et al. (2009) made every effort to overestimate (rather than
underestimate) exposure," including "select[ing] the highest time
weighted average (TWA) value from the work areas or activities
associated with a worker's job and tenure" and not adjusting for
"potential protective effects of respirators, which were reportedly
used for some tasks and during workplace events potentially associated
with uncontrolled higher exposures." Even so, "the available TWA data
did not exceed 100 μg/m3\ even on days with evacuations."
(Document ID 1725, p. 3). Furthermore, OSHA notes that, the discussion
in Cummings et al. (2009) stated, "we cannot rule out the possibility
of unusually elevated airborne concentrations of beryllium that went
unmeasured." (Document ID 1550, p. 5).
In response to Materion's contention that OSHA should eliminate the
section on ABD because this disease is no longer a concern today
(Document ID 1661, p. 2), OSHA notes that the discussion on ABD is
included for thoroughness in review of the health effects caused by
exposure to beryllium. As indicated above, the Agency acknowledges that
ABD is extremely rare, but not non-existent, in workplaces today due to
the more stringent exposure controls implemented since OSHA's inception
(OSHA, 1971, see 39 FR 23513).
D. Beryllium Sensitization and Chronic Beryllium Disease
This section provides an overview of the immunology and
pathogenesis of BeS and CBD, with particular attention to the role of
skin sensitization, particle size, beryllium compound solubility, and
genetic variability in individuals' susceptibility to beryllium
sensitization and CBD.
Chronic beryllium disease (CBD), formerly known as "berylliosis"
or "chronic berylliosis," is a granulomatous disorder primarily
affecting the lungs. CBD was first described in the literature by Hardy
and Tabershaw (1946) as a chronic granulomatous pneumonitis (Document
ID 1516). It was proposed as early as 1951 that CBD could be a chronic
disease resulting from sensitization to beryllium (Sterner and
Eisenbud, 1951, Document ID 1396; Curtis, 1959 (1273); Nishimura, 1966
(1435)). However, for a time, there remained some controversy as to
whether CBD was a delayed-onset hypersensitivity disease or a toxicant-
induced disease (NAS, 2008, Document ID 1355). Wide acceptance of CBD
as a hypersensitivity lung disease did not occur until bronchoscopy
studies and bronchoalveolar lavage (BAL) studies were performed
demonstrating that BAL cells from CBD patients responded to beryllium
challenge (Epstein et al., 1982, Document ID 0436; Rossman et al., 1988
(0476); Saltini et al., 1989 (1351)).
CBD shares many clinical and histopathological features with
pulmonary sarcoidosis, a granulomatous lung disease of unknown
etiology. These similarities include such debilitating effects as
airway obstruction, diminishment of physical capacity associated with
reduced lung function, possible depression associated with decreased
physical capacity, and decreased life expectancy. Without appropriate
information, CBD may be difficult to distinguish from sarcoidosis. It
is estimated that up to 6 percent of all patients diagnosed with
sarcoidosis may actually have CBD (Fireman et al., 2003, Document ID
1533; Rossman and Kreider, 2003 (1423)). Among patients diagnosed with
sarcoidosis in which beryllium exposure can be confirmed, as many as 40
percent may actually have CBD (Muller-Quernheim et al., 2005, Document
ID 1262; Cherry et al., 2015 (0463)).
Clinical signs and symptoms of CBD may include, but are not limited
to, a simple cough, shortness of breath or dypsnea, fever, weight loss
or anorexia, skin lesions, clubbing of fingers, cyanosis, night sweats,
cor pulmonale, tachycardia, edema, chest pain and arthralgia. Changes
or loss of pulmonary function also occur with CBD such as decrease in
vital capacity, reduced diffusing capacity, and restrictive breathing
patterns. The signs and symptoms of CBD constitute a continuum of
symptoms that are progressive in nature with no clear demarcation
between any stages in the disease (Pappas and Newman, 1993, Document ID
1433; Rossman, 1996 (1283); NAS, 2008 (1355)). These symptoms are
consistent with the CBD symptoms described during the public hearing by
Dr. Kristin Cummings of NIOSH and Dr. Lisa Maier of National Jewish
Health (Document ID 1755, Tr. 70-71; 1756, Tr. 105-107).
Besides these listed symptoms from CBD patients, there have been
reported cases of CBD that remained asymptomatic (Pappas and Newman,
1993, Document ID 1433; Muller-Querheim, 2005 (1262); NAS, 2008 (1355);
NIOSH, 2011 (0544)). Asymptomatic CBD refers to those patients that
have physiological changes upon clinical evaluation yet exhibit no
outward signs or symptoms (also referred to as subclinical CBD).
Unlike ABD, CBD can result from inhalation exposure to beryllium at
levels below the preceding OSHA PEL, can take months to years after
initial beryllium exposure before signs and symptoms of CBD occur
(Newman 1996, Document ID 1283, 2005 (1437) and 2007 (1335);
Henneberger, 2001 (1313); Seidler et al., 2012 (0457); Schuler et al.,
2012 (0473)), and may continue to progress following removal from
beryllium exposure (Newman, 2005, Document ID 1437; Sawyer et al., 2005
(1415); Seidler et al., 2012 (0457)). Patients with CBD can progress to
a chronic obstructive lung disorder resulting in loss of quality of
life and the potential for decreased life expectancy (Rossman, et al.,
1996, Document ID 1425; Newman et al., 2005 (1437)). The National
Academy of Sciences (NAS) report (2008) noted the general lack of
published studies on progression of CBD from an early asymptomatic
stage to functionally significant lung disease (NAS, 2008, Document ID
1355). The report emphasized that risk factors and
time course for clinical disease have not been fully delineated.
However, for people now under surveillance, clinical progression from
sensitization and early pathological lesions (i.e., granulomatous
inflammation) prior to onset of symptoms to symptomatic disease appears
to be slow, although more follow-up is needed (NAS, 2008, Document ID
1355). A study by Newman (1996) emphasized the need for prospective
studies to determine the natural history and time course from beryllium
sensitization and asymptomatic CBD to full-blown disease (Newman, 1996,
Document ID 1283). Drawing from his own clinical experience, Dr. Newman
was able to identify the sequence of events for those with symptomatic
disease as follows: Initial determination of beryllium sensitization;
gradual emergence of chronic inflammation of the lung; pathologic
alterations with measurable physiologic changes (e.g., pulmonary
function and gas exchange); progression to a more severe lung disease
(with extrapulmonary effects such as clubbing and cor pulmonale in some
cases); and finally death in some cases (reported between 5.8 to 38
percent) (NAS, 2008, Document ID 1355; Newman, 1996 (1283)).
In contrast to some occupationally related lung diseases, the early
detection of chronic beryllium disease may be useful since treatment of
this condition can lead not only to regression of the signs and
symptoms, but also may prevent further progression of the disease in
certain individuals (Marchand-Adam et al., 2008, Document ID 0370; NAS,
2008 (1355)). The management of CBD is based on the hypothesis that
suppression of the hypersensitivity reaction (i.e., granulomatous
process) will prevent the development of fibrosis. However, once
fibrosis has developed, therapy cannot reverse the damage.
A study by Pappas and Newman (1993) observed that patients with
known prior beryllium exposure and identified as confirmed positive for
beryllium sensitization through the beryllium lymphocyte proliferation
test (BeLPT) screening were evaluated for physiological changes in the
lung. Pappas and Newman categorized the patients as being either
"clinically identified," meaning they had known physiological
abnormalities (e.g., abnormal chest radiogram, respiratory symptoms) or
"surveillance-identified," meaning they had BeLPT positive results
with no reported symptoms, to differentiate state of disease
progression. Physiological changes were identified by three factors:
(1) Reduced tolerance to exercise; (2) abnormal pulmonary function test
during exercise; (3) abnormal arterial blood gases during exercise. Of
the patients identified as "surveillance identified," 52 percent had
abnormal exercise physiologies while 87 percent of the "clinically
identified" patients had abnormal physiologies (Pappas and Newman,
1993, Document ID 1433). During the public hearing, Dr. Newman noted
that:
. . . one of the sometimes overlooked points is that in that study .
. . the majority of people who were found to have early stage
disease already had physiologic impairment. So before the x-ray or
the CAT scan could find it the BeLPT had picked it up, we had made a
diagnosis of pathology in those people, and their lung function
tests--their measures of gas exchange, were already abnormal. Which
put them on our watch list for early and more frequent monitoring so
that we could observe their worsening and then jump in with
treatment at the earliest appropriate time. So there is advantage of
having that early diagnosis in terms of the appropriate tracking and
appropriate timing of treatment. (Document ID 1756, p. 112).
OSHA was unable to find any controlled studies to determine the
optimal treatment for CBD (see Rossman, 1996, Document ID 1425; NAS
2008 (1355); Sood, 2009 (0456)), and none were added to the record
during the public comment period. Management of CBD is generally
modeled after sarcoidosis treatment. Oral corticosteroid treatment can
be initiated in patients with evidence of disease (either by
bronchoscopy or other diagnostic measures before progression of disease
or after clinical signs of pulmonary deterioration occur). This
includes treatment with other anti-inflammatory agents (NAS, 2008.
Document ID 1355; Maier et al., 2012 (0461); Salvator et al., 2013
(0459)) as well. It should be noted, however, that treatment with
corticosteroids has side-effects of their own that need to be measured
against the possibility of progression of disease (Gibson et al., 1996,
Document ID 1521; Zaki et al., 1987 (1374)). Alternative treatments
such as azathioprine and infliximab, while successful at treating
symptoms of CBD, have been demonstrated to have side effects as well
(Pallavicino et al., 2013, Document ID 0630; Freeman, 2012 (0655)).
1. Development of Beryllium Sensitization
Sensitization to beryllium is an essential step for worker
development of CBD. Sensitization to beryllium can result from
inhalation exposure to beryllium (Newman et al., 2005, Document ID
1437; NAS, 2008 (1355)), as well as from skin exposure to beryllium
(Curtis, 1951, Document ID 1273; Newman et al., 1996 (1439); Tinkle et
al., 2003 (1483); Rossman, et al., 1991, (1332); Deubner et al., 2001
(1542); Tinkle et al., 2003 (1483); Sutton et al., 2003 (1393);
Stefaniak et al., 2011 (0537) and 2014 (0517); Duling et al., 2012
(0539); Document ID 1755, Tr. 36-37). Representative Robert C.
"Bobby" Scott, Ranking Member of Committee on Education and the
Workforce, the U.S. House of Representatives, provided comments to the
record stating that "studies have demonstrated that beryllium
sensitization, an indicator of immune response to beryllium, can occur
from both soluble and poorly soluble beryllium particles." (Document
ID 1672, p. 3).
Sensitization is currently detected using the BeLPT (a laboratory
blood test) described in section V.D.5. Although there may be no
clinical symptoms associated with beryllium sensitization, a sensitized
worker's immune system has been activated to react to beryllium
exposures such that subsequent exposure to beryllium can progress to
serious lung disease (Kreiss et al., 1996, Document ID 1477; Newman et
al., 1996 (1439); Kreiss et al., 1997 (1360); Kelleher et al., 2001
(1363); Rossman, 2001 (1424); Newman et al., 2005 (1437)). Since the
pathogenesis of CBD involves a beryllium-specific, cell-mediated immune
response, CBD cannot occur in the absence of sensitization (NAS, 2008,
Document ID 1355). The expert peer reviewers agreed that the scientific
evidence supported sensitization as a necessary condition and an early
endpoint in the development of CBD (ERG, 2010, Document ID 1270, pp.
19-21). Dr. John Balmes remarked that the "scientific evidence
reviewed in the [Health Effects] document supports consideration of
beryllium sensitization as an early endpoint and as a necessary
condition in the development of CBD." Dr. Patrick Breysee stated that
"there is strong scientific consensus that sensitization is a key
first step in the progression of CBD." Dr. Terry Gordon stated that
"[a]s discussed in the draft [Health Effects] document, beryllium
sensitization should be considered as an early endpoint in the
development of CBD." Finally, Dr. Milton Rossman agreed "that
sensitization is necessary for someone to develop CBD and should be
considered a condition/risk factor for the development of CBD."
Various factors, including genetic susceptibility, have been shown to
influence risk of developing sensitization and CBD (NAS 2008, Document
ID 1355) and will be discussed later in this section.
While various mechanisms or pathways may exist for beryllium
sensitization, the most plausible mechanisms supported by the best
available and most current science are discussed below. Sensitization
occurs via the formation of a beryllium-protein complex (an antigen)
that causes an immunological response. In some instances, onset of
sensitization has been observed in individuals exposed to beryllium for
only a few months (Kelleher et al., 2001, Document ID 1363; Henneberger
et al., 2001 (1313)). This suggests the possibility that relatively
brief, short-term beryllium exposures may be sufficient to trigger the
immune hypersensitivity reaction. Several studies (Newman et al., 2001,
Document ID 1354; Henneberger et al., 2001 (1313); Rossman, 2001
(1424); Schuler et al., 2005 (0919); Donovan et al., 2007 (0491),
Schuler et al., 2012 (0473)) have detected a higher prevalence of
sensitization among workers with less than one year of employment
compared to some cross-sectional studies which, due to lack of
information regarding initial exposure, cannot determine time of
sensitization (Kreiss et al., 1996, Document ID 1477; Kreiss et al.,
1997 (1360)). While only very limited evidence has described humoral
changes in certain patients with CBD (Cianciara et al., 1980, Document
ID 1553), clear evidence exists for an immune cell-mediated response,
specifically the T-cell (NAS, 2008, Document ID 1355). Figure 2
delineates the major steps required for progression from beryllium
contact to sensitization to CBD.
[GRAPHIC] [TIFF OMITTED] TR09JA17.001
Beryllium presentation to the immune system is believed to occur
either by direct presentation or by antigen processing. It has been
postulated that beryllium must be presented to the immune system in an
ionic form for cell-mediated immune activation to occur (Kreiss et al.,
2007, Document ID 1475). Some soluble forms of beryllium are readily
presented, since the soluble beryllium form disassociates into its
ionic components. However, for poorly soluble forms, dissolution may
need to occur. A study by Harmsen et al. (1986) suggested that a
sufficient rate of dissolution of small amounts of poorly soluble
beryllium compounds might occur in the lungs to allow persistent
low-level beryllium presentation to the immune system (Document ID
1257). Stefaniak et al. (2006 and 2012) reported that poorly soluble
beryllium particles phagocytized by macrophages were dissolved in
phagolysomal fluid (Stefaniak et al., 2006, Document ID 1398; Stefaniak
et al., 2012 (0469)) and that the dissolution rate stimulated by
phagolysomal fluid was different for various forms of beryllium
(Stefaniak et al., 2006, Document ID 1398; Duling et al., 2012 (0539)).
Several studies have demonstrated that macrophage uptake of beryllium
can induce aberrant apoptotic processes leading to the continued
release of beryllium ions which will continually stimulate T-cell
activation (Sawyer et al., 2000, Document ID 1417; Sawyer et al., 2004
(1416); Kittle et al., 2002 (0485)). Antigen processing can be mediated
by antigen-presenting cells (APC). These may include macrophages,
dendritic cells, or other antigen-presenting cells, although this has
not been well defined in most studies (NAS, 2008, Document ID 1355).
Because of their strong positive charge, beryllium ions have the
ability to haptenate and alter the structure of peptides occupying the
antigen-binding cleft of major histocompatibility complex (MHC) class
II on antigen-presenting cells (APC). The MHC class II antigen-binding
molecule for beryllium is the human leukocyte antigen (HLA) with
specific alleles (e.g., HLA-DP, HLA-DR, HLA-DQ) associated with the
progression to CBD (NAS, 2008, Document ID 1355; Yucesoy and Johnson,
2011 (0464); Petukh et al., 2014 (0397)). Several studies have also
demonstrated that the electrostatic charge of HLA may be a factor in
binding beryllium (Snyder et al., 2003, Document ID 0524; Bill et al.,
2005 (0499); Dai et al., 2010 (0494)). The strong positive ionic charge
of the beryllium ion would have a strong attraction for the negatively
charged patches of certain HLA alleles (Snyder et al., 2008, Document
ID 0471; Dai et al., 2010 (0494); Petukh et al., 2014 (0397)).
Alternatively, beryllium oxide has been demonstrated to bind to the MHC
class II receptor in a neutral pH. The six carboxylates in the amino
acid sequence of the binding pocket provide a stable bond with the Be-
O-Be molecule when the pH of the substrate is neutral (Keizer et al.,
2005, Document ID 0455). The direct binding of BeO may eliminate the
biological requirement for antigen processing or dissolution of
beryllium oxide to activate an immune response.
Once the beryllium-MHC-APC complex is established, the complex
binds to a T-cell receptor (TCR) on a na[iuml]ve T-cell which
stimulates the proliferation and accumulation of beryllium-specific
CD4+ (cluster of differentiation 4\+\) T-cells (Saltini et al., 1989,
Document ID 1351 and 1990 (1420); Martin et al., 2011 (0483)) as
depicted in Figure 3. Fontenot et al. (1999) demonstrated that
diversely different variants of TCR were expressed by CD4+ T-cells in
peripheral blood cells of CBD patients. However, the CD4+ T-cells
from the lung were more homologous in expression of TCR variants in CBD
patients, suggesting clonal expansion of a subset of T-cells in the
lung (Fontenot et al., 1999, Document ID 0489). This may also indicate
a pathogenic potential for subsets of T-cell clones expressing this
homologous TCR (NAS, 2008, Document ID 1355). Fontenot et al. (2006)
(Document ID 0487) reported beryllium self-presentation by HLA-DP
expressing BAL CD4+ T-cells. According the NAS report, BAL T-cell
self-presentation in the lung granuloma may result in cell death,
leading to oligoclonality (only a few clones) of the T-cell population
characteristic of CBD (NAS, 2008, Document ID 1355).
[GRAPHIC] [TIFF OMITTED] TR09JA17.002
As CD4+ T-cells proliferate, clonal expansion of various subsets
of the CD4+ beryllium specific T-cells occurs (Figure 3). In the
peripheral blood, the beryllium-specific CD4+ T cells require co-
stimulation with a co-stimulant CD28 (cluster of differentiation 28).
During the proliferation and differentiation process CD4+ T-cells
secrete pro-inflammatory cytokines that may influence this process
(Sawyer et al., 2004, Document ID 1416; Kimber et al., 2011 (0534)).
In summary, OSHA concludes that sensitization is a necessary and
early functional change in the immune system that leads to the
development of CBD.
2. Development of CBD
The continued presence of residual beryllium in the lung leads to a
T-cell maturation process. A large portion of beryllium-specific CD4+
T cells were shown to cease expression of CD28 mRNA and protein,
indicating these cells no longer required co-stimulation with the CD28
ligand (Fontenot et al., 2003, Document ID 1529). This change in
phenotype correlated with lung inflammation (Fontenot et al., 2003,
Document ID 1529). While these CD4+ independent cells continued to
secrete cytokines necessary for additional recruitment of inflammatory
and immunological cells, they were less proliferative and less
susceptible to cell death compared to the CD28 dependent cells
(Fontenot et al., 2005, Document ID 1528; Mack et al., 2008 (1460)).
These beryllium-specific CD4+ independent cells are considered to be
mature memory effector cells (Ndejembi et al., 2006, Document ID 0479;
Bian et al., 2005 (0500)). Repeat exposure to beryllium in the lung
resulting in a mature population of T cell development independent of
co-stimulation by CD28 and development of a population of T effector
memory cells (Tem cells) may be one of the mechanisms that
lead to the more severe reactions observed specifically in the lung
(Fontenot et al., 2005, Document ID 1528).
CD4+ T cells created in the sensitization process recognize the
beryllium antigen, and respond by proliferating and secreting cytokines
and inflammatory mediators, including IL-2, IFN-[gamma], and TNF-
α (Tinkle et al., 1997, Document ID 1387; Tinkle et al., 1997
(1388); Fontenot et al., 2002 (1530)) and MIP-1α and GRO-1 (Hong-
Geller, 2006, Document ID 1511). This also results in the accumulation
of various types of inflammatory cells including mononuclear cells
(mostly CD4+ T cells) in the BAL fluid (Saltini et al., 1989,
Document ID 1351, 1990 (1420)).
The development of granulomatous inflammation in the lung of CBD
patients has been associated with the accumulation of beryllium
responsive CD4+ Tem cells in BAL fluid (NAS, 2008,
Document ID 1355). The subsequent release of pro-inflammatory
cytokines, chemokines and reactive oxygen species by these cells may
lead to migration of additional inflammatory/immune cells and the
development of a microenvironment that contributes to the development
of CBD (Sawyer et al., 2005, Document ID 1415; Tinkle et al., 1996
(0468); Hong-Geller et al., 2006 (1511); NAS, 2008 (1355)).
The cascade of events described above results in the formation of a
noncaseating granulomatous lesion. Release of cytokines by the
accumulating T cells leads to the formation of granulomatous lesions
that are characterized by an outer ring of histiocytes surrounding non-
necrotic tissue with embedded multi-nucleated giant cells (Saltini et
al., 1989, Document ID 1351, 1990 (1420)).
Over time, the granulomas spread and can lead to lung fibrosis and
abnormal
pulmonary function, with symptoms including a persistent dry cough and
shortness of breath (Saber and Dweik, 2000, Document ID 1421). Fatigue,
night sweats, chest and joint pain, clubbing of fingers (due to
impaired oxygen exchange), loss of appetite or unexplained weight loss,
and cor pulmonale have been experienced in certain patients as the
disease progresses (Conradi et al., 1971, Document ID 1319; ACCP, 1965
(1286); Kriebel et al., 1988, Document ID 1292; Kriebel et al., 1988
(1473)). While CBD primarily affects the lungs, it can also involve
other organs such as the liver, skin, spleen, and kidneys (ATSDR, 2002,
Document ID 1371).
As previously mentioned, the uptake of beryllium may lead to an
aberrant apoptotic process with rerelease of beryllium ions and
continual stimulation of beryllium-responsive CD4+ cells in the lung
(Sawyer et al., 2000, Document ID 1417; Kittle et al., 2002 (0485);
Sawyer et al., 2004 (1416)). Several research studies suggest apoptosis
may be one mechanism that enhances inflammatory cell recruitment,
cytokine production and inflammation, thus creating a scenario for
progressive granulomatous inflammation (Palmer et al., 2008, Document
ID 0478; Rana, 2008 (0477)). Macrophages and neutrophils can
phagocytize beryllium particles in an attempt to remove the beryllium
from the lung (Ding, et al., 2009, Document ID 0492)). Multiple studies
(Sawyer et al., 2004, Document ID 1416; Kittle et al., 2002 (0485))
using BAL cells (mostly macrophages and neutrophils) from patients with
CBD found that in vitro stimulation with beryllium sulfate induced the
production of TNF-α (one of many cytokines produced in response
to beryllium), and that production of TNF-α might induce
apoptosis in CBD and sarcoidosis patients (Bost et al., 1994, Document
ID 1299; Dai et al., 1999 (0495)). The stimulation of CBD-derived
macrophages by beryllium sulfate resulted in cells becoming apoptotic,
as measured by propidium iodide. These results were confirmed in a
mouse macrophage cell-line (p388D1) (Sawyer et al., 2000, Document ID
1417). However, other factors, such as genetic factors and duration or
level of exposure leading to a continued presence of beryllium in the
lung, may influence the development of CBD and are outlined in the
following sections V.D.3 and V.D.4.
In summary, the persistent presence of beryllium in the lung of a
sensitized individual creates a progressive inflammatory response that
can culminate in the granulomatous lung disease, CBD.
3. Genetic and Other Susceptibility Factors
Evidence from a variety of sources indicates genetic susceptibility
may play an important role in the development of CBD in certain
individuals, especially at levels low enough not to invoke a response
in other individuals. Early occupational studies proposed that CBD was
an immune reaction based on the high susceptibility of some individuals
to become sensitized and progress to CBD and the lack of CBD in others
who were exposed to levels several orders of magnitude higher (Sterner
and Eisenbud, 1951, Document ID 1396). Recent studies have confirmed
genetic susceptibility to CBD involves either, HLA variants, T-cell
receptor clonality, tumor necrosis factor (TNF-α) polymorphisms
and/or transforming growth factor-beta (TGF-β) polymorphisms
(Fontenot et al., 2000, Document ID 1531; Amicosante et al., 2005
(1564); Tinkle et al., 1996 (0468); Gaede et al., 2005 (0486); Van Dyke
et al., 2011 (1696); Silveira et al., 2012 (0472)).
Potential sources of variation associated with genetic
susceptibility have been investigated. Single Nucleotide Polymorphisms
(SNPs) have been studied with regard to genetic variations associated
with increased risk of developing CBD. SNPs are the most abundant type
of human genetic variation. Polymorphisms in MHC class II and pro-
inflammatory genes have been shown to contribute to variations in
immune responses contributing to the susceptibility and resistance in
many diseases including auto-immunity, beryllium sensitization, and CBD
(McClesky et al., 2009, as cited in Document ID 1808, p. 3). Specific
SNPs have been evaluated as a factor in the Glu69 variant from the HLA-
DPB1 locus (Richeldi et al., 1993, Document ID 1353; Cai et al., 2000
(0445); Saltini et al., 2001 (0448); Silviera et al., 2012 (0472); Dai
et al., 2013 (0493)). Other SNPs lacking the Glu69 variant, such as
HLA-DRPheβ47, have also been evaluated for an association with CBD
(Amicosante et al., 2005, Document ID 1564).
HLA-DPB1 (one of 2 subtypes of HLA-DP) with a glutamic acid at
amino position 69 (Glu69) has been shown to confer increased risk of
beryllium sensitization and CBD (Richeldi et al., 1993, Document ID
1353; Saltini et al., 2001 (0448); Amicosante et al., 2005 (1564); Van
Dyke et al., 2011 (1696); Silveira et al., 2012 (0472)). In vitro human
research has identified genes coding for specific protein molecules on
the surface of the immune cells of sensitized individuals from a cohort
of beryllium workers (McCanlies et al., 2004, Document ID 1449). The
research identified the HLA-DPB1 (Glu69) allele that place carriers at
greater risk of becoming sensitized to beryllium and developing CBD
than those not carrying this allele (McCanlies et al., 2004, Document
ID 1449). Fontenot et al. (2000) demonstrated that beryllium
presentation by certain alleles of the class II human leukocyte
antigen-DP (HLA-DP 3) to CD4+ T cells is the mechanism underlying
the development of CBD (Document ID 1531). Richeldi et al. (1993)
reported a strong association between the MHC class II allele HLA-DPB 1
and the development of CBD in beryllium-exposed workers from a Tucson,
AZ facility (Document ID 1353). This marker was found in 32 of the 33
workers who developed CBD, but in only 14 of 44 similarly exposed
workers without CBD. The more common alleles of the HLA-DPB 1
containing a variant of Glu69 are negatively charged at this site and
could directly interact with the positively charged beryllium ion.
Additional studies by Amicosante et al. (2005) (Document ID 1564) using
blood lymphocytes derived from beryllium-exposed workers found a high
frequency of this gene in those sensitized to beryllium. In a study of
82 CBD patients (beryllium-exposed workers), Stubbs et al. (1996)
(Document ID 1394) also found a relationship between the HLA-DP 1
allele and beryllium sensitization. The glutamate-69 allele was present
in 86 percent of sensitized subjects, but in only 48 percent of
beryllium-exposed, non-sensitized subjects. Some variants of the HLA-
DPB1 allele convey higher risk of sensitization and CBD than others.
For example, HLA-DPB1*0201 yielded an approximately 3-fold increase in
disease outcome relative to controls; HLA-DPB1*1901 yielded an
approximately 5-fold increase, and HLA-DPB1*1701 yielded an
approximately 10-fold increase (Weston et al., 2005, Document ID 1345;
Snyder et al., 2008 (0471)). Specifically, Snyder et al. (2008) found
that variants of the Glu69 allele with the greatest negative charge may
confer greater risk for developing CBD (Document ID 0471). The study by
Weston et al. (2005) assigned odds ratios for specific alleles on the
basis of previous studies discussed above (Document ID 1345). The
researchers found a strong
correlation (88 percent) between the reported risk of CBD and the
predicted surface electrostatic potential and charge of the isotypes of
the genes. They were able to conclude that the alleles associated with
the most negatively charged proteins carry the greatest risk of
developing beryllium sensitization and CBD (Weston et al., 2005,
Document ID 1345). This confirms the importance of beryllium charge as
a key factor in its ability to induce an immune response.
---------------------------------------------------------------------------
3 HLA-DP and HLA DPB1 alleles have been associated with
genetic susceptibility for developing CBD. HLA-DP has 2 subtypes,
HLA-DPA and HLA-DPB. HLA-DBP1 is involved with the Glu69 allele most
associated with genetic susceptibility.
---------------------------------------------------------------------------
In contrast, the HLA-DRB1 allele, which lacks Glu69, has also been
shown to increase the risk of developing sensitization and CBD
(Amicosante et al., 2005, Document ID 1564; Maier et al., 2003 (0484)).
Bill et al. (2005) found that HLA-DR has a glutamic acid at position 71
of the β chain, functionally equivalent to the Glu69 of HLA-DP
(Bill et al., 2005, Document ID 0499). Associations with BeS and CBD
have also been reported with the HLA-DQ markers (Amicosante et al.,
2005, Document ID 1564; Maier et al., 2003 (0484)). Stubbs et al. also
found a biased distribution of the MHC class II HLA-DR gene between
sensitized and non-sensitized subjects. Neither of these markers was
completely specific for CBD, as each study found beryllium
sensitization or CBD among individuals without the genetic risk factor.
While there remains uncertainty as to which of the MHC class II genes
interact directly with the beryllium ion, antibody inhibition data
suggest that the HLA-DR gene product may be involved in the
presentation of beryllium to T lymphocytes (Amicosante et al., 2002,
Document ID 1370). In addition, antibody blocking experiments revealed
that anti-HLA-DP strongly reduced proliferation responses and cytokine
secretion by BAL CD4 T cells (Chou et al., 2005, Document ID 0497). In
the study by Chou (2005), anti-HLA-DR ligand antibodies mainly affected
beryllium-induced proliferation responses with little impact on
cytokines other than IL-2, thus implying that non-proliferating BAL CD4
T cells may still contribute to inflammation leading to the progression
of CBD (Chou et al., 2005, Document ID 0497).
TNF alpha (TNF-α) polymorphisms and TGF beta (TGF-β)
polymorphisms have also been shown to confer a genetic susceptibility
for developing CBD in certain individuals. TNF-α is a pro-
inflammatory cytokine that may be associated with a more progressive
form of CBD (NAS, 2008). Beryllium exposure has been shown to
upregulate transcription factors AP-1 and NF-[kappa]B (Sawyer et al.,
2007, as cited in Document ID 1355) inducing an inflammatory response
by stimulating production of pro-inflammatory cytokines such as TNF-
α by inflammatory cells. Polymorphisms in the 308 position of the
TNF-α gene have been demonstrated to increase production of the
cytokine and increase severity of disease (Maier et al., 2001, Document
ID 1456; Saltini et al., 2001 (0448); Dotti et al., 2004 (1540)). While
a study by McCanlies et al. (2007) (Document ID 0482) of 886 beryllium
workers (including 64 sensitized for beryllium and 92 with CBD) found
no relationship between TNF-α polymorphism and sensitization or
CBD, the National Academies of Sciences noted that "discrepancies
between past studies showing associations and the more recent studies
may be due to misclassification, exposure differences, linkage
disequilibrium between HLA-DRB1 and TNF-α genes, or statistical
power." (NAS, 2008, Document ID 1355).
Other genetic variations have been shown to be associated with
increased risk of beryllium sensitization and CBD (NAS, 2008, Document
ID 1355). These include TGF-β (Gaede et al., 2005, Document ID
0486), angiotensin-1 converting enzyme (ACE) (Newman et al., 1992,
Document ID 1440; Maier et al., 1999 (1458)) and an enzyme involved in
glutathione synthesis (glutamate cysteine ligase) (Bekris et al., 2006,
as cited in Document ID 1355). McCanlies et al. (2010) evaluated the
association between polymorphisms in a select group of interleukin
genes (IL-1A; IL-1B, IL-1RN, IL-2, IL-9, IL-9R) due to their role in
immune and inflammatory processes (Document ID 0481). The study
evaluated SNPs in three groups of workers from large beryllium
manufacturing facilities in OH and AZ. The investigators found a
significant association between variants IL-1A-1142, IL-1A-3769 and IL-
1A-4697 and CBD but not between those variants and beryllium
sensitization.
In addition to the genetic factors which may contribute to the
susceptibility and severity of disease, other factors such as smoking
and sex may play a role in the development of CBD (NAS, 2008, Document
ID 1355). A recent longitudinal cohort study by Mroz et al. (2009) of
229 individuals identified with beryllium sensitization or CBD through
workplace medical surveillance found that the prevalence of CBD among
ever smokers was significantly lower than among never smokers (38.1
percent versus 49.4 percent, p = 0.025). BeS subjects that never smoked
were found to be more likely to develop CBD over the course of the
study compared to current smokers (12.6 percent versus 6.4 percent, p =
0.10). The authors suggested smoking may confer a protective effect
against development of lung granulomas as has been demonstrated with
hypersensitivity pneumonitis (Mroz et al., 2009, Document ID 1356).
4. Beryllium Sensitization and CBD in the Workforce
Sensitization to beryllium is currently detected in the workforce
with the beryllium lymphocyte proliferation test (BeLPT), a laboratory
blood test developed in the 1980s, also referred to as the LTT
(Lymphocyte Transformation Test) or BeLTT (Beryllium Lymphocyte
Transformation Test). In this test, lymphocytes obtained from either
bronchoalveolar lavage fluid (the BAL BeLPT) or from peripheral blood
(the blood BeLPT) are cultured in vitro and exposed to beryllium
sulfate to stimulate lymphocyte proliferation. The observation of
beryllium-specific proliferation indicates beryllium sensitization.
Hereafter, "BeLPT" generally refers to the blood BeLPT, which is
typically used in screening for beryllium sensitization. This test is
described in more detail in subsection D.5.b.
CBD can be detected at an asymptomatic stage by a number of
techniques including bronchoalveolar lavage and biopsy (Cordeiro et
al., 2007, Document ID 1552; Maier, 2001 (1456)). Bronchoalveolar
lavage is a method of "washing" the lungs with fluid inserted via a
flexible fiberoptic instrument known as a bronchoscope, removing the
fluid and analyzing the content for the inclusion of immune cells
reactive to beryllium exposure, as described earlier in this section.
Fiberoptic bronchoscopy can be used to detect granulomatous lung
inflammation prior to the onset of CBD symptoms as well, and has been
used in combination with the BeLPT to diagnose pre-symptomatic CBD in a
number of recent screening studies of beryllium-exposed workers, which
are discussed in the following section detailing diagnostic procedures.
Of workers who were found to be sensitized and underwent clinical
evaluation, 31 to 49 percent of them were diagnosed with CBD (Kreiss et
al., 1993, Document ID 1479; Newman et al., 1996 (1283), 2005 (1437),
2007 (1335); Mroz, 2009 (1356)), although some estimate that with
increased surveillance that percentage could be much higher (Newman,
2005, Document ID 1437; Mroz, 2009 (1356)). It has been estimated from
ongoing surveillance studies of sensitized individuals with an average
follow-up time of 4.5 years that
31 percent of beryllium-sensitized employees were estimated to progress
to CBD (Newman et al., 2005, Document ID 1437). The study by Newman et
al. (2005) was the first longitudinal study to assess the progression
from beryllium sensitization to CBD in individuals undergoing clinical
evaluation at National Jewish Medical and Research Center from 1988
through 1998. Approximately 50 percent of sensitized individuals (as
identified by BeLPT) had CBD at their initial clinical evaluation. The
remaining 50 percent, or 76 individuals, without evidence of CBD were
monitored at approximately two year intervals for indication of disease
progression by pulmonary function testing, chest radiography (with
International Labour Organization B reading), fiberoptic bronchoscopy
with bronchoalveolar lavage, and transbronchial lung biopsy. Fifty-five
of the 76 individuals were monitored with a range of two to five
clinical evaluations each. The Newman et al. (2005) study found that
CBD developed in 31 percent of individuals (17 of the 55) in a period
ranging from 1.0 to 9.5 years (average 3.8 years). After an average of
4.8 years (range 1.7 to 11.6 years) the remaining individuals showed no
signs of progression to CBD. A study of nuclear weapons facility
employees enrolled in an ongoing medical surveillance program found
that the sensitization rate in exposed workers increased rapidly over
the first 10 years of beryllium exposure and then more gradually in
succeeding years. On the other hand, the rate of CBD pathology
increased slowly over the first 15 years of exposure and then climbed
more steeply following 15 to 30 years of beryllium exposure (Stange et
al., 2001, Document ID 1403). The findings from these longitudinal
studies of sensitized workers provide evidence of CBD progression over
time from asymptomatic to symptomatic disease. One limitation for all
these studies is lack of long-term follow-up. Newman suggested that it
may be necessary to continue to monitor these workers in order to
determine whether all sensitized workers will develop CBD (Newman et
al., 2005, Document ID 1437).
CBD has a clinical spectrum ranging from evidence of beryllium
sensitization and granulomas in the lung with little symptomatology to
loss of lung function and end stage disease, which may result in the
need for lung transplantation and decreased life expectancy.
Unfortunately, there are very few published clinical studies describing
the full range and progression of CBD from the beginning to the end
stages and very few of the risk factors for progression of disease have
been delineated (NAS, 2008, Document ID 1355). OSHA requested
additional information in the NPRM, but no additional studies were
added during the public comment period. Clinical management of CBD is
modeled after sarcoidosis where oral corticosteroid treatment is
initiated in patients who have evidence of progressive lung disease,
although progressive lung disease has not been well defined (NAS, 2008,
Document ID 1355). In advanced cases of CBD, corticosteroids are the
standard treatment (NAS, 2008, Document ID 1355). No comprehensive
studies have been published measuring the overall effect of removal of
workers from beryllium exposure on sensitization and CBD (NAS, 2008,
Document ID 1355) although this has been suggested as part of an
overall treatment regime for CBD (Mapel et al., 2002, as cited in
Document ID 1850; Sood et al., 2004 (1331); Sood, 2009 (0456); Maier et
al., 2012 (0461)). Expert testimony from Dr. Lee Newman and Dr. Lisa
Maier agreed that while no studies exist on the efficacy of removal
from beryllium exposure, it is medically prudent to reduce beryllium
exposure once someone is sensitized (Document ID 1756, Tr. 142). Sood
et al. reported that cessation of exposure can sometimes have
beneficial effects on lung function (Sood et al., 2004, Document ID
1331). However, this was based on anecdotal evidence from six patients
with CBD, while this indicates a benefit of removal of patients from
exposure, more research is needed to better determine the relationship
between exposure duration and disease progression.
Materion commented that sensitization should be defined as a test
result indicating an immunological sensitivity to beryllium without
identifiable adverse health effects or other signs of illness or
disability. It went on to say that, for these reasons, sensitization is
not on a pathological continuum with CBD (Document ID 1661, pp. 4-7).
Other commenters disagreed. NIOSH addressed whether sensitization
should be considered an adverse health effect and said the following in
their written hearing testimony:
Some have questioned whether BeS should be considered an adverse
health effect. NIOSH views it as such, since it is a biological
change in people exposed to beryllium that is associated with
increased risk for developing CBD. BeS refers to the immune system's
ability to recognize and react to beryllium. BeS is an antigen-
specific cell mediated immunity to beryllium, in which CD4+ T cells
recognize a complex composed of beryllium ion, self-peptide, and
major histocompatibility complex (MHC) Class II molecule on an
antigen-presenting cell [Falta et al. (2013); Fontenot et al.
(2016)]. BeS necessarily precedes CBD. Pathogenesis depends on the
immune system's recognition of and reaction to beryllium in the
lung, resulting in granulomatous lung disease. BeS can be detected
with tests that assess the immune response, such as the beryllium
lymphocyte proliferation test (BeLPT), which measures T cell
activity in the presence of beryllium salts [Balmes et al. (2014)].
Furthermore, after the presence of BeS has been confirmed, periodic
medical evaluation at 1-3 year intervals thereafter is required to
assess whether BeS has progressed to CBD [Balmes et al. (2014)].
Thus, BeS is not just a test result, but an adverse health effect
that poses risk of the irreversible lung disease CBD. (Document ID
1725, p. 2)
The American College of Occupational and Environmental Medicine
(ACOEM) also commented that the term pathological "continuum" should
only refer to signs and symptoms associated with CBD because some
sensitized workers never develop CBD (Document ID 1685, p. 6). However,
Dr. Newman, testifying on behalf of ACOEM, clarified that not all
members of the ACOEM task force agreed:
So I hope I'm reflecting to you the range and variety of
outcomes relating to this. My own view is that it's on a continuum.
I do want to reflect back that the divided opinion among people on
the ACOEM task force was that we should call it a spectrum because
not everybody is necessarily lock step into a continuum that goes
from sensitization to fatality. (Document ID 1756, Tr. 133).
Lisa Maier, MD of National Jewish Health agreed with Dr. Newman
(Document ID 1756, Tr. 133-134). Additionally, Dr. Weissman of NIOSH
testified that sensitization is "a biological change in people exposed
to beryllium that is associated with increased risk for developing
CBD" and should be considered an adverse health effect (Document ID
1755, Tr. 13).
OSHA agrees that not every sensitized worker develops CBD, and that
other factors such as extent of exposure, particulate characteristics,
and genetic susceptibility influence the development and progression of
disease. The mechanisms by which beryllium sensitization leads to CBD
are described in earlier sections and are supported by numerous studies
(Newman et al., 1996a, Document ID 1439; Newman et al., 2005 (1437);
Saltini et al., 1989 (1351); Amicosante et al., 2005a (1564);
Amicosante et al., 2006 (1465); Fontenot et al., 1999 (0489); Fontenot
et al., 2005 (1528)). OSHA concludes that sensitization is an
immunological condition that increases one's likelihood
of developing CBD. As such, sensitization is a necessary step along a
continuum to clinical lung disease.
5. Human Epidemiological Studies
This section describes the human epidemiological data supporting
the mechanistic overview of beryllium-induced disease in workers. It
has been divided into reviews of epidemiological studies performed
prior to development and implementation of the BeLPT in the late 1980s
and after wide use of the BeLPT for screening purposes. Use of the
BeLPT has allowed investigators to screen for beryllium sensitization
and CBD prior to the onset of clinical symptoms, providing a more
sensitive and thorough analysis of the worker population. The
discussion of the studies has been further divided by manufacturing
processes that may have similar exposure profiles. Table A.1 in the
Supplemental Information for the Beryllium Health Effects Section
summarizes the prevalence of beryllium sensitization and CBD, range of
exposure measurements, and other salient information from the key
epidemiological studies (Document ID 1965).
It has been well-established that beryllium exposure, either via
inhalation or skin, may lead to beryllium sensitization, or, with
inhalation exposure, may lead to the onset and progression of CBD. The
available published epidemiological literature discussed below provides
strong evidence of beryllium sensitization and CBD in workers exposed
to airborne beryllium well below the preceding OSHA PEL of 2 μg/
m3\. Several studies demonstrate the prevalence of sensitization and
CBD is related to the level of airborne exposure, including a cross-
sectional survey of employees at a beryllium ceramics plant in Tucson,
AZ (Henneberger et al., 2001, Document ID 1313), case-control studies
of workers at the Rocky Flats nuclear weapons facility (Viet et al.,
2000, Document ID 1344), and workers from a beryllium machining plant
in Cullman, AL (Kelleher et al., 2001, Document ID 1363). The
prevalence of beryllium sensitization also may be related to dermal
exposure. An increased risk of CBD has been reported in workers with
skin lesions, potentially increasing the uptake of beryllium (Curtis,
1951, Document ID 1368; Johnson et al., 2001 (1505); Schuler et al.,
2005 (0919)). Three studies describe comprehensive preventive programs,
which included expanded respiratory protection, dermal protection, and
improved control of beryllium dust migration, that substantially
reduced the rate of beryllium sensitization among new hires (Cummings
et al., 2007; Thomas et al., 2009 (0590); Bailey et al., 2010 (0676);
Schuler et al., 2012(0473)).
Some of the epidemiological studies presented in this section
suffer from challenges common to many published epidemiological
studies: Limitations in study design (particularly cross-sectional);
small sample size; lack of personal and/or short-term exposure data,
particularly those published before the late 1990s; and incomplete
information regarding specific chemical form and/or particle
characterization. Challenges that are specific to beryllium
epidemiological studies include: uncertainty regarding the contribution
of dermal exposure; use of various BeLPT protocols; a variety of case
definitions for determining CBD; and use of various exposure sampling/
assessment methods (e.g., daily weighted average (DWA), lapel
sampling). Even with these limitations, the epidemiological evidence
presented in this section clearly demonstrates that beryllium
sensitization and CBD are continuing to occur from present-day
exposures below OSHA's preceding PEL of 2 μg/m3\. The available
literature also indicates that the rate of beryllium sensitization can
be substantially lowered by reducing inhalation exposure and minimizing
dermal contact.
a. Studies Conducted Prior to the BeLPT
First reports of CBD came from studies performed by Hardy and
Tabershaw (1946) (Document ID 1516). Cases were observed in industrial
plants that were refining and manufacturing beryllium metal and
beryllium alloys and in plants manufacturing fluorescent light bulbs
(NAS, 2008, Document ID 1355). From the late 1940s through the 1960s,
clusters of non-occupational CBD cases were identified around beryllium
refineries in Ohio and Pennsylvania, and outbreaks in family members of
beryllium factory workers were assumed to be from exposure to
contaminated clothes (Hardy, 1980, Document ID 1514). It had been
established that the risk of disease among beryllium workers was
variable and generally rose with the levels of airborne concentrations
(Machle et al., 1948, Document ID 1461). And while there was a
relationship between air concentrations of beryllium and risk of
developing disease both in and surrounding these plants, the disease
rates outside the plants were higher than expected and not very
different from the rate of CBD within the plants (Eisenbud et al.,
1949, Document ID 1284; Lieben and Metzner, 1959 (1343)). There
remained considerable uncertainty regarding diagnosis due to lack of
well-defined cohorts, modern diagnostic methods, or inadequate follow-
up. In fact, many patients with CBD may have been misdiagnosed with
sarcoidosis (NAS, 2008, Document ID 1355).
The difficulties in distinguishing lung disease caused by beryllium
from other lung diseases led to the establishment of the BCR in 1952 to
identify and track cases of ABD and CBD. A uniform diagnostic criterion
was introduced in 1959 as a way to delineate CBD from sarcoidosis.
Patient entry into the BCR required either: Documented past exposure to
beryllium or the presence of beryllium in lung tissue as well as
clinical evidence of beryllium disease (Hardy et al., 1967, Document ID
1515); or any three of the six criteria listed below (Hasan and Kazemi,
1974, Document ID 0451). Patients identified using the above criteria
were registered and added to the BCR from 1952 through 1983 (Eisenbud
and Lisson, 1983, Document ID 1296).
The BCR listed the following criteria for diagnosing CBD (Eisenbud
and Lisson, 1983, Document ID 1296):
(1) Establishment of significant beryllium exposure based on sound
epidemiologic history;
(2) Objective evidence of lower respiratory tract disease and
clinical course consistent with beryllium disease;
(3) Chest X-ray films with radiologic evidence of interstitial
fibronodular disease;
(4) Evidence of restrictive or obstructive defect with diminished
carbon monoxide diffusing capacity (DL CO) by physiologic
studies of lung function;
(5) Pathologic changes consistent with beryllium disease on
examination of lung tissue; and
(6) Presence of beryllium in lung tissue or thoracic lymph nodes.
Prevalence of CBD in workers during the time period between the
1940s and 1950s was estimated to be between 1-10% (Eisenbud and Lisson,
1983, Document ID 1296). In a 1969 study, Stoeckle et al. presented 60
case histories with a selective literature review utilizing the above
criteria except that urinary beryllium was substituted for lung
beryllium to demonstrate beryllium exposure. Stoeckle et al. (1969)
were able to demonstrate corticosteroids as a successful treatment
option in one case of confirmed CBD (Document ID 0447). This study also
presented a 28 percent mortality rate from complications of CBD at the
time of publication. However, even with the improved
methodology for determining CBD based on the BCR criteria, these
studies suffered from lack of well-defined cohorts, modern diagnostic
techniques or adequate follow-up.
b. Criteria for Beryllium Sensitization and CBD Case Definition
Following the Development of the BeLPT
The criteria for diagnosis of CBD have evolved over time as more
advanced diagnostic technology, such as the blood BeLPT and BAL BeLPT,
has become available. More recent diagnostic criteria have both higher
specificity than earlier methods and higher sensitivity, identifying
subclinical effects. Recent studies typically use the following
criteria (Newman et al., 1989, Document ID 0196; Pappas and Newman,
1993 (1433); Maier et al., 1999 (1458)):
(1) History of beryllium exposure;
(2) Histopathological evidence of non-caseating granulomas or
mononuclear cell infiltrates in the absence of infection; and
(3) Positive blood or BAL BeLPT (Newman et al., 1989, Document ID
0196).
The availability of transbronchial lung biopsy facilitates the
evaluation of the second criterion, by making histopathological
confirmation possible in almost all cases.
A significant component for the identification of CBD is the
demonstration of a confirmed abnormal BeLPT result in a blood or BAL
sample (Newman, 1996, Document ID 1283). Since the development of the
BeLPT in the 1980s, it has been used to screen beryllium-exposed
workers for sensitization in a number of studies to be discussed below.
The BeLPT is a non-invasive in vitro blood test that measures the
beryllium antigen-specific T-cell mediated immune response and is the
most commonly available diagnostic tool for identifying beryllium
sensitization. The BeLPT measures the degree to which beryllium
stimulates lymphocyte proliferation under a specific set of conditions,
and is interpreted based upon the number of stimulation indices that
exceed the normal value. The "cut-off" is based on the mean value of
the peak stimulation index among controls plus 2 or 3 standard
deviations. This methodology was modeled into a statistical method
known as the "least absolute values" or "statistical-biological
positive" method and relies on natural log modeling of the median
stimulation index values (DOE, 2001, Document ID 0068; Frome, 2003
(0462)). In most applications, two or more stimulation indices that
exceed the cut-off constitute an abnormal test.
Early versions of the BeLPT test had high variability, but the use
of tritiated thymidine to identify proliferating cells has led to a
more reliable test (Mroz et al., 1991, 0435; Rossman et al., 2001
(1424)). In recent years, the peripheral blood test has been found to
be as sensitive as the BAL assay, although larger abnormal responses
have been observed with the BAL assay (Kreiss et al., 1993, Document ID
1478; Pappas and Newman, 1993 (1433)). False negative results have also
been observed with the BAL BeLPT in cigarette smokers who have marked
excess of alveolar macrophages in lavage fluid (Kreiss et al., 1993,
Document ID 1478). The BeLPT has also been a useful tool in animal
studies to identify those species with a beryllium-specific immune
response (Haley et al., 1994, Document ID 1364).
Screenings for beryllium sensitization have been conducted using
the BeLPT in several occupational surveys and surveillance programs,
including nuclear weapons facilities operated by the Department of
Energy (Viet et al., 2000, Document ID 1344; Stange et al., 2001
(1403); DOE/HSS Report, 2006 (0664)), a beryllium ceramics plant in
Arizona (Kreiss et al., 1996, Document ID 1477; Henneberger et al.,
2001 (1313); Cummings et al., 2007 (1369)), a beryllium production
plant in Ohio (Kreiss et al., 1997, Document ID 1476; Kent et al., 2001
(1112)), a beryllium machining facility in Alabama (Kelleher et al.,
2001, Document ID 1363; Madl et al., 2007 (1056)), a beryllium alloy
plant (Schuler et al., 2005, Document ID 0473; Thomas et al., 2009
(0590)), and another beryllium processing plant (Rosenman et al., 2005,
Document ID 1352) in Pennsylvania. In most of these studies,
individuals with an abnormal BeLPT result were retested and were
identified as sensitized (i.e., confirmed positive) if the abnormal
result was repeated.
In order to investigate the reliability and laboratory variability
of the BeLPT, Stange et al. (2004, Document ID 1402) studied the BeLPT
by splitting blood samples and sending samples to two laboratories
simultaneously for BeLPT analysis. Stange et al. found the range of
agreement on abnormal (positive BeLPT) results was 26.2--61.8 percent
depending upon the labs tested (Stange et al., 2004, Document ID 1402).
Borak et al. (2006) contended that the positive predictive value (PPV)
4 is not high enough to meet the criteria of a good screening tool
(Document ID 0498). Middleton et al. (2008) used the data from the
Stange et al. (2004) study to estimate the PPV and determined that the
PPV of the BeLPT could be improved from 0.383 to 0.968 when an abnormal
BeLPT result is confirmed with a second abnormal result (Middleton et
al., 2008, Document ID 0480). In April 2006, the Agency for Toxic
Substances and Disease Registry (ATSDR) convened an expert panel of
seven physicians and scientists to discuss the BeLPT and to consider
what algorithm should be used to interpret BeLPT results to establish
beryllium sensitization (Middleton et al., 2008, Document ID 0480). The
three criteria proposed by panel members were Criterion A (one abnormal
BeLPT result establishes sensitization); Criterion B (one abnormal and
one borderline result establish sensitization); and Criterion C (two
abnormal results establish sensitization). Using the single-test
outcome probabilities developed by Stange et al., the panel convened by
ATSDR calculated and compared the sensitivity, specificity, and
positive predictive values (PPVs) for each algorithm. The
characteristics for each algorithm were as follows:
---------------------------------------------------------------------------
4 PPV is the portion of patients with positive test result
correctly diagnosed.
Table 2--Characteristics of BeLPT Algorithms (Adapted from Middleton et al., (2008)
[Adapted from Middleton et al., 2008, Document ID 0480]
----------------------------------------------------------------------------------------------------------------
Criterion B
Criterion A (1 abnormal + Criterion C
(1 abnormal) 1 borderline) (2 abnormal)
----------------------------------------------------------------------------------------------------------------
Sensitivity..................................................... 68.2% 65.7% 61.2%
Specificity..................................................... 98.89% 99.92% 99.98%
PPV at 1% prevalence............................................ 38.3% 89.3% 96.8%
PPV at 10% prevalence........................................... 87.2% 98.9% 99.7%
False positives per 10,000...................................... 111 8 2
----------------------------------------------------------------------------------------------------------------
The Middleton et al. (2008) study demonstrated that confirmation of
BeLPT results, whether as one abnormal and one borderline abnormal or
as two abnormals, enhances the test's PPV and protects the persons
tested from unnecessary and invasive medical procedures. In populations
with a high prevalence of beryllium sensitization (i.e., 10 percent or
more), however, a single test may be adequate to predict sensitization
(Middleton et al., 2008, Document ID 0480).
Still, there has been criticism regarding the reliability and
specificity of the BeLPT as a screening tool and that the BeLPT has not
been validated appropriately (Cher et al., 2006, as cited in Document
ID 1678; Borak et al., 2006 (0498); Donovan et al., 2007 (0491);
Document ID 1678, Attachment 1, p. 6). Even when a confirmational
second test is performed, an apparent false positive can occur in
people not occupationally exposed to beryllium (NAS, 2008, Document ID
1355). An analysis of survey data from the general workforce and new
employees at a beryllium manufacturer was performed to assess the
reliability of the BeLPT (Donovan et al. 2007, Document ID 0491).
Donovan et al. analyzed more than 10,000 test results from nearly 2400
participants over a 12-year period. Donovan et al. found that
approximately 2 percent of new employees had at least one positive
BeLPT at the time of hire and 1 percent of new hires with no known
occupational exposure were confirmed positive at the time of hire with
two BeLPTs. However, this should not be considered unusual because
there have been reported incidences of non-occupational and community-
based beryllium sensitization (Eisenbud et al., 1949, Document ID 1284;
Leiben and Metzner, 1959 (1343); Newman and Kreiss, 1992 (1440); Maier
and Rossman, 2008 (0598); NAS, 2008 (1355); Harber et al., 2014 (0415),
Harber et al., 2014 (0421)).
Materion objected to OSHA treating "two or three uninterpretable
or borderline abnormal BeLPT test results as confirmation of BeS for
the purposes of the standard" (Document ID 1808, p. 4). In order to
address some criticism regarding the PPV of the BeLPT, Middleton et al.
(2011) conducted another study to evaluate borderline results from
BeLPT testing (Document ID 0399). Utilizing the common clinical
algorithm with a criterion that accepted one abnormal result and one
borderline result as establishing beryllium sensitization resulted in a
PPV of 94.4 percent. This study also found that three borderline
results resulted in a PPV of 91 percent. Both of these PPVs were based
on a population prevalence of 2 percent. This study further
demonstrates the value of borderline results in predicting beryllium
sensitization using the BeLPT. OSHA finds that multiple, consistent
borderline BeLPT results (as found with three borderline results)
recognize a change in a person's immune system to beryllium exposure.
In addition, a study by Harber et al. (2014) reexamined the algorithms
to determine sensitization and CBD data using the BioBank data.5 The
study suggested that changing the algorithm could potentially help
distinguish sensitization from progression to CBD (Harber et al., 2014,
Document ID 0363).
---------------------------------------------------------------------------
5 BioBank is a repository of biological specimens and clinical
data collected from beryllium-exposed Department of Energy workers
and contractors.
---------------------------------------------------------------------------
Materion further contended that "[w]hile some refer to BeLPT
testing as a `gold' standard for BeS, it is hardly `golden,' as
numerous commentators have noted." (Document ID 1808, p. 4). NIOSH
submitted testimony to OSHA comparing the use of the BeLPT for
determining beryllium sensitization to other common medical screening
tools such as mammography for breast cancer, tuberculin skin test for
latent tuberculosis infection, prostate-specific antigen (PSA) for
prostate cancer, and fecal occult blood testing for colon cancer. NIOSH
stated that "[a]lthough there is no gold standard test to identify
beryllium sensitization, BeLPT has been estimated to have a sensitivity
of 66-86% and a specificity of >99% for sensitization [Middleton et al.
(2006)]. These values are comparable or superior to those of other
common medical screening tests." (Document ID 1725, pp. 32-33). In
addition, Dr. Maier of National Jewish Health stated during the public
hearing that "medical surveillance should rely on the BeLPT or a
similar test if validated in the future, as it detects early and late
beryllium health effects. It has been validated in many population-
based studies." (Document ID 1756, Tr. 103).
Since there are currently no alternatives to the BeLPT in a
beryllium sensitization screening program, many programs rely on a
second test to confirm a positive result (NAS, 2008). Various expert
organizations support the use of the BeLPT (with a second
confirmational test) as a screening tool for beryllium sensitization
and CBD. The American Thoracic Society (ATS), based on a systematic
review of the literature, noted that "the BeLPT is the cornerstone of
medical surveillance" (Balmes et al., 2014; Document ID 0364, pp. 1-
2). The use of the BeLPT in medical surveillance has been endorsed by
the National Academies in their review of beryllium-related diseases
and disease prevention programs for the U. S. Air Force (NAS, 2008,
Document ID 1355). In 2011, NIOSH issued an alert "Preventing
Sensitization and Disease from Beryllium Exposure" where the BeLPT is
recommended as part of a medical screening and surveillance program
(NIOSH, 2011, Document ID 0544). OSHA finds that the BeLPT is a useful
and reliable test method that has been utilized in numerous studies and
validated and improved through multiple studies.
The epidemiological studies presented in this section utilized the
BeLPT as either a surveillance tool or a screening tool for determining
sensitization status and/or sensitization/CBD prevalence in workers for
inclusion in the published studies. Most epidemiological studies have
reported rates of sensitization and disease based on a single screening
of a working population ("cross-sectional" or "population
prevalence" rates). Studies of workers in a beryllium machining plant
and a nuclear weapons facility have included follow-up of the
population originally screened, resulting in the detection of
additional cases of sensitization over several years (Newman et al.,
2001, Document ID 1354; Stange et al., 2001 (1403)). Based on the
studies above, as well as comments from NIOSH, ATS, and National Jewish
Health, OSHA regards
the BeLPT as a reliable medical surveillance tool.
c. Beryllium Mining and Extraction
Mining and extraction of beryllium usually involves the two major
beryllium minerals, beryl (an aluminosilicate containing up to 4
percent beryllium) and bertrandite (a beryllium silicate hydrate
containing generally less than 1 percent beryllium) (WHO, 2001,
Document ID 1282). The United States is the world leader in beryllium
extraction and also leads the world in production and use of beryllium
and its alloys (WHO, 2001, Document ID 1282). Most exposures from
mining and extraction come in the form of beryllium ore, beryllium
salts, beryllium hydroxide (NAS, 2008, Document ID 1355) or beryllium
oxide (Stefaniak et al., 2008, Document ID 1397).
Deubner et al. published a study of 75 workers employed at a
beryllium mining and extraction facility in Delta, UT (Deubner et al.,
2001b, Document ID 1543). Of the 75 workers surveyed for sensitization
with the BeLPT, three were identified as sensitized by an abnormal
BeLPT result. One of those found to be sensitized was diagnosed with
CBD. Exposures at the facility included primarily beryllium ore and
salts. General area (GA), breathing zone (BZ), and personal lapel (LP)
exposure samples were collected from 1970 to 1999. Jobs involving
beryllium hydrolysis and wet-grinding activities had the highest air
concentrations, with an annual median GA concentration ranging from 0.1
to 0.4 μg/m3\. Median BZ concentrations were higher than either LP
or GA concentrations. The average duration of exposure for beryllium
sensitized workers was 21.3 years (27.7 years for the worker with CBD),
compared to an average duration for all workers of 14.9 years. However,
these exposures were less than either the Elmore, OH, or Tucson, AZ,
facilities described below, which also had higher reported rates of BeS
and CBD. A study by Stefaniak et al. (2008) demonstrated that beryllium
was present at the mill in three forms: Mineral, poorly crystalline
oxide, and hydroxide (Document ID 1397).
There was no sensitization or CBD among those who worked only at
the mine where exposure to beryllium resulted solely from working with
bertrandite ore. The authors concluded that the results of this study
indicated that beryllium ore and salts may pose less of a hazard than
beryllium metal and beryllium hydroxide. These results are consistent
with the previously discussed animal studies examining solubility and
particle size.
d. Beryllium Metal Processing and Alloy Production
Kreiss et al. (1997) conducted a study of workers at a beryllium
production facility in Elmore, OH (Document ID 1360). The plant, which
opened in 1953 and initially specialized in production of beryllium-
copper alloy, later expanded its operations to include beryllium metal,
beryllium oxide, and beryllium-aluminum alloy production; beryllium and
beryllium alloy machining; and beryllium ceramics production, which was
moved to a different factory in the early 1980s. Production operations
included a wide variety of jobs and processes, such as work in arc
furnaces and furnace rebuilding, alloy melting and casting, beryllium
powder processing, and work in the pebble plant. Non-production work
included jobs in the analytical laboratory, engineering research and
development, maintenance, laundry, production-area management, and
office-area administration. While the publication refers to the use of
respiratory protection in some areas, such as the pebble plant, the
extent of its use across all jobs or time periods was not reported. Use
of dermal PPE was not reported.
The authors characterized exposures at the plant using industrial
hygiene (IH) samples collected between 1980 and 1993. The exposure
samples and the plant's formulas for estimating workers' DWA exposures
were used, together with study participants' work histories, to
estimate their cumulative and average beryllium exposure levels.
Exposure concentrations reflected the high exposures found historically
in beryllium production and processing. Short-term BZ measurements had
a median of 1.4 μg/m3\, with 18.5 percent of samples exceeding
OSHA's preceding permissible ceiling concentration of 5.0 μg/m3\.
Particularly high beryllium concentrations were reported in the areas
of beryllium powder production, laundry, alloy arc furnace
(approximately 40 percent of DWA estimates over 2.0 μg/m3\) and
furnace rebuild (28.6 percent of short-term BZ samples over the
preceding OSHA permissible ceiling concentration of 5 μg/m3\). LP
samples (n = 179), which were available from 1990 to 1992, had a median
value of 1 μg/m3\.
Of 655 workers employed at the time of the study, 627 underwent
BeLPT screening. Blood samples were divided and split between two labs
for analysis, with repeat testing for results that were abnormal or
indeterminate. Thirty-one workers had an abnormal blood test result
upon initial testing and at least one of two subsequent test results
for each of those workers confirmed the worker as sensitized. These
workers, together with 19 workers who had an initial abnormal result
and one subsequent indeterminate result, were offered clinical
evaluation for CBD including the BAL-BeLPT and transbronchial lung
biopsy. Nine workers with an initial abnormal test followed by two
subsequent normal tests were not clinically evaluated, although four
were found to be sensitized upon retesting in 1995. Of 47 workers who
proceeded with evaluation for CBD (3 of the 50 initial workers with
abnormal results declined to participate), 24 workers were diagnosed
with CBD based on evidence of granulomas on lung biopsy (20 workers) or
on other findings consistent with CBD (4 workers) (Kreiss et al., 1997,
Document ID 1360). After including five workers who had been diagnosed
prior to the study, a total of 29 (4.6 percent of the 627 workers who
underwent BeLPT screening) workers still employed at the time of the
study were found to have CBD. In addition, the plant medical department
identified 24 former workers diagnosed with CBD before the study.
Kreiss et al. reported that the highest prevalence of sensitization
and CBD occurred among workers employed in beryllium metal production,
even though the highest airborne total mass concentrations of beryllium
were generally among employees operating the beryllium alloy furnaces
in a different area of the plant (Kreiss et al., 1997, Document ID
1360). Preliminary follow-up investigations of particle size-specific
sampling at five furnace sites within the plant determined that the
highest respirable (i.e., particles <10 μm in diameter as defined by
the authors) and alveolar-deposited (i.e., particles <1 μm in
diameter as defined by the authors) beryllium mass and particle number
concentrations, as collected by a general area impactor device, were
measured at the beryllium metal production furnaces rather than the
beryllium alloy furnaces (Kent et al., 2001, Document ID 1361; McCawley
et al., 2001 (1357)). A statistically significant linear trend was
reported between the above alveolar-deposited particle mass
concentration and prevalence of CBD and sensitization in the furnace
production areas. The authors concluded that alveolar-deposited
particles may be a more relevant exposure metric for predicting the
incidence of CBD or sensitization
than the total mass concentration of airborne beryllium.
Bailey et al. (2010) (Document ID 0610) evaluated the effectiveness
of a workplace preventive program in lowering incidences of
sensitization at the beryllium metal, oxide, and alloy production plant
studied by Kreiss et al. (1997) (Document ID 1360). The preventive
program included use of administrative and PPE controls (e.g., improved
training, skin protection and other PPE, half-mask or air-purified
respirators, medical surveillance, improved housekeeping standards,
clean uniforms) as well as engineering and administrative controls
(e.g., migration controls, physical separation of administrative
offices from production facilities) implemented over the course of five
years.
In a cross-sectional/longitudinal hybrid study, Bailey et al.
compared rates of sensitization in pre-program workers to those hired
after the preventive program began. Pre-program workers were surveyed
cross-sectionally in 1993-1994, and again in 1999 using the BeLPT to
determine sensitization and CBD prevalence rates. The 1999 cross-
sectional survey was conducted to determine if improvements in
engineering and administrative controls were successful. However,
results indicated no improvement in reducing rates of sensitization or
CBD.
An enhanced preventive program including particle migration
control, respiratory and dermal protection, and process enclosure was
implemented in 2000, with continuing improvements made to the program
in 2001, 2002-2004, and 2005. Workers hired during this period were
longitudinally surveyed for sensitization using the BeLPT. Both the
pre-program and program survey of worker sensitization status utilized
split-sample testing to verify positive test results using the BeLPT.
Of the total 660 workers employed at the production plant, 258 workers
participated from the pre-program group while 290 participated from the
program group (206 partial program, 84 full program). Prevalence
comparisons of the pre-program and program groups (partial and full)
were performed by calculating prevalence ratios. A 95 percent
confidence interval (95 percent CI) was derived using a cohort study
method that accounted for the variance in survey techniques (cross-
sectional versus longitudinal) (Bailey et al., 2010). The sensitization
prevalence of the pre-program group was 3.8 times higher (95 percent
CI, 1.5-9.3) than the program group, 4.0 times higher (95 percent CI,
1.4-11.6) than the partial program subgroup, and 3.3 times higher (95
percent CI, 0.8-13.7) than the full program subgroup indicating that a
comprehensive preventive program can reduce, but not eliminate,
occurrence of sensitization among non-sensitized workers (Bailey et
al., 2010, Document ID 0610).
Rosenman et al. (2005) studied a group of several hundred workers
who had been employed at a beryllium production and processing facility
that operated in eastern Pennsylvania between 1957 and 1978 (Document
ID 1352). Of 715 former workers located, 577 were screened for
beryllium sensitization with the BLPT and 544 underwent chest
radiography to identify cases of beryllium sensitization and CBD.
Workers were reported to have exposure to beryllium dust and fume in a
variety of chemical forms including beryl ore, beryllium metal,
beryllium fluoride, beryllium hydroxide, and beryllium oxide.
Rosenman et al. used the plant's DWA formulas to assess workers'
full-shift exposure levels, based on IH data collected between 1957-
1962 and 1971-1976, to calculate exposure metrics including cumulative,
average, and peak for each worker in the study (Document ID 1352). The
DWA was calculated based on air monitoring that consisted of GA and
short-term task-based BZ samples. Workers' exposures to specific
chemical and physical forms of beryllium were assessed, including
poorly soluble beryllium (metal and oxide), soluble beryllium (fluoride
and hydroxide), mixed soluble and poorly soluble beryllium, beryllium
dust (metal, hydroxide, or oxide), fume (fluoride), and mixed dust and
fume. Use of respiratory or dermal protection by workers was not
reported. Exposures in the plant were high overall. Representative
task-based IH samples ranged from 0.9 μg/m3\ to 84 μg/m3\ in
the 1960s, falling to a range of 0.5-16.7 μg/m3\ in the 1970s. A
large number of workers' mean DWA estimates (25 percent) were above the
preceding OSHA PEL of 2.0 μg/m3\, while most workers had mean DWA
exposures between 0.2 and 2.0 μg/m3\ (74 percent) or below 0.02
μg/m3\ (1 percent) (Rosenman et al., Table 11; revised erratum
April, 2006, Document ID 1352).
Blood samples for the BeLPT were collected from the former workers
between 1996 and 2001 and were evaluated at a single laboratory.
Individuals with an abnormal test result were offered repeat testing,
and were classified as sensitized if the second test was also abnormal.
Sixty workers with two positive BeLPTs and 50 additional workers with
chest radiography suggestive of disease were offered clinical
evaluation, including bronchoscopy with bronchial biopsy and BAL-BeLPT.
Seven workers met both criteria. Only 56 (51 percent) of these workers
proceeded with clinical evaluation, including 57 percent of those
referred on the basis of confirmed abnormal BeLPT and 47 percent of
those with abnormal radiographs (Document ID 1352).
Of the 577 workers who were evaluated for CBD, 32 (5.5 percent)
with evidence of granulomas were classified as "definite" CBD cases
(as identified by bronchoscopy). Twelve (2.1 percent) additional
workers with positive BAL-BeLPT or confirmed positive BeLPT and
radiographic evidence of upper lobe fibrosis were classified as
"probable" CBD cases. Forty workers (6.9 percent) without upper lobe
fibrosis who had confirmed abnormal BeLPT, but who were not biopsied or
who underwent biopsy with no evidence of granuloma, were classified as
sensitized without disease. It is not clear how many of those 40
workers underwent biopsy. Another 12 (2.1 percent) workers with upper
lobe fibrosis and negative or unconfirmed positive BeLPT were
classified as "possible" CBD cases. Nine additional workers who were
diagnosed with CBD before the screening were included in some parts of
the authors' analysis (Document ID 1352).
The authors reported a total prevalence of 14.5 percent for CBD
(definite and probable) and sensitization. This rate, considerably
higher than the overall prevalence of sensitization and disease in
several other worker cohorts as described earlier in this section,
reflects in part the very high exposures experienced by many workers
during the plant's operation in the 1950s, 1960s and 1970s. A total of
115 workers had mean DWAs above the preceding OSHA PEL of 2 μg/m3\.
Of those, seven (6.0 percent) had definite or probable CBD and another
13 (11 percent) were classified as sensitized without disease. The true
prevalence of CBD in the group may be higher than reported, due to the
low rate of clinical evaluation among sensitized workers (Document ID
1352).
Although most of the workers in this study had high exposures,
sensitization and CBD also were observed within the small subgroup of
participants believed to have relatively low beryllium exposures.
Thirty-three cases of CBD and 24 additional cases of sensitization
occurred among 339 workers with mean DWA exposures below OSHA's PEL of
2.0 μg/m3\ (Rosenman et al., Table 11, erratum 2006, Document ID
1352). Ten cases of sensitization and five cases of
CBD were found among office and clerical workers, who were believed to
have low exposures (levels not reported).
Follow-up time for sensitization screening of workers in this study
who became sensitized during their employment had a minimum of 20 years
to develop CBD prior to screening. In this sense the cohort is
especially well suited to compare the exposure patterns of workers with
CBD and those sensitized without disease, in contrast to several other
studies of workers with only recent beryllium exposures. Rosenman et
al. characterized and compared the exposures of workers with definite
and probable CBD, sensitization only, and no disease or sensitization
using chi-squared tests for discrete outcomes and analysis of variance
(ANOVA) for continuous variables (cumulative, mean, and peak exposure
levels). Exposure-response relationships were further examined with
logistic regression analysis, adjusting for potential confounders
including smoking, age, and beryllium exposure from outside of the
plant. The authors found that cumulative, peak, and duration of
exposure were significantly higher for workers with CBD than for
sensitized workers without disease (p <0.05), suggesting that the risk
of progressing from sensitization to CBD is related to the level or
extent of exposure a worker experiences. The risk of developing CBD
following sensitization appeared strongly related to exposure to poorly
soluble forms of beryllium, which are cleared slowly from the lung and
increase beryllium lung burden more rapidly than quickly mobilized
soluble forms. Individuals with CBD had higher exposures to poorly
soluble beryllium than those classified as sensitized without disease,
while exposure to soluble beryllium was higher among sensitized
individuals than those with CBD (Document ID 1352).
Cumulative, mean, peak, and duration of exposure were found to be
comparable for workers with CBD and workers without sensitization or
CBD ("normal" workers). Cumulative, peak, and duration of exposure
were significantly lower for sensitized workers without disease than
for normal workers. Rosenman et al. suggested that genetic
predisposition to sensitization and CBD may have obscured an exposure-
response relationship in this study, and plan to control for genetic
risk factors in future studies. Exposure misclassification from the
1950s and 1960s may have been another limitation in this study,
introducing bias that could have influenced the lack of exposure
response. It is also unknown if the 25 percent who died from CBD-
related conditions may have had higher exposures (Document ID 1352).
A follow-up was conducted of the cross-sectional study of a
population of workers first evaluated by Kreiss et al. (1997) (Document
ID 1360) and Rosenman et al. (2005) (Document ID 1352) by Schuler et
al. (2012) (Document ID 0473), and in a companion study by Virji et al.
(2012) (Document ID 0466). Schuler et al. evaluated the worker
population employed in 1999 with six years or less work tenure in a
cross-sectional study. The investigators evaluated the worker
population by administering a work history questionnaire with a follow-
up examination for sensitization and CBD. A job-exposure matrix (JEM)
was combined with work histories to create individual estimates of
average, cumulative, and highest-job-related exposure for total,
respirable, and sub-micron beryllium mass concentration. Of the 291
eligible workers, 90.7 percent (264) participated in the study.
Sensitization prevalence was 9.8 percent (26/264) with CBD prevalence
of 2.3 percent (6/264). The investigators found a general pattern of
increasing sensitization prevalence as the exposure quartile increased
indicating an exposure-response relationship. The investigators found
positive associations with both total and respirable mass concentration
with sensitization (average and highest job) and CBD (cumulative).
Increased sensitization prevalence was observed with metal oxide
production alloy melting and casting, and maintenance. CBD was
associated with melting and casting. The investigators summarized that
both total and respirable mass concentration were relevant predictors
of risk (Schuler et al., 2012, Document ID 0473).
In the companion study by Virji et al. (2012), the investigators
reconstructed historical exposure from 1994 to 1999 utilizing the
personal sampling data collected in 1999 as baseline exposure estimates
(BEE) (Document ID 0466). The study evaluated techniques for
reconstructing historical data to evaluate exposure-response
relationships for epidemiological studies. The investigators
constructed JEMs using the BEE and estimates of annual changes in
exposure for 25 different process areas. The investigators concluded
these reconstructed JEMs could be used to evaluate a range of exposure
parameters from total, respirable and submicron mass concentration
including cumulative, average, and highest exposure.
e. Beryllium Machining Operations
Newman et al. (2001) (Document ID 1354) and Kelleher et al. (2001)
(Document ID 1363) studied a group of 235 workers at a beryllium metal
machining plant. Since the plant opened in 1969, its primary operations
have been machining and polishing beryllium metal and high-beryllium
content composite materials, with occasional machining of beryllium
oxide/metal matrix (`E-metal'), and beryllium alloys. Other functions
include machining of metals other than beryllium; receipt and
inspection of materials; acid etching; final inspection, quality
control, and shipping of finished materials; tool making; and
engineering, maintenance, administrative, and supervisory functions
(Newman et al., 2001, Document ID 1354; Madl et al., 2007 (1056)).
Machining operations, including milling, grinding, lapping, deburring,
lathing, and electrical discharge machining (EDM) were performed in an
open-floor plan production area. Most non-machining jobs were located
in a separate, adjacent area; however, non-production employees had
access to the machining area.
Engineering and administrative controls, rather than PPE, were
primarily used to control beryllium exposures at the plant (Madl et
al., 2007, Document ID 1056). Based on interviews with long-standing
employees of the plant, Kelleher et al. reported that work practices
were relatively stable until 1994, when a worker was diagnosed with CBD
and a new exposure control program was initiated. Between 1995 and
1999, new engineering and work practice controls were implemented,
including removal of pressurized air hoses and discouragement of dry
sweeping (1995), enclosure of deburring processes (1996), mandatory
uniforms (1997), and installation or updating of local exhaust
ventilation (LEV) in EDM, lapping, deburring, and grinding processes
(1998) (Madl et al., 2007, Document ID 1056). Throughout the plant's
history, respiratory protection was used mainly for "unusually large,
anticipated exposures" to beryllium (Kelleher et al., 2001, Document
ID 1363), and was not routinely used otherwise (Newman et al., 2001,
Document ID 1354).
All workers at the plant participated in a beryllium disease
surveillance program initiated in 1994, and were screened for beryllium
sensitization with the BeLPT beginning in 1995. A BeLPT result was
considered abnormal if two or more of six stimulation indices exceeded
the normal range (see section
on BeLPT testing above), and was considered borderline if one of the
indices exceeded the normal range. A repeat BeLPT was conducted for
workers with abnormal or borderline initial results. Workers were
identified as beryllium sensitized and referred for a clinical
evaluation, including BAL and transbronchial lung biopsy, if the repeat
test was abnormal. CBD was diagnosed upon evidence of sensitization
with granulomas or mononuclear cell infiltrates in the lung tissue
(Newman et al., 2001, Document ID 1354). Following the initial plant-
wide screening, plant employees were offered BeLPT testing at two-year
intervals. Workers hired after the initial screening were offered a
BeLPT within 3 months of their hire date, and at 2-year intervals
thereafter (Madl et al., 2007, Document ID 1056).
Kelleher et al. performed a nested case-control study of the 235
workers evaluated in Newman et al. (2001) to evaluate the relationship
between beryllium exposure levels and risk of sensitization and CBD
(Kelleher et al., 2001, Document ID 1363). The authors evaluated
exposures at the plant using IH samples they had collected between 1996
and 1999, using personal cascade impactors designed to measure the mass
of beryllium particles less than 6 μm in diameter, particles less
than 1 μm in diameter, and total mass. The great majority of
workers' exposures were below the preceding OSHA PEL of 2 μg/m3\.
However, a few higher exposure levels were observed in machining jobs
including deburring, lathing, lapping, and grinding. Based on a
statistical comparison between their samples and historical data
provided by the plant, the authors concluded that worker beryllium
exposures across all time periods included in the study parameters
(1981 to 1984, 1995 to 1997, and 1998 to 1999) could be approximated
using the 1996-1999 data. They estimated workers' cumulative and
"lifetime weighted" (LTW) beryllium exposure based on the exposure
samples they collected for each job in 1996-1999 and company records of
each worker's job history.
Twenty workers with beryllium sensitization or CBD (cases) were
compared to 206 workers (controls) for the case-control analysis from
the study evaluating workers originally conducted by Newman et al. Of
the 20 workers composing the case group, thirteen workers were
diagnosed with CBD based on lung biopsy evidence of granulomas and/or
mononuclear cell infiltrates (11) or positive BAL results with evidence
of lymphocytosis (2). The other seven were evaluated for CBD and found
to be sensitized only. Nine of the remaining 215 workers first
identified in original study (Newman et al., 2001, Document ID 1354)
were excluded due to incomplete job history information, leaving 206
workers in the control group.
Kelleher et al.'s analysis included comparisons of the case and
control groups' median exposure levels; calculation of odds ratios for
workers in high, medium, and low exposure groups; and logistic
regression testing of the association of sensitization or CBD with
exposure level and other variables. Median cumulative exposures for
total mass, particles less than 6 μm in diameter, and particles less
than 1 μm in diameter were approximately three times higher among
the cases than controls, although the relationships observed were not
statistically significant (p values ~ 0.2). No clear difference between
cases and controls was observed for the median LTW exposures. Odds
ratios with sensitization and CBD as outcomes were elevated in high
(upper third) and intermediate exposure groups relative to low (lowest
third) exposure groups for both cumulative and LTW exposure, though the
results were not statistically significant (p >0.1). In the logistic
regression analysis, only machinist work history was a significant
predictor of case status in the final model. Quantitative exposure
measures were not significant predictors of sensitization or disease
risk.
Citing an 11.5 percent prevalence of beryllium sensitization or CBD
among machinists as compared with 2.9 percent prevalence among workers
with no machinist work history, the authors concluded that the risk of
sensitization and CBD is increased among workers who machine beryllium.
Although differences between cases and controls in median cumulative
exposure did not achieve conventional thresholds for statistical
significance, the authors noted that cumulative exposures were
consistently higher among cases than controls for all categories of
exposure estimates and for all particle sizes, suggesting an effect of
cumulative exposure on risk. The levels at which workers developed CBD
and sensitization were predominantly below OSHA's preceding PEL of 2
μg/m3\, and no cases of sensitization or CBD were observed among
workers with LTW exposure less than 0.02 μg/m3\. Twelve (60
percent) of the 20 sensitized workers had LTW exposures >0.20 μg/
m3\.
In 2007, Madl et al. published an additional study of 27 workers at
the machining plant who were found to be sensitized or diagnosed with
CBD between the start of medical surveillance in 1995 and 2005 (Madl et
al., 2007, Document ID 1056). As previously described, workers were
offered a BeLPT in the initial 1995 screening (or within 3 months of
their hire date if hired after 1995) and at 2-year intervals after
their first screening. Workers with two positive BeLPTs were identified
as sensitized and offered clinical evaluation for CBD, including
bronchoscopy with BAL and transbronchial lung biopsy. The criteria for
CBD in this study were somewhat stricter than those used in the Newman
et al. study, requiring evidence of granulomas on lung biopsy or
detection of X-ray or pulmonary function changes associated with CBD,
in combination with two positive BeLPTs or one positive BAL-BeLPT.
Based on the history of the plant's control efforts and their
analysis of historical IH data, Madl et al. identified three "exposure
control eras": A relatively uncontrolled period from 1980-1995; a
transitional period from 1996 to 1999; and a relatively well-controlled
"modern" period from 2000-2005. They found that the engineering and
work practice controls instituted in the mid-1990s reduced workers'
exposures substantially, with nearly a 15-fold difference in reported
exposure levels between the pre-control and the modern period (Madl et
al., 2007, Document ID 1056). Madl et al. estimated workers' exposures
using LP samples collected between 1980 and 2005, including those
collected by Kelleher et al., and work histories provided by the plant.
As described more fully in the study, they used a variety of approaches
to describe individual workers' exposures, including approaches
designed to characterize the highest exposures workers were likely to
have experienced. Their exposure-response analysis was based primarily
on an exposure metric they derived by identifying the year and job of
each worker's pre-diagnosis work history with the highest reported
exposures. They used the upper 95th percentile of the LP samples
collected in that job and year (in some cases supplemented with data
from other years) to characterize the worker's upper-level exposures.
Based on their estimates of workers' upper level exposures, Madl et
al. concluded that sensitized workers or workers with CBD were likely
to have been exposed to airborne beryllium levels greater than 0.2
μg/m3\ as an 8-hour TWA at some point in their history of
employment in the plant. Madl et al. also concluded that most
sensitization and CBD cases were likely to have been exposed to levels
greater than 0.4 μg/m3\
at some point in their work at the plant. Madl et al. did not
reconstruct exposures for workers at the plant who were not sensitized
and did not develop CBD and therefore could not determine whether non-
cases had upper-bound exposures lower than these levels. They found
that upper-bound exposure estimates were generally higher for workers
with CBD than for those who were sensitized but not diagnosed with CBD
at the conclusion of the study (Madl et al., 2007, Document ID 1056).
Because CBD is an immunological disease and beryllium sensitization has
been shown to occur within a year of exposure for some workers, Madl et
al. argued that their estimates of workers' short-term upper-bound
exposures may better capture the exposure levels that led to
sensitization and disease than estimates of long-term cumulative or
average exposures such as the LTW exposure measure constructed by
Kelleher et al. (Madl et al., 2007, Document ID 1056).
f. Beryllium Oxide Ceramics
Kreiss et al. (1993) conducted a screening of current and former
workers at a plant that manufactured beryllium ceramics from beryllium
oxide between 1958 and 1975, and then transitioned to metalizing
circuitry onto beryllium ceramics produced elsewhere (Document ID
1478). Of the plant's 1,316 current and 350 retired workers, 505
participated who had not previously been diagnosed with CBD or
sarcoidosis, including 377 current and 128 former workers. Although
beryllium exposure was not estimated quantitatively in this survey, the
authors conducted a questionnaire to assess study participants'
exposures qualitatively. Results showed that 55 percent of participants
reported working in jobs with exposure to beryllium dust. Close to 25
percent of participants did not know if they had exposure to beryllium,
and just over 20 percent believed they had not been exposed.
BeLPT tests were administered to all 505 participants in the 1989-
1990 screening period and evaluated at a single lab. Seven workers had
confirmed abnormal BeLPT results and were identified as sensitized;
these workers were also diagnosed with CBD based on findings of
granulomas upon clinical evaluation. Radiograph screening led to
clinical evaluation and diagnosis of two additional CBD cases, who were
among three participants with initially abnormal BeLPT results that
could not be confirmed on repeat testing. In addition, nine workers had
been previously diagnosed with CBD, and another five were diagnosed
shortly after the screening period, in 1991-1992.
Eight of the 9 CBD cases identified in the screening population
were hired before the plant stopped producing beryllium ceramics in
1975, and were among the 216 participants who had reported having been
near or exposed to beryllium dust. Particularly high CBD rates of 11.1
to 15.8 percent were found among screening participants who had worked
in process development/engineering, dry pressing, and ventilation
maintenance jobs believed to have high or uncontrolled dust exposure.
One case (0.6 percent) of CBD was diagnosed among the 171 study
participants who had been hired after the plant stopped producing
beryllium ceramics. Although this worker was hired eight years after
the end of ceramics production, he had worked in an area later found to
be contaminated with beryllium dust. The authors concluded that the
study results suggested an exposure-response relationship between
beryllium exposure and CBD, and recommended beryllium exposure control
to reduce workers' risk of CBD.
Kreiss et al. later published a study of workers at a second
ceramics plant located in Tucson, AZ (Kreiss et al., 1996, Document ID
1477), which since 1980 had produced beryllium ceramics from beryllium
oxide powder manufactured elsewhere. IH measurements collected between
1981 and 1992, primarily GA or short-term BZ samples and a few (<100)
LP samples, were available from the plant. Airborne beryllium exposures
were generally low. The majority of area samples were below the
analytical detection limit of 0.1 μg/m3\, while LP and short-term
BZ samples had medians of 0.3 μg/m3\. However, 3.6 percent of
short-term BZ samples and 0.7 percent of GA samples exceeded 5.0 μg/
m3\, while LP samples ranged from 0.1 to 1.8 μg/m3\. Machining
jobs had the highest beryllium exposure levels among job tasks, with
short-term BZ samples significantly higher for machining jobs than for
non-machining jobs (median 0.6 μg/m3\ vs. 0.3 μg/m3\, p =
0.0001). The authors used DWA formulas provided by the plant to
estimate workers' full-shift exposure levels, and to calculate
cumulative and average beryllium exposures for each worker in the
study. The median cumulative exposure was 591.7 mg-days/m3\ and the
median average exposure was 0.35 μg/m3\ as a DWA.
One hundred thirty-six of the 139 workers employed at the plant at
the time of the Kreiss et al. (1996) study underwent BeLPT screening
and chest radiographs in 1992 (Document ID 1477). Blood samples were
split between two laboratories. If one or both test results were
abnormal, an additional sample was collected and split between the
labs. Seven workers with an abnormal result on two draws were initially
identified as sensitized. Those with confirmed abnormal BeLPTs or
abnormal chest X-rays were offered clinical evaluation for CBD,
including transbronchial lung biopsy and BAL BeLPT. CBD was diagnosed
based on observation of granulomas on lung biopsy, in five of the six
sensitized workers who accepted evaluation. An eighth case of
sensitization and sixth case of CBD were diagnosed in one worker hired
in October 1991 whose initial BeLPT was normal, but who was confirmed
as sensitized and found to have lung granulomas less than two years
later, after sustaining a beryllium-contaminated skin wound. The plant
medical department reported 11 additional cases of CBD among former
workers (Kreiss et al., 1996, Document ID 1477). The overall prevalence
of sensitization in the plant was 5.9 percent, with a 4.4 percent
prevalence of CBD.
Kreiss et al. (1996) (Document ID 1477) reported that six (75
percent) of the eight sensitized workers were exposed as machinists
during or before the period October 1985-March 1988, when measurements
were first available for machining jobs. The authors reported that 14.3
percent of machinists were sensitized, compared to 1.2 percent of
workers who had never been machinists (p <0.01). Workers' estimated
cumulative and average beryllium exposures did not differ significantly
for machinists and non-machinists, or for cases and non-cases. As in
the previous study of the same ceramics plant published by Kreiss et
al. in 1993 (Document ID 1478), one case of CBD was diagnosed in a
worker who had never been employed in a production job. This worker was
employed in office administration, a job with a median DWA of 0.1
μg/m3\ (range 0.1-0.3 μg/m3\).
In 1998, Henneberger et al. conducted a follow-up cross-sectional
survey of 151 employees employed at the beryllium ceramics plant
studied by Kreiss et al. (1996) (Henneberger et al., 2001, Document ID
1313). All current plant employees were eligible for the study unless
they had previously been diagnosed with CBD. The study tracked two sets
of workers in presenting prevalence outcomes and exposure
characterization. "Short-term workers" were those hired since the
last plant survey in 1992. "Long-term workers"
were those hired before 1992 and had a longer history of beryllium
exposures. There were 74 short-term and 77 long-term workers in the
survey (Henneberger et al., 2001, Document ID 1313).
The authors estimated workers' cumulative, average, and peak
beryllium exposures based on the plant's formulas for estimating job-
specific DWA exposures, participants' work histories, and area and
short-term task-specific BZ samples collected from the start of full
production at the plant in 1981 to 1998. The long-term workers, who
were hired before the 1992 study was conducted, had generally higher
estimated exposures (median--0.39 μg/m3\; mean--14.9 μg/m3\)
than the short-term workers, who were hired after 1992 (median--0.28
μg/m3\, mean--6.1 μg/m3\).
Fifteen cases of sensitization were found in the 151 study
participants (15/151; 9.9%), including seven among short-term (7/74;
9.5%) and eight among long-term workers (8/77; 10.4%). There were eight
cases of CBD (8/151; 5.3%) identified in the study. One sensitized
short-term worker developed CBD (1/74; 1.4%). Seven of the eight
sensitized long-term workers developed CBD (7/77; 9.1%). The other
sensitized long-term worker declined to participate in the clinical
evaluation.
Henneberger et al. (2001) reported a higher prevalence of
sensitization among long-term workers with "high" (greater than
median) peak exposures compared to long-term workers with "low"
exposures; however, this relationship was not statistically significant
(Document ID 1313). No association was observed for average or
cumulative exposures. The authors reported higher (but not
statistically significant) prevalence of sensitization among short-term
workers with "high" (greater than median) average, cumulative, and
peak exposures compared to short-term workers with "low" exposures of
each type.
The cumulative incidence of sensitization and CBD was investigated
in a cohort of 136 workers at the beryllium ceramics plant previously
studied by the Kreiss and Henneberger groups (Schuler et al., 2008.
Document ID 1291). The study cohort consisted of those who participated
in the plant-wide BeLPT screening in 1992. Both current and former
workers from this group were invited to participate in follow-up BeLPT
screenings in 1998, 2000, and 2002-2003. A total of 106 of the 128 non-
sensitized individuals in 1992 participated in the 11-year follow-up.
Sensitization was defined as a confirmed abnormal BeLPT based on the
split blood sample-dual laboratory protocol described earlier. CBD was
diagnosed in sensitized individuals based on pathological findings from
transbronchial biopsy and BAL fluid analysis. The 11-year crude
cumulative incidence of sensitization and CBD was 13 percent (14 of
106) and 8 percent (9 of 106) respectively. The cumulative prevalence
was about triple the point prevalences determined in the initial 1992
cross-sectional survey. The corrected cumulative prevalences for those
that ever worked in machining were nearly twice that for non-
machinists. The data illustrate the value of longitudinal medical
screening over time to obtain a more accurate estimate of the
occurrence of sensitization and CBD among an exposed working
population.
Following the 1998 survey, the company continued efforts to reduce
exposures and risk of sensitization and CBD by implementing additional
engineering, administrative, and PPE measures (Cummings et al., 2007,
Document ID 1369). Respirator use was required in production areas
beginning in 1999, and latex gloves were required beginning in 2000.
The lapping area was enclosed in 2000, and enclosures were installed
for all mechanical presses in 2001. Between 2000 and 2003, water-
resistant or water-proof garments, shoe covers, and taped gloves were
incorporated to keep beryllium-containing fluids from wet machining
processes off the skin. The new engineering measures did not appear to
substantially reduce airborne beryllium levels in the plant. LP samples
collected between 2000 and 2003 had a median of 0.18 μg/m3\ in
production, similar to the 1994-1999 samples. However, respiratory
protection requirements to control workers' airborne beryllium
exposures were instituted prior to the 2000 sample collections, so
actual exposure to the production workers may have been lower than the
airborne beryllium levels indicate.
To test the efficacy of the new measures instituted after 1998, in
January 2000 the company began screening new workers for sensitization
at the time of hire and at 3, 6, 12, 24, and 48 months of employment.
These more stringent measures appear to have substantially reduced the
risk of sensitization among new employees. Of 126 workers hired between
2000 and 2004, 93 completed BeLPT testing at hire and at least one
additional test at 3 months of employment. One case of sensitization
was identified at 24 months of employment (1 percent of 126 workers).
This worker had experienced a rash after an incident of dermal exposure
to lapping fluid through a gap between his glove and uniform sleeve,
indicating that he may have become sensitized via the skin. He was
tested again at 48 months of employment, with an abnormal result.
A second worker in the 2000-2004 group had two abnormal BeLPT tests
at the time of hire, and a third had one abnormal test at hire and a
second abnormal test at 3 months. Both had normal BeLPTs at 6 months,
and were not tested thereafter. A fourth worker had one abnormal BeLPT
result at the time of hire, a normal result at 3 months, an abnormal
result at 6 months, and a normal result at 12 months. Four additional
workers had one abnormal result during surveillance, which could not be
confirmed upon repeat testing.
Cummings et al. (2007) calculated two sensitization rates based on
these screening results: (1) A rate using only the sensitized worker
identified at 24 months, and (2) a rate including all four workers who
had repeated abnormal results (Document ID 1369). They reported a
sensitization incidence rate (IR) of 0.7 per 1,000 person-months to 2.7
per 1,000 person-months for the workers hired between 2000 and 2004,
using the sum of sensitization-free months of employment among all 93
workers as the denominator.
The authors also estimated an incidence rate (IR) of 5.6 per 1,000
person-months for workers hired between 1993 and the 1998 survey. This
estimated IR was based on one BeLPT screening, rather than BeLPTs
conducted throughout the workers' employment. The denominator in this
case was the total months of employment until the 1998 screening.
Because sensitized workers may have been sensitized prior to the
screening, the denominator may overestimate sensitization-free time in
the legacy group, and the actual sensitization IR for legacy workers
may be somewhat higher than 5.6 per 1,000 person-months. Based on
comparison of the IRs, the authors concluded that the addition of
respirator use, dermal protection, and particle migration control
(housekeeping) improvements appeared to have reduced the risk of
sensitization among workers at the plant, even though airborne
beryllium levels in some areas of the plant had not changed
significantly since the 1998 survey.
g. Copper-Beryllium Alloy Processing and Distribution
Schuler et al. (2005) studied a group of 152 workers at a facility
who processed copper-beryllium alloys and small quantities of nickel-
beryllium alloys and converted semi-finished alloy
strip and wire into finished strip, wire, and rod. Production
activities included annealing, drawing, straightening, point and
chamfer, rod and wire packing, die grinding, pickling, slitting, and
degreasing. Periodically in the plant's history, it also performed salt
baths, cadmium plating, welding and deburring. Since the late 1980s,
rod and wire production processes have been physically segregated from
strip metal production. Production support jobs included mechanical
maintenance, quality assurance, shipping and receiving, inspection, and
wastewater treatment. Administration was divided into staff primarily
working within the plant and personnel who mostly worked in office
areas (Schuler, et al., 2005, Document ID 0919). Workers' respirator
use was limited, mostly to occasional tasks where high exposures were
anticipated.
Following the 1999 diagnosis of a worker with CBD, the company
surveyed the workforce, offering all current employees BeLPT testing in
2000 and offering sensitized workers clinical evaluation for CBD,
including BAL and transbronchial biopsy. Of the facility's 185
employees, 152 participated in the BeLPT screening. Samples were split
between two laboratories, with additional draws and testing for
confirmation if conflicting tests resulted in the initial draw. Ten
participants (7 percent) had at least two abnormal BeLPT results. The
results of nine workers who had abnormal BeLPT results from only one
laboratory were not included because the authors believed the
laboratory was experiencing technical problems with the test (Schuler
et al., 2005, Document ID 0919). CBD was diagnosed in six workers (4
percent) on evidence of pathogenic abnormalities (e.g., granulomas) or
evidence of clinical abnormalities consistent with CBD based on
pulmonary function testing, pulmonary exercise testing, and/or chest
radiography. One worker diagnosed with CBD had been exposed to
beryllium during previous work at another copper-beryllium processing
facility.
Schuler et al. (2005) evaluated airborne beryllium levels at the
plant using IH samples collected between 1969 and 2000, including 4,524
GA samples, 650 LP samples and 815 short-duration (3-5 min) high volume
(SD-HV) BZ task-specific samples (Document ID 0919). Occupational
exposures to airborne beryllium were generally low. Ninety-nine percent
of all LP measurements were below the preceding OSHA PEL of 2.0 μg/
m3\ (8-hr TWA); 93 percent were below the new final OSHA PEL of 0.2
μg/m3\ and the median value was 0.02 μg/m3\. The SD-HV BZ
samples had a median value of 0.44 μg/m3\, with 90 percent below
the preceding OSHA ceiling limit of 5.0 μg/m3\. The highest levels
of beryllium exposure were found in rod and wire production,
particularly in wire annealing and pickling, the only production job
with a median personal sample measurement greater than 0.1 μg/m3\
(median 0.12 μg/m3\; range 0.01-7.8 μg/m3\) (Schuler et al.,
Table 4). These concentrations were significantly higher than the
exposure levels in the strip metal area (median 0.02 μg/m3\, range
0.01-0.72 μg/m3\), in production support jobs (median 0.02 μg/
m3\, range <0.01-0.33 μg/m3\), plant administration (median 0.02
μg/m3\, range <0.01-0.11 μg/m3\), and office administration
jobs (median 0.01 μg/m3\, range <0.01-0.06 μg/m3\).
The authors reported that eight of the ten sensitized employees,
including all six CBD cases, had worked in both major production areas
during their tenure with the plant. The 7 percent prevalence (6 of 81
workers) of CBD among employees who had ever worked in rod and wire was
statistically significantly elevated compared with employees who had
never worked in rod and wire (p <0.05), while the 6 percent prevalence
(6 of 94 workers) among those who had worked in strip metal was not
significantly elevated compared to workers who had never worked in
strip metal (p > 0.1). Based on these results, together with the higher
exposure levels reported for the rod and wire production area, Schuler
et al. (2005) concluded that work in rod and wire was a key risk factor
for CBD in this population. Schuler et al. also found a high prevalence
(13 percent) of sensitization among workers who had been exposed to
beryllium for less than a year at the time of the screening, a rate
similar to that found by Henneberger et al. (2001) among beryllium
ceramics workers exposed for one year or less (16 percent) (Henneberger
et al., 2001, Document ID 1313). All four workers who were sensitized
without disease had been exposed for 5 years or less; conversely, all
six of the workers with CBD had first been exposed to beryllium at
least five years prior to the screening (Schuler et al., 2005, Table 2,
Document ID 0919).
As has been seen in other studies, beryllium sensitization and CBD
were found among workers who were typically exposed to low time-
weighted average airborne concentrations of beryllium. While jobs in
the rod and wire area had the highest exposure levels in the plant, the
median personal sample value was only 0.12 μg/m3\ as a DWA.
However, workers may have occasionally been exposed to higher beryllium
levels for short periods during specific tasks. A small fraction of
personal samples recorded in rod and wire were above the preceding OSHA
PEL of 2.0 μg/m3\, and half of workers with sensitization or CBD
reported that they had experienced a "high-exposure incident" at some
point in their work history (Schuler et al., 2005, Document ID 0919).
The only group of workers with no cases of sensitization or CBD, a
group of 26 office administration workers, was the group with the
lowest recorded exposures (median personal sample 0.01 μg/m3\,
range <0.01-0.06 μg/m3\).
After the BeLPT screening was conducted in 2000, the company began
implementing new measures to further reduce workers' exposure to
beryllium (Thomas et al., 2009, Document ID 1061). Measures designed to
minimize dermal contact with beryllium, including long-sleeve facility
uniforms and polymer gloves, were instituted in production areas in
2000. In 2001, the company installed LEV in die grinding and polishing.
LP samples collected between June 2000 and December 2001 show reduced
exposures plant-wide. Of 2,211 exposure samples collected, 98 percent
were below 0.2 μg/m3\, and 59 percent below the limit of detection
(LOD), which was either 0.02 µg/m3\ or 0.2 µg/m3\
depending on the method of sample analysis (Thomas et al., 2009).
Median values below 0.03 μg/m3\ were reported for all processes
except the wire annealing and pickling process. Samples for this
process remained somewhat elevated, with a median of 0.1 μg/m3\. In
January 2002, the plant enclosed the wire annealing and pickling
process in a restricted access zone (RAZ), requiring respiratory
protection in the RAZ and implementing stringent measures to minimize
the potential for skin contact and beryllium transfer out of the zone.
While exposure samples collected by the facility were sparse following
the enclosure, they suggest exposure levels comparable to the 2000-2001
samples in areas other than the RAZ. Within the RAZ, required use of
powered air-purifying respirators indicates that actual respiratory
exposure was negligible (Thomas et al., 2009, Document ID 1061).
To test the efficacy of the new measures in preventing
sensitization and CBD, in June 2000 the facility began an intensive
BeLPT screening program for all new workers. The company screened
workers at the time of hire; at intervals of 3, 6, 12, 24, and 48
months;
and at 3-year intervals thereafter. Among 82 workers hired after 1999,
three (3.7 percent) cases of sensitization were found. Two (5.4
percent) of 37 workers hired prior to enclosure of the wire annealing
and pickling process were found to be sensitized within 6 months of
beginning work at the plant. One (2.2 percent) of 45 workers hired
after the enclosure was confirmed as sensitized (Thomas et al., 2009,
Document ID 1061).
Thomas et al. (2009) calculated a sensitization IR of 1.9 per 1,000
person-months for the workers hired after the exposure control program
was initiated in 2000 ("program workers"), using the sum of
sensitization-free months of employment among all 82 workers as the
denominator (Thomas et al., 2009, Document ID 1061). They calculated an
estimated IR of 3.8 per 1,000 person-months for 43 workers hired
between 1993 and 2000 who had participated in the 2000 BeLPT screening
("legacy workers"). This estimated IR was based on one BeLPT
screening, rather than BeLPTs conducted throughout the legacy workers'
employment. The denominator in this case is the total months of
employment until the 2000 screening. Because sensitized workers may
have been sensitized prior to the screening, the denominator may
overestimate sensitization-free time in the legacy group, and the
actual sensitization IR for legacy workers may be somewhat higher than
3.8 per 1,000 person-months. Based on comparison of the IRs and the
prevalence rates discussed previously, the authors concluded that the
combination of dermal protection, respiratory protection, housekeeping
improvements and engineering controls implemented beginning in 2000
appeared to have reduced the risk of sensitization among workers at the
plant. However, they noted that the small size of the study population
and the short follow-up time for the program workers suggested that
further research is needed to confirm the program's efficacy (Thomas et
al., 2009, Document ID 1061).
Stanton et al. (2006) (Document ID 1070) conducted a study of
workers in three different copper-beryllium alloy distribution centers
in the United States. The distribution centers, consisting of one bulk
products center established in 1963 and strip metal centers established
in 1968 and 1972, sell products received from beryllium production and
finishing facilities and small quantities of copper-beryllium,
aluminum-beryllium, and nickel-beryllium alloy materials. Work at
distribution centers does not require large-scale heat treatment or
manipulation of material typical of beryllium processing and machining
plants, but involves final processing steps that can generate airborne
beryllium. Slitting, the main production activity at the two strip
product distribution centers, generates low levels of airborne
beryllium particles, while operations such as tensioning and welding
used more frequently at the bulk products center can generate somewhat
higher levels. Non-production jobs at all three centers included
shipping and receiving, palletizing and wrapping, production-area
administrative work, and office-area administrative work.
Stanton et al. (2006) estimated workers' beryllium exposures using
IH data from company records and job history information collected
through interviews conducted by a company occupational health nurse
(Document ID 1090). Stanton et al. evaluated airborne beryllium levels
in various jobs based on 393 full-shift LP samples collected from 1996
to 2004. Airborne beryllium levels at the plant were generally very
low, with 54 percent of all samples at or below the LOD, which ranged
from 0.02 to 0.1 μg/m3\. The authors reported a median of 0.03
μg/m3\ and an arithmetic mean of 0.05 μg/m3\ for the 393 full-
shift LP samples, where samples below the LOD were assigned a value of
half the applicable LOD. Median values for specific jobs ranged from
0.01-0.07 µg/m3\ while geometric mean values for specific jobs
ranged from 0.02-0.07 µg/m3\. All measurements were below the
preceding OSHA PEL of 2.0 μg/m3\ and 97 percent were below the new
final OSHA PEL of 0.2 μg/m3\. The study does not report use of
respiratory or skin protection.
Eighty-eight of the 100 workers (88 percent) employed at the three
centers at the time of the study participated in screening for
beryllium sensitization. Blood samples were collected between November
2000 and March 2001 by the company's medical staff. Samples collected
from employees of the strip metal centers were split and evaluated at
two laboratories, while samples from the bulk product center workers
were evaluated at a single laboratory. Participants were considered to
be "sensitized" to beryllium if two or more BeLPT results, from two
laboratories or from repeat testing at the same laboratory, were found
to be abnormal. One individual was found to be sensitized and was
offered clinical evaluation, including BAL and fiberoptic bronchoscopy.
He was found to have lung granulomas and was diagnosed with CBD.
The worker diagnosed with CBD had been employed at a strip metal
distribution center from 1978 to 2000 as a shipper and receiver,
loading and unloading trucks delivering materials from a beryllium
production facility and to the distribution center's customers.
Although the LP samples collected for his job between 1996 and 2000
were generally low (n = 35, median 0.01 µg/m3\, range <0.02-0.13
µg/m3\), it is not clear whether these samples adequately
characterize his exposure conditions over the course of his work
history. He reported that early in his work history, containers of
beryllium oxide powder were transported on the trucks he entered. While
he did not recall seeing any breaks or leaks in the beryllium oxide
containers, some containers were known to have been punctured by
forklifts on trailers used by the company during the period of his
employment, and could have contaminated trucks he entered. With 22
years of employment at the facility, this worker had begun beryllium-
related work earlier and performed it longer than about 90 percent of
the study population (Stanton et al., 2006, Document ID 1090).
h. Nuclear Weapons Production Facilities and Cleanup of Former
Facilities
Primary exposure from nuclear weapons production facilities comes
from beryllium metal and beryllium alloys. A study conducted by Kreiss
et al. (1989) (Document ID 1480) documented sensitization and CBD among
beryllium-exposed workers in the nuclear industry. A company medical
department identified 58 workers with beryllium exposure among a work
force of 500, of whom 51 (88 percent) participated in the study.
Twenty-four workers were involved in research and development (R&D),
while the remaining 27 were production workers. The R&D workers had a
longer tenure with a mean time from first exposure of 21.2 years,
compared to a mean time since first exposure of 5 years among the
production workers. Six workers had abnormal BeLPT readings, and four
were diagnosed with CBD. This study classified workers as sensitized
after one abnormal BeLPT reading, so this resulted in an estimated 11.8
percent prevalence of sensitization.
Kreiss et al. (1993) expanded the work of Kreiss et al. (1989)
(Document ID 1480) by performing a cross-sectional study of 895 current
and former beryllium workers in the same nuclear weapons plant
(Document ID 1479). Participants were placed in qualitative exposure
groups ("no exposure," "minimal exposure," "intermittent
exposure," and "consistent exposure") based on questionnaire
responses. Eighteen workers had abnormal BeLPT test results, with 12
being diagnosed with CBD. Three additional sensitized workers (those
with abnormal BeLPT results) developed CBD over the next 2 years.
Sensitization occurred in all of the qualitatively defined exposure
groups. Individuals who had worked as machinists were statistically
overrepresented among beryllium-sensitized cases, compared with non-
cases. Cases were more likely than non-cases to report having had a
measured overexposure to beryllium (p = 0.009), a factor which proved
to be a significant predictor of sensitization in logistic regression
analyses, as was exposure to beryllium prior to 1970. Beryllium
sensitized cases were also significantly more likely to report having
had cuts that were delayed in healing (p = 0.02). The authors concluded
that both individual susceptibility to sensitization and exposure
circumstance affect the development of beryllium sensitization and CBD.
In 1991, the Beryllium Health Surveillance Program (BHSP) was
established at the Rocky Flats Nuclear Weapons Facility to offer BeLPT
screening to current and former employees who may have been exposed to
beryllium (Stange et al., 1996, Document ID 0206). Participants
received an initial BeLPT and follow-ups at one and three years. Based
on histologic evidence of pulmonary granulomas and a positive BAL-
BeLPT, Stange et al. published a study of 4,397 BHSP participants
tested from June 1991 to March 1995, including current employees (42.8
percent) and former employees (57.2 percent). Twenty-nine cases of CBD
and 76 cases of sensitization were identified. The sensitization rate
for the population was 2.43 percent. Available exposure data included
fixed airhead exposure samples collected between 1970 and 1988 (mean
concentration 0.016 µg/m3\) and personal samples collected
between 1984 and 1987 (mean concentration 1.04 µg/m3\). Cases of
CBD and sensitization were noted in individuals in all jobs
classifications, including those believed to involve minimal exposure
to beryllium. The authors recommended ongoing surveillance for workers
in all jobs with potential for beryllium exposure.
Stange et al. (2001) extended the previous study, evaluating 5,173
participants in the Rocky Flats BHSP who were tested between June 1991
and December 1997 (Document ID 1403). Three-year serial testing was
offered to employees who had not been tested for three years or more
and did not show beryllium sensitization during the previous study.
This resulted in 2,891 employees being tested. Of the 5,173 workers
participating in the study, 172 were found to have abnormal BeLPT test
results. Ninety-eight (3.33 percent) of the workers were found to be
sensitized (confirmed abnormal BeLPT results) in the initial screening,
conducted in 1991. Of these workers 74 were diagnosed with CBD, based
on a history of beryllium exposure, evidence of non-caseating
granulomas or mononuclear cell infiltrates on lung biopsy, and a
positive BeLPT or BAL-BeLPT. A follow-up survey of 2,891 workers three
years later identified an additional 56 sensitized workers and an
additional seven cases of CBD. Sensitization and CBD rates were
analyzed with respect to gender, building work locations, and length of
employment. Historical employee data included hire date, termination
date, leave of absences, and job title changes. Exposure to beryllium
was determined by job categories and building or work area codes. In
order to determine beryllium exposure for all participants in the
study, personal beryllium air monitoring results were used, when
available, from employees with the same job title or similar job.
However, no quantitative exposure information was presented in the
study. The authors conclude that for some individuals, exposure to
beryllium at levels below the preceding OSHA PEL appears to cause
sensitization and CBD.
Viet et al. (2000) conducted a case-control study of the Rocky
Flats worker population studied by Stange et al. (1996 and 2001,
Document ID 0206 and 1403) to examine the relationship between
estimated beryllium exposure level and risk of sensitization or CBD.
The worker population included 74 beryllium-sensitized workers and 50
workers diagnosed with CBD. Beryllium exposure levels were estimated
based on fixed airhead samples from Building 444, the beryllium machine
shop, where machine operators were considered to have the highest
exposures at the Rocky Flats facility. These fixed air samples were
collected away from the breathing zone of the machine operator and
likely underestimated exposure. To estimate levels in other locations,
these air sample concentrations were used to construct a job exposure
matrix that included the determination of the Building 444 exposure
estimates for a 30-year period; each subject's work history by job
location, task, and time period; and assignment of exposure estimates
to each combination of job location, task, and time period as compared
to Building 444 machinists. The authors adjusted the levels observed in
the machine shop by factors based on interviews with former workers.
Workers' estimated mean exposure concentrations ranged from 0.083
µg/m3\ to 0.622 µg/m3\. Estimated maximum air
concentrations ranged from 0.54 µg/m3\ to 36.8 µg/m3\.
Cases were matched to controls of the same age, race, gender, and
smoking status (Viet et al., 2000, Document ID 1344).
Estimated mean and cumulative exposure levels and duration of
employment were found to be significantly higher for CBD cases than for
controls. Estimated mean exposure levels were significantly higher for
sensitization cases than for controls but no significant difference was
observed for estimated cumulative exposure or duration of exposure.
Similar results were found using logistic regression analysis, which
identified statistically significant relationships between CBD and both
cumulative and mean estimated exposure, but did not find significant
relationships between estimated exposure levels and sensitization
without CBD. Comparing CBD with sensitization cases, Viet et al. found
that workers with CBD had significantly higher estimated cumulative and
mean beryllium exposure levels than workers who were sensitized but did
not have CBD.
Johnson et al. (2001) conducted a review of personal sampling
records and medical surveillance reports at an atomic weapons
establishment in Cardiff, United Kingdom (Document ID 1505). The study
evaluated airborne samples collected over the 36-year period of
operation for the plant. Data included 367,757 area samples and 217,681
personal lapel samples from 194 workers from 1981-1997. The authors
estimated that over the 17 years of measurement data analyzed, airborne
beryllium concentrations did exceed 2.0 µg/m3\, but due to the
limitations with regard to collection times, it is difficult to assess
the full reliability of this estimate. The authors noted that in the
entire plant's history, only one case of CBD had been diagnosed. It was
also noted that BeLPT had not been routinely conducted among any of the
workers at this facility.
Arjomandi et al. (2010) (Document ID 1275) conducted a cross-
sectional study of workers at a nuclear weapons research and
development (R&D) facility to determine the risk of developing CBD in
sensitized workers at facilities with exposures much lower than
production plants (Document ID 1275). Of the 1,875 current or former
workers at the R&D facility, 59 were determined to be
sensitized based on at least two positive BeLPTs (i.e., samples drawn
on two separate occasions or on split samples tested in two separate
DOE-approved laboratories) for a sensitization rate of 3.1 percent.
Workers found to have positive BeLPTs were further evaluated in an
Occupational Medicine Clinic between 1999 and 2005. Arjomandi et al.
(2010) evaluated 50 of the sensitized workers who also had medical and
occupational histories, physical examination, chest imaging with high-
resolution computed tomography (HRCT) (N = 49), and pulmonary function
testing (nine of the 59 workers refused physical examinations so were
not included in this study). Forty of the 50 workers chosen for this
study underwent bronchoscopy for bronchoalveolar lavage and
transbronchial biopsies in additional to the other testing. Five of the
49 workers had CBD at the time of evaluation (based on histology or
high-resolution computed tomography); three others had evidence of
probable CBD; however, none of these cases were classified as severe at
the time of evaluation. The rate of CBD at the time of study among
sensitized individuals was 12.5 percent (5/40) for those using
pathologic review of lung tissue, and 10.2 percent (5/49) for those
using HRCT as a criteria for diagnosis. The rate of CBD among the
entire population (5/1875) was 0.3 percent.
The mean duration of employment at the facility was 18 years, and
the mean latency period (from first possible exposure) to time of
evaluation and diagnosis was 32 years. There was no available exposure
monitoring in the breathing zone of workers at the facility, but the
authors believed beryllium levels were relatively low (possibly less
than 0.1 μg/m3\ for most jobs). There was not an apparent exposure-
response relationship for sensitization or CBD. The sensitization
prevalence was similar across exposure categories and the CBD
prevalence higher among workers with the lower-exposure jobs. The
authors concluded that these sensitized workers, who were subjected to
an extended duration of low potential beryllium exposures over a long
latency period, had a low prevalence of CBD (Arjomandi et al., 2010,
Document ID 1275).
i. Aluminum Smelting
Bauxite ore, the primary source of aluminum, contains naturally
occurring beryllium. Worker exposure to beryllium can occur at aluminum
smelting facilities where aluminum extraction occurs via electrolytic
reduction of aluminum oxide into aluminum metal. Characterization of
beryllium exposures and sensitization prevalence rates were examined by
Taiwo et al. (2010) in a study of nine aluminum smelting facilities
from four different companies in the U.S., Canada, Italy, and Norway
(Document ID 0621).
Of the 3,185 workers determined to be potentially exposed to
beryllium, 1,932 (60 percent) agreed to participate in a medical
surveillance program between 2000 and 2006. The medical surveillance
program included BeLPT analysis, confirmation of an abnormal BeLPT with
a second BeLPT, and follow-up of all confirmed positive BeLPT results
by a pulmonary physician to evaluate for progression to CBD.
Eight-hour TWA exposures were assessed utilizing 1,345 personal
samples collected from the 9 smelters. The personal beryllium samples
obtained showed a range of 0.01-13.00 μg/m3\ TWA with an arithmetic
mean of 0.25 μg/m3\ and geometric mean of 0.06 μg/m3\. Based on
a survey of published studies, the investigators concluded that
exposure levels to beryllium observed in aluminum smelters were similar
to those seen in other industries that utilize beryllium. Of the 1,932
workers surveyed by BeLPT, nine workers were diagnosed with
sensitization (prevalence rate of 0.47 percent, 95% confidence interval
= 0.21-0.88 percent) with 2 of these workers diagnosed with probable
CBD after additional medical evaluations.
The authors concluded that compared with beryllium-exposed workers
in other industries, the rate of sensitization among aluminum smelter
workers appears lower. The authors speculated that this lower observed
rate could be related to a more soluble form of beryllium found in the
aluminum smelting work environment as well as the consistent use of
respiratory protection. However, the authors also speculated that the
low participation rate of 60 percent may have underestimated the
sensitization rate in this worker population.
A study by Nilsen et al. (2010) also found a low rate of
sensitization among aluminum workers in Norway. Three-hundred sixty-two
workers and thirty-one control individuals were tested for beryllium
sensitization based on the BeLPT. The results found that one (0.28%) of
the smelter workers had been sensitized. No borderline results were
reported. The exposures estimated in this plant were 0.1 µg/m3\
to 0.31 µg/m3\ (Nilsen et al., 2010, Document ID 0460).
6. Animal Models of CBD
This section reviews the relevant animal studies supporting the
biological mechanisms outlined above. In order for an animal model to
be useful for investigating the mechanisms underlying the development
of CBD, the model should include: The demonstration of a beryllium-
specific immune response; the formation of immune granulomas following
inhalation exposure to beryllium; and progression of disease as
observed in human disease. While exposure to beryllium has been shown
to cause chronic granulomatous inflammation of the lung in animal
studies using a variety of species, most of the granulomatous lesions
were not immune-induced reactions (which would predominantly consist of
T-cells or lymphocytes), but were foreign-body-induced reactions, which
predominantly consist of macrophages and monocytes, with only a small
numbers of lymphocytes. Although no single model has completely
mimicked the disease process as it progresses in humans, animal studies
have been useful in providing biological plausibility for the role of
immunological alterations and lung inflammation and in clarifying
certain specific mechanistic aspects of beryllium disease, such as
sensitization and CBD. However, there is no dependable animal model
that mimics all facets of the human response, and studies thus far have
been limited by single dose experiments, too few animals, or
abbreviated observation periods. Therefore, the utility of this data is
limited. The following is a discussion of the most relevant animal
studies regarding the mechanisms of sensitization and CBD development
in humans. Table A.2 in the Supplemental Information for the Beryllium
Health Effects Section summarizes species, route, chemical form of
beryllium, dose levels, and pathological findings of the key studies
(Document ID 1965).
Harmsen et al. performed a study to assess whether the beagle dog
could provide an adequate model for the study of beryllium-induced lung
diseases (Harmsen et al., 1986, Document ID 1257). One group of dogs
served as an air inhalation control group and four other groups
received high (approximately 50 μg/kg) and low (approximately 20
μg/kg) doses of beryllium oxide calcined at 500 [deg]C or 1,000
[deg]C, administered as aerosols in a single exposure.6
---------------------------------------------------------------------------
6 As discussed above, calcining temperature affects the
solubility and SSA of beryllium particles. Those particles calcined
at higher temperatures (e.g., 1,000 [deg]C) are less soluble and
have lower SSA than particles calcined at lower temperatures (e.g.,
500 [deg]C). Solubility and SSA are factors in determining the toxic
potential of beryllium compounds or materials.
---------------------------------------------------------------------------
BAL content was collected at 30, 60, 90, 180, and 210 days after
exposure, and lavage fluid and cellular content was evaluated for
neutrophilic and lymphocytic infiltration. In addition, BAL cells were
evaluated at the 210 day period to determine activation potential by
phytohemagglutinin (PHA) or beryllium sulfate as mitogen. BAL
neutrophils were significantly elevated only at 30 days with exposure
to either dose of 500 [deg]C beryllium oxide. BAL lymphocytes were
significantly elevated at all time points of the high dose of beryllium
oxide. No significant effect of 1,000 [deg]C beryllium oxide exposure
on mitogenic response of any lymphocytes was seen. In contrast,
peripheral blood lymphocytes from the 500 [deg]C beryllium oxide
exposed groups were significantly stimulated by beryllium sulfate
compared with the phytohemagglutinin exposed cells. Only the BAL
lymphocytes from animals exposed to the 500 [deg]C beryllium oxide
responded to stimulation by either PHA or beryllium sulfate.
In a series of studies, Haley et al. also found that the beagle dog
models certain aspects of human CBD (Haley et al., 1989, 1991 and 1992;
Document ID 1366, 1315, 1365. Briefly, dogs were exposed by inhalation
to a single exposure to beryllium aerosol generated from beryllium
oxide calcined at 500 [deg]C or 1,000 [deg]C for initial lung burdens
of 17 or 50 μg beryllium/kg body weight (Haley et al., 1989,
Document ID 1366; 1991 (1315)). The dogs were monitored for lung
pathologic effects, particle clearance, and immune sensitization of
peripheral blood leukocytes. Lung retention was higher in the 1,000
[deg]C treated beryllium oxide group (Haley et al., 1989, Document ID
1366).
Haley et al. (1989) described the bronchoalveolar lavage (BAL) and
histopathological changes in dogs exposed as described above. One group
of dogs underwent BAL for lung lymphocyte analysis at 3, 6, 7, 11, 15,
18, and 22 months post exposure. The investigators found an increase in
the percentage and numbers of lymphocytes in BAL fluid at 3 months
post-exposure in dogs exposed to either dose of beryllium oxide
calcined at 500 [deg]C and 1,000 [deg]C. Positive BeLPT results were
observed with BAL lymphocytes only in the group with a high initial
lung burden of the material calcined at 500 [deg]C at 3 and 6 month
post exposure. Another group underwent histopathological examination at
days 8, 32, 64, 180, and 365 (Haley et al., 1989, Document ID 1366;
1991 (1315)). Histopathologic examination revealed peribronchiolar and
perivascular lymphocytic histiocytic inflammation, peaking at 64 days
after beryllium oxide exposure. Lymphocytes were initially well
differentiated, but progressed to lymphoblastic cells and aggregated in
lymphofollicular nodules or microgranulomas over time. Although there
was considerable inter-animal variation, lesions were generally more
severe in the dogs exposed to material calcined at 500 [deg]C. The
investigators observed granulomatous lesions and lung lymphocyte
responses consistent with those observed in humans with CBD, including
perivascular and peribronchiolar infiltrates of lymphocytes and
macrophages, progressing to microgranulomas with areas of granulomatous
pneumonia and interstitial fibrosis. However, lesions declined in
severity after 64 days post-exposure. The lesions found in dog lungs
closely resembled those found in humans with CBD: Severe granulomas,
lymphoblast transformation, increased pulmonary lymphocyte
concentrations and variation in beryllium sensitivity. It was concluded
that the canine model for CBD may provide insight into this disease.
In a follow-up experiment, control dogs and those exposed to
beryllium oxide calcined at 500 [deg]C were allowed to rest for 2.5
years, and then re-exposed to filtered air (controls) or beryllium
oxide calcined at 500 [deg]C (cases) for an initial lung burden target
of 50 μg beryllium oxide/kg body weight (Haley et al., 1992,
Document ID 1365). Immune responses of blood and BAL lymphocytes, as
well as lung lesions in dogs sacrificed 210 days post-exposure, were
compared with results following the initial exposure. The severity of
lung lesions was comparable under both conditions, suggesting that a
2.5-year interval was sufficient to prevent cumulative pathologic
effects in beagle dogs.
In a comparison study of dogs and monkeys, Conradi et al. (1971)
exposed animals via inhalation to an average aerosol to either 0, 3,300
or 4,380 μg/m3\ of beryllium as beryllium oxide calcined at 1,400
[deg]C for 30 minutes, once per month for 3 months (Document ID 1319).
Conradi et al. found no changes in the histological or ultrastructure
of the lung of animals exposed to beryllium versus control animals.
This was in contrast to previous findings reported in other studies
cited by Conradi et al. The investigators speculated that the
differences may be due in part to calcination temperature or follow-up
time after initial exposure. The findings from Haley et al. (1989,
Document ID 1366; 1991 (1915); and 1992 (1365)) as well as Harmsen et
al. (1986, Document ID 1257) suggest that the beagle model for
sensitization of CBD is more closely related to the human response that
other species such as the monkey (and those reviewed in Table A2 of the
Supplemental Information for the Beryllium Health Effects Section).
A 1994 study by Haley et al. comparing the potential toxicity of
beryllium oxide versus beryllium metal showed that instillation of both
beryllium oxide and beryllium metal induced an immune response in
monkeys. Briefly, male cynomolgus monkeys were exposed to either
beryllium metal or beryllium oxide calcined at 500 [deg]C via
intrabronchiolar instillation as a saline suspension. Lymphocyte counts
in BAL fluid were observed through bronchoalveolar lavage at 14, 30,
60, 90, and 120 days post exposure, and were found to be significantly
increased in monkeys exposed to beryllium metal on post-exposure days
14, 30, 60, and 90, and in monkeys exposed to beryllium oxide on post-
exposure day 30 and 60. Histological examination of lung tissue
revealed that monkeys exposed to beryllium metal developed interstitial
fibrosis, Type II cell hyperplasia with increased lymphocytes
infiltration, and lymphocytic mantles accumulating around alveolar
macrophages. Similar but much less severe lesions were observed in
beryllium-oxide-exposed monkeys. Only monkeys exposed to beryllium
metal had positive BAL BeLPT results (Haley et al., 1994, Document ID
1364).
As discussed earlier in this Health Effects section, at the
cellular level, beryllium dissolution may be necessary in order for
either a dendritic cell or a macrophage to present beryllium as an
antigen to induce the cell-mediated CBD immune reactions (NAS, 2008,
Document ID 1355). Several studies have shown that low-fired beryllium
oxide, which is predominantly made up of poorly crystallized small
particles, is more immunologically reactive than beryllium oxide
calcined at higher firing temperatures that result in less reactivity
due to increasing crystal size (Stefaniak et al., 2006, Document ID
1398). As discussed previously, Haley et al. (1989, Document ID 1366)
found more severe lung lesions and a stronger immune response in beagle
dogs receiving a single inhalation exposure to beryllium oxide calcined
at 500 [deg]C than in dogs receiving an equivalent initial lung burden
of beryllium oxide calcined at 1,000 [deg]C. Haley et al. found that
beryllium oxide calcined at 1,000 [deg]C
elicited little local pulmonary immune response, whereas the much more
soluble beryllium oxide calcined at 500 [deg]C produced a beryllium-
specific, cell-mediated immune response in dogs (Haley et al., 1989,
Document ID 1366 and 1991 (1315)).
In a later study, beryllium metal appeared to induce a greater
toxic response than beryllium oxide following intrabronchiolar
instillation in cynomolgus monkeys, as evidenced by more severe lung
lesions, a larger effect on BAL lymphocyte counts, and a positive
response in the BeLPT with BAL lymphocytes only after exposure to
beryllium metal (Haley et al., 1994, Document ID 1364). A study by
Mueller and Adolphson (1979) observed that an oxide layer can develop
on beryllium-metal surfaces after exposure to air (Mueller and
Adolphson, 1979, Document ID 1260). According to the NAS report,
Harmesen et al (1994) suggested that the presence of beryllium metal
could lead to persistent exposures of small amounts beryllium oxide
sufficient for presentation to the immune system (NAS, 2008, Document
ID 1355).
Genetic studies in humans led to the creation of an animal model
containing different human HLA-DP alleles inserted into FVB/N mice for
mechanistic studies of CBD. Three strains of genetically engineered
mice (transgenic mice) were created that conferred different risks for
developing CBD based on human studies (Weston et al., 2005, Document ID
1345; Snyder et al., 2008 (0471)): (1) The HLA-DPB1*0401 transgenic
strain, where the transgene codes for lysine residue at the 69th
position of the B-chain conferred low risk of CBD; (2) the HLA-
DPB1*0201 mice, where the transgene codes for glutamic acid residue at
the 69th position of the B-chain conferred medium risk of CBD; and (3)
the HLA-DPB1*1701 mice, where the transgene codes for glutamic acid at
the 69th position of the B-chain but coded for a more negatively
charged protein to confer higher risk of CBD (Tarantino-Hutchinson et
al., 2009, Document ID 0536).
In order to validate the transgenic model, Tarantino-Hutchison et
al. challenged the transgenic mice along with seven different inbred
mouse strains to determine the susceptibility and sensitivity to
beryllium exposure. Mice were dermally exposed with either saline or
beryllium, then challenged with either saline or beryllium (as
beryllium sulfate) using the MEST protocol (mouse ear-swelling test).
The authors determined that the high risk HLA-DPB1*1701 transgenic
strain responded 4 times greater (as measured via ear swelling) than
control mice and at least 2 times greater than other strains of mice.
The findings correspond to epidemiological study results reporting an
enhanced CBD odds ratio for the HLA-DPB1*1701 in humans (Weston et al.,
2005, Document ID 1345; Snyder et al., 2008 (0471)). Transgenic mice
with the genes corresponding to the low and medium odds ratio study did
not respond significantly over the control group. The authors concluded
that while HLA-DPB1*1701 is important to beryllium sensitization and
progression to CBD, other genetic and environmental factors contribute
to the disease process as well.
7. Beryllium Sensitization and CBD Conclusions
There is substantial evidence that skin and inhalation exposure to
beryllium may lead to sensitization (section V.D.1) and that inhalation
exposure, or skin exposure coupled with inhalation exposure, may lead
to the onset and progression of CBD (section V.D.2). These conclusions
are supported by extensive human studies (section V.D.5). While all
facets of the biological mechanism for this complex disease have yet to
be fully elucidated, many of the key events in the disease sequence
have been identified and described in the earlier sections (sections
V.D.1-5). Sensitization is considered to be a necessary first step to
the onset of CBD (NAS, 2008, Document ID 1355; ERG, 2010 (1270)).
Sensitization is the process by which the immune system recognizes
beryllium as a foreign substance and responds in a manner that may lead
to development of CBD. It has been documented that a substantial
proportion of sensitized workers exposed to airborne beryllium can
progress to CBD (Rosenman et al., 2005, Document ID 1352; NAS, 2008
(1355); Mroz et al., 2009 (1356)). Animal studies, particularly in dogs
and monkeys, have provided supporting evidence for T cell lymphocyte
proliferation in the development of granulomatous lung lesions after
exposure to beryllium (Harmsen et al., 1986, Document ID 1257; Haley et
al., 1989 (1366), 1992 (1365), 1994 (1364)). The animal studies have
also provided important insights into the roles of chemical form,
genetic susceptibility, and residual lung burden in the development of
beryllium lung disease (Harmsen et al., 1986, Document ID 1257; Haley
et al., 1992 (1365); Tarantino-Hutchison et al., 2009 (0536)). The
evidence supports sensitization as an early functional change that
allows the immune system to recognize and adversely react to beryllium.
As such, OSHA regards beryllium sensitization as a necessary first step
along a continuum that can culminate in clinical lung disease.
The epidemiological evidence presented in section V.D.5
demonstrates that sensitization and CBD are continuing to occur from
exposures below OSHA's preceding PEL. The prevalence of sensitization
among beryllium-exposed workers, as measured by the BeLPT and reported
in 16 surveys of occupationally exposed cohorts reviewed by the Agency,
ranged from 0.3 to 14.5 percent (Deubner et al., 2001, Document ID
1543; Kreiss et al., 1997 (1360); Rosenman et al., 2005 (1352); Schuler
et al., 2012 (0473); Bailey et al., 2010 (0676); Newman et al., 2001
(1354); OSHA, 2014 (1589); Kreiss et al., 1996 (1477); Henneberger et
al., 2001 (0589); Cummings et al., 2007 (1369); Schuler et al., 2005
(0919); Thomas et al., 2009 (1061); Kreiss et al., 1989 (1480);
Arjomandi et al., 2010 (1275); Taiwo et al., 2011 (0621); Nilson et
al., 2010 (0460)). The lower prevalence estimates (0.3 to 3.7 percent)
were from facilities known to have implemented respiratory protection
programs and have lower personal exposures (Cummings et al., 2007,
Document ID 1369; Thomas et al., 2009 (1061); Bailey et al., 2010
(0676); Taiwo et al, 2011 (0621), Nilson et al., 2010 (0460); Arjomandi
et al., 2010 (1275)). Thirteen of the surveys also evaluated workers
for CBD and reported prevalences of CBD ranging from 0.1 to 7.8
percent. The cohort studies cover workers across many different
industries and processes as discussed in section V.D.5. Several studies
show that incidence of sensitization among workers can be reduced by
reducing inhalation exposure and that minimizing skin exposure may
serve to further reduce sensitization (Cummings et al., 2007, Document
ID 1369; Thomas et al., 2009 (1061); Bailey et al., 2010 (0676)). The
risk assessment further discusses the effectiveness of interventions to
reduce beryllium exposures and the risk of sensitization and CBD (see
section VI of this preamble, Risk Assessment).
Longitudinal studies of sensitized workers found early signs of
asymptomatic CBD that can progress to clinical disease in some
individuals. One study found that 31 percent of beryllium-exposed
sensitized employees progressed to CBD with an average follow-up time
of 3.8 years (Newman, 2005, Document ID 1437). However, Newman (2005)
went on to suggest that if follow-up times were much longer, the rate
of progression from
sensitization to CBD could be much higher. Mroz et al. (2009) (Document
ID 1356) conducted a longitudinal study between 1982 and 2002 in which
they followed 171 cases of CBD and 229 cases of sensitization initially
evaluated through workforce medical surveillance by National Jewish
Health. All study subjects had abnormal BeLPTs upon study entry and
were then clinically evaluated and treated for CBD. Over the 20-year
study period, 22 sensitized individuals went on to develop CBD which
was an incidence of 8.8 percent (i.e., 22 cases out of 251 sensitized,
calculated by adding those 22 cases to the 229 initially classified as
sensitized). The findings from this study indicated that the average
span of time from initial beryllium exposure to CBD diagnosis for those
22 workers was 24 years (Mroz et al., 2009, Document ID 1356).
A study of sensitized workers believed to have been exposed to low
levels of airborne beryllium metal (e.g., 0.01 µg/m3\ or less)
at a nuclear weapons research and development facility were clinically
evaluated between 1999 and 2005 (Arjomandi et al., 2010, Document ID
1275). Five of 49 sensitized workers (10.2 percent incidence) were
found to have pathology consistent with CBD. The CBD was asymptomatic
and had not progressed to clinical disease. The mean duration of
employment among workers in the study was 18 years with mean latency of
32 years to time of CBD diagnosis (Arjomandi et al., 2010, Document ID
1275). This suggests that some sensitized individuals can develop CBD
even from low levels of beryllium exposure. Another study of nuclear
weapons facility employees enrolled in an ongoing medical surveillance
program found that sensitization rate among exposed workers was highest
over the first 10 years of beryllium exposure while onset of CBD
pathology was greatest following 15 to 30 years of exposure (Stange et
al., 2001, Document ID 1403). This indicates length of exposure may
play a role in further development of the disease. OSHA concludes from
the study evidence that the persistent presence of beryllium in the
lungs of sensitized workers can lead to a progression of CBD over time
from an asymptomatic stage to serious clinical disease.
E. Beryllium Lung Cancer Section
Beryllium exposure is associated with a variety of adverse health
effects, including lung cancer. The potential for beryllium and its
compounds to cause cancer has been previously assessed by various other
agencies (EPA, ATSDR, NAS, NIEHS, and NIOSH), with each agency
identifying beryllium as a potential carcinogen. In addition, IARC did
an extensive evaluation in 1993 (Document ID 1342) and reevaluation in
April 2009 (IARC, 2012, Document ID 0650). In brief, IARC determined
beryllium and its compounds to be carcinogenic to humans (Group 1
category), while EPA considers beryllium to be a probable human
carcinogen (EPA, 1998, Document ID 0661), and the National Toxicology
Program (NTP) classifies beryllium and its compounds as known
carcinogens (NTP, 2014, Document ID 0389). OSHA has conducted an
independent evaluation of the carcinogenic potential of beryllium and
these compounds. The following is a summary of the studies used to
support the Agency's finding that beryllium and its compounds are human
carcinogens.
1. Genotoxicity Studies
Genotoxicity can be an important indicator for screening the
potential of a material to induce cancer and an important mechanism
leading to tumor formation and carcinogenesis. In a review conducted by
the National Academy of Science, beryllium and its compounds have
tested positively in nearly 50 percent of the genotoxicity studies
conducted without exogenous metabolic activity. However, they were
found to be non-genotoxic in most bacterial assays (NAS, 2008, Document
ID 1355).
Non-mammalian test systems (generally bacterial assays) are often
used to identify genotoxicity of a compound. In bacteria studies
evaluating beryllium sulfate for mutagenicity, all studies performed
utilizing the Ames assay (Simmon, 1979, Document ID 0434; Dunkel et
al., 1981 (0432); Arlauskas et al., 1985 (0454); Ashby et al., 1990
(0437)) and other bacterial assays (E. coli pol A (Rosenkranz and
Poirer, 1979, Document ID 1426); E. coli WP2 uvrA (Dunkel et al., 1981,
Document ID 0432), as well as those utilizing Saccharomyces cerevisiae
(Simmon, 1979, Document ID 0434)) were reported as negative, with the
exception of results reported for Bacillus subtilis rec assay (Kada et
al., 1980, Document ID 0433; Kanematsu et al., 1980 (1503)). Beryllium
nitrate was also reported as negative in the Ames assay (Tso and Fung,
1981, Document ID 0446; Kuroda et al., 1991 (1471)) but positive in a
Bacillus subtilis rec assay (Kuroda et al., 1991, Document ID 1471). In
addition, beryllium chloride was reported as negative using the Ames
assay (Ogawa et al., 1987, as cited in Document ID 1341, p. 112; Kuroda
et al., 1991 (1471)) and other bacterial assays (E. coli WP2 uvrA
(Rossman et al., 1984, Document ID 0431), as well as the Bacillus
subtilis rec assay (Nishioka, 1975, Document ID 0449)) and failed to
induce SOS DNA repair in E. coli (Rossman et al., 1984, Document ID
0431). Positive results for beryllium chloride were reported for
Bacillus subtilis rec assay using spores (Kuroda et al., 1991, Document
ID 1471) as well as increased mutations in the lacI gene of E. coli
KMBL 3835 (Zakour and Glickman, 1984, Document ID 1373). Beryllium
oxide was reported to be negative in the Ames assay and Bacillus
subtilis rec assays (Kuroda et al., 1991, Document ID 1471; EPA, 1998
(0661)).
Mutations using in vitro mammalian systems were also evaluated.
Beryllium chloride induced mutations in V79 and CHO cultured cells
(Miyaki et al., 1979, Document ID 0450; Hsie et al., 1978 (0427);
Vegni-Talluri and Guiggiani, 1967 (1382)), and beryllium sulfate
induced clastogenic alterations, producing breakage or disrupting
chromosomes in mammalian cells (Brooks et al., 1989, Document ID 0233;
Larramendy et al., 1981 (1468); Gordon and Bowser, 2003 (1520)).
However, beryllium sulfate did not induce unscheduled DNA synthesis in
primary rat hepatocytes and was not mutagenic when injected
intraperitoneally in adult mice in a host-mediated assay using
Salmonella typhimurium (Williams et al., 1982). Positive results were
found for beryllium chloride when evaluating the hprt gene in Chinese
hamster lung V79 cells (Miyaki et al., 1979, Document ID 0450).
Data from in vivo genotoxicity testing of beryllium are limited.
Beryllium metal was found to induce methylation of the p16 gene in the
lung tumors of rats exposed to beryllium metal (Swafford et al., 1997,
Document ID 1392) (described in more detail in section V.E.3). A study
by Nickell-Brady et al., (1994) found that beryllium sulfate (1.4 and
2.3 g/kg, 50 percent and 80 percent of median lethal dose) administered
by gavage did not induce micronuclei in the bone marrow of CBA mice.
However, a marked depression of red blood cell production was
suggestive of bone marrow toxicity, which was evident 24 hours after
dosing. No mutations were seen in p53 or c-raf-1 and only weak
mutations were detected in K-ras in lung carcinomas from F344/N rats
given a single nose-only exposure to beryllium metal (described in more
detail in section V. E. 3) (Nickell-Brady et al., 1994, Document ID
1312). On the other hand, beryllium chloride evaluated in a mouse model
indicated increased DNA strand breaks and the formation of micronuclei
in bone marrow (Attia et al., 2013, Document ID 0501).
In summary, genetic mutations have been observed in mammalian
systems (in vitro and in vivo) with beryllium chloride, beryllium
sulfate, and beryllium metal in a number of studies (Miyaki et al.,
1979, Document ID 0450; Hsie et al., 1978 (0427); Vegni-Talluri and
Guiggiani, 1967 (1382); Brooks et al., 1989 (0233); Larramendy et al.,
1981 (1468); Miyaki et al., 1979 (0450); Swafford et al., 1997 (1392);
Attia et al., 2013 (0501); EPA, 1998 (0661); Gordon and Bowser, 2003
(1520)). However, most studies utilizing non-mammalian test systems
(either with or without metabolic activity) have found that beryllium
chloride, beryllium nitrate, beryllium sulfate, and beryllium oxide did
not induce gene mutations, with the exception of Kada et al. (1980,
Document ID 0433) (Kanematsu et al.,1980, Document ID 1503; Kuroda et
al., 1991 (1471)).
2. Human Epidemiological Studies
This section describes the human epidemiological data supporting
the mechanistic overview of beryllium-induced lung cancer in workers.
It has been divided into reviews of epidemiological studies by industry
and beryllium form. The epidemiological studies utilizing data from the
BCR, in general, focus on workers mainly exposed to soluble forms of
beryllium. Those studies evaluating the epidemiological evidence by
industry or process are, in general, focused on exposures to poorly
soluble or mixed (soluble and poorly soluble) compounds. Table A.3 in
the Supplemental Information for the Beryllium Health Effects Section
summarizes the important features and characteristics of each study
discussed herein (Document ID 1965).
a. Beryllium Case Registry (BCR)
Two studies evaluated participants in the BCR (Infante et al.,
1980, Document ID 1507; Steenland and Ward, 1991 (1400)). Infante et
al. (1980) evaluated the mortality patterns of white male participants
in the BCR diagnosed with non-neoplastic respiratory symptoms of
beryllium disease. Of the 421 cases evaluated, 7 of the participants
had died of lung cancer. Six of the deaths occurred more than 15 years
after initial beryllium exposure. The duration of exposure for 5 of the
7 participants with lung cancer was less than 1 year, with the time
since initial exposure ranging from 12 to 29 years. One of the
participants was exposed for 4 years with a 26-year interval since the
initial exposure. Exposure duration for one participant diagnosed with
pulmonary fibrosis could not be determined; however, it had been 32
years since the initial exposure. Based on BCR records, the
participants were classified as being in the acute respiratory group
(i.e., those diagnosed with acute respiratory illness at the time of
entry in the registry) or the chronic respiratory group (i.e., those
diagnosed with pulmonary fibrosis or some other chronic lung condition
at the time of entry into the BCR). The 7 participants with lung cancer
were in the BCR because of diagnoses of acute respiratory illness. For
only one of those individuals was initial beryllium exposure less than
15 years prior. Only 1 of the 6 (with greater than 15 years since
initial exposure to beryllium) had been diagnosed with chronic
respiratory disease. The study did not report exposure concentrations
or smoking habits. The authors concluded that the results from this
cohort agreed with previous animal studies and with epidemiological
studies demonstrating an increased risk of lung cancer in workers
exposed to beryllium.
Steenland and Ward (1991) (Document ID 1400) extended the work of
Infante et al. (1980) (Document ID 1507) to include females and to
include 13 additional years of follow-up. At the time of entry in the
BCR, 93 percent of the women in the study, but only 50 percent of the
men, had been diagnosed with CBD. In addition, 61 percent of the women
had worked in the fluorescent tube industry and 50 percent of the men
had worked in the basic manufacturing industry with confirmed beryllium
exposure. A total of 22 males and 6 females died of lung cancer. Of the
28 total deaths from lung cancer, 17 had been exposed to beryllium for
less than 4 years and 11 had been exposed for greater than 4 years. The
study did not report exposure concentrations. Survey data collected in
1965 provided information on smoking habits for 223 cohort members (32
percent), on the basis of which the authors suggested that the rate of
smoking among workers in the cohort may have been lower than U.S.
rates. The authors concluded that there was evidence of increased risk
of lung cancer in workers exposed to beryllium and then diagnosed with
beryllium disease (ABD and CBD).
b. Beryllium Manufacturing and/or Processing Plants (Extraction,
Fabrication, and Processing)
Several epidemiological cohort studies have reported excess lung
cancer mortality among workers employed in U.S. beryllium production
and processing plants during the 1930s to 1960s.
Bayliss et al. (1971) (Document ID 1285) performed a nested cohort
study of 7,948 former workers from the beryllium processing industry
who were employed from 1942-1967. Information for the workers was
collected from the personnel files of participating companies. Of the
7,948 employees, a cause of death was known for 753 male workers. The
number of observed lung cancer deaths was 36 compared to 34.06 expected
for a standardized mortality ratio (SMR) of 1.06. When evaluated by the
number of years of employment, 24 of the 36 men were employed for less
than 1 year in the industry (SMR = 1.24), 8 were employed for 1 to 5
years (SMR 1.40), and 4 were employed for more than 5 years (SMR =
0.54). Half of the workers who died from lung cancer began employment
in the beryllium production industry prior to 1947. When grouped by job
classification, over two thirds of the workers with lung cancer were in
production-related jobs while the rest were classified as office
workers. The authors concluded that while the lung cancer mortality
rates were the highest of all other mortality rates, the SMR for lung
cancer was still within range of the expected based on death rates in
the United States. The limitations of this study included the lack of
information regarding exposure concentrations, smoking habits, and the
age and race of the participants.
Mancuso (1970, Document ID 1453; 1979, (0529); 1980 (1452)) and
Mancuso and El-Attar (1969) (Document ID 1455) performed a series of
occupational cohort studies on a group of workers (primarily white
males) employed in the beryllium manufacturing industry during 1937-
1948. The cohort identified in Mancuso and El-Attar (1969) was a study
of 3,685 workers (primarily white males) while Mancuso (1970, 1976,
1980) continued the study follow-up with 3266 workers due to several
limitations in identifying specific causes for mortality as identified
in Mancuso and El-Attar (1969). The beryllium production facilities
were located in Ohio and Pennsylvania and the records for the
employees, including periods of employment, were obtained from the
Social Security Administration. These studies did not include analyses
of mortality by job title or exposure category (exposure data was taken
from a study by Zielinsky et al., 1961 (as cited in Mancuso, 1970)). In
addition, there were no exposure concentrations estimated or
adjustments for smoking. The estimated duration of employment ranged
from less than 1 year to greater than 5 years. In the most recent study
(Mancuso, 1980), employees from the
viscose rayon industry served as a comparison population. There was a
significant excess of lung cancer deaths based on the total number of
80 observed lung cancer mortalities at the end of 1976 compared to an
expected number of 57.06 based on the comparison population resulting
in an SMR of 1.40 (p <0.01) (Mancuso, 1980). There was a statistically
significant excess in lung cancer deaths for the shortest duration of
employment (<12 months, p <0.05) and the longest duration of employment
(>49 months, p <0.01). Based on the results of this study, the author
concluded that the ability of beryllium to induce cancer in workers
does not require continuous exposure and that it is reasonable to
assume that the amount of exposure required to produce lung cancer can
occur within a few months of initial exposure regardless of the length
of employment.
Wagoner et al. (1980) (Document ID 1379) expanded the work of
Mancuso (1970, Document ID 1453; 1979 (0529); 1980 (1452)) using a
cohort of 3,055 white males from the beryllium extraction, processing,
and fabrication facility located in Reading, Pennsylvania. The men
included in the study worked at the facility sometime between 1942 and
1968, and were followed through 1976. The study accounted for length of
employment. Other factors accounted for included age, smoking history,
and regional lung cancer mortality. Forty-seven members of the cohort
died of lung cancer compared to an expected 34.29 based on U.S. white
male lung cancer mortality rates (p <.05). The results of this cohort
showed an excess risk of lung cancer in beryllium-exposed workers at
each duration of employment (<5 years and >=5 years), with a
statistically significant excess noted at <5 years of employment and a
>=25-year interval since the beginning of employment (p <0.05). The
study was criticized by two epidemiologists (MacMahon, 1978, Document
ID 0107; Roth, 1983 (0538)), by a CDC Review Committee appointed to
evaluate the study (as cited in Document ID 0067), and by one of the
study's coauthors (Bayliss, 1980, Document ID 0105) for inadequate
discussion of possible alternative explanations of excess lung cancer
in the cohort. The specific issues identified include the use of 1965-
1967 U.S. white male lung cancer mortality rates to generate expected
numbers of lung cancers in the period 1968-1975 (which may
underestimate the expected number of lung cancer deaths for the cohort)
and inadequate adjustment for smoking.
One occupational nested case-control study evaluated lung cancer
mortality in a cohort of 3,569 male workers employed at a beryllium
alloy production plant in Reading, PA, from 1940 to 1969 and followed
through 1992 (Sanderson et al., 2001, Document ID 1250). There were a
total of 142 known lung cancer cases and 710 controls. For each lung
cancer death, 5 age- and race-matched controls were selected by
incidence density sampling. Confounding effects of smoking were
evaluated. Job history and historical air measurements at the plant
were used to estimate job-specific beryllium exposures from the 1930s
to 1990s. Calendar-time-specific beryllium exposure estimates were made
for every job and used to estimate workers' cumulative, average, and
maximum exposures. Because of the long period of time required for the
onset of lung cancer, an "exposure lag" was employed to discount
recent exposures less likely to contribute to the disease.
The largest and most comprehensive study investigated the mortality
experience of 9,225 workers employed in 7 different beryllium
processing plants over a 30-year period (Ward et al., 1992, Document ID
1378). The workers at the two oldest facilities (i.e., Lorain, OH, and
Reading, PA) were found to have significant excess lung cancer
mortality relative to the U.S. population. The workers at these two
plants were believed to have the highest exposure levels to beryllium.
Ward et al. (1992) performed a retrospective mortality cohort study of
9,225 male workers employed at seven beryllium processing facilities,
including the Ohio and Pennsylvania facilities studied by Mancuso and
El-Attar (1969) (Document ID 1455), Mancuso (1970, Document ID 1453;
1979 (0529); 1980 (1452)), and Wagoner et al. (1980) (Document ID
1379). The men were employed for no less than 2 days between January
1940 and December 1969. Medical records were followed through 1988. At
the end of the study 61.1 percent of the cohort was known to be living
and 35.1 percent was known to be deceased. The duration of employment
ranged from 1 year or less to greater than 10 years with the largest
percentage of the cohort (49.7 percent) employed for less than one
year, followed by 1 to 5 years of employment (23.4 percent), greater
than 10 years (19.1 percent), and 5 to 10 years (7.9 percent). Of the
3,240 deaths, 280 observed deaths were caused by lung cancer compared
to 221.5 expected deaths, yielding a statistically significant SMR of
1.26 (p <0.01). Information on the smoking habits of 15.9 percent of
the cohort members, obtained from a 1968 Public Health Service survey
conducted at four of the plants, was used to calculate a smoking-
adjusted SMR of 1.12, which was not statistically significant. The
number of deaths from lung cancer was also examined by decade of hire.
The authors reported a relationship between earlier decades of hire and
increased lung cancer risk.
A different analysis of the lung cancer mortality in this cohort
using various local reference populations and alternate adjustments for
smoking generally found smaller, non-significant rates of excess
mortality among the beryllium-exposed employees (Levy et al., 2002,
Document ID 1463). Both cohort studies (Levy et al., 2002, Document ID
1463; Ward et al., 1992 (1378)) are limited by a lack of job history
and air monitoring data that would allow investigation of mortality
trends with different levels and durations of beryllium exposure. The
majority of employees at the Lorain, OH, and Reading, PA, facilities
were employed for a relatively short period of less than one year.
Levy et al. (2002) (Document ID 1463) questioned the results of
Ward et al. (1992) (Document ID 1378) and performed a reanalysis of the
Ward et al. data. The Levy et al. reanalysis differed from the Ward et
al. analysis in the following significant ways. First, Levy et al.
(2002) (Document ID 1463) examined two alternative adjustments for
smoking, which were based on (1) a different analysis of the American
Cancer Society (ACS) data used by Ward et al. (1992) (Document ID 1378)
for their smoking adjustment, or (2) results from a smoking/lung cancer
study of veterans. Second, Levy et al. (2002) also examined the impact
of computing different reference rates derived from information about
the lung cancer rates in the cities in which most of the workers at two
of the plants lived (Document ID 1463). Finally, Levy et al. (2002)
considered a meta-analytical approach to combining the results across
beryllium facilities (Document ID 1463). For all of the alternatives
Levy et al. (2002) (Document ID 1463) considered, except the meta-
analysis, the facility-specific and combined SMRs derived were lower
than those reported by Ward et al. (1992) (Document ID 1378). Only the
SMR for the Lorain, OH, facility remained statistically significantly
elevated in some reanalyses. The SMR obtained when combining over the
plants was not statistically significant in eight of the nine
approaches they examined, leading
Levy et al. (2002) (Document ID 1463) to conclude that there was little
evidence of statistically significant elevated SMRs in those plants.
This study was not included in the synthesis of epidemiological studies
assessed by IARC due to several methodological limitations (IARC, 2012,
Document ID 0650).
The EPA Integrated Risk Information System (IRIS), IARC, and
California EPA Office of Environmental Health Hazard Assessment (OEHHA)
all based their cancer assessments on the Ward et al. 1992 study, with
supporting data concerning exposure concentrations from Eisenbud and
Lisson (1983) (Document ID 1296) and NIOSH (1972) (Document ID 0560),
who estimated that the lower-bound estimate of the median exposure
concentration exceeded 100 µg/m3\ and found that concentrations
in excess of 1,000 µg/m3\ were common. The IRIS cancer risk
assessment recalculated expected lung cancers based on U.S. white male
lung cancer rates (including the period 1968-1975) and used an
alternative adjustment for smoking. In addition, one individual with
lung cancer, who had not worked at the plant, was removed from the
cohort. After these adjustments were made, an elevated rate of lung
cancer was still observed in the overall cohort (46 cases vs. 41.9
expected cases). However, based on duration of employment or interval
since beginning of employment, neither the total cohort nor any of the
subgroups had a statistically significant increase in lung cancer
deaths (EPA, 1987, Document ID 1295). Based on its evaluation of this
and other epidemiological studies, the EPA characterized the human
carcinogenicity data then available as "limited" but "suggestive of
a causal relationship between beryllium exposure and an increased risk
of lung cancer" (EPA, 1998, Document ID 0237). The EPA report includes
quantitative estimates of risk that were derived using the information
presented in Wagoner et al. (1980), the expected lung cancers
recalculated by the EPA, and bounds on presumed exposure levels.
Sanderson et al. (2001) (Document ID 1419) estimated the
cumulative, average, and maximum beryllium exposure concentration for
the 142 known lung cancer cases to be 46.06 9.3µg/
m3\-days, 22.8 3.4 µg/m3\, and 32.4
13.8 µg/m3\, respectively. The lung cancer mortality rate was
1.22 (95 percent CI = 1.03 - 1.43). Exposure estimates were lagged by
10 and 20 years in order to account for exposures that did not
contribute to lung cancer because they occurred after the induction of
cancer. In the 10- and 20-year lagged exposures the geometric mean
tenures and cumulative exposures of the lung cancer mortality cases
were higher than the controls. In addition, the geometric mean and
maximum exposures of the workers were significantly higher than
controls when the exposure estimates were lagged 10 and 20 years (p
<0.01).
Results of a conditional logistic regression analysis indicated
that there was an increased risk of lung cancer in workers with higher
exposures when dose estimates were lagged by 10 and 20 years (Sanderson
et al., 2001, Document ID 1419). There was also a lack of evidence that
confounding factors such as smoking affected the results of the
regression analysis. The authors noted that there was considerable
uncertainty in the estimation of exposure in the 1940s and 1950s and
the shape of the dose-response curve for lung cancer (Sanderson et al.,
2001, Document ID 1419). Another analysis of the study data using a
different statistical method did not find a significantly greater
relative risk of lung cancer with increasing beryllium exposures (Levy
et al., 2007). The average beryllium air levels for the lung cancer
cases were estimated to be an order of magnitude above the preceding 8-
hour OSHA TWA PEL (2 μg/m3\) and roughly two orders of magnitude
higher than the typical air levels in workplaces where beryllium
sensitization and pathological evidence of CBD have been observed. IARC
evaluated this reanalysis in 2012 and found the study introduced a
downward bias into risk estimates (IARC, 2012, Document ID 0650). NIOSH
comments in the rulemaking docket support IARC's finding (citing
Schubauer-Berigan et al., 2007; Hein et al., 2009, 2011; Langholz and
Richardson 2009; Wacholder 2009) (Document ID 1671, Attachment 1, p.
10).
Schubauer-Berigan et al. (2008) (Document ID 1350) reanalyzed data
from the Sanderson et al. (2001) nested case-control study of 142 lung
cancer cases in the Reading, PA, beryllium processing plant. This
dataset was reanalyzed using conditional (stratified by case age)
logistic regression. Independent adjustments were made for potential
confounders of birth year and hire age. Average and cumulative
exposures were analyzed using the values reported in the original
study. The objective of the reanalysis was to correct for the known
differences in smoking rates by birth year. In addition, the authors
evaluated the effects of age at hire to determine differences observed
by Sanderson et al. in 2001 (Document ID 1419). The effect of birth
cohort adjustment on lung cancer rates in beryllium-exposed workers was
evaluated by adjusting in a multivariable model for indicator variables
for the birth cohort quartiles.
Unadjusted analyses showed little evidence of lung cancer risk
associated with beryllium occupational exposure using cumulative
exposure until a 20-year lag was used. Adjusting for either birth
cohort or hire age attenuated the risk for lung cancer associated with
cumulative exposure. Using a 10- or 20-year lag in workers born after
1900 also showed little evidence of lung cancer risk, while those born
prior to 1900 did show a slight elevation in risk. Unlagged and lagged
analysis for average exposure showed an increase in lung cancer risk
associated with occupational exposure to beryllium. The finding was
consistent for either workers adjusted or unadjusted for birth cohort
or hire age. Using a 10-year lag for average exposure showed a
significant effect by birth cohort.
Schubauer-Berigan et al. stated that the reanalysis indicated that
differences in the hire ages among cases and controls, first noted by
Deubner et al. (2001) (Document ID 0109) and Levy et al. (2007)
(Document ID 1462), were primarily due to the fact that birth years
were earlier among controls than among cases, resulting from much lower
baseline risk of lung cancer for men born prior to 1900 (Schubauer-
Berigan et al., 2008, Document ID 1350). The authors went on to state
that the reanalysis of the previous NIOSH case-control study suggested
the relationship observed previously between cumulative beryllium
exposure and lung cancer was greatly attenuated by birth cohort
adjustment.
Hollins et al. (2009) (Document ID 1512) re-examined the weight of
evidence of beryllium as a lung carcinogen in a recent publication.
Citing more than 50 relevant papers, the authors noted the
methodological shortcomings examined above, including lack of well-
characterized historical occupational exposures and inadequacy of the
availability of smoking history for workers. They concluded that the
increase in potential risk of lung cancer was observed among those
exposed to very high levels of beryllium and that beryllium's
carcinogenic potential in humans at these very high exposure levels was
not relevant to today's industrial settings. IARC performed a similar
re-evaluation in 2009 (IARC, 2012, Document ID 0650) and found that the
weight of evidence for beryllium lung carcinogenicity, including the
animal studies described below, still warranted a Group I
classification, and that
beryllium should be considered carcinogenic to humans.
Schubauer-Berigan et al. (2011) (Document ID 1266) extended their
analysis from a previous study estimating associations between
mortality risk and beryllium exposure to include workers at 7 beryllium
processing plants. The study followed the mortality incidences of 9,199
workers from 1940 through 2005 at the 7 beryllium plants. JEMs were
developed for three plants in the cohort: The Reading plant, the
Hazleton plant, and the Elmore plant. The last is described in Couch et
al. 2010. Including these JEMs substantially improved the evidence base
for evaluating the carcinogenicity of beryllium, and this change
represents more than an update of the beryllium cohort. Standardized
mortality ratios (SMRs) were estimated based on U.S. population
comparisons for lung, nervous system and urinary tract cancers, chronic
obstructive pulmonary disease (COPD), chronic kidney disease, and
categories containing chronic beryllium disease (CBD) and cor
pulmonale. Associations with maximum and cumulative exposure were
calculated for a subset of the workers.
Overall mortality in the cohort compared with the U.S. population
was elevated for lung cancer (SMR 1.17; 95% CI 1.08 to 1.28), COPD (SMR
1.23; 95% CI 1.13 to 1.32), and the categories containing CBD (SMR
7.80; 95% CI 6.26 to 9.60) and cor pulmonale (SMR 1.17; 95% CI 1.08 to
1.26) (Schubauer-Berigan et al., 2011, Document ID 1266). Mortality
rates for most diseases of interest increased with time since hire. For
the category including CBD, rates were substantially elevated compared
to the U.S. population across all exposure groups. Workers whose
maximum beryllium exposure was >=10 μg/m3\ had higher rates of lung
cancer, urinary tract cancer, COPD and the category containing cor
pulmonale than workers with lower exposure. These studies showed strong
associations for cumulative exposure (when short-term workers were
excluded), maximum exposure, or both. Significant positive trends with
cumulative exposure were observed for nervous system cancers (p =
0.0006) and, when short-term workers were excluded, lung cancer (p =
0.01), urinary tract cancer (p = 0.003), and COPD (p <0.0001).
The authors concluded that the findings from this reanalysis
reaffirmed that lung cancer and CBD are related to beryllium exposure.
The authors went on to suggest that beryllium exposures may be
associated with nervous system and urinary tract cancers and that
cigarette smoking and other lung carcinogens were unlikely to explain
the increased incidences in these cancers. The study corrected an error
that was discovered in the indirect smoking adjustment initially
conducted by Ward et al., concluding that cigarette smoking rates did
not differ between the cohort and the general U.S. population. No
association was found between cigarette smoking and either cumulative
or maximum beryllium exposure, making it very unlikely that smoking was
a substantial confounder in this study (Schubauer-Berigan et al., 2011,
Document ID 1266).
A study by Boffetta et al. (2014, Document ID 0403) and an abstract
by Boffetta et al., (2015, Document ID 1661, Attachment 1) were
submitted by Materion for Agency consideration (Document ID 1661, p.
3). Briefly, Boffetta et al. investigated lung cancer and other
diseases in a cohort of 4,950 workers in four beryllium manufacturing
facilities. Based on available process information from the facilities,
the cohort of workers included only those working with poorly soluble
beryllium. Workers having potential for soluble beryllium exposure were
excluded from the study. Boffetta et al. reported a slight increase in
lung cancer rates among workers hired prior to 1960, but the increase
was reported as not statistically significant. Bofetta et al. (2014)
indicated that "[t]his study confirmed the lack of an increase in
mortality from lung cancer and nonmalignant respiratory diseases
related to [poorly] soluble beryllium compounds" (Document ID 0403, p.
587). OSHA disagrees, and a more detailed analysis of the Boffetta et
al. (2014, Document ID 0403) study is provided in the Risk Assessment
section (VI) of this preamble. The Boffetta et al. (2015, Document ID
1661, Attachment 1) study cited by Materion was an abstract to the 48th
annual Society of Epidemiological Research conference and does not
provide sufficient information for OSHA to consider.
To summarize, most of the epidemiological studies reviewed in this
section show an elevated lung cancer rate in beryllium-exposed workers
compared to control groups. While exposure data was incomplete in many
studies inferences can be made based on industry profiles.
Specifically, studies reviewing excess lung cancer in workers
registered in the BCR found an elevated lung cancer rate in those
patients identified as having acute beryllium disease (ABD). ABD
patients are most closely associated with exposure to soluble forms of
beryllium (Infante et al., 1980, Document ID 1507; Steenland and Ward,
1991 (1348)). Industry profiles in processing and extraction indicate
that most exposures would be due to poorly soluble forms of beryllium.
Excess lung cancer rates were observed in workers in industries
associated with extraction and processing (Schubauer-Berigan et al.,
2008, Document ID 1350; Schubauer-Berigan et al. 2011 (1266, 1815
Attachment 105); Ward et al., 1992 (1378); Hollins et al., 2009 (1512);
Sanderson et al., 2001 (1419); Mancuso et al., 1980 (1452); Wagoner et
al., 1980 (1379)). During the public comment period NIOSH noted that:
. . . in Table 1 of Ward et al. (1992), all three of these beryllium
plants were engaged in operations associated with both soluble and
[poorly soluble] forms of beryllium. Industrial hygienists from
NIOSH [Sanderson et al. (2001); Couch et al. (2011)] and elsewhere
[Chen (2001); Rosenman et al. (2005)] created job-exposure matrices
(JEMs), which estimated the form of beryllium exposure (soluble,
consisting of beryllium salts; [poorly soluble], consisting of
beryllium metal, alloys, or beryllium oxide; and mixed forms)
associated with each job, department and year combination at each
plant. Unpublished evaluations of these JEM estimates linked to the
employee work histories in the NIOSH risk assessment study
[Schubauer-Berigan et al., 2011b, Document ID 0521] show that the
vast majority of beryllium work-time at all three of these
facilities was due to either [poorly] soluble or mixed chemical
forms. In fact, [poorly] soluble beryllium was the largest single
contributor to work-time (for beryllium exposure of known solubility
class) at the three facilities across most time periods . . . .
Therefore, the strong and consistent exposure-response pattern that
was observed in the published NIOSH studies was very likely
associated with exposure to [poorly] soluble as well as soluble
forms of beryllium. (Document ID 1725, p. 9)
Taken collectively, the Agency finds that the epidemiological data
presented in the reviewed studies provides sufficient evidence to
demonstrate carcinogenicity in humans of both soluble and poorly
soluble forms of beryllium.
3. Animal Cancer Studies
This section reviews the animal literature used to support the
findings for beryllium-induced lung cancer. Early animal studies
revealed that some beryllium compounds are carcinogenic when inhaled
(ATSDR, 2002, Document ID 1371). Lung tumors have been induced via
inhalation and intratracheal administration of beryllium to rats and
monkeys, and osteosarcomas have been induced via intravenous and
intramedullary (inside the bone) injection of beryllium in rabbits and
mice. In addition to lung cancer,
osteosarcomas have been produced in mice and rabbits exposed to various
beryllium salts by intravenous injection or implantation into the bone
(NTP, 1999, Document ID 1341: IARC, 2012 (0650)). While not completely
understood, experimental studies in animals (in vitro and in vivo) have
found that a number of mechanisms are likely involved in beryllium-
induced carcinogenicity, including chronic inflammation, genotoxicity,
mitogenicity, oxidative stress, and epigenetic changes.
In an inhalation study assessing the potential tumorigenicity of
beryllium, Schepers et al. (1957) (Document ID 0458) exposed 115 albino
Sherman and Wistar rats (male and female) via inhalation to 0.0357 mg
beryllium/m3\ (1 [gamma] beryllium/ft3) 7 as an aqueous aerosol of
beryllium sulfate for 44 hours/week for 6 months, and observed the rats
for 18 months after exposure. Three to four control rats were killed
every two months for comparison purposes. Seventy-six lung
neoplasms,8 including adenomas, squamous-cell carcinomas, acinous
adenocarcinomas, papillary adenocarcinomas, and alveolar-cell
adenocarcinomas, were observed in 52 of the rats exposed to the
beryllium sulfate aerosol. Adenocarcinomas were the most numerous.
Pulmonary metastases tended to localize in areas with foam cell
clustering and granulomatosis. No neoplasia was observed in any of the
control rats. The incidence of lung tumors in exposed rats is presented
in the following Table 3:
---------------------------------------------------------------------------
7 Schepers et al. (1957) reported concentrations in [gamma]
Be/ft3; however, [gamma]/ft3 is no longer a common unit.
Therefore, the concentration was converted to mg/m3\.
8 While a total of 89 tumors were observed or palpated at the
time of autopsy in the BeSO4-exposed animals, only 76
tumors are listed as histologically neoplastic. Only the new growths
identified in single midcoronal sections of both lungs were
recorded.
Table 3--Neoplasm Analysis, Based on Schepers et al. (1957)
------------------------------------------------------------------------
Neoplasm Number Metastases
------------------------------------------------------------------------
Adenoma........................................ 18 0
Squamous carcinoma............................. 5 1
Acinous adenocarcinoma......................... 24 2
Papillary adenocarcinoma....................... 11 1
Alveolar-cell adenocarcinoma................... 7 0
Mucigenous tumor............................... 7 1
Endothelioma................................... 1 0
Retesarcoma.................................... 3 3
------------------------
Total...................................... 76 8
------------------------------------------------------------------------
Schepers (1962) (Document ID 1414) reviewed 38 existing beryllium
studies that evaluated seven beryllium compounds and seven mammalian
species. Beryllium sulfate, beryllium fluoride, beryllium phosphate,
beryllium alloy (BeZnMnSiO4), and beryllium oxide were
proven to be carcinogenic. Ten varieties of tumors were observed, with
adenocarcinoma being the most common variety.
In another study, Vorwald and Reeves (1959) (Document ID 1482)
exposed Sherman albino rats via the inhalation route to aerosols of
0.006 mg beryllium/m3\ as beryllium oxide and 0.0547 mg beryllium/m3\
as beryllium sulfate for 6 hours/day, 5 days/week for an unspecified
duration. Lung tumors (single or multifocal) were observed in the
animals sacrificed following 9 months of daily inhalation exposure. The
histologic pattern of the cancer was primarily adenomatous; however,
epidermoid and squamous cell cancers were also observed. Infiltrative,
vascular, and lymphogenous extensions often developed with secondary
metastatic growth in the tracheobronchial lymph nodes, the mediastinal
connective tissue, the parietal pleura, and the diaphragm.
In the first of two articles, Reeves et al. (1967) investigated the
carcinogenic process in lungs resulting from chronic (up to 72 weeks)
beryllium sulfate inhalation (Document ID 1310). One hundred fifty male
and female Sprague Dawley C.D. strain rats were exposed to beryllium
sulfate aerosol at a mean atmospheric concentration of 34.25 μg
beryllium/m3\ (with an average particle diameter of 0.12 µm).
Prior to initial exposure and again during the 67-68 and 75-76 weeks of
life, the animals received prophylactic treatments of tetracycline-HCl
to combat recurrent pulmonary infections.
The animals entered the exposure chamber at 6 weeks of age and were
exposed 7 hours per day/5 days per week for up to 2,400 hours of total
exposure time. An equal number of unexposed controls were held in a
separate chamber. Three male and three female rats were sacrificed
monthly during the 72-week exposure period. Mortality due to
respiratory or other infections did not appear until 55 weeks of age,
and 87 percent of all animals survived until their scheduled
sacrifices.
Average lung weight towards the end of exposure was 4.25 times
normal with progressively increasing differences between control and
exposed animals. The increase in lung weight was accompanied by notable
changes in tissue texture with two distinct pathological processes--
inflammatory and proliferative. The inflammatory response was
characterized by marked accumulation of histiocytic elements forming
clusters of macrophages in the alveolar spaces. The proliferative
response progressed from early epithelial hyperplasia of the alveolar
surfaces, through metaplasia (after 20-22 weeks of exposure), anaplasia
(cellular dedifferentiation) (after 32-40 weeks of exposure), and
finally to lung tumors.
Although the initial proliferative response occurred early in the
exposure period, tumor development required considerable time. Tumors
were first identified after nine months of beryllium sulfate exposure,
with rapidly increasing rates of incidence until tumors were observed
in 100 percent of exposed animals by 13 months. The 9-to-13-month
interval is consistent with earlier studies. The tumors showed a high
degree of local invasiveness. No tumors were observed in control rats.
All 56 tumors studied appeared to be alveolar adenocarcinomas and 3
were "fast-growing" tumors that reached a very large size
comparatively early. About one-third of the tumors showed small foci
where the histologic pattern differed. Most of the early tumor foci
appeared to be alveolar rather than bronchiolar, which is consistent
with the expected pathogenesis, since permanent deposition of beryllium
was more likely on the alveolar epithelium rather than on the
bronchiolar epithelium. Female rats appeared to have an increased
susceptibility to beryllium exposure. Not only did they have a higher
mortality (control males [n = 8], exposed males [n = 9] versus control
females [n = 4], exposed females [n = 17]) and body weight loss than
male rats, but the three "fast-growing" tumors occurred in females.
In the second article, Reeves et al. (1967) (Document ID 1309)
described the rate of accumulation and clearance of beryllium sulfate
aerosol from the same experiment (Reeves et al., 1967) (Document ID
1310). At the time of the monthly sacrifice, beryllium assays were
performed on the lungs, tracheobronchial lymph nodes, and blood of the
exposed rats. The pulmonary beryllium levels of rats showed a rate of
accumulation which
decreased during continuing exposure and reached a plateau (defined as
equilibrium between deposition and clearance) of about 13.5 μg
beryllium for males and 9 μg beryllium for females in whole lungs
after approximately 36 weeks. Females were notably less efficient than
males in utilizing the lymphatic route as a method of clearance,
resulting in slower removal of pulmonary beryllium deposits, lower
accumulation of the inhaled material in the tracheobronchial lymph
nodes, and higher morbidity and mortality.
There was no apparent correlation between the extent and severity
of pulmonary pathology and total lung load. However, when the beryllium
content of the excised tumors was compared with that of surrounding
nonmalignant pulmonary tissues, the former showed a notable decrease
(0.50 0.35 μg beryllium/gram versus 1.50
0.55 μg beryllium/gram). This was believed to be largely a result of
the dilution factor operating in the rapidly growing tumor tissue.
However, other factors, such as lack of continued local deposition due
to impaired respiratory function and enhanced clearance due to high
vascularity of the tumor, may also have played a role. The portion of
inhaled beryllium retained in the lungs for a longer duration, which is
in the range of one-half of the original pulmonary load, may have
significance for pulmonary carcinogenesis. This pulmonary beryllium
burden becomes localized in the cell nuclei and may be an important
factor in eliciting the carcinogenic response associated with beryllium
inhalation.
Groth et al. (1980) (Document ID 1316) conducted a series of
experiments to assess the carcinogenic effects of beryllium, beryllium
hydroxide, and various beryllium alloys. For the beryllium metal/alloys
experiment, 12 groups of 3-month-old female Wistar rats (35 rats/group)
were used. All rats in each group received a single intratracheal
injection of either 2.5 or 0.5 mg of one of the beryllium metals or
beryllium alloys as described in Table 3 below. These materials were
suspended in 0.4 cc of isotonic saline followed by 0.2 cc of saline.
Forty control rats were injected with 0.6 cc of saline. The geometric
mean particle sizes varied from 1 to 2 µm. Rats were sacrificed
and autopsied at various intervals ranging from 1 to 18 months post-
injection.
Table 4--Summary of Beryllium Dose, Based on Groth et al. (1980)
[Document ID 1316]
----------------------------------------------------------------------------------------------------------------
Percent other Total Number Compound
Form of Be Percent Be compounds rats autopsied dose(mg) Be dose(mg)
----------------------------------------------------------------------------------------------------------------
Be metal..................... 100............. None........... 16 2.5 2.5
21 0.5 0.5
Passivated Be metal.......... 99.............. 0.26% Chromium. 26 2.5 2.5
20 0.5 0.5
BeAl alloy................... 62.............. 38% Aluminum... 24 2.5 1.55
21 0.5 0.3
BeCu alloy................... 4............... 96% Copper..... 28 2.5 0.1
24 0.5 0.02
BeCuCo alloy................. 2.4............. 0.4% Cobalt.... 33 2.5 0.06
96% Copper..... 30 0.5 0.012
BeNi alloy................... 2.2............. 97.8% Nickel... 28 2.5 0.056
27 0.5 0.011
----------------------------------------------------------------------------------------------------------------
Lung tumors were observed only in rats exposed to beryllium metal,
passivated beryllium metal, and beryllium-aluminum alloy. Passivation
refers to the process of removing iron contamination from the surface
of beryllium metal. As discussed, metal alloys may have a different
toxicity than beryllium alone. Rats exposed to 100 percent beryllium
exhibited relatively high mortality rates, especially in the groups
where lung tumors were observed. Nodules varying from 1 to 10 mm in
diameter were also observed in the lungs of rats exposed to beryllium
metal, passivated beryllium metal, and beryllium-aluminum alloy. These
nodules were suspected of being malignant.
To test this hypothesis, transplantation experiments involving the
suspicious nodules were conducted in nine rats. Seven of the nine
suspected tumors grew upon transplantation. All transplanted tumor
types metastasized to the lungs of their hosts. Lung tumors were
observed in rats injected with both the high and low doses of beryllium
metal, passivated beryllium metal, and beryllium-aluminum alloy. No
lung tumors were observed in rats injected with the other compounds. Of
a total of 32 lung tumors detected, most were adenocarcinomas and
adenomas; however, two epidermoid carcinomas and at least one poorly
differentiated carcinoma were observed. Bronchiolar alveolar cell
tumors were frequently observed in rats injected with beryllium metal,
passivated beryllium metal, and beryllium-aluminum alloy. All stages of
cuboidal, columnar, and squamous cell metaplasia were observed on the
alveolar walls in the lungs of rats injected with beryllium metal,
passivated beryllium metal, and beryllium-aluminum alloy. These lesions
were generally reduced in size and number or absent from the lungs of
animals injected with the other alloys (BeCu, BeCuCo, BeNi).
The extent of alveolar metaplasia could be correlated with the
incidence of lung cancer. The incidences of lung tumors in the rats
that received 2.5 mg of beryllium metal, and 2.5 and 0.5 mg of
passivated beryllium metal, were significantly different (p <=0.008)
from controls. When autopsies were performed at the 16-to-19-month
interval, the incidence (2/6) of lung tumors in rats exposed to 2.5 mg
of beryllium-aluminum alloy was statistically significant (p = 0.004)
when compared to the lung tumor incidence (0/84) in rats exposed to
BeCu, BeNi, and BeCuCo alloys, which contained much lower
concentrations of Be (Groth et al., 1980, Document ID 1316).
Finch et al. (1998b) (Document ID 1367) investigated the
carcinogenic effects of inhaled beryllium on heterozygous TSG-p53
knockout (p53 +/-) mice and wild-type (p53+/+) mice.
Knockout mice can be valuable tools in determining the role played by
specific genes in the toxicity of a material of interest, in this case
beryllium. Equal numbers of approximately 10-week-old male and female
mice were used for this study. Two exposure groups were used to provide
dose-response information on lung carcinogenicity. The maximum initial
lung burden (ILB) target of 60 μg
beryllium was based on previous acute inhalation exposure studies in
mice. The lower exposure target level of 15 μg was selected to
provide a lung burden significantly less than the high-level group, but
high enough to yield carcinogenic responses. Mice were exposed in
groups to beryllium metal or to filtered air (controls) via nose-only
inhalation. The specific exposure parameters are presented in Table 4
below. Mice were sacrificed 7 days post exposure for ILB analysis, and
either at 6 months post exposure (n = 4-5 mice per group per gender) or
when 10 percent or less of the original population remained (19 months
post exposure for p53 +/- knockout and 22.5 months post
exposure for p53+/+ wild-type mice). The sacrifice time was extended in
the study because a significant number of lung tumors were not observed
at 6 months post exposure.
Table 5--Summary of Animal Data, Based on Finch et al. (1998)
[Document ID 1367]
----------------------------------------------------------------------------------------------------------------
Number of
Target Mean daily mice with 1
Mean exposure beryllium lung Number of exposure Mean ILB or more lung
Mouse strain concentration burden mice duration (μg) tumors/total
(μg Be/L) (μg) (minutes) number
examined
----------------------------------------------------------------------------------------------------------------
Knockout (p53 34 15 30 112 (single) NA 0/29
+/-) 36 60 30 139 NA 4/28
Wild-type (p53 34 15 6 112 (single) 12 4 0/28
54 6
Knockout (p53 NA (air) Control 30 60-180 NA 0/30
+/-) (single)
----------------------------------------------------------------------------------------------------------------
Lung burdens of beryllium measured in wild-type mice at 7 days post
exposure were approximately 70-90 percent of target levels. No
exposure-related effects on body weight were observed in mice; however,
lung weights and lung-to-body-weight ratios were somewhat elevated in
60 μg target ILB p53 +/- knockout mice compared to
controls (0.05 +/- knockout mice and beryllium exposure
tended to decrease survival time in both groups. The incidence of
beryllium-induced lung tumors was marginally higher in the 60 μg
target ILB p53 +/- knockout mice compared to 60 μg target
ILB p53+/+ wild-type mice (p= 0.056). The incidence of lung tumors in
the 60 μg target ILB p53 +/- knockout mice was also
significantly higher than controls (p = 0.048). No tumors developed in
the control mice, 15 μg target ILB p53 +/- knockout mice,
or 60 μg target ILB p53+/+ wild-type mice throughout the length of
the study. Most lung tumors in beryllium-exposed mice were squamous
cell carcinomas, three of four of which were poorly circumscribed and
all of which were associated with at least some degree of granulomatous
pneumonia. The study results suggest that having an inactivated p53
allele is associated with lung tumor progression in p53 +/-
knockout mice. This is based on the significant difference seen in the
incidence of beryllium-induced lung neoplasms for the p53
+/- knockout mice compared with the p53 \+/+\ wild-type
mice. The authors conclude that since there was a relatively late onset
of tumors in the beryllium-exposed p53 +/- knockout mice, a
6-month bioassay in this mouse strain might not be an appropriate model
for lung carcinogenesis (Finch et al., 1998, Document ID 1367).
During the public comment period Materion submitted correspondence
from Dr. Finch speculating on the reason for the less-robust lung
cancer response observed in mice (versus that observed in rats)
(Document ID 1807, Attachment 11, p. 1). Materion contended that this
was support for their assertion of evidence that "directly contradicts
the claims that beryllium metal causes cancer in animals" (Document ID
1807, p. 6). OSHA reviewed this correspondence and disagrees with
Materion's assertion. While Dr. Finch did suggest that the mouse lung
cancer response was less robust, it was still present. Dr. Finch went
on to suggest that while the rat has a more profound neutrophilic
response (typical of a "foreign body response), the mouse has a lung
response more typical of humans (neutrophilic and lymphocytic)
(Document ID 1807, Attachment 11, p. 1).
Nickell-Brady et al. (1994) investigated the development of lung
tumors in 12-week-old F344/N rats after a single nose-only inhalation
exposure to beryllium aerosol, and evaluated whether beryllium lung
tumor induction involves alterations in the K-ras, p53, and c-raf-1
genes (Document ID 1312). Four groups of rats (30 males and 30 females
per group) were exposed to different mass concentrations of beryllium
(Group 1: 500 mg/m3\ for 8 min; Group 2: 410 mg/m3\ for 30 min; Group
3: 830 mg/m3\ for 48 min; Group 4: 980 mg/m3\ for 39 min). The
beryllium mass median aerodynamic diameter was 1.4 μm
([sigma]g= 1.9). The mean beryllium lung burdens for each
exposure group were 40, 110, 360, and 430 μg, respectively.
To examine genetic alterations, DNA isolation and sequencing
techniques (PCR amplification and direct DNA sequence analysis) were
performed on wild-type rat lung tissue (i.e., control samples) along
with two mouse lung tumor cell lines containing known K-ras mutations,
12 carcinomas induced by beryllium (i.e., experimental samples), and 12
other formalin-fixed specimens. Tumors appeared in beryllium-exposed
rats by 14 months, and 64 percent of exposed rats developed lung tumors
during their lifetime. Lungs frequently contained multiple tumor sites,
with some of the tumors greater than 1 cm. A total of 24 tumors were
observed. Most of the tumors (n = 22) were adenocarcinomas exhibiting a
papillary pattern characterized by cuboidal or columnar cells, although
a few had a tubular or solid pattern. Fewer than 10 percent of the
tumors were adenosquamous (n = 1) or squamous cell (n = 1) carcinomas.
No transforming mutations of the K-ras gene (codons 12, 13, or 61)
were detected by direct sequence analysis in any of the lung tumors
induced by beryllium. However, using a more sensitive sequencing
technique (PCR enrichment restriction fragment length polymorphism
(RFLP) analysis) resulted in the detection of K-ras codon 12 GGT to GTT
transversions in 2 of 12 beryllium-induced adenocarcinomas. No p53 or
c-raf-1 alterations were observed in any of the tumors induced by
beryllium exposure (i.e., no differences observed between beryllium-
exposed and control rat tissues). The authors note that the results
suggest that
activation of the K-ras proto-oncogene is both a rare and late event,
possibly caused by genomic instability during the progression of
beryllium-induced rat pulmonary adenocarcinomas. It is unlikely that
the K-ras gene plays a role in the carcinogenicity of beryllium. The
results also indicate that p53 mutation is unlikely to play a role in
tumor development in rats exposed to beryllium.
Belinsky et al. (1997) reviewed the findings by Nickell-Brady et
al. (1994) (Document ID 1312) to further examine the role of the K-ras
and p53 genes in lung tumors induced in the F344 rat by non-mutagenic
(non-genotoxic) exposures to beryllium. Their findings are discussed
along with the results of other genomic studies that look at
carcinogenic agents that are either similarly non-mutagenic or, in
other cases, mutagenic. The authors concluded that the identification
of non-ras transforming genes in rat lung tumors induced by non-
mutagenic exposures, such as beryllium, as well as mutagenic exposures
will help define some of the mechanisms underlying cancer induction by
different types of DNA damage.
The inactivation of the p16 INK4a(p16) gene is a contributing
factor in disrupting control of the normal cell cycle and may be an
important mechanism of action in beryllium-induced lung tumors.
Swafford et al. (1997) investigated the aberrant methylation and
subsequent inactivation of the p16 gene in primary lung tumors induced
in F344/N rats exposed to known carcinogens via inhalation (Document ID
1392). The research involved a total of 18 primary lung tumors that
developed after exposing rats to five agents, one of which was
beryllium. In this study, only one of the 18 lung tumors was induced by
beryllium exposure; the majority of the other tumors were induced by
radiation (x-rays or plutonium-239 oxide). The authors hypothesized
that if p16 inactivation plays a central role in development of non-
small-cell lung cancer, then the frequency of gene inactivation in
primary tumors should parallel that observed in the corresponding cell
lines. To test the hypothesis, a rat model for lung cancer was used to
determine the frequency and mechanism for inactivation of p16 in
matched primary lung tumors and derived cell lines. The methylation-
specific PCR (MSP) method was used to detect methylation of p16
alleles. The results showed that the presence of aberrant p16
methylation in cell lines was strongly correlated with absent or low
expression of the gene. The findings also demonstrated that aberrant
p16 CpG island methylation, an important mechanism in gene silencing
leading to the loss of p16 expression, originates in primary tumors.
Building on the rat model for lung cancer and associated findings
from Swafford et al. (1997) (Document ID 1392), Belinsky et al. (2002)
(Document ID 1300) conducted experiments in 12-week-old F344/N rats
(male and female) to determine whether beryllium-induced lung tumors
involve inactivation of the p16 gene and estrogen receptor α (ER)
gene. Rats received a single nose-only inhalation exposure to beryllium
aerosol at four different exposure levels. The mean lung burdens
measured in each exposure group were 40, 110, 360, and 430 μg. The
methylation status of the p16 and ER genes was determined by MSP. A
total of 20 tumors detected in beryllium-exposed rats were available
for analysis of gene-specific promoter methylation. Three tumors were
classified as squamous cell carcinomas and the others were determined
to be adenocarcinomas. Methylated p16 was present in 80 percent (16/
20), and methylated ER was present in one-half (10/20), of the lung
tumors induced by exposure to beryllium. Additionally, both genes were
methylated in 40 percent of the tumors. The authors noted that four
tumors from beryllium-exposed rats appeared to be partially methylated
at the p16 locus. Bisulfite sequencing of exon 1 of the ER gene was
conducted on normal lung DNA and DNA from three methylated, beryllium-
induced tumors to determine the density of methylation within amplified
regions of exon 1 (referred to as CpG sites). Two of the three
methylated, beryllium-induced lung tumors showed extensive methylation,
with more than 80 percent of all CpG sites methylated.
The overall findings of this study suggest that inactivation of the
p16 and ER genes by promoter hypermethylation are likely to contribute
to the development of lung tumors in beryllium-exposed rats. The
results showed a correlation between changes in p16 methylation and
loss of gene transcription. The authors hypothesize that the mechanism
of action for beryllium-induced p16 gene inactivation in lung tumors
may be inflammatory mediators that result in oxidative stress. The
oxidative stress damages DNA directly through free radicals or
indirectly through the formation of 8-hydroxyguanosine DNA adducts,
resulting primarily in a single-strand DNA break.
Wagner et al. (1969) (Document ID 1481) studied the development of
pulmonary tumors after intermittent daily chronic inhalation exposure
to beryllium ores in three groups of male squirrel monkeys. One group
was exposed to bertrandite ore, a second to beryl ore, and the third
served as unexposed controls. Each of these three exposure groups
contained 12 monkeys. Monkeys from each group were sacrificed after 6,
12, or 23 months of exposure. The 12-month sacrificed monkeys (n = 4
for bertrandite and control groups; n = 2 for beryl group) were
replaced by a separate replacement group to maintain a total animal
population approximating the original numbers and to provide a source
of confirming data for biologic responses that might arise following
the ore exposures. Animals were exposed to bertrandite and beryl ore
concentrations of 15 mg/m3\, corresponding to 210 μg beryllium/m3\
and 620 μg beryllium/m3\ in each exposure chamber, respectively.
The parent ores were reduced to particles with geometric mean diameters
of 0.27 μm ( 2.4) for bertrandite and 0.64 μm ( 2.5) for beryl. Animals were exposed for approximately 6 hours/
day, 5 days/week. The histological changes in the lungs of monkeys
exposed to bertrandite and beryl ore exhibited a similar pattern. The
changes generally consisted of aggregates of dust-laden macrophages,
lymphocytes, and plasma cells near respiratory bronchioles and small
blood vessels. There were, however, no consistent or significant
pulmonary lesions or tumors observed in monkeys exposed to either of
the beryllium ores. This is in contrast to the findings in rats exposed
to beryl ore and to a lesser extent bertrandite, where atypical cell
proliferation and tumors were frequently observed in the lungs. The
authors hypothesized that the rats' greater susceptibility may be
attributed to the spontaneous lung disease characteristic of rats,
which might have interfered with lung clearance.
As previously described, Conradi et al. (1971) investigated changes
in the lungs of monkeys and dogs two years after intermittent
inhalation exposure to beryllium oxide calcined at 1,400 [deg]C
(Document ID 1319). Five adult male and female monkeys (Macaca irus)
weighing between 3 and 5.75 kg were used in the study. The study
included two control monkeys. Beryllium concentrations in the
atmosphere of whole-body exposed monkeys varied between 3.30 and 4.38
mg/m3\. Thirty-minute exposures occurred once a month for three
months, with beryllium oxide concentrations increasing at each exposure
interval. Lung tissue was investigated using electron microscopy
and morphometric methods. Beryllium content in portions of the lungs of
five monkeys was measured two years following exposure by emission
spectrography. The reported concentrations in monkeys (82.5, 143.0, and
112.7 μg beryllium per 100 gm of wet tissue in the upper lobe, lower
lobe, and combined lobes, respectively) were higher than those in dogs.
No neoplastic or granulomatous lesions were observed in the lungs of
any exposed animals and there was no evidence of chronic proliferative
lung changes after two years.
To summarize, animal studies show that multiple forms of beryllium,
when inhaled or instilled in the respiratory tract of rats, mice, and
monkeys, lead to increased incidence of lung tumors. Animal studies
have demonstrated a consistent scenario of beryllium exposure resulting
in chronic pulmonary inflammation and tumor formation at levels below
overload conditions (Groth et al., 1980, Document ID 1316; Finch et
al., 1998 (1367); Nickel-Brady et al., 1994 (1312)). The animal studies
support the human epidemiological evidence and contributed to the
findings of the NTP, IARC, and others that beryllium and beryllium-
containing material should be regarded as known human carcinogens. The
beryllium compounds found to be carcinogenic in animals include both
soluble beryllium compounds, such as beryllium sulfate and beryllium
hydroxide, as well as poorly soluble beryllium compounds, such as
beryllium oxide and beryllium metal. The doses that produce tumors in
experimental animal are fairly large and also lead to chronic pulmonary
inflammation. The exact tumorigenic mechanism for beryllium is unclear
and a number of mechanisms are likely involved, including chronic
inflammation, genotoxicity, mitogenicity, oxidative stress, and
epigenetic changes.
4. In Vitro Studies
The exact mechanism by which beryllium induces pulmonary neoplasms
in animals remains unknown (NAS 2008, Document ID 1355). Keshava et al.
(2001) performed studies to determine the carcinogenic potential of
beryllium sulfate in cultured mammalian cells (Document ID 1362).
Joseph et al. (2001) investigated differential gene expression to
understand the possible mechanisms of beryllium-induced cell
transformation and tumorigenesis (Document ID 1490). Both
investigations used cell transformation assays to study the cellular/
molecular mechanisms of beryllium carcinogenesis and assess
carcinogenicity. Cell lines were derived from tumors developed in nude
mice injected subcutaneously with non-transformed BALB/c-3T3 cells that
were morphologically transformed in vitro with 50-200 μg beryllium
sulfate/ml for 72 hours. The non-transformed cells were used as
controls.
Keshava et al. (2001) found that beryllium sulfate is capable of
inducing morphological cell transformation in mammalian cells and that
transformed cells are potentially tumorigenic (Document ID 1362). A
dose-dependent increase (9-41 fold) in transformation frequency was
noted. Using differential polymerase chain reaction (PCR), gene
amplification was investigated in six proto-oncogenes (K-ras, c-myc, c-
fos, c-jun, c-sis, erb-B2) and one tumor suppressor gene (p53). Gene
amplification was found in c-jun and K-ras. None of the other genes
tested showed amplification. Additionally, Western blot analysis showed
no change in gene expression or protein level in any of the genes
examined. Genomic instability in both the non-transformed and
transformed cell lines was evaluated using random amplified polymorphic
DNA fingerprinting (RAPD analysis). Using different primers, 5 of the
10 transformed cell lines showed genomic instability when compared to
the non-transformed BALB/c-3T3 cells. The results indicate that
beryllium sulfate-induced cell transformation might, in part, involve
gene amplification of K-ras and c-jun and that some transformed cells
possess neoplastic potential resulting from genomic instability.
Using the Atlas mouse 1.2 cDNA expression microarrays, Joseph et
al. (2001) studied the expression profiles of 1,176 genes belonging to
several different functional categories after beryllium sulfate
exposure in a mouse cell line (Document ID 1490). Compared to the
control cells, expression of 18 genes belonging to two functional
groups (nine cancer-related genes and nine DNA synthesis, repair, and
recombination genes) was found to be consistently and reproducibly
different (at least 2-fold) in the tumor cells. Differential gene
expression profile was confirmed using reverse transcription-PCR with
primers specific to the differentially expressed genes. Two of the
differentially expressed genes (c-fos and c-jun) were used as model
genes to demonstrate that the beryllium-induced transcriptional
activation of these genes was dependent on pathways of protein kinase C
and mitogen-activated protein kinase and independent of reactive oxygen
species in the control cells. These results indicate that beryllium-
induced cell transformation and tumorigenesis are associated with up-
regulated expression of the cancer-related genes (such as c-fos, c-jun,
c-myc, and R-ras) and down-regulated expression of genes involved in
DNA synthesis, repair, and recombination (such as MCM4, MCM5, PMS2,
Rad23, and DNA ligase I).
In summary, in vitro studies have been used to evaluate the
neoplastic potential of beryllium compounds and the possible underlying
mechanisms. Both Keshava et al. (2001) (Document ID 1362) and Joseph et
al. (2001) (Document ID 1490) have found that beryllium sulfate induced
a number of onco-genes (c-fos, c-jun, c-myc, and R-ras) and down-
regulated genes responses for normal cellular function and repair
(including those involved in DNA synthesis, repair, and recombination).
5. Lung Cancer Conclusions
OSHA has determined that substantial evidence in the record
indicates that beryllium compounds should be regarded as occupational
lung carcinogens. Many well-respected scientific organizations,
including IARC, NTP, EPA, NIOSH, and ACGIH, have reached similar
conclusions with respect to the carcinogenicity of beryllium.
While some evidence exists for direct-acting genotoxicity as a
possible mechanism for beryllium carcinogenesis, the weight of evidence
suggests that an indirect mechanism, such as inflammation or other
epigenetic changes, may be responsible for most tumorigenic activity of
beryllium in animals and humans (IARC, 2012, Document ID 0650).
Inflammation has been postulated to be a key contributor to many
different forms of cancer (Jackson et al., 2006; Pikarsky et al., 2004;
Greten et al., 2004; Leek, 2002). In fact, chronic inflammation may be
a primary factor in the development of up to one-third of all cancers
(Ames et al., 1990; NCI, 2010).
In addition to a T-cell-mediated immunological response, beryllium
has been demonstrated to produce an inflammatory response in animal
models similar to the response produced by other particles (Reeves et
al., 1967, Document ID 1309; Swafford et al., 1997 (1392); Wagner et
al., 1969 (1481)), possibly contributing to its carcinogenic potential.
Studies conducted in rats have demonstrated that chronic inhalation of
materials similar in solubility to beryllium results in increased
pulmonary inflammation,
fibrosis, epithelial hyperplasia, and, in some cases, pulmonary
adenomas and carcinomas (Heinrich et al., 1995, Document ID 1513; NTP,
1993 (1333); Lee et al., 1985 (1466); Warheit et al., 1996 (1377)).
This response is generally referred to as an "overload" response and
is specific to particles of low solubility with a low order of
toxicity, which are non-mutagenic and non-genotoxic (i.e., poorly
soluble particles like titanium dioxide and non-asbestiform talc); this
response is observed only in rats (Carter et al., 2006, Document ID
1556). "Overload" is described in ECETOC (2013) as inhalation of high
concentrations of low solubility particles resulting in lung burdens
that impair particle clearance mechanisms (ECETOC, 2013 as cited in
Document ID 1807, Attachment 10, p. 3 (pdf p. 87)). Substantial data
indicate that tumor formation in rats after exposure to some poorly
soluble particles at doses causing marked, chronic inflammation is due
to a secondary mechanism unrelated to the genotoxicity (or lack
thereof) of the particle itself. Because these specific particles
(i.e., titanium dioxide and non-asbestiform talc) exhibit no
cytotoxicity or genotoxicity, they are considered to be biologically
inert (ECETOC, 2013; see Document ID 1807, Attachment 10, p. 3 (pdf p.
87)). Animal studies, as summarized above, have demonstrated a
consistent scenario of beryllium exposure resulting in chronic
pulmonary inflammation below an overload scenario. NIOSH submitted
comments describing the findings from a low-dose study of beryllium
metal among male and female F344 rats (Document ID 1960, p. 11). The
study by Finch et al. (2000) indicated lung tumor rates of 4, 4, 12,
50, 61, and 91 percent in animals with beryllium metal lung burdens of
0, 0.3, 1, 3, 10, and 50 μg respectively (Finch et al., 2000 as
cited in Document ID 1960, p. 11). NIOSH noted the lung burden levels
were much lower than those from previous studies, such as a 1998 Finch
et al. study with initial lung burdens of 15 and 60 μg (Document ID
1960, p. 11). Based on evidence from mammalian studies of the
mutagenicity and genotoxicity of beryllium (as described in above in
section V.E.1) and the evidence of tumorigenicity at lung burden levels
well below overload, OSHA concludes that beryllium particles are not
poorly soluble particles like titanium dioxide and non-asbestiform
talc.
It has been hypothesized that the recruitment of neutrophils during
the inflammatory response and subsequent release of oxidants from these
cells play an important role in the pathogenesis of rat lung tumors
(Borm et al., 2004, Document ID 1559; Carter and Driscoll, 2001 (1557);
Carter et al., 2006 (1556); Johnston et al., 2000 (1504); Knaapen et
al., 2004 (1499); Mossman, 2000 (1444)). This is one potential
carcinogenic pathway for beryllium particles. Inflammatory mediators,
acting at levels below overload doses as characterized in many of the
studies summarized above, have been shown to play a significant role in
the recruitment of cells responsible for the release of reactive oxygen
and hydrogen species. These species have been determined to be highly
mutagenic as well as mitogenic, inducing a proliferative response
(Ferriola and Nettesheim, 1994, Document ID 0452; Coussens and Werb,
2002 (0496)). The resultant effect is an environment rich for
neoplastic transformations and the progression of fibrosis and tumor
formation. This is consistent with findings from the National Cancer
Institute, which has estimated that one-third of all cancers may be due
to chronic inflammation (NCI, 2010, Document ID 0532). However, an
inflammation-driven contribution to the neoplastic transformation does
not imply no risk at levels below inflammatory response; rather, the
overall weight of evidence suggests a mechanism of an indirect
carcinogen at levels where inflammation is seen. While tumorigenesis
secondary to inflammation is one reasonable mode of action, other
plausible modes of action independent of inflammation (e.g.,
epigenetic, mitogenic, reactive oxygen mediated, indirect genotoxicity,
etc.) may also contribute to the lung cancer associated with beryllium
exposure. As summarized above, animal studies have consistently
demonstrated beryllium exposure resulting in chronic pulmonary
inflammation below overload conditions in multiple species (Groth et
al., 1980, Document ID 1316; Finch et al., 1998 (1367); Nickel-Brady et
al., 1994 (1312)). While OSHA recognizes chronic inflammation as one
potential pathway to carcinogencity the Agency finds that other
carcinogenic pathways such as genotoxicity and epigenetic changes may
also contribute to beryllium-induced carcinogenesis.
During the public comment period OSHA received several comments on
the carcinogenicity of beryllium. The NFFS agreed with OSHA that "the
science is quite clear in linking these soluble Beryllium compounds"
to lung cancer (Document ID 1678, p. 6). It also, however, contended
that there is considerable scientific dispute regarding the
carcinogenicity of beryllium metal (i.e., poorly soluble beryllium),
citing findings by the EU's REACH Beryllium Commission (later clarified
as the EU Beryllium Science and Technology Association) (Document ID
1785, p. 1; Document ID 1814) and a study by Strupp and Furnes (2010)
(Document ID 1678, pp. 6-7, and Attachment 1). Materion, similarly,
commented that "[a] report conclusion during the recent review of the
European Cancer Directive for the European Commission stated regarding
beryllium: `There was little evidence for any important health impact
from current or recent past exposures in the EU' " (Document ID 1958,
p. 4).
The contentions of both Materion and NFFS regarding scientific
findings from the EU is directly contradicted by the document submitted
to the docket by the European Commission on Health, Safety and Hygiene
at Work, discussed above. This document states that the European
Chemicals Agency (ECHA) has determined that all forms of beryllium
(soluble and poorly soluble) are carcinogenic (Category 1B) with the
exception of aluminum beryllium silicates (which have not been
allocated a classification) (Document ID 1692, pp. 2-3).
OSHA also disagrees with NFFS's other contention that there is a
scientific dispute regarding the carcinogenicity of poorly soluble
forms of beryllium. In coming to the conclusion that all forms of
beryllium and beryllium compounds are carcinogenic, OSHA independently
evaluated the scientific literature, including the findings of
authoritative entities such as NIOSH, NTP, EPA, and IARC (see section
V.E). The evidence from human, animal, and mechanistic studies together
demonstrates that both soluble and poorly soluble beryllium compounds
are carcinogenic (see sections V.E.2, V.E.3, V.E.4). The well-respected
scientific bodies mentioned above came to the same conclusion: That
both soluble and poorly soluble beryllium compounds are carcinogenic to
humans.
As supporting documentation the NFFS submitted an "expert
statement" by Strupp and Furnes (2010), which reviews the
toxicological and epidemiological information regarding beryllium
carcinogenicity. Based on select information in the scientific
literature on lung cancer, the Strupp and Furnes (2010) study concluded
that there was insufficient evidence in humans and animals to conclude
that insoluble (poorly soluble) beryllium was carcinogenic (Document ID
1678, Attachment 1, pp. 21-23). Strupp and Furnes (2010) asserted that
this was based on criteria established under
Annex VI of Directive 67/548/EEC which establishes criteria for
classification and labelling of hazardous substances under the UN
Globally Harmonized System of Classification and Labelling of Chemicals
(GHS). OSHA reviewed the Strupp and Furnes (2010) "expert statement"
submitted by NFFS and found it to be unpersuasive. Its review of the
epidemiological evidence mischaracterized the findings from the NIOSH
cohort and the nested case-control studies (Ward et al., 1992;
Sanderson et al., 2001; Schubauer-Berigan et al., 2008) and
misunderstood the methods commonly used to analyze occupational cohort
studies (Document ID 1725, pp. 27-28).
The Strupp and Furnes statement also did not include the more
recent studies by Schubauer-Berigan et al. (2011, Document ID 1815,
Attachment 105, 2011 (0626)), which demonstrated elevated rates for
lung cancer (SMR 1.17; 95% CI 1.08 to 1.28) in a study of 7 beryllium
processing plants. In addition, Strupp and Furnes did not consider
expert criticism from IARC on the studies by Levy et al. (2007) and
Deubner et al., (2007), which formed the basis of their findings. NIOSH
submitted comments that stated:
The Strupp (2011b) review of the epidemiological evidence for
lung carcinogenicity of beryllium contained fundamental
mischaracterizations of the findings of the NIOSH cohort and nested
case-control studies (Ward et al. 1992; Sanderson et al. 2001;
Schubauer-Berigan et al. 2008), as well as an apparent
misunderstanding of the methods commonly used to analyze
occupational cohort studies (Document ID 1960, Attachment 2, p. 10).
As further noted by NIOSH:
Strupp's epidemiology summary mentions two papers that were
critical of the Sanderson et al. (2001) nested case-control study.
The first of these, Levy et al. (2007a), was a re-analysis that
incorporated a nonstandard method of selecting control subjects and
the second, Deubner et al. (2007), was a simulation study designed
to evaluate Sanderson's study design. Both of these papers have
themselves been criticized for using faulty methods (Schubauer-
Berigan et al. 2007; Kriebel, 2008; Langholz and Richardson, 2008);
however, Strupp's coverage of this is incomplete. (Document ID 1960,
Attachment 2, Appendix, p. 19).
NIOSH went on to state that while the Sanderson et al. (2001) used
standard accepted methods for selecting the control group, the Deubner
et al. (2007) study limited control group eligibility and failed to
adequately match control and case groups (Document ID 1960, Attachment
2, Appendix, pp. 19-20). NIOSH noted that an independent analysis
published by Langholz and Richardson (2009) and Hein et al., (2009) (as
cited in Document ID 1960, Attachment 2, Appendix, p. 20) found that
Levy et al.'s method of eliminating controls from the study had the
effect of "always produc[ing] downwardly biased effect estimates and
for many scenarios the bias was substantial." (Document ID 1960,
Attachment 2, Appendix, p. 20). NIOSH went on to cite numerous errors
in the studies cited by Strupp (2011) (Document ID 1794, 1795).9 OSHA
finds NIOSH's criticisms of the Strupp (2011) studies as well as their
criticism of studies by Levy et al., 2007 and Deubner et al., 2007 to
be reliable and credible.
---------------------------------------------------------------------------
9 Strupp and Furnes was the background information for the
Strupp (2011) publications (Document ID, Attachment 2, Appendix, p.
20).
---------------------------------------------------------------------------
The Strupp and Furnes (2010) statement provided insufficient
information on the extraction of beryllium metal for OSHA to fully
evaluate the merit of the studies regarding potential genotoxicity of
poorly soluble beryllium (Document ID 1678, Attachment 1, pp. 18-20).
In addition, Strupp and Furnes did not consider the peer-reviewed
published studies evaluating the genotoxicity of beryllium metal (see
section V.E.1 and V.E.2).
In coming to the conclusion that the evidence is insufficient for
classification under GHS, Strupp and Furnes failed to consider the full
weight of evidence in their evaluation using the criteria set forth
under Annex VI of Directive 67/548/EEC which establishes criteria for
classification and labelling of hazardous substances under the UN
Globally Harmonized System of Classification and Labelling of Chemicals
(GHS) (Document ID 1678, attachment 1, pp. 21-23). Thus, the Agency
concludes that the Strupp and Furnes statement does not constitute the
best available scientific evidence for the evaluation of whether poorly
soluble forms of beryllium cause cancer.
Materion also submitted comments indicating there is an ongoing
scientific debate regarding the relevance of the rat lung tumor
response to humans with respect to poorly soluble beryllium compounds
(Document ID 1807, Attachment 10, pp. 1-3 (pdf pp. 85-87)), Materion
contended that the increased lung cancer risk in beryllium-exposed
animals is due to a particle overload phenomenon, in which lung
clearance of beryllium particles initiates a non-specific neutrophilic
response that results in intrapulmonary lung tumors. The materials
cited by Materion as supportive of its argument--Obedorster (1995), a
2009 working paper to the UN Subcommittee on the Globally Harmonized
System of Classification and Labelling of Chemicals (citing ILSI (2000)
as supporting evidence for poorly soluble particles), Snipes (1996),
the Health Risk Assessment Guidance for Metals, ICMM (2007), and ECETOC
(2013)--discuss the inhalation of high exposure levels of poorly
soluble particles in rats and the relevance of these studies to the
human carcinogenic response (Document ID 1807, Attachment 10, pp. 1-3
(pdf pp. 85-87)). Using particles such as titanium dioxide, carbon
black, non-asbestiform talc, coal dust, and diesel soot as models, ILSI
(2000) and ECETOC (2013) describe studies that have demonstrated that
chronic inhalation of poorly soluble particles can result in pulmonary
inflammation, fibrosis, epithelial cell hyperplasia, and adenomas and
carcinomas in rats at exposure levels that exceed lung clearance
mechanisms (the "overload" phenomenon) (ILSI (2000) \10\, p. 2, as
cited in Document ID 1807, Attachment 10, pp. 1-3 (pdf pp. 85-87)).
---------------------------------------------------------------------------
\10\ It is important to note that the ILSI report states that in
interpreting data from rat studies alone, "in the absence of
mechanistic data to the contrary it must be assumed that the rat
model can identify potential hazards to humans" (ILSI, 2000, p. 2,
as cited in Document ID 1807, Attachment 10, p. 1 (pdf p. 85)). The
report by Oberdorster has similar language to the ILSI report (see
Document ID 1807, Attachment 10, pp. 1, 3 (pdf pp. 85, 87). It
should also be noted that the working paper to the UN Subcommittee
on the Globally Harmonized System of Classification and Labelling of
Chemicals, which cited ILSI (2000), was not adopted and has not been
included in any revision to the GHS (http://www.unece.org/fileadmin/DAM/trans/doc/2009/ac10c4/ST-SG-AC10-C4-34e.pdf).
---------------------------------------------------------------------------
However, these expert reports indicate that the "overload"
phenomenon caused by biologically inert particles (poorly soluble
particles of low cytotoxicity for which there is no evidence of
genotoxicity) is relevant only to the rat species. (Document ID 1807,
Attachment 10, pp. 1-3 (pdf pp. 85-87)). OSHA finds that this model is
not in keeping with the data presented for beryllium for several
reasons. First, beryllium has been shown to be a "biologically
active" particle due to its ability to induce an immune response in
multiple species including humans, has been shown to be genotoxic in
certain mammalian test systems, and induces epigenetic changes (e.g.
DNA methylation) (as described in detail in sections V. D. 6, V.E.1,
V.E.3 and V.E.4). Second, beryllium has been shown to produce lung
tumors after inhalation or instillation in several animal species,
including rats, mice, and monkeys (Finch et al., 1998, Document ID
1367; Schepers et al., 1957 (0458) and 1962 (1414); Wagner et al., 1969
(1481); Belinsky et al., 2002 (1300); Groth et al.,
1980 (1316); Vorwald and Reeves, 1957 (1482); Nickell-Brady et al.,
1994 (1312); Swafford et al., 1997 (1392); IARC, 2012 (1355)). In
addition, poorly soluble beryllium has been demonstrated to produce
chronic inflammation at levels below overload (Groth et al., 1980,
Document ID 1316; Nickell-Brady et al., 1994 (1312); Finch et al., 1998
(1367); Finch et al., 2000 (as cited in Document ID 1960, p. 11)).
In addition, IARC and NAS performed an extensive review of the
available animal studies and their findings were supportive of the OSHA
findings of carcinogenicity (IARC, 2012, Document ID 0650; NAS, 2008
(1355)). OSHA performed an independent evaluation as outlined in
section V.E.3 and found sufficient evidence of tumor formation in
multiple species (rats, mice, and monkeys) after inhalation at levels
below overload conditions. The Agency has found evidence supporting the
hypothesis that multiple mechanisms may be at work in the development
of cancer in experimental animals and humans and cannot dismiss the
roles of inflammation (neutrophilic and T-cell mediated), genotoxicity,
and epigenetic factors (see section V.E.1, V.E. 3, V.E.4). After
evaluating the best scientific evidence available from epidemiological
and animal studies (see section V.E) OSHA concludes the weight of
evidence supports a mechanistic finding that both soluble and poorly
soluble forms of beryllium and beryllium-containing compounds are
carcinogenic.
F. Other Health Effects
Past studies on other health effects have been thoroughly reviewed
by several scientific organizations (NTP, 1999, Document ID 1341; EPA,
1998 (0661); ATSDR, 2002 (1371); WHO, 2001 (1282); HSDB, 2010 (0533)).
These studies include summaries of animal studies, in vitro studies,
and human epidemiological studies associated with cardiovascular,
hematological, hepatic, renal, endocrine, reproductive, ocular and
mucosal, and developmental effects. High-dose exposures to beryllium
have been shown to have an adverse effect upon a variety of organs and
tissues in the body, particularly the liver. The adverse systemic
effects on humans mostly occurred prior to the introduction of
occupational and environmental standards set in 1970-1972 OSHA, 1971,
see 39 FR 23513; EPA, 1973 (38 FR 8820)). (OSHA, 1971, see 39 FR 23513;
ACGIH, 1971 (0543); ANSI, 1970 (1303)) and EPA, 1973 (38 FR 8820) and
therefore are less relevant today than in the past. The available data
is fairly limited. The hepatic, cardiovascular, renal, and ocular and
mucosal effects are briefly summarized below. Health effects in other
organ systems listed above were only observed in animal studies at very
high exposure levels and are, therefore, not discussed here. During the
public comment period OSHA received comments suggesting that OSHA add
dermal effects to this section. Therefore, dermal effects have been
added, below, and are also discussed in the section on kinetics and
metabolism (section V.B.2).
1. Hepatic Effects
Beryllium has been shown to accumulate in the liver and a
correlation has been demonstrated between beryllium content and hepatic
damage. Different compounds have been shown to distribute differently
within the hepatic tissues. For example, in one study, beryllium
phosphate accumulated almost exclusively within sinusoidal (Kupffer)
cells of the liver, while beryllium sulfate was found mainly in
parenchymal cells. Conversely, beryllium sulphosalicylic acid complexes
were rapidly excreted (Skilleter and Paine, 1979, Document ID 1410).
According to a few autopsies, beryllium-laden livers had central
necrosis, mild focal necrosis and inflammation, as well as,
occasionally, beryllium granuloma (Sprince et al., 1975, Document ID
1405).
2. Cardiovascular Effects
Severe cases of CBD can result in cor pulmonale, which is
hypertrophy of the right heart ventricle. In a case history study of 17
individuals exposed to beryllium in a plant that manufactured
fluorescent lamps, autopsies revealed right atrial and ventricular
hypertrophy (Hardy and Tabershaw, 1946, Document ID 1516). It is not
likely that these cardiac effects were due to direct toxicity to the
heart, but rather were a response to impaired lung function. However,
an increase in deaths due to heart disease or ischemic heart disease
was found in workers at a beryllium manufacturing facility (Ward et
al., 1992, Document ID 1378). Additionally, a study by Schubauer-
Berigan et al. (2011) found an increase in mortality due to cor
pulmonale in a follow-up study of workers at seven beryllium processing
plants who were exposed to beryllium levels near the preceding OSHA PEL
of 2.0 μg/m3\ (Schubauer-Berigan et al., 2011, Document ID 1266).
Animal studies performed in monkeys indicate heart enlargement
after acute inhalation exposure to 13 mg beryllium/m3\ as beryllium
hydrogen phosphate, 0.184 mg beryllium/m3\ as beryllium fluoride, or
0.198 mg beryllium/m3\ as beryllium sulfate (Schepers, 1957, Document
ID 0458). Decreased arterial oxygen tension was observed in dogs
exposed to 30 mg beryllium/m3\ as beryllium oxide for 15 days (HSDB,
2010, Document ID 0533), 3.6 mg beryllium/m3\ as beryllium oxide for
40 days (Hall et al., 1950, Document ID 1494), and 0.04 mg beryllium/
m3\ as beryllium sulfate for 100 days (Stokinger et al., 1950,
Document ID 1484). These are thought to be indirect effects on the
heart due to pulmonary fibrosis and toxicity, which can increase
arterial pressure and restrict blood flow.
3. Renal Effects
Renal or kidney stones have been found in severe cases of CBD that
resulted from high levels of beryllium exposure. Renal stones
containing beryllium occurred in about 10 percent of patients affected
by high exposures (Barnett et al., 1961, Document ID 0453). The ATSDR
reported that 10 percent of the CBD cases found in the BCR reported
kidney stones. In addition, an excess of calcium in the blood and urine
was frequently found in patients with CBD (ATSDR, 2002, Document ID
1371).
4. Ocular and Mucosal Effects
Soluble and poorly soluble beryllium compounds have been shown to
cause ocular irritation in humans (VanOrdstrand et al., 1945, Document
ID 1383; De Nardi et al., 1953 (1545); Nishimura, 1966 (1435); Epstein,
1991 (0526); NIOSH, 1994 (1261). In addition, soluble and poorly
soluble beryllium has been shown to induce acute conjunctivitis with
corneal maculae and diffuse erythema (HSDB, 2010, Document ID 0533).
The mucosa (mucosal membrane) is the moist lining of certain
tissues/organs including the eyes, nose, mouth, lungs, and the urinary
and digestive tracts. Soluble beryllium salts have been shown to be
directly irritating to mucous membranes (HSDB, 2010, Document ID 0533).
5. Dermal Effects
Several commenters suggested OSHA add dermal effects to this Health
Effects section. National Jewish Health noted that rash and
granulomatous reactions of the skin still occur in occupational
settings (Document ID 1664, p. 5). The National Supplemental Screening
Program also recommended including skin conditions such as dermatitis
and nodules (Document ID 1677, p. 3). The American Thoracic Society
also recommended including "beryllium sensitization, CBD, and skin
disease as the major adverse health effects
associated with exposure to beryllium at or below 0.1 μg/m3\ and
acute beryllium disease at higher exposures based on the currently
available epidemiologic and experimental studies" (Document ID 1688,
p. 2). OSHA agrees and has included dermal effects in this section of
the final preamble.
As summarized in Epstein (1991), skin exposure to soluble beryllium
compounds (mainly beryllium fluoride but also beryllium metal which may
contain beryllium fluoride) resulted in irritant dermatitis with
inflammation, and local edema. Beryllium oxide, beryllium alloys and
nearly pure beryllium metal did not produce such responses in the skin
of workers (Epstein, 1991, Document ID 0526). Skin lacerations or
abrasions contaminated with soluble beryllium can lead to skin
ulcerations (Epstein, 1991, Document ID 0526). Soluble and poorly
soluble beryllium-compounds that penetrate the skin as a result of
abrasions or cuts have been shown to result in chronic ulcerations and
skin granulomas (VanOrdstrand et al., 1945, Document ID 1383; Lederer
and Savage, 1954 (1467)). However, ulcerating granulomatous formation
of the skin is generally associated with poorly soluble forms of
beryllium (Epstein, 1991, Document ID 0526). Beryllium, beryllium oxide
and other soluble and poorly soluble forms of beryllium have been
classified as a skin irritant (category 2) in accordance with the EU
Classification, Labelling and Packaging Regulation (Document ID 1669,
p. 2). Contact dermatitis (skin hypersensitivity) was observed in some
individuals exposed via skin to soluble forms of beryllium, especially
individuals with a dermal irritant response (Epstein, 1991, Document ID
0526). Contact allergy has been observed in workers exposed to
beryllium chloride (Document ID 0522).
G. Summary of Conclusions Regarding Health Effects
Through careful analysis of the best available scientific
information outlined in this section, OSHA has determined that
beryllium and beryllium-containing compounds can cause sensitization,
CBD, and lung cancer. The Agency has determined through its review and
evaluation of the studies outlined in section V.A.2 of this health
effects section that skin and inhalation exposure to beryllium can lead
to sensitization; and inhalation exposure, or skin exposure coupled
with inhalation, can cause onset and progression of CBD. In addition,
the Agency's review and evaluation of the studies outlined in section
V.E. of this health effects section led to a finding that inhalation
exposure to beryllium and beryllium-containing materials can cause lung
cancer.
1. OSHA's Evaluation of the Evidence Finds That Beryllium Causes
Sensitization Below the Preceding PEL and Sensitization is a Precursor
to CBD
Through the biological and immunological processes outlined in
section V.B. of the Health Effects, the Agency has concluded that the
scientific evidence supports the following mechanisms for the
development of sensitization and CBD.
Inhaled beryllium and beryllium-containing materials able
to be retained and solubilized in the lungs have the ability to
initiate sensitization and facilitate CBD development (section V.B.5).
Genetic susceptibility may play a role in the development of
sensitization and progression to CBD in certain individuals.
Beryllium compounds that dissolve in biological fluids,
such as sweat, can penetrate intact skin and initiate sensitization
(section V.A.2; V.B). Phagosomal fluid and lung fluid have the capacity
to dissolve beryllium compounds in the lung (section V.A.2a).
Sensitization occurs through a T-cell mediated process
with both soluble and poorly soluble beryllium and beryllium-containing
compounds through direct antigen presentation or through further
antigen processing in the skin or lung. T-cell mediated responses, such
as sensitization, are generally regarded as long-lasting (e.g., not
transient or readily reversible) immune conditions (section V.D.1).
Beryllium sensitization and CBD are adverse events along a
pathological continuum in the disease process with sensitization being
the necessary first step in the progression to CBD (section V.D).
Particle characteristics such as size, solubility, surface
area, and other properties may play a role in the rate of development
of beryllium sensitization and CBD. However, there is currently not
sufficient information to delineate the biological role these
characteristics may play.
Animal studies have provided supporting evidence for T-
cell proliferation in the development of granulomatous lung lesions
after beryllium exposure (sections V.D.2; V.D.6).
Since the pathogenesis of CBD involves a beryllium-
specific, cell-mediated immune response, CBD cannot occur in the
absence of beryllium sensitization (section V.D.1). While no clinical
symptoms are associated with sensitization, a sensitized worker is at
risk of developing CBD when inhalation exposure to beryllium has
occurred. Epidemiological evidence that covers a wide variety of
beryllium compounds and industrial processes demonstrates that
sensitization and CBD are continuing to occur at present-day exposures
below OSHA's preceding PEL (sections V.D.4; V.D.5 and section VI of
this preamble).
OSHA considers CBD to be a progressive illness with a
continuous spectrum of symptoms ranging from its earliest asymptomatic
stage following sensitization through to full-blown CBD and death
(section V.D.7).
Genetic variabilities appear to enhance risk for
developing sensitization and CBD in some groups (section V.D.3).
In addition, epidemiological studies outlined in section V.D.5 have
demonstrated that efforts to reduce exposures have succeeded in
reducing the frequency of sensitization and CBD.
2. OSHA's Evaluation of the Evidence Has Determined Beryllium To Be a
Human Carcinogen
OSHA conducted an evaluation of the available scientific
information regarding the carcinogenic potential of beryllium and
beryllium-containing compounds (section V.E). Based on the weight of
evidence and plausible mechanistic information obtained from in vitro
and in vivo animal studies as well as clinical and epidemiological
investigations, the Agency has determined that beryllium and beryllium-
containing materials are properly regarded as human carcinogens. This
information is in accordance with findings from IARC, NTP, EPA, NIOSH,
and ACGIH (section V.E). Key points from this analysis are summarized
briefly here.
Epidemiological cohort studies have reported statistically
significant excess lung cancer mortality among workers employed in U.S.
beryllium production and processing plants during the 1930s to 1970s
(section V.E.2).
Significant positive associations were found between lung
cancer mortality and both average and cumulative beryllium exposures
when appropriately adjusted for birth cohort and short-term work status
(section V.E.2).
Studies in which large amounts of different beryllium
compounds were inhaled or instilled in the respiratory tracts in
multiple species of laboratory animals resulted in an increased
incidence of lung tumors (section V.E.3).
Authoritative scientific organizations, such as the IARC,
NTP, and EPA, have classified beryllium as a known or probable human
carcinogen (section V.E).
While OSHA has determined there is sufficient evidence of beryllium
carcinogenicity, the Agency acknowledges that the exact tumorigenic
mechanism for beryllium has yet to be determined. A number of
mechanisms are likely involved, including chronic inflammation,
genotoxicity, mitogenicity, oxidative stress, and epigenetic changes
(section V.E.3).
Studies of beryllium-exposed animals have consistently
demonstrated chronic pulmonary inflammation after exposure (section
V.E.3). Substantial data indicate that tumor formation in certain
animals after inhalation exposure to poorly soluble particles at doses
causing marked, chronic inflammation is due to a secondary mechanism
unrelated to the genotoxicity of the particles (section V.E.5).
A review conducted by the NAS (2008) (Document ID 1355)
found that beryllium and beryllium-containing compounds tested positive
for genotoxicity in nearly 50 percent of studies without exogenous
metabolic activity, suggesting a possible direct-acting mechanism may
exist (section V.E.1) as well as the potential for epigenetic changes
(section V.E.4).
Other health effects are discussed in sections F of the Health
Effects Section and include hepatic, cardiovascular, renal, ocular, and
mucosal effects. The adverse systemic effects from human exposures
mostly occurred prior to the introduction of occupational and
environmental standards set in 1970-1973 (ACGIH, 1971, Document ID
0543; ANSI, 1970 (1303); OSHA, 1971, see 39 FR 23513; EPA, 1973 (38 FR
8820)) and therefore are less relevant.
VI. Risk Assessment
To promulgate a standard that regulates workplace exposure to toxic
materials or harmful physical agents, OSHA must first determine that
the standard reduces a "significant risk" of "material impairment."
Section 6(b)(5) of the OSH Act, 29 U.S.C. 655(b). The first part of
this requirement, "significant risk," refers to the likelihood of
harm, whereas the second part, "material impairment," refers to the
severity of the consequences of exposure. Section II, Pertinent Legal
Authority, of this preamble addresses the statutory bases for these
requirements and how they have been construed by the Supreme Court and
federal courts of appeals.
It is OSHA's practice to evaluate risk to workers and determine the
significance of that risk based on the best available evidence. Using
that evidence, OSHA identifies material health impairments associated
with potentially hazardous occupational exposures, assesses whether
exposed workers' risks are significant, and determines whether a new or
revised rule will substantially reduce these risks. As discussed in
Section II, Pertinent Legal Authority, when determining whether a
significant risk exists OSHA considers whether there is a risk of at
least one-in-a-thousand of developing amaterial health impairment from
a working lifetime of exposure at the prevailing OSHA standard
(referred to as the "preceding standard" or "preceding TWA PEL" in
this preamble). For this purpose, OSHA generally assumes that a term of
45 years constitutes a working life. The Supreme Court has found that
OSHA is not required to support its finding of significant risk with
scientific certainty, but may instead rely on a body of reputable
scientific thought and may make conservative assumptions (i.e., err on
the side of protecting the worker) in its interpretation of the
evidence (see Section II, Pertinent Legal Authority).
For single-substance standards governed by section 6(b)(5) of the
OSH Act, 29 U.S.C. 655(b)(5), OSHA sets a permissible exposure limit
(PEL) based on its risk assessment as well as feasibility
considerations. These health and risk determinations are made in the
context of a rulemaking record in which the body of evidence used to
establish material impairment, assess risks, and identify affected
worker population, as well as the Agency's preliminary risk assessment,
are placed in a public rulemaking record and subject to public comment.
Final determinations regarding the standard, including final
determinations of material impairment and risk, are thus based on
consideration of the entire rulemaking record.
OSHA's approach for the risk assessment for beryllium incorporates
both: (1) A review of the literature on populations of workers exposed
to beryllium at and below the preceding time-weighted average
permissible exposure limit (TWA PEL) of 2 μg/m3\; and (2) OSHA's
own analysis of a data set of beryllium-exposed machinists. The
Preliminary Risk Assessment included in the NPRM evaluated risk at
several alternate TWA PELs that the Agency was considering (1 μg/
m3\, 0.5 μg/m3\, 0.2 μg/m3\, and 0.1 μg/m3\), as well as
OSHA's preceding TWA PEL of 2 μg/m3\. OSHA's risk assessment relied
on available epidemiological studies to evaluate the risk of
sensitization and CBD for workers exposed to beryllium at and below the
preceding TWA PEL and the effectiveness of exposure control programs in
reducing risk. OSHA also conducted a statistical analysis of the
exposure-response relationship for sensitization and CBD at the
preceding PEL and alternate PELs the Agency was considering. For this
analysis, OSHA used data provided by National Jewish Health (NJH), a
leading medical center specializing in the research and treatment of
CBD, on a population of workers employed at a beryllium machining plant
in Cullman, AL. The review of the epidemiological studies and OSHA's
own analysis both show significant risk of sensitization and CBD among
workers exposed at and below the preceding TWA PEL of 2 μg/m3\.
They also show substantial reduction in risk where employers
implemented a combination of controls, including stringent control of
airborne beryllium levels and additional measures, such as respirators
and dermal personal protective equipment (PPE) to further protect
workers against dermal contact and airborne beryllium exposure.
To evaluate lung cancer risk, OSHA relied on a quantitative risk
assessment published in 2011 by Schubauer-Berigan et al. (Document ID
1265). Schubauer-Berigan et al. found that lung cancer risk was
strongly and significantly related to mean, cumulative, and maximum
measures of workers' exposure; the authors predicted significant risk
of lung cancer at the preceding TWA PEL, and substantial reductions in
risk at the alternate PELs OSHA considered in the proposed rule,
including the final TWA PEL of 0.2 μg/m3\ (Schubauer-Berigan et
al., 2011).
OSHA requested input on the preliminary risk assessment presented
in the NPRM, and received comments from a variety of public health
experts and organizations, unions, industrial organizations, individual
employers, and private citizens. While many comments supported OSHA's
general approach to the risk assessment and the conclusions of the risk
assessment, some commenters raised specific concerns with OSHA's
analytical methods or recommended additional studies for OSHA's
consideration. Comments about the risk assessment as a whole are
reviewed here, while comments on specific aspects of the risk
assessment are addressed in the relevant sections throughout the
remainder of
this chapter and in the background document, Risk Analysis of the NJH
Data Set from the Beryllium Machining Facility in Cullman, Alabama--CBD
and Sensitization (OSHA, 2016), which can be found in the rulemaking
docket (docket number OSHA-H005C-2006-0870) at www.regulations.gov.
Following OSHA's review of all the comments submitted on the
preliminary risk assessment, and its incorporation of suggested changes
to the risk assessment, where appropriate, the Agency reaffirms its
conclusion that workers' risk of material impairment of health from
beryllium exposure at the preceding PEL of 2 μg/m3\ is significant,
and is substantially reduced but still significant at the new PEL of
0.2 μg/m3\ (see this preamble at Section VII, Significance of
Risk).
The comments OSHA received on its preliminary risk analysis
generally supported OSHA's overall approach and conclusions. NIOSH
indicated that OSHA relied on the best available evidence in its risk
assessment and concurred with "OSHA's careful review of the available
literature on [beryllium sensitization] and CBD, OSHA's recognition of
dermal exposure as a potential pathway for sensitization, and OSHA's
careful approach to assessing risk for [beryllium sensitization] and
CBD" (Document ID 1725, p. 3). NIOSH agreed with OSHA's approach to
the preliminary lung cancer risk assessment (Document ID 1725, p. 7)
and the selection of a 2011 analysis (Schubauer-Berigan et al., 2011,
Document ID 1265) as the basis of that risk assessment (Document ID
1725, p. 7). NIOSH further supported OSHA's preliminary conclusions
regarding the significance of risk of material health impairment at the
preceding TWA PEL of 2 μg/m3\, and the substantial reduction of
such risk at the new TWA PEL of 0.2 μg/m3\ (Document ID 1725, p.
3). Finally, NIOSH agreed with OSHA's preliminary conclusion that
compliance with the new PEL would lessen but not eliminate risk to
exposed workers, noting that OSHA likely underestimated the risks of
beryllium sensitization and CBD (Document ID 1725, pp. 3-4).
Other commenters also agreed with the general approach and
conclusions of OSHA's preliminary risk assessment. NJH, for example,
determined that "OSHA performed a thorough assessment of risk for
[beryllium sensitization], CBD and lung cancer using all available
studies and literature" (Document ID 1664, p. 5). Dr. Kenny Crump and
Ms. Deborah Proctor commented, on behalf of beryllium producer
Materion, that they "agree with OSHA's conclusion that there is a
significant risk (>1/1000 risk of CBD) at the [then] current PEL, and
that risk is reduced at the proposed PEL (0.2 μg/m3\) in
combination with stringent measures (ancillary provisions) to reduce
worker's exposures" (Document ID 1660, p. 2). They further stated that
OSHA's "finding is evident based on the available literature . . . and
the prevalence data [OSHA] presented for the Cullman facility"
(Document ID 1660, p. 2).
OSHA also received comments objecting to OSHA's conclusions
regarding risk of lung cancer from beryllium exposure and suggesting
additional published analyses for OSHA's consideration (e.g., Document
ID 1659; 1661, pp. 1-3). One comment critiqued the statistical
exposure-response model OSHA presented as one part of its preliminary
risk analysis for sensitization and CBD (Document ID 1660). These
comments are discussed and addressed in the remainder of this chapter.
A. Review of Epidemiological Literature on Sensitization and Chronic
Beryllium Disease
As discussed in the Health Effects section, studies of beryllium-
exposed workers conducted using the beryllium lymphocyte proliferation
test (BeLPT) have found high rates of beryllium sensitization and CBD
among workers in many industries, including at some facilities where
exposures were primarily below OSHA's preceding PEL of 2 μg/m3\
(e.g., Kreiss et al., 1993, Document ID 1478; Henneberger et al., 2001
(1313); Schuler et al., 2005 (0919); Schuler et al., 2012 (0473)). In
the mid-1990s, some facilities using beryllium began to aggressively
monitor and reduce workplace exposures. In the NPRM, OSHA reviewed
studies of workers at four plants where several rounds of BeLPT
screening were conducted before and after implementation of new
exposure control methods. These studies provide the best available
evidence on the effectiveness of various exposure control measures in
reducing the risk of sensitization and CBD. The experiences of these
plants--a copper-beryllium processing facility in Reading, PA, a
ceramics facility in Tucson, AZ, a beryllium processing facility in
Elmore, OH, and a machining facility in Cullman, AL--show that
comprehensive exposure control programs that used engineering controls
to reduce airborne exposure to beryllium, required the use of
respiratory protection, controlled dermal contact with beryllium using
PPE, and employed stringent housekeeping methods to keep work areas
clean and prevent transfer of beryllium between work areas, sharply
curtailed new cases of sensitization among newly-hired workers. In
contrast, efforts to prevent sensitization and CBD by using engineering
controls to reduce workers' beryllium exposures to median levels around
0.2 μg/m3\, with no corresponding emphasis on PPE, were less
effective than comprehensive exposure control programs implemented more
recently. OSHA also reviewed additional, but more limited, information
on the occurrence of sensitization and CBD among workers with low-level
beryllium exposures at nuclear facilities and aluminum smelting plants.
A summary discussion of the experiences at all of these facilities is
provided in this section. Additional discussion of studies on these
facilities and several other studies of sensitization and CBD among
beryllium-exposed workers is provided in Section V, Health Effects.
The Health Effects section also discusses OSHA's findings and the
supporting evidence concerning the role of particle characteristics and
beryllium compound solubility in the development of sensitization and
CBD among beryllium-exposed workers. First, it finds that respirable
particles small enough to reach the deep lung are responsible for CBD.
However, larger inhalable particles that deposit in the upper
respiratory tract may lead to sensitization. Second, it finds that both
soluble and poorly soluble forms of beryllium are able to induce
sensitization and CBD. Poorly soluble forms of beryllium that persist
in the lung for longer periods may pose greater risk of CBD while
soluble forms may more easily trigger immune sensitization. Although
particle size and solubility may influence the toxicity of beryllium,
the available data are too limited to reliably account for these
factors in the Agency's estimates of risk.
1. Reading, PA, Plant
Schuler et al. (2005, Document ID 0919) and Thomas et al. (2009,
Document ID 0590) conducted studies of workers at a copper-beryllium
processing facility in Reading, PA. Exposures at this plant were
believed to be low throughout its history due to both the low
percentage of beryllium in the metal alloys used and the relatively low
exposures found in general area samples collected starting in 1969
(sample median <=0.1 μg/m3\, 97% < 0.5 μg/m3\) (Schuler et al.,
2005). Ninety-nine percent of personal lapel sample measurements were
below the preceding OSHA TWA PEL of 2 μg/m3\; 93 percent were below
the new TWA
PEL of 0.2 μg/m3\ (Schuler et al., 2005). Schuler et al. (2005)
screened 152 workers at the facility with the BeLPT in 2000. The
reported prevalences of sensitization (6.5 percent) and CBD (3.9
percent) showed substantial risk at this facility, even though airborne
exposures were primarily below both the preceding and final TWA
PELs.\11\ The only group of workers with no cases of sensitization or
CBD, a group of 26 office administration workers, was the group with
the lowest recorded exposures (median personal sample 0.01 μg/m3\,
range <0.01-0.06 μg/m3\ (Schuler et al., 2005).
---------------------------------------------------------------------------
\11\ Although OSHA reports percentages to indicate the risks of
sensitization and CBD in this section, the benchmark OSHA typically
uses to demonstrate significant risk, as discussed in Pertinent
Legal Authority, is greater than or equal to 1 in 1,000 workers. One
in 1,000 workers is equivalent to 0.1 percent. Therefore, any value
of 0.1 percent or higher when reporting occurrence of a health
effect is considered by OSHA to indicate a significant risk.
---------------------------------------------------------------------------
After the initial BeLPT screening was conducted in 2000, the
company began implementing new measures to further reduce workers'
exposure to beryllium (Thomas et al. 2009, Document ID 0590).
Requirements designed to minimize dermal contact with beryllium,
including long-sleeve facility uniforms and polymer gloves, were
instituted in production areas in 2000-2002. In 2001, the company
installed local exhaust ventilation (LEV) in die grinding and polishing
operations (Thomas et al., 2009, Figure 1). Personal lapel samples
collected between June 2000 and December 2001, showed reduced exposures
plant-wide (98 percent were below 0.2 μg/m3\). Median, arithmetic
mean, and geometric mean values less than or equal to 0.03 μg/m3\
were reported in this period for all processes except one, a wire
annealing and pickling process. Samples for this process remained
elevated, with a median of 0.1 μg/m3\ (arithmetic mean of 0.127
μg/m3\, geometric mean of 0.083 μg/m3\) (Thomas et al., 2009,
Table 3). In January 2002, the company enclosed the wire annealing and
pickling process in a restricted access zone (RAZ). Beginning in 2002,
the company required use of powered air-purifying respirators (PAPRs)
in the RAZ, and implemented stringent measures to minimize the
potential for skin contact and beryllium transfer out of the zone, such
as requiring RAZ workers to shower before leaving the zone (Thomas et
al., 2009, Figure 1). While exposure samples collected by the facility
were sparse following the enclosure, they suggest exposure levels
comparable to the 2000-2001 samples in areas other than the RAZ (Thomas
et al., 2009, Table 3). The authors reported that outside the RAZ,
"the vast majority of employees do not wear any form of respiratory
protection due to very low airborne beryllium concentrations" (Thomas
et al., 2009, p. 122).
To test the efficacy of the new measures in preventing
sensitization and CBD, in June 2000 the facility began an intensive
BeLPT screening program for all new workers (Thomas et al., 2009,
Document ID 0590). Among 82 workers hired after 1999, three cases of
sensitization were found (3.7 percent). Two (5.4 percent) of 37 workers
hired prior to enclosure of the wire annealing and pickling process,
which had been releasing beryllium into the surrounding area, were
found to be sensitized within 3 and 6 months of beginning work at the
plant. One (2.2 percent) of 45 workers hired after the enclosure was
built was confirmed as sensitized. From these early results comparing
the screening conducted on workers hired before 2000 and those hired in
2000 and later, especially following the enclosure of the RAZ, it
appears that the greatest reduction in sensitization risk (to one
sensitized worker, or 2.2 percent) was achieved after workers'
exposures were reduced to below 0.1 μg/m3\ and PPE to prevent
dermal contact was instituted (Thomas et al., 2009).
2. Tucson, AZ, Plant
Kreiss et al. (1996, Document ID 1477), Cummings et al. (2007,
Document ID 1369), and Henneberger et al. (2001, Document ID 1313)
conducted studies of workers at a beryllia ceramics plant in Tucson,
Arizona. Kreiss et al. (1996) screened 136 workers at this plant with
the BeLPT in 1992. Full-shift area samples collected between 1983 and
1992 showed primarily low airborne beryllium levels at this facility
(76 percent of area samples were at or below 0.1 μg/m3\ and less
than 1 percent exceeded 2 μg/m3\). 4,133 short-term breathing zone
measurements collected between 1981 and 1992 had a median of 0.3 μg/
m3\. A small set (75) of personal lapel samples collected at the plant
beginning in 1991 had a median of 0.2 μg/m3\ and ranged from 0.1 to
1.8 μg/m3\ (arithmetic and geometric mean values not reported)
(Kreiss et al., 1996).
Kreiss et al. reported that eight (5.9 percent) of the 136 workers
tested in 1992 were sensitized, six (4.4 percent) of whom were
diagnosed with CBD. One sensitized worker was one of 13 administrative
workers screened, and was among those diagnosed with CBD. Exposures of
administrative workers were not well characterized, but were believed
to be among the lowest in the plant. Personal lapel samples taken on
administrative workers during the 1990s were below the detection limit
at the time, 0.2 μg/m3\ (Cummings et al., 2007, Document ID 1369).
Following the 1992 screening, the facility reduced exposures in
machining areas (for example, by enclosing additional machines and
installing additional exhaust ventilation), resulting in median
exposures of 0.2 μg/m3\ in production jobs and 0.1 μg/m3\ in
production support jobs (Cummings et al., 2007). In 1998, a second
screening found that 7 out of 74 tested workers hired after the 1992
screening (9.5 percent) were sensitized, one of whom was diagnosed with
CBD. All seven of these sensitized workers had been employed at the
plant for less than two years (Henneberger et al., 2001, Document ID
1313, Table 3). Of 77 Tucson workers hired prior to 1992 who were
tested in 1998, 8 (10.4 percent) were sensitized and 7 of these (9.7
percent) were diagnosed with CBD (Henneberger et al., 2001).
Following the 1998 screening, the company continued efforts to
reduce exposures, along with risk of sensitization and CBD, by
implementing additional engineering and administrative controls and a
comprehensive PPE program which included the use of respiratory
protection (1999) and latex gloves (2000) (Cummings et al., 2007,
Document ID 1369). Enclosures were installed for various beryllium-
releasing processes by 2001. Between 2000 and 2003, water-resistant or
water-proof garments, shoe covers, and taped gloves were incorporated
to keep beryllium-containing fluids from wet machining processes off
the skin. To test the efficacy of the new measures instituted after
1998, in January 2000 the company began screening new workers for
sensitization at the time of hire and at 3, 6, 12, 24, and 48 months of
employment. These more stringent measures appear to have substantially
reduced the risk of sensitization among new employees. Of 97 workers
hired between 2000 and 2004, one case of sensitization was identified
(1 percent) (Cummings et al., 2007).
3. Elmore, OH, Plant
Kreiss et al. (1997, Document ID 1360), Bailey et al. (2010,
Document ID 0676), and Schuler et al. (2012, Document ID 0473)
conducted studies of workers at a beryllium metal, alloy, and oxide
production plant in Elmore, Ohio. Workers participated in several
plant-wide BeLPT surveys beginning in 1993-1994 (Kreiss et al., 1997;
Schuler et al., 2012) and in a series of screenings
for workers hired in 2000 and later, conducted beginning in 2000
(Bailey et al., 2010).
Exposure levels at the plant between 1984 and 1993 were
characterized using a mixture of general area, short-term breathing
zone, and personal lapel samples (Kreiss et al., 1997, Document ID
1360). Kreiss et al. reported that the median area samples for various
work areas ranged from 0.1 to 0.7 µg/m3\, with the highest
values in the alloy arc furnace and alloy melting-casting areas.
Personal lapel samples were available from 1990-1992, and showed high
exposures overall (median value of 1.0 µg/m3\), with very high
exposures for some processes. Kreiss et al. reported median sample
values from the personal lapel samples of 3.8 µg/m3\ for
beryllium oxide production, 1.75 µg/m3\ for alloy melting and
casting, and 1.75 µg/m3\ for the arc furnace. The authors
reported that 43 (6.9 percent) of 627 workers tested in 1993-1994 were
sensitized. 29 workers (including 5 previously identified) were
diagnosed with CBD (29/632, or 4.6 percent) (Kreiss et al., 1997).
In 1996-1999, the company took further steps to reduce workers'
beryllium exposures, including enclosure of some beryllium-releasing
processes, establishment of restricted-access zones, and installation
or updating of certain engineering controls (Bailey et al., 2010,
Document ID 0676, Tables 1-2). Beginning in 1999, all new employees
were required to wear loose-fitting PAPRs in manufacturing buildings.
Skin protection became part of the protection program for new employees
in 2000, and glove use was required in production areas and for
handling work boots beginning in 2001. By 2001, either half-mask
respirators or PAPRs were required throughout the production facility
(type determined by airborne beryllium levels) and respiratory
protection was required for roof work and during removal of work boots
(Bailey et al., 2010).
Beginning in 2000, newly hired workers were offered periodic BeLPT
testing to evaluate the effectiveness of the new exposure control
program implemented by the company (Bailey et al., 2010). Bailey et al.
compared the occurrence of beryllium sensitization and disease among
258 employees who began work at the Elmore plant between January 15,
1993 and August 9, 1999 (the "pre-program group") with that of 290
employees who were hired between February 21, 2000 and December 18,
2006, and were tested at least once after hire (the "program group").
They found that, as of 1999, 23 (8.9 percent) of the pre-program group
were sensitized to beryllium. Six (2.1 percent) of the program group
had confirmed abnormal results on their final round of BeLPTs, which
occurred in different years for different employees. This four-fold
reduction in sensitization suggests that beryllium-exposed workers'
risk of sensitization (and therefore of CBD, which develops only
following sensitization) can be much reduced by the combination of
process controls, respiratory protection requirements, and PPE
requirements applied in this facility. Because most of the workers in
the study had been employed at the facility for less than two years,
and CBD typically develops over a longer period of time (see section V,
Health Effects), Bailey et al. did not report the incidence of CBD
among the sensitized workers (Bailey et al., 2010). Schuler et al.
(2012, Document ID 0473) published a study examining beryllium
sensitization and CBD among short-term workers at the Elmore, OH plant,
using exposure estimates created by Virji et al. (2012, Document ID
0466). The study population included 264 workers employed in 1999 with
up to 6 years tenure at the plant (91 percent of the 291 eligible
workers). By including only short-term workers, Virji et al. were able
to construct participants' exposures with more precision than was
possible in studies involving workers exposed for longer durations and
in time periods with less exposure sampling. A set of 1999 exposure
surveys and employee work histories was used to estimate employees'
long-term lifetime weighted (LTW) average, cumulative, and highest-job-
worked exposures for total, respirable, and submicron beryllium mass
concentrations (Schuler et al., 2012; Virji et al., 2012).
As reported by Schuler et al. (2012), the overall prevalence of
sensitization was 9.8 percent (26/264). Sensitized workers were offered
further evaluation for CBD. Twenty-two sensitized workers consented to
clinical testing for CBD via transbronchial biopsy. Although follow-up
time was too short (at most 6 years) to fully evaluate CBD in this
group, 6 of those sensitized were diagnosed with CBD (2.3 percent, 6/
264). Schuler et al. (2012) found 17 cases of sensitization (8.6%)
within the first 3 quartiles of LTW average exposure (198 workers with
LTW average total mass exposures lower than 1.1 µg/m3\) and 4
cases of CBD (2.2%) within those first 3 quartiles (183 workers with
LTW average total mass exposures lower than 1.07 µg/m3\)\12\ The
authors found 3 cases (4.6%) of sensitization among 66 workers with
total mass LTW average exposures below 0.1 µg/m3\, and no cases
of sensitization among workers with total mass LTW average exposures
below 0.09 µg/m3\, suggesting that beryllium-exposed workers'
risk can be much reduced or eliminated by reducing airborne exposures
to average levels below 0.1 µg/m3\.
---------------------------------------------------------------------------
\12\ The total number of workers Schuler et al. reported in
their table of LTW average quartiles for sensitization differs from
the total number of workers reported in their table of LTW average
quartiles for CBD. The table for CBD appeared to exclude 20 workers
with sensitization and no CBD.
---------------------------------------------------------------------------
Schuler et al. (2012, Document ID 0473) then used logistic
regression to explore the relationship between estimated beryllium
exposure and sensitization and CBD. For beryllium sensitization, the
logistic models by Schuler et al. showed elevated odds ratios (OR) for
LTW average (OR 1.48) and highest job (OR 1.37) exposure for total mass
exposure; the OR for cumulative exposure was smaller (OR 1.23) and
borderline statistically significant (95 percent CI barely included
unity).\13\ Relationships between sensitization and respirable exposure
estimates were similarly elevated for LTW average (OR 1.37) and highest
job (OR 1.32) exposures. Among the submicron exposure estimates, only
highest job (OR 1.24) had a 95 percent CI that just included unity for
sensitization. For CBD, elevated odds ratios were observed only for the
cumulative exposure estimates and were similar for total mass and
respirable exposure (total mass OR 1.66, respirable OR 1.68).
Cumulative submicron exposure showed an elevated, borderline
significant odds ratio (OR 1.58). The odds ratios for average exposure
and highest-exposed job were not statistically significantly elevated.
Schuler et al. concluded that both total and respirable mass
concentrations of beryllium exposure were relevant predictors of risk
for beryllium sensitization and CBD. Average and highest job exposures
were predictive of risk for sensitization, while cumulative exposure
was predictive of risk for CBD (Schuler et al., 2012).
---------------------------------------------------------------------------
\13\ An odds ratio (OR) is a measure of association between an
exposure and an outcome. The OR represents the odds that an outcome
will occur given a particular exposure, compared to the odds of the
outcome occurring in the absence of that exposure.
---------------------------------------------------------------------------
Materion submitted comments supporting OSHA's use of the Schuler et
al. (2012) study as a basis for the final TWA PEL of 0.2 µg/m3\.
Materion stated that "the best available evidence to establish a risk-
based OEL [occupational exposure limit] is the study conducted by NIOSH
and presented in Schuler 2012. The exposure assessment in
Schuler et al. was based on a highly robust workplace monitoring
dataset and the study provides improved data for determining OELs"
(Document ID 1661, pp. 9-10). Materion also submitted an unpublished
manuscript documenting an analysis it commissioned, entitled "Derived
No-Effect Levels for Occupational Beryllium Exposure Using Cluster
Analysis and Benchmark Dose Modeling" (Proctor et al., Document ID
1661, Attachment 5). In this document, Proctor et al. used data from
Schuler et al. 2012 to develop a Derived No-Effect Level (DNEL) for
beryllium measured as respirable beryllium, total mass of beryllium,
and inhalable beryllium.\14\ OSHA's beryllium standard measures
beryllium as total mass; thus, the results for total mass are most
relevant to OSHA's risk analysis for the beryllium standard. The
assessment reported a DNEL of 0.14 µg/m3\ for total mass
beryllium (Document ID 1661, Attachment 5, p. 16). Materion commented
that this finding "add[s] to the body of evidence that supports the
fact that OSHA is justified in lowering the existing PEL to 0.2
µg/m3\" (Document ID 1661, p. 11).
---------------------------------------------------------------------------
\14\ Derived No-Effect Level (DNEL) is used in REACH
quantitative risk characterizations to mean the level of exposure
above which humans should not be exposed. It is intended to
represent a safe level of exposure for humans., REACH is the
European Union's regulation on Registration, Evaluation,
Authorization and Restriction of Chemicals.
---------------------------------------------------------------------------
Proctor et al. characterized the DNEL of 0.14 µg/m3\ as
"inherently conservative because average exposure metrics were used to
determine DNELs, which are limits not [to] be exceeded on a daily
basis" (Document ID 1661, Attachment 5, p. 22). Materion referred to
the DNELs derived by Proctor et al. as providing an "additional margin
of safety" for similar reasons (Document ID 1661, p. 11).
Consistent with NIOSH comments discussed in the next paragraph,
OSHA disagrees with this characterization of the DNEL as representing a
"no effect level" for CBD or as providing a margin of safety for
several reasons. The DNEL from Proctor et al. is based on CBD findings
among a short-term worker population and thus cannot represent the risk
presented to workers who are exposed over a working lifetime. Proctor
et al. noted that it is "important to consider that these data are
from relatively short-term exposures [median tenure 20.9 months] and
are being used to support DNELs for lifetime occupational exposures,"
but considered the duration of exposure to be sufficient because "CBD
can develop with latency as short as 3 months of exposure, and . . .
the risk of CBD declines over time" (Document ID 1661, Attachment 5,
p. 19). In stating this, Procter et al. cite studies by Newman et al.
(2001, Document ID 1354) and Harber et al. (2009, as cited in Document
ID 1661). Newman et al. (2001) studied a group of workers in a
machining plant with job tenures averaging 11.7 years, considerably
longer than the worker cohort from the study used by Procter et al.,
and identified new cases of CBD from health screenings conducted up to
4 years after an initial screening. Harber et al., (2009) developed an
analytic model of disease progression from beryllium exposure and found
that, although the rate at which new cases of CBD declined over time,
the overall proportion of individuals with CBD increased over time from
initial exposure (see Figure 2 of Haber et al., 2009). Furthermore, the
study used by Proctor et al. to derive the DNEL, Schuler et al. (2012),
did report finding that the risk of CBD increased with cumulative
exposure to beryllium, as summarized above. Therefore, OSHA is not
convinced that a "no effect level" for beryllium that is based on the
health experience of workers with a median job tenure of 20.9 months
can represent a "no-effect level" for workers exposed to beryllium
for as long as 45 years.
NIOSH commented on the results of Proctor et al.'s analysis and the
underlying data set, noting several features of the dataset that are
common to the beryllium literature, such as uncertain date of
sensitization or onset of CBD and no "background" rate of beryllium
sensitization or CBD, that make statistical analyses of the data
difficult and add uncertainty to the derivation of a DNEL (Document ID
1725, p. 5). NIOSH also noted that risk of CBD may be underestimated in
the underlying data set if workers with CBD were leaving employment
due, in part, to adverse health effects ("unmeasured survivor bias")
and estimated that as much as 30 percent of the cohort could have been
lost over the 6-year testing period (Document ID 1725, p. 5). NIOSH
concluded that Proctor et al.'s analysis "does not contribute to the
risk assessment for beryllium workers" (Document ID 1725, p. 5). OSHA
agrees with NIOSH that the DNEL identified by Proctor et al. cannot be
considered a reliable estimate of a no-effect level for beryllium.
4. Cullman, AL, Plant
Newman et al. (2001, Document ID 1354), Kelleher et al. (2001,
Document ID 1363), and Madl et al. (2007, Document ID 1056) studied
beryllium workers at a precision machining facility in Cullman,
Alabama. After a case of CBD was diagnosed at the plant in 1995, the
company began BeLPT screenings to identify workers at risk of CBD and
implemented engineering and administrative controls designed to reduce
workers' beryllium exposures in machining operations. Newman et al.
(2001) conducted a series of BeLPT screenings of workers at the
facility between 1995 and 1999. The authors reported 22 (9.4 percent)
sensitized workers among 235 tested, 13 of whom were diagnosed with CBD
within the study period. Personal lapel samples collected between 1980
and 1999 indicate that median exposures were generally well below the
preceding PEL (<=0.35 µg/m3\ in all job titles except
maintenance (median 3.1 µg/m3\ during 1980-1995) and gas
bearings (1.05 µg/m3\ during 1980-1995)).
Between 1995 and 1999, the company built enclosures around several
beryllium-releasing operations; installed or updated LEV for several
machining departments; replaced pressurized air hoses and dry sweeping
with wet methods and vacuum systems for cleaning; changed the layout of
the plant to keep beryllium-releasing processes close together; limited
access to the production area of the plant; and required the use of
company uniforms. Madl et al. (2007, Document ID 1056) reported that
engineering and work process controls, rather than personal protective
equipment, were used to limit workers' exposure to beryllium. In
contrast to the Reading and Tucson plants, gloves were not required at
this plant. Personal lapel samples collected extensively between 1996
and 1999 in machining and non-machining jobs had medians of 0.16
µg/m3\ and 0.08 µg/m3\, respectively (Madl et al., 2007,
Table IV). At the time that Newman et al. reviewed the results of BeLPT
screenings conducted in 1995-1999, a subset of 60 workers had been
employed at the plant for less than a year and had therefore benefitted
to some extent from the controls described above. Four (6.7 percent) of
these workers were found to be sensitized, of whom two were diagnosed
with CBD and one with probable CBD (Newman et al., 2001, Document ID
1354). The later study by Madl. et al. reported seven sensitized
workers who had been hired between 1995 and 1999, of whom four had
developed CBD as of 2005 (2007, Table II) (total number of workers
hired between 1995 and 1999 not reported).
Beginning in 2000 (after the implementation of controls between
1997 and 1999), exposures in all jobs at the machining facility were
reduced to
extremely low levels (Madl et al., 2007, Document ID 1056). Personal
lapel samples collected between 2000 and 2005 had a median of 0.12
µg/m3\ or less in all machining and non-machining processes
(Madl. et al., 2007, Table IV). Only one worker hired after 1999 became
sensitized (Madl et al. 2007, Table II). The worker had been employed
for 2.7 years in chemical finishing, which had the highest median
exposure of 0.12 µg/m3\ (medians for other processes ranged from
0.02 to 0.11 µg/m3\); Madl et al. 2007, Table II). This result
from Madl et al. (2007) suggests that beryllium-exposed workers' risk
of sensitization can be much reduced by steps taken to reduce workers'
airborne exposures in this facility, including enclosure of beryllium-
releasing processes, LEV, wet methods and vacuum systems for cleaning,
and limiting worker access to production areas.
The Cullman, AL facility was also the subject of a case-control
study published by Kelleher et al. in 2001 (Document ID 1363). After
the diagnosis of a case of CBD at the plant in 1995, NJH researchers,
including Kelleher, worked with the plant to conduct the medical
surveillance program mentioned above, using the BeLPT to screen workers
biennially for beryllium sensitization and offering sensitized workers
further evaluation for CBD (Kelleher et al., 2001). Concurrently,
research was underway by Martyny et al. to characterize the particle
size distribution of beryllium exposures generated by processes at this
plant (Martyny et al., 2000, Document ID 1358). Kelleher et al. used
the dataset of 100 personal lapel samples collected by Martyny et al.
and other NJH researchers to characterize exposures for each job in the
plant. Detailed work history information gathered from plant data and
worker interviews was used in combination with job exposure estimates
to characterize cumulative and LTW average beryllium exposures for
workers in the surveillance program. In addition to cumulative and LTW
average exposure estimates based on the total mass of beryllium
reported in their exposure samples, Kelleher et al. calculated
cumulative and LTW average estimates based specifically on exposure to
particles <6 μm and particles <1 μm in diameter. To analyze the
relationship between exposure level and risk of sensitization and CBD,
Kelleher et al. performed a case-control analysis using measures of
both total beryllium exposure and particle size-fractionated exposure.
The results, however, were inconclusive, probably due to the relatively
small size of the dataset (Kelleher et al., 2001).
5. Aluminum Smelting Plants
Taiwo et al. (2008, Document ID 0621; 2010 (0583) and Nilsen et al.
(2010, Document ID 0460) studied the relationship between beryllium
exposure and adverse health effects among workers at aluminum smelting
plants. Taiwo et al. (2008) studied a population of 734 employees at 4
aluminum smelters located in Canada (2), Italy (1), and the United
States (1). In 2000, a company-wide beryllium exposure limit of 0.2
μg/m3\ and an action level of 0.1 μg/m3\, expressed as 8-hour
TWAs, and a short-term exposure limit (STEL) of 1.0 μg/m3\ (15-
minute sample) were instituted at these plants. Sampling to determine
compliance with the exposure limit began at all four smelters in 2000.
Table VI-1 below, adapted from Taiwo et al. (2008), shows summary
information on samples collected from the start of sampling through
2005.
Table VI-1--Exposure Sampling Data By Plant--2000-2005
----------------------------------------------------------------------------------------------------------------
Arithmetic
Smelter Number samples Median (μg/ mean (μg/ Geometric mean
m3\) m3\) (μg/m3\)
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1.............................. 246 0.03 0.09 0.03
Canadian smelter 2.............................. 329 0.11 0.29 0.08
Italian smelter................................. 44 0.12 0.14 0.10
US smelter...................................... 346 0.03 0.26 0.04
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Document ID 0621, Table 1.
All employees potentially exposed to beryllium levels at or above
the action level for at least 12 days per year, or exposed at or above
the STEL 12 or more times per year, were offered medical surveillance,
including the BeLPT (Taiwo et al., 2008). Table VI-2 below, adapted
from Taiwo et al. (2008), shows test results for each facility between
2001 and 2005.
Table VI-2--BeLPT Results By Plant--2001-2005
----------------------------------------------------------------------------------------------------------------
Abnormal
Smelter Employees Normal BeLPT Confirmed
tested (unconfirmed) sensitized
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1.............................. 109 107 1 1
Canadian smelter 2.............................. 291 290 1 0
Italian smelter................................. 64 63 0 1
US smelter...................................... 270 268 2 0
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Document ID 0621, Table 2
The two workers with confirmed beryllium sensitization were offered
further evaluation for CBD. Both were diagnosed with CBD, based on
broncho-alveolar lavage (BAL) results in one case and pulmonary
function tests, respiratory symptoms, and radiographic evidence in the
other.
In 2010, Taiwo et al. (Document ID 0583) published a study of
beryllium-exposed workers from four companies, with a total of nine
smelting operations. These workers included some of the workers from
the 2008 study. 3,185 workers were determined to be "significantly
exposed" to beryllium and invited to participate in BeLPT screening.
Each company used different
criteria to determine "significant" exposure, and the criteria
appeared to vary considerably (Taiwo et al., 2010); thus, it is
difficult to compare rates of sensitization across companies in this
study. 1932 workers, about 60 percent of invited workers, participated
in the program between 2000 and 2006, of whom 9 were determined to be
sensitized (.4 percent). The authors stated that all nine workers were
referred to a respiratory physician for further evaluation for CBD. Two
were diagnosed with CBD (.1 percent), as described above (see Taiwo et
al., 2008).
In general, there appeared to be a low level of sensitization and
CBD among employees at the aluminum smelters studied by Taiwo et al.
(2008; 2010). This is striking in light of the fact that many of the
employees tested had worked at the smelters long before the institution
of exposure limits for beryllium at some smelters in 2000. However, the
authors noted that respiratory and dermal protection had been used at
these plants to protect workers from other hazards (Taiwo et al.,
2008).
A study by Nilsen et al. (2010, Document ID 0460) of aluminum
workers in Norway also found a low rate of sensitization. In the study,
362 workers and 31 control individuals received BeLPT testing for
beryllium sensitization. The authors found one sensitized worker (0.28
percent). No borderline results were reported. The authors reported
that exposure measurements in this plant ranged from 0.1 μg/m3\ to
0.31 μg/m3\ (Nilsen et al., 2010) and that respiratory protection
was in use, as was the case in the smelters studied by Taiwo et al.
(2008; 2010).
6. Nuclear Weapons Facilities
Viet et al. (2000, Document ID 1344) and Arjomandi et al. (2010,
Document ID 1275) evaluated beryllium-exposed nuclear weapons workers.
In 2000, Viet et al. published a case-control study of participants in
the Rocky Flats Beryllium Health Surveillance Program (BHSP), which was
established in 1991 to screen workers at the Department of Energy's
Rocky Flats, CO, nuclear weapons facility for beryllium sensitization
and evaluate sensitized workers for CBD. The program, which the authors
reported had tested over 5,000 current and former Rocky Flats employees
for sensitization, had identified a total of 127 sensitized individuals
as of 1994 when Viet et al. initiated their study; 51 of these
sensitized individuals had been diagnosed with CBD.
Using subjects from the BHSP, Viet et al. (2000) matched a total of
50 CBD cases to 50 controls who tested negative for beryllium
sensitization and had the same age ( 3 years), gender, race
and smoking status, and were otherwise randomly selected from the
database. Using the same matching criteria, 74 sensitized workers who
were not diagnosed with CBD were matched to 74 control individuals from
the BHSP database who tested negative for beryllium sensitization.
Viet et al. (2000) developed exposure estimates for the cases and
controls based on daily fixed airhead (FAH) beryllium air samples
collected in one of 36 buildings at Rocky Flats where beryllium was
used, the Building 444 Beryllium Machine Shop. Annual mean FAH samples
in Building 444 collected between 1960 and 1988 ranged from a low of
0.096 μg/m3\ (1988) to a high of 0.622 μg/m3\ (1964) (Viet et
al., 2000, Table II). Because exposures in this shop were better
characterized than in other buildings, the authors developed estimates
of exposures for all workers based on samples from Building 444. The
authors' statistical analysis of the resulting data set included
conditional logistic regression analysis, modeling the relationship
between risk of each health outcome and individuals' log-transformed
cumulative exposure estimate (CEE) and mean exposure estimate (MEE).
These coefficients corresponded to odds ratios of 6.9 and 7.2 per 10-
fold increase in exposure, respectively. Risk of sensitization without
CBD did not show a statistically significant relationship with log-CEE
(coef = 0.111, p = 0.32), but showed a nearly-significant relationship
with log-MEE (coef = 0.230, p = 0.097). Viet et al. found highly
statistically significant relationships between log-CEE and risk of CBD
(coef = 0.837, p = 0.0006) and between log-MEE (coef = 0.855, p =
0.0012) and risk of CBD, indicating that risk of CBD increases with
exposure level.
Arjomandi et al. (2010) published a study of 50 sensitized workers
from a nuclear weapons research and development facility who were
evaluated for CBD. Quantitative exposure estimates for the workers were
not presented; however, the authors characterized their likely
exposures as low (possibly below 0.1 μg/m3\ for most jobs). In
contrast to the studies of low-exposure populations discussed
previously, this group had much longer follow-up time (mean time since
first exposure = 32 years) and length of employment at the facility
(mean of 18 years).
Five of the 50 evaluated workers (10 percent) were diagnosed with
CBD based on histology or high-resolution computed tomography. An
additional three (who had not undergone full clinical evaluation for
CBD) were identified as probable CBD cases, bringing the total
prevalence of CBD and probable CBD in this group to 16 percent. OSHA
notes that this prevalence of CBD among sensitized workers is lower
than the prevalence of CBD that has been observed in some other worker
groups known to have exposures exceeding the action level of 0.1 μg/
m3\. For example, as discussed above, Newman et al. (2001, Document ID
1354) reported 22 sensitized workers, 13 of whom (59 percent) were
diagnosed with CBD within the study period. Comparison of these results
suggests that controlling respiratory exposure to beryllium may reduce
risk of CBD among already-sensitized workers as well as reducing risk
of CBD via prevention of sensitization. However, it also demonstrates
that some workers in low-exposure environments can become sensitized
and then develop CBD.
7. Conclusions
The published literature on beryllium sensitization and CBD
discussed above shows that risk of both health effects can be
significant in workplaces in compliance with OSHA's preceding PEL
(e.g., Kreiss et al., 1996, Document ID 1477; Henneberger et al., 2001
(1313); Newman et al., 2001 (1354); Schuler et al., 2005 (0919), 2012
(0473); Madl et al., 2007 (1056)). For example, in the Tucson beryllia
ceramics plant discussed above, Kreiss et al. (1996) reported that 8
(5.9 percent) of the 136 workers tested in 1992 were sensitized, 6 (4.4
percent) of whom were diagnosed with CBD. In addition, of 77 Tucson
workers hired prior to 1992 who were tested in 1998, 8 (10.4 percent)
were sensitized and 7 of these (9.7 percent) were diagnosed with CBD
(Henneberger et al., 2001, Document ID 1313). Full-shift area samples
showed airborne beryllium levels below the preceding PEL (76 percent of
area samples collected between 1983 and 1992 were at or below 0.1
μg/m3\ and less than 1 percent exceeded 2 μg/m3\; short-term
breathing zone measurements collected between 1981 and 1992 had a
median of 0.3 μg/m3\; personal lapel samples collected at the plant
beginning in 1991 had a median of 0.2 μg/m3\) (Kreiss et al.,
1996).
Results from the Elmore, OH beryllium metal, alloy, and oxide
production plant and Cullman, AL machining facility also showed
significant risk of sensitization and CBD
among workers with exposures below the preceding TWA PEL. Schuler et
al. (2012, Document ID 0473) found 17 cases of sensitization (8.6%)
among Elmore, OH workers within the first three quartiles of LTW
average exposure (198 workers with LTW average total mass exposures
lower than 1.1 μg/m3\) and 4 cases of CBD (2.2%) within the first
three quartiles of LTW average exposure (183 workers with LTW average
total mass exposures lower than 1.07 μg/m3\; note that follow-up
time of up to 6 years for all study participants was very short for
development of CBD). At the Cullman, AL machining facility, Newman et
al. (2001, Document ID 1354) reported 22 (9.4 percent) sensitized
workers among 235 tested in 1995-1999, 13 of whom were diagnosed with
CBD. Personal lapel samples collected between 1980 and 1999 indicate
that median exposures were generally well below the preceding PEL
(<=0.35 μg/m3\ in all job titles except maintenance (median 3.1
μg/m3\ during 1980-1995) and gas bearings (1.05 μg/m3\ during
1980-1995)).
There is evidence in the literature that although risk will be
reduced by compliance with the new TWA PEL, significant risk of
sensitization and CBD will remain in workplaces in compliance with
OSHA's new TWA PEL of 0.2 μg/m3\ and could extend down to the new
action level of 0.1 μg/m3\, although there is less information and
therefore greater uncertainty with respect to significant risk from
airborne beryllium exposures at and below the action level. For
example, Schuler et al. (2005, Document ID 0919) reported substantial
prevalences of sensitization (6.5 percent) and CBD (3.9 percent) among
152 workers at the Reading, PA facility who had BeLPT screening in
2000. These results showed significant risk at this facility, even
though airborne exposures were primarily below both the preceding and
final TWA PELs due to the low percentage of beryllium in the metal
alloys used (median general area samples <=0.1 μg/m3\, 97% <=0.5
μg/m3\); 93% of personal lapel samples were below the new TWA PEL
of 0.2 μg/m3\). The only group of workers with no cases of
sensitization or CBD, a group of 26 office administration workers, was
the group with exposures below the new action level of 0.1 μg/m3\
(median personal sample 0.01 μg/m3\, range <0.01-0.06 μg/m3\
(Schuler et al., 2005). The Schuler et al. (2012, Document ID 0473)
study of short-term workers in the Elmore, OH facility found 3 cases
(4.6%) of sensitization among 66 workers with total mass LTW average
exposures below 0.1 μg/m3\; 3 of these workers had LTW average
exposures of approximately 0.09 μg/m3\.
Furthermore, cases of sensitization and CBD continued to arise in
the Cullman, AL machining plant after control measures implemented
beginning in 1995 brought median airborne exposures below 0.2 μg/
m3\ (personal lapel samples between 1996 and 1999 in machining jobs
had a median of 0.16 μg/m3\ and 0.08 μg/m3\ in non-machining
jobs) (Madl et al., 2007, Document ID 1056, Table IV). At the time that
Newman et al. (2001, Document ID 1354) reviewed the results of BeLPT
screenings conducted in 1995-1999, a subset of 60 workers had been
employed at the plant for less than a year and had therefore benefitted
to some extent from the exposure reductions. Four (6.7 percent) of
these workers were found to be sensitized, two of whom were diagnosed
with CBD and one with probable CBD (Newman et al., 2001). A later study
by Madl. et al. (2007, Document ID 1056) reported seven sensitized
workers who had been hired between 1995 and 1999, of whom four had
developed CBD as of 2005 (Table II; total number of workers hired
between 1995 and 1999 not reported).
The experiences of several facilities in developing effective
industrial hygiene programs have shown the importance of minimizing
both airborne exposure and dermal contact to effectively reduce risk of
sensitization and CBD. Exposure control programs that have used a
combination of engineering controls and PPE to reduce workers' airborne
exposure and dermal contact have substantially lowered risk of
sensitization among newly hired workers.\15\ Of 97 workers hired
between 2000 and 2004 in the Tucson, AZ plant after the introduction of
mandatory respirator use in production areas beginning in 1999 and
mandatory use of latex gloves beginning in 2000, one case of
sensitization was identified (1 percent) (Cummings et al., 2007,
Document ID 1369). In Elmore, OH, where all workers were required to
wear respirators and skin PPE in production areas beginning in 2000-
2001, the estimated prevalence of sensitization among workers hired
after these measures were put in place was around 2 percent (Bailey et
al., 2010, Document ID 0676). In the Reading, PA facility, only one
(2.2 percent) of 45 workers hired after workers' exposures were reduced
to below 0.1 μg/m3\ and PPE to prevent dermal contact was
instituted was sensitized (Thomas et al., 2009, Document ID 0590). And,
in the aluminum smelters discussed by Taiwo et al. (2008, Document ID
0621), where available exposure samples from four plants indicated
median beryllium levels of about 0.1 μg/m3\ or below (measured as
an 8-hour TWA) and workers used respiratory and dermal protection,
confirmed cases of sensitization were rare (zero or one case per
location).
---------------------------------------------------------------------------
\15\ As discussed in Section V, Health Effects, beryllium
sensitization can occur from dermal contact with beryllium. Studies
conducted in the 1950s by Curtis et al. showed that soluble
beryllium particles could cause beryllium hypersensitivity (Curtis,
1951, Document ID 1273; NAS, 2008, Document ID 1355). Tinkle et al.
established that 0.5- and 1.0-μm particles can penetrate intact
human skin surface and reach the epidermis, where beryllium
particles would encounter antigen-presenting cells and initiate
sensitization (Tinkle et al., 2003, Document ID 1483). Tinkle et al.
further demonstrated that beryllium oxide and beryllium sulfate,
applied to the skin of mice, generate a beryllium-specific, cell-
mediated immune response similar to human beryllium sensitization.
---------------------------------------------------------------------------
OSHA recognizes that the studies on recent programs to reduce
workers' risk of sensitization and CBD were conducted on populations
with very short exposure and follow-up time. Therefore, they could not
adequately address the question of how frequently workers who become
sensitized in environments with extremely low airborne exposures
(median <0.1 μg/m3\) develop CBD. Clinical evaluation for CBD was
not reported for sensitized workers identified in the studies examining
the post-2000, very low-exposed worker cohorts in Tucson, Reading, and
Elmore (Cummings et al. 2007, Document ID 1369; Thomas et al. 2009
(0590); Bailey et al. 2010 (0676)). In Cullman, however, two of the
workers with CBD had been employed for less than a year and worked in
jobs with very low exposures (median 8-hour personal sample values of
0.03-0.09 μg/m3\) (Madl et al., 2007, Document ID 1056, Table III).
The body of scientific literature on occupational beryllium disease
also includes case reports of workers with CBD who are known or
believed to have experienced minimal beryllium exposure, such as a
worker employed only in shipping at a copper-beryllium distribution
center (Stanton et al., 2006, Document ID 1070), and workers employed
only in administration at a beryllium ceramics facility (Kreiss et al.,
1996, Document ID 1477). Therefore, there is some evidence that cases
of CBD can occur in work environments where beryllium exposures are
quite low.
8. Community-Acquired CBD
In the NPRM, OSHA discussed an additional source of information on
low-level beryllium exposure and CBD: Studies of community-acquired
chronic beryllium disease (CA-CBD) in residential areas surrounding
beryllium
production facilities. The literature on CA-CBD, including the Eisenbud
(1949, Document ID 1284), Leiben and Metzner (1959, Document ID 1343),
and Maier et al. (2008, Document ID 0598) studies, documents cases of
CBD among individuals exposed to airborne beryllium at concentrations
below the new PEL. OSHA included a review of these studies in the NPRM
as a secondary source of information on risk of CBD from low-level
beryllium exposure. However, the available studies of CA-CBD have
important limitations. These case studies do not provide information on
how frequently individuals exposed to very low airborne levels develop
CBD. In addition, the reconstructed exposure estimates for CA-CBD cases
are less reliable than the exposure estimates for working populations
reviewed in the previous sections. The literature on CA-CBD therefore
was not used by OSHA as a basis for its quantitative risk assessment
for CBD, and the Agency did not receive any comments or testimony on
this literature. Nevertheless, these case reports and the broader CA-
CBD literature indicate that individuals exposed to airborne beryllium
below the final TWA PEL can develop CBD (e.g., Leiben and Metzner,
1959; Maier et al., 2008).
B. OSHA's Prevalence Analysis for Sensitization and CBD
OSHA evaluated exposure and health outcome data on a population of
workers employed at the Cullman machining facility as one part of the
Agency's Preliminary Risk Analysis presented in the NPRM. A summary of
OSHA's preliminary analyses of these data, a discussion of comments
received on the analyses and OSHA's responses to these comments, as
well as a summary OSHA's final quantitative analyses, are presented in
the remainder of this section. A more detailed discussion of the data,
background information on the facility, and OSHA's analyses appears in
the background document OSHA has placed in the record (Risk Analysis of
the NJH Data Set from the Beryllium Machining Facility in Cullman,
Alabama--CBD and Sensitization, OSHA, 2016).
NJH researchers, with consent and information provided by the
Cullman facility, compiled a dataset containing employee work
histories, medical diagnoses, and air sampling results and provided it
to OSHA for analysis. OSHA's contractors from Eastern Research Group
(ERG) gathered additional information about work operations and
conditions at the plant, developed exposure estimates for individual
workers in the dataset, and helped to conduct quantitative analyses of
the data to inform OSHA's risk assessment (Document ID tbd).
1. Worker Exposure Reconstruction
The work history database contains job history records for 348
workers. ERG calculated cumulative and average exposure estimates for
each worker in the database. Cumulative exposure was calculated as,
[GRAPHIC] [TIFF OMITTED] TR09JA17.003
where e(i) is the exposure level for job (i), and t(i) is the time
spent in job (i). Cumulative exposure was divided by total exposure
time to estimate each worker's long-term average exposure. These
exposures were computed in a time-dependent manner for the statistical
modeling.\16\ For workers with beryllium sensitization or CBD, exposure
estimates excluded exposures following diagnosis.
---------------------------------------------------------------------------
\16\ Each worker's exposure was calculated at each time that
BeLPT testing was conducted.
---------------------------------------------------------------------------
Workers who were employed for long time periods in jobs with low-
level exposures tend to have low average and cumulative exposures due
to the way these measures are constructed, incorporating the worker's
entire work history. As discussed in the Health Effects chapter,
higher-level exposures or short-term peak exposures such as those
encountered in machining jobs may be highly relevant to risk of
sensitization. However, individuals' beryllium exposure levels and
sensitization status are not continuously monitored, so it is not known
exactly when workers became sensitized or what their "true" peak
exposures leading up to sensitization were. Only a rough approximation
of the upper levels of exposure a worker experienced is possible. ERG
attempted to represent workers' highest exposures by constructing a
third type of exposure estimate reflecting the exposure level
associated with the highest-exposure job (HEJ) and time period
experienced by each worker. This exposure estimate (HEJ), the
cumulative exposure estimate, and the average exposure were used in the
quartile analysis and statistical analyses presented below.
2. Prevalence of Sensitization and CBD
In the database provided to OSHA, 7 workers were reported as
sensitized only (that is, sensitized with no known development of CBD).
Sixteen workers were listed as sensitized and diagnosed with CBD upon
initial clinical evaluation. Three workers, first shown to be
sensitized only, were later diagnosed with CBD. Tables VI-3, VI-4, and
VI-5 below present the prevalence of sensitization and CBD cases across
several categories of LTW average, cumulative, and HEJ exposure.
Exposure values were grouped by quartile. For this analysis, OSHA
excluded 8 workers with no job title listed in the data set (because
their exposures could not be estimated); 7 workers whose date of hire
was before 1969 (because this indicates they worked in the company's
previous plant, for which no exposure measurements were available); and
14 workers who had zero exposure time in the data set, perhaps
indicating that they had been hired but had not come to work at
Cullman. After these exclusions, a total of 319 workers remained. None
of the excluded workers were identified as having beryllium
sensitization or CBD.
Note that all workers with CBD are also sensitized. Thus, the
columns "Total Sensitized" and "Total %" refer to all sensitized
workers in the dataset, including workers with and without a diagnosis
of CBD.
Table VI-3--Prevalence of Sensitization and CBD by LTW Average Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized Total
LTW average exposure (μg/m3\) Group size only CBD sensitized Total (%) CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.080............................................... 91 1 1 2 2.2 1.0
0.081-0.18.............................................. 73 2 4 6 8.2 5.5
0.19-0.51............................................... 77 0 6 6 7.8 7.8
0.51-2.15............................................... 78 4 8 12 15.4 10.3
=================
=================
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table VI-4--Prevalence of Sensitization and CBD by Cumulative Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized Total
Cumulative exposure (μg/m3\-yrs) Group size only CBD sensitized Total (%) CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.147............................................... 81 2 2 4 4.9 2.5
0.148-1.467............................................. 79 0 2 2 2.5 2.5
1.468-7.008............................................. 79 3 8 11 13.9 8.0
7.009-61.86............................................. 80 2 7 9 11.3 8.8
-----------------------------------------------------------------------------------------------
Total............................................... 319 7 19 26 8.2% 6.0%
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table VI-5--Prevalence of Sensitization and CBD by Highest-Exposed Job Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized Total
HEJ exposure (μg/m3\) Group size only CBD sensitized Total (%) CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.086............................................... 86 1 0 1 1.2 0.0
0.091-0.214............................................. 81 1 6 7 8.6 7.4
0.387-0.691............................................. 76 2 9 11 14.5 11.8
0.954-2.213............................................. 76 3 4 7 9.2 5.3
-----------------------------------------------------------------------------------------------
Total............................................... 319 7 19 26 8.2 6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table VI-3 shows increasing prevalence of total sensitization and
CBD with increasing LTW average exposure. The lowest prevalence of
sensitization and CBD was observed among workers with average exposure
levels less than or equal to 0.08 μg/m3\, where two sensitized
workers (2.2 percent), including one case of CBD (1.0 percent), were
found. The sensitized worker in this category without CBD had worked at
the facility as an inspector since 1972, one of the lowest-exposed jobs
at the plant. Because the job was believed to have very low exposures,
it was not sampled prior to 1998. Thus, estimates of exposures in this
job are based on data from 1998-2003 only. It is possible that
exposures earlier in this worker's employment history were somewhat
higher than reflected in his estimated average exposure. The worker
diagnosed with CBD in this group had been hired in 1996 in production
control, and had an estimated average exposure of 0.08 μg/m3\. This
worker was diagnosed with CBD in 1997.
The second quartile of LTW average exposure (0.081-0.18 μg/m3\)
shows a marked rise in overall prevalence of beryllium-related health
effects, with 6 workers sensitized (8.2 percent), of whom 4 (5.5
percent) were diagnosed with CBD. Among 6 sensitized workers in the
third quartile (0.19-0.51 μg/m3\), all were diagnosed with CBD (7.8
percent). Another increase in prevalence is seen from the third to the
fourth quartile, with 12 cases of sensitization (15.4 percent),
including eight (10.3 percent) diagnosed with CBD.
The quartile analysis of cumulative exposure also shows generally
increasing prevalence of sensitization and CBD with increasing
exposure. As shown in Table VI-4, the lowest prevalences of CBD and
sensitization are in the first two quartiles of cumulative exposure
(0.0-0.147 μg/m3\-yrs, 0.148-1.467 μg/m3\-yrs). The upper bound
on this cumulative exposure range, 1.467 μg/m3\-yrs, is the
cumulative exposure that a worker would have if exposed to beryllium at
a level of 0.03 μg/m3\ for a working lifetime of 45 years; 0.15
μg/m3\ for ten years; or 0.3 μg/m3\ for five years. These
exposure levels are in the range of those OSHA was interested in
evaluating for purposes of this rulemaking.
A sharp increase in prevalence of sensitization and CBD occurs in
the third quartile (1.468-7.008 μg/m3\-yrs), with roughly similar
levels of both in the highest group (7.009-61.86 μg/m3\-yrs).
Cumulative exposures in the third quartile would be experienced by a
worker exposed for 45 years to levels between 0.03 and 0.16 μg/m3\,
for 10 years to levels between 0.15 and 0.7 μg/m3\, or for 5 years
to levels between 0.3 and 1.4 μg/m3\.
When workers' exposures from their highest-exposed job are
considered, the exposure-response pattern is similar to that for LTW
average exposure in the lower quartiles. In Table VI-5, the lowest
prevalence is observed in the first quartile (0.0-0.086 μg/m3\),
with sharply rising prevalence from first to second and second to third
exposure quartiles. The prevalence of sensitization and CBD in the top
quartile (0.954-2.213 μg/m3\) decreases relative to the third, with
levels similar to the overall prevalence in the dataset. Many workers
in the highest exposure quartiles are long-time employees, who were
hired during the early years of the shop when exposures were highest.
One possible explanation for the drop in prevalence in the highest
exposure quartiles is that other highly-exposed workers from early
periods may have developed CBD and left the plant before sensitization
testing began in 1995 (i.e., the healthy worker survivor effect).
The results of this prevalence analysis support OSHA's conclusion
that maintaining exposure levels below the new TWA PEL will help to
reduce risk
of beryllium sensitization and CBD, and that maintaining exposure
levels below the action level can further reduce risk of beryllium
sensitization and CBD. However, risk of both sensitization and CBD
remains even among the workers with the lowest airborne exposures in
this data set.
C. OSHA's Statistical Modeling for Sensitization and CBD
1. OSHA's Preliminary Analysis of the NJH Data Set
In the course of OSHA's development of the proposed rule, OSHA's
contractor (ERG) also developed a statistical analysis using the NJH
data set and a discrete time proportional hazards analysis (DTPHA).
This preliminary analysis predicted significant risks of both
sensitization (96-394 cases per 1,000, or 9.6-39.4 percent) and CBD
(44-313 cases per 1,000, or 4.4-31.3 percent) at the preceding TWA PEL
of 2 μg/m3\ for an exposure duration of 45 years (90 μg/m3\-
yr). The predicted risks of 8.2-39.9 cases of sensitization per 1,000
(0.8-3.9 percent) and 3.6 to 30.0 cases of CBD per 1,000 (0.4-3
percent) were approximately 10-fold less, but still significant, for a
45-year exposure at the new TWA PEL of 0.2 μg/m3\ (9 μg/m3\-
yr).
In interpreting the risk estimates, OSHA took into consideration
limitations in the preliminary statistical analysis, primarily study
size-related constraints. Consequently, as discussed in the NPRM, OSHA
did not rely on the preliminary statistical analysis for its
significance of risk determination or to develop its benefits analysis.
The Agency relied primarily on the previously-presented analysis of the
epidemiological literature and the prevalence analysis of the Cullman
data for its preliminary significance of risk determination, and on the
prevalence analysis for its preliminary estimate of benefits. Although
OSHA did not rely on the results of the preliminary statistical
analysis for its findings, the Agency presented the DTPHA in order to
inform the public of its results, explain its limitations, and solicit
public comment on the Agency's approach.
Dr. Kenny Crump and Ms. Deborah Proctor submitted comments on
OSHA's preliminary risk assessment (Document ID 1660). Crump and
Proctor agreed with OSHA's review of the epidemiological literature and
the prevalence analysis presented previously in this section. They
stated, "we agree with OSHA's conclusion that there is a significant
risk (>1/1000 risk of CBD) at the [then] current PEL, and that risk is
reduced at the [then] proposed PEL (0.2 μg/m3\) in combination with
stringent measures (ancillary provisions) to reduce worker's exposures.
This finding is evident based on the available literature, as described
by OSHA, and the prevalence data presented for the Cullman facility"
(Document ID 1660, p. 2). They also presented a detailed evaluation of
the statistical analysis of the Cullman data presented in the NPRM,
including a critique of OSHA's modeling approach and interpretation and
suggestions for alternate analyses. However, they emphasized that the
new beryllium rule should not be altered or delayed due to their
comments regarding the statistical model (Document ID 1660, p. 2).
After considering comments on this preliminary model, OSHA
instructed its contractor to change the statistical analysis to address
technical concerns and to incorporate suggestions from Crump and
Proctor, as well as NIOSH (Document ID 1660; 1725). OSHA reviews and
addresses these comments on the preliminary statistical analysis and
provides a presentation of the final statistical analysis in the
background document (Risk Analysis of the NJH Data Set from the
Beryllium Machining Facility in Cullman, Alabama--CBD and
Sensitization, OSHA, 2016). The results of the final statistical
analysis are summarized here.
2. OSHA's Final Statistical Analysis of the NJH Data Set
As noted above, Dr. Roslyn Stone of University of Pittsburgh School
of Public Health reanalyzed for OSHA the Cullman data set in order to
address concerns raised by Crump and Proctor (Document ID 1660). The
reanalysis uses a Cox proportional hazards model instead of the DTPHA.
The Cox model, a regression method for survival data, provides an
estimate of the hazard ratio (HR) and its confidence interval.\17\ Like
the DTPHA, the Cox model can accommodate time-dependent data; however,
the Cox model has an advantage over the DTPHA for OSHA's purpose of
estimating risk to beryllium-exposed workers in that it does not
estimate different "baseline" rates of sensitization and CBD for
different years. Time-specific risk sets were constructed to
accommodate the time-dependent exposures. P-values were based on
likelihood ratio tests (LRTs), with p-values <0.05 considered to be
statistically significant.
---------------------------------------------------------------------------
\17\ The hazard ratio is an estimate of the ratio of the hazard
rate in the exposed group to that of the control group.
---------------------------------------------------------------------------
As in the preliminary statistical analysis, Dr. Stone used
fractional polynomials \18\ to check for possible nonlinearities in the
exposure-response models, and checked the effects of age and smoking
habits using data on birth year and smoking (current, former, never)
provided in the Cullman data set. Data on workers' estimated exposures
and health outcomes through 2005 were included in the reanalysis.\19\
The 1995 risk set (e.g., analysis of cases of sensitization and CBD
identified in 1995) was excluded from all models in the reanalysis so
as not to analyze long-standing (prevalent) cases of sensitization and
CBD together with newly arising (incident) cases of sensitization and
CBD. Finally, Dr. Stone used the testing protocols provided in the
literature on the Cullman study population to determine the years in
which each employee was scheduled to be tested, and excluded employees
from the analysis for years in which they were not scheduled to be
tested (Newman et al., 2001, Document ID 1354).
---------------------------------------------------------------------------
\18\ Fractional polynomials are linear combinations of
polynomials that provide flexible shapes of exposure response.
\19\ Data from 2003 to 2005 were excluded in some previous
analyses due to uncertainty in some employees' work histories. OSHA
accepted the.Crump and Proctor recommendation that these data should
be included, so as to treat uncertain exposure estimates
consistently in the reanalysis (data prior to the start of sampling
in 1980 were included in the previous analysis and most models in
the reanalysis).
---------------------------------------------------------------------------
In the reanalysis of the NJH data set, the HR for sensitization
increased significantly with increasing LTW average exposure (HR =
2.92, 95% CI = 1.51-5.66, p = 0.001; note that HRs are rounded to the
second decimal place). Cumulative exposure was also a statistically
significant predictor for beryllium sensitization, although it was not
as strongly related to sensitization as LTW average exposure (HR =
1.04, 95% CI 1.00-1.07, p = 0.03). The HR for CBD increased
significantly with increasing cumulative exposure (HR = 1.04, 95% CI =
1.01-1.08, p = 0.02). The HR for CBD increased somewhat with increasing
LTW average exposure, but this increase was not significant at the 0.05
level (HR = 2.25, 95% CI = 0.94-5.35, p = 0.07).
None of the analyses Dr. Stone performed to check for
nonlinearities in exposure-response or the effects of smoking or age
substantially impacted the results of the analyses for beryllium
sensitization or CBD. The sensitivity analysis recommended by Crump and
Proctor, excluding workers hired prior to 1980 (see Document ID 1660,
p. 11), did not substantially impact the results
of the analyses for beryllium sensitization, but did affect the results
for CBD. The HR for CBD using cumulative exposure dropped to slightly
below 1 and was not statistically significant following exclusion of
workers hired before 1980 (HR 0.96, 95% CI 0.81-1.13, p = 0.6). OSHA
discusses this result further in the background document, concluding
that the reduced follow-up time for CBD in the subcohort hired in 1980
or later, in combination with genetic risk factors that may attenuate
both exposure-response and disease latency in some people, may explain
the lack of significant exposure-response observed in this sensitivity
analysis.
Because LTW average exposure was most strongly associated with
beryllium sensitization, OSHA used the final model for LTW average
exposure to estimate risk of sensitization at the preceding TWA PEL,
the final TWA PEL, and several alternate TWA PELs it considered.
Similarly, because cumulative exposure was most strongly associated
with CBD, OSHA used the final model for cumulative exposure to estimate
risk of CBD at the preceding, final, and alternate TWA PELs. In
calculating these risks, OSHA used a small, fixed estimate of
"baseline" risk (i.e., risk of sensitization or CBD among persons
with no known exposure to beryllium), as suggested by Crump and Proctor
(Document ID 1660) and NIOSH (Document ID 1725). Table VI-6 presents
the risk estimates for sensitization and the corresponding 95 percent
confidence intervals using two different fixed "background" rates of
sensitization, 1 percent and 0.5 percent. Table VI-7 presents the risk
estimates for sensitization and the corresponding 95 percent confidence
intervals using a fixed "background" rate of CBD of 0.5 percent. The
corresponding interval is based on the uncertainty in the exposure
coefficient (i.e., the predicted values based on the 95 percent
confidence limits for the exposure coefficient). Since the Cox
proportional hazards model does not estimate a baseline risk, this 95
percent interval fully represents statistical uncertainty in the risk
estimates.
Table VI-6--Predicted Cases of Sensitization per 1,000 Workers Exposed at the Preceding and Alternate PELs Based
on Cox Proportional Hazards Model, LTW Average Exposure Metric, With Corresponding Interval Based on the
Uncertainty in the Exposure Coefficient.
[1 Percent and 0.5 percent baselines]
----------------------------------------------------------------------------------------------------------------
Estimated Estimated
Exposure level (μg/m3\) cases/1000, 95% CI cases/1000, 95% CI
.5% baseline 1% baseline
----------------------------------------------------------------------------------------------------------------
2.0............................................. 42.75 11.4-160.34 85.49 22.79-320.69
1.0............................................. 14.62 7.55-28.31 29.24 15.10-56.63
0.5............................................. 8.55 6.14-11.90 17.10 12.29-23.80
0.2............................................. 6.20 5.43-7.07 12.39 10.86-14.15
0.1............................................. 5.57 5.21-5.95 11.13 10.42-11.89
----------------------------------------------------------------------------------------------------------------
Table VI-7--Predicted Cases of CBD per 1,000 Workers Exposed at the Preceding and Alternative PELs Based on Cox Proportional Hazards Model, Cumulative
Exposure Metric, with Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
[0.5 percent baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Exposure Duration
----------------------------------------------------------------------------------------------------------
5 years 10 years 20 years 45 years
Exposure level (μg/m3\) ----------------------------------------------------------------------------------------------------------
Cumulative Estimated Estimated Estimated Estimated
(μg/m3\- cases/1000 μg/m3\- cases/1000 μg/m3\- cases/1000 μg/m3\- cases/1000
yrs) 95% CI yrs 95% CI yrs 95% CI yrs 95% CI
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.......................................... 10.0 7.55 20.0 11.39 40.0 25.97 90.0 203.60
5.34-10.67 5.70-22.78 6.5-103.76 9.02-4595.6
7
1.0.......................................... 5.0 6.14 10.0 7.55 20.0 11.39 45.0 31.91
5.17-7.30 5.34-10.67 5.70-22.78 6.72-151.59
0.5.......................................... 2.5 5.54 5.0 6.14 10.0 7.55 22.5 12.63
5.08-6.04 5.17-7.30 5.34-10.67 5.79-27.53
0.2.......................................... 1.0 5.21 2.0 5.43 4.0 5.9 9.0 7.24
5.03-5.39 5.07-5.82 5.13-6.77 5.30-9.89
0.1.......................................... 0.5 5.1 1.0 5.21 2.0 5.43 4.5 6.02
5.02-5.19 5.03-5.39 5.07-5.82 5.15-7.03
--------------------------------------------------------------------------------------------------------------------------------------------------------
The Cox proportional hazards model, used with the fixed
"baseline" rates of 0.5 percent and 1 percent, predicted risks of
sensitization totaling 43 and 86 cases per 1,000 workers, respectively,
or 4.3 and 8.6 percent, at the preceding PEL of 2 μg/m3\. The
predicted risk of CBD is 203 cases per 1,000 workers, or 20.3 percent,
at the preceding PEL of 2 μg/m3\, assuming 45 years of exposure
(cumulative exposure of 90 μg/m3\-yr).\20\ The predicted risks of
sensitization at the new PEL of 0.2 μg/m3\ are substantially lower,
at 6 and 12 cases per 1,000 for the baselines of 0.5% and 1.0%,
respectively. The predicted risk of CBD is also much lower at the new
TWA PEL of 0.2 μg/m3\ (9 μg/m3\-year), at 7 cases per 1,000
assuming 45 years of exposure.
---------------------------------------------------------------------------
\20\ The predictions for each model represent the estimated
probability of being sensitized or having CBD at one point in time,
rather than the cumulative risk over a lifetime of exposure, which
would be higher. Lifetime risks are presented in the FEA, Benefits
Analysis.
---------------------------------------------------------------------------
Due to limitations in the Cox analysis, including the small size of
the dataset, relatively limited exposure data from the plant's early
years, study size-related constraints on the statistical analysis of
the dataset, limited follow-
up time on many workers, and sensitivity of the results to the
"baseline" values assumed for sensitization and CBD, OSHA must
interpret the model-based risk estimates presented in Tables VI-6 and
VI-7 with caution. Uncertainties in these risk estimates are discussed
in the background document (Risk Analysis of the NJH Data Set from the
Beryllium Machining Facility in Cullman, Alabama--CBD and
Sensitization, OSHA, 2016). However, these uncertainties do not alter
OSHA's conclusions with regard to the significance of risk at the
preceding PEL and alternate PELs that OSHA considered, which are based
primarily on the Agency's review of the literature and the prevalence
analysis presented earlier in this section (also see Section VII,
Significance of Risk).
D. Lung Cancer
As discussed more fully in the Health Effects section of the
preamble, OSHA has determined beryllium to be a carcinogen based on an
extensive review of the scientific literature regarding beryllium and
cancer (see Section V.E). This review included an evaluation of the
human epidemiological, animal cancer, and mechanistic studies described
in the Health Effects section of this preamble. OSHA's conclusion is
supported by the findings of public health organizations such as the
International Agency for Research on Cancer (IARC), which has
determined beryllium and its compounds to be carcinogenic to humans
(Group 1 category) (IARC 2012, Document ID 0650); the National
Toxicology Program (NTP), which classifies beryllium and its compounds
as known carcinogens (NTP 2014, Document ID 0389); and the
Environmental Protection Agency (EPA), which considers beryllium to be
a probable human carcinogen (EPA 1998, Document ID 0661).
The Sanderson et al. study previously discussed in Health Effects
evaluated the association between beryllium exposure and lung cancer
mortality based on data from a beryllium processing plant in Reading,
PA (Sanderson et al., 2001, Document ID 1419). Specifically, this case-
control study evaluated lung cancer mortality in a cohort of 3,569 male
workers employed at the plant from 1940 to 1969 and followed through
1992. For each lung cancer victim, 5 age- and race-matched controls
were selected by incidence density sampling, for a total of 142
identified lung cancer cases and 710 controls.
A conditional logistic regression analysis showed an increased risk
of death from lung cancer in workers with higher exposures when dose
estimates were lagged by 10 and 20 years (Sanderson et al., 2001,
Document ID 1419). This lag was incorporated in order to account for
exposures that did not contribute to lung cancer because they occurred
after the induction of cancer. The authors noted that there was
considerable uncertainty in the estimation of exposure levels for the
1940s and 1950s and in the shape of the dose-response curve for lung
cancer. In a 2008 study, Schubauer-Berigan et al. reanalyzed the data,
adjusting for potential confounders of hire age and birth year
(Schubauer-Berigan et al., 2008, Document ID 1350). The study reported
a significant increasing trend (p < 0.05) in lung cancer mortality when
average (log transformed) exposure was lagged by 10 years. However, it
did not find a significant trend when cumulative (log transformed)
exposure was lagged by 0, 10, or 20 years (Schubauer-Berigan et al.,
2008, Table 3).
In formulating the final rule, OSHA was particularly interested in
lung cancer risk estimates from a 45-year (i.e., working lifetime)
exposure to beryllium levels between 0.1 μg/m3\ and 2 μg/m3\.
The majority of case and control workers in the Sanderson et al. (2001,
Document ID 1419) case-control analysis were first hired during the
1940s and 50s when exposures were extremely high (estimated daily
weighted averages (DWAs) >20 μg/m3\ for most jobs) in comparison to
the exposure range of interest to OSHA (Sanderson et al. 2001, Document
ID 1419, Table II). About two-thirds of cases and half of controls
worked at the plant for less than a year. Thus, a risk assessment based
on this exposure-response analysis would have needed to extrapolate
from very high to low exposures, based on a working population with
extremely short tenure. While OSHA risk assessments must often make
extrapolations to estimate risk within the range of exposures of
interest, the Agency acknowledges that these issues of short tenure and
high exposures would have created substantial uncertainty in a risk
assessment based on this particular study population.
In addition, the relatively high exposures of the least-exposed
workers in the study population might have created methodological
issues for the lung cancer case-control study design. Mortality risk is
expressed as an odds ratio that compares higher exposure quartiles to
the lowest quartile. It is preferable that excess risks attributable to
occupational beryllium be determined relative to an unexposed or
minimally exposed reference population. However, in this study
population, workers in the lowest quartile were exposed well above the
preceding OSHA TWA PEL (average exposure <11.2 μg/m3\) and may have
had a significant lung cancer risk. This issue would have introduced
further uncertainty into the lung cancer risks.
In 2011, Schubauer-Berigan et al. published a quantitative risk
assessment that addressed several of OSHA's concerns regarding the
Sanderson et al. analysis. This new risk assessment was based on an
update of the Reading cohort analyzed by Sanderson et al., as well as
workers from two smaller plants (Schubauer-Berigan et al. 2011,
Document ID 1265). This study population was exposed, on average, to
lower levels of beryllium and had fewer short-term workers than the
previous cohort analyzed by Sanderson et al. (2001, Document ID 1250)
and Schubauer-Berigan et al. (2008, Document ID 1350). Schubauer-
Berigan et al. (2011) followed the study population through 2005 where
possible, increasing the length of follow-up time overall by an
additional 17 years of observation compared to the previous analyses.
For these reasons, OSHA considered the Schubauer-Berigan (2011)
analysis more appropriate than Sanderson et al. (2001) and Schubauer-
Berigan (2008) for its risk assessment. OSHA therefore based its
preliminary QRA for lung cancer on the results from Schubauer-Berigan
et al. (2011).
OSHA received several comments about its choice of Schubauer-
Berigan et al. (2011) as the basis for its preliminary QRA for lung
cancer. NIOSH commented that OSHA's choice of Schubauer-Berigan et al.
for its preliminary analysis was appropriate because "[n]o other study
is available that presents quantitative dose-response information for
lung cancer, across a range of beryllium processing facilities"
(Document ID 1725, p. 7). In supporting OSHA's use of this study, NIOSH
emphasized in particular the study's inclusion of relatively low-
exposed workers from two facilities that began operations in the 1950s
(after employer awareness of acute beryllium disease (ABD) and CBD led
to efforts to minimize worker exposures to beryllium), as well as the
presence of both soluble and poorly soluble forms of beryllium in the
facilities studied (Document ID 1725, p. 7).
According to Dr. Paolo Boffetta, who submitted comments on this
study,
Schubauer-Berigan et al. (2011) is not the most relevant study
available to OSHA for its lung cancer risk analysis. Dr. Boffetta
argued that the most informative study of lung cancer risk in the
beryllium industry after 1965 is one that he developed in 2015
(Boffetta et al., 2015), which he described as a pooled analysis of 11
plants and 4 distribution centers (Document ID 1659, p. 1). However,
Dr. Boffetta did not provide OSHA with the manuscript of his study,
which he stated was under review for publication. Instead, he reported
some results of the study and directed OSHA to an abstract of the study
in the 2015 Annual Conference of the Society for Epidemiologic Research
(Document ID 1659; Document ID 1661, Attachment 1).
Because only an abstract of Boffetta et al.'s 2015 study was
available to OSHA (see Document ID 1661, Attachment 1), OSHA could not
properly evaluate it or use it as the basis of a quantitative risk
assessment for lung cancer. Nevertheless, OSHA has addressed comments
Dr. Boffetta submitted based on his analyses in the relevant sections
of the final QRA for lung cancer below. Because it was not possible to
use this study for its lung cancer QRA and OSHA is not aware of other
studies appropriate for use in its lung cancer QRA (nor did commenters
besides Dr. Boffetta suggest that OSHA use any additional studies for
this purpose), OSHA finds that the body of available evidence has not
changed since the Agency conducted its preliminary QRA based on
Schubauer-Berigan et al. (2011, Document ID 1265). Therefore, OSHA
concludes that Schubauer-Berigan et al. (2011) is the most appropriate
study for its final lung cancer QRA, presented below.
1. QRA for Lung Cancer Based on Schubauer-Berigan et al. (2011)
The cohort studied by Schubauer-Berigan et al. (2011, Document ID
1265) included 5,436 male workers who had worked for at least 2 days at
the Reading facility or at the beryllium processing plants in Hazleton,
PA and Elmore, OH prior to 1970. The authors developed job-exposure
matrices (JEMs) for the three plants based on extensive historical
exposure data, primarily short-term general area and personal breathing
zone samples, collected on a quarterly basis from a wide variety of
operations. These samples were used to create DWA estimates of workers'
full-shift exposures, using records of the nature and duration of tasks
performed by workers during a shift. Details on the JEM and DWA
construction can be found in Sanderson et al. (2001, Document ID 1250),
Chen et al. (2001, Document ID 1593), and Couch et al. (2010, Document
ID 0880).
Workers' cumulative exposures (μg/m3\-days) were estimated by
summing daily average exposures (assuming five workdays per week)
(Schubauer-Berigan et al., 2011). To estimate mean exposure (μg/
m3\), cumulative exposure was divided by exposure time (in days),
accounting where appropriate for lag time. Maximum exposure (μg/
m3\) was calculated as the highest annual DWA on record for a worker
from the first exposure until the study cutoff date of December 31,
2005, again accounting where appropriate for lag time. Exposure
estimates were lagged by 5, 10, 15, and 20 years in order to account
for exposures that may not have contributed to lung cancer because of
the long latency required for manifestation of the disease. The authors
also fit models with no lag time.
As shown in Table VI-8 below, estimated exposure levels for workers
from the Hazleton and Elmore plants were on average far lower than
those for workers from the Reading plant (Schubauer-Berigan et al.,
2011). Whereas the median worker from Hazleton had a mean exposure
across his tenure of less than 1.5 μg/m3\ and the median worker
from Elmore had a mean exposure of less than 1 μg/m3\, the median
worker from Reading had a mean exposure of 25 μg/m3\. The Elmore
and Hazleton worker populations also had fewer short-term workers than
the Reading population. This was particularly evident at Hazleton,
where the median value for cumulative exposure among cases was higher
than at Reading despite the much lower mean and maximum exposure
levels.
Table VI-8--Cohort Description and Distribution of Cases by Exposure Level
--------------------------------------------------------------------------------------------------------------------------------------------------------
All plants Reading plant Hazleton plant Elmore plant
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of cases................................ ....................................... 293 218 30 45
Number of non-cases............................ ....................................... 5143 3337 583 1223
Median value for mean exposure................. No lag................................. 15.42 25 1.443 0.885
(μg/m3\) among cases....................... 10-year lag............................ 15.15 25 1.443 0.972
Median value for cumulative exposure........... No lag................................. 2843 2895 3968 1654
(μg/m3\-days) among cases.................. 10-year lag............................ 2583 2832 3648 1449
Median value for maximum exposure.............. No lag................................. 25 25.1 3.15 2.17
(μg/m3\) among cases....................... 10-year lag............................ 25 25 3.15 2.17
Number of cases with potential asbestos ....................................... 100 (34%) 68 (31%) 16 (53%) 16 (36%)
exposure.
Number of cases who were professional workers.. ....................................... 26 (9%) 21 (10%) 3 (10%) 2 (4%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table adapted from Schubauer-Berigan et al., 2011, Document ID 1265, Table 1.
Schubauer-Berigan et al. analyzed the data set using a variety of
exposure-response modeling approaches, including categorical analyses,
continuous-variable piecewise log-linear models, and power models
(2011, Document ID 1265). All models adjusted for birth cohort and
plant. Because exposure values were log-transformed for the power model
analyses, the authors added small values to exposures of 0 in lagged
analyses (0.05 μg/m3\ for mean and maximum exposure, 0.05 μg/
m3\-days for cumulative exposure). The authors used restricted cubic
spline models to assess the shape of the exposure-response curves and
suggest appropriate parametric model forms. The Akaike Information
Criterion (AIC) value was used to evaluate the fit of different model
forms and lag times.
Because smoking information was available for only about 25 percent
of the cohort (those employed in 1968), smoking could not be controlled
for directly in the models. Schubauer-Berigan et al. reported that
within the subset with smoking information, there was little difference
in smoking by cumulative or maximum exposure category, suggesting that
smoking was unlikely to act as a confounder in the cohort. In addition
to models based on the full cohort, Schubauer-Berigan et al. also
prepared risk estimates based on models excluding professional workers
(ten percent of cases) and workers believed to have asbestos exposure
(one-third of cases). These models were
intended to mitigate the potential impact of smoking and asbestos as
confounders.\21\
---------------------------------------------------------------------------
\21\ The authors appeared to reason that if professional workers
had both lower beryllium exposures and lower smoking rates than
production workers, smoking could be a confounder in the cohort
comprising both production and professional workers. However,
smoking was unlikely to be correlated with beryllium exposure among
production workers, and would therefore probably not act as a
confounder in a cohort excluding professional workers.
---------------------------------------------------------------------------
The authors found that lung cancer risk was strongly and
significantly related to mean, cumulative, and maximum measures of
workers' exposure (all models reported in Schubauer-Berigan et al.,
2011, Document ID 1265). They selected the best-fitting categorical,
power, and monotonic piecewise log-linear (PWL) models with a 10-year
lag to generate HRs for male workers with a mean exposure of 0.5 μg/
m3\ (the current NIOSH Recommended Exposure Limit for beryllium).\22\
In addition, they estimated the daily weighted average exposure that
would be associated with an excess lung cancer mortality risk of one in
one thousand (.005 μg/m3\ to .07 μg/m3\ depending on model
choice). To estimate excess risk of cancer, they multiplied these
hazard ratios by the 2004 to 2006 background lifetime lung cancer rate
among U.S. males who had survived, cancer-free, to age 30. At OSHA's
request, Dr. Schubauer-Berigan also estimated excess lung cancer risks
for workers with mean exposures at the preceding PEL of 2 μg/m3\
and at each of the other alternate PELs that were under consideration:
1 μg/m3\, 0.2 μg/m3\, and 0.1 μg/m3\ (Document ID 0521).
The resulting risk estimates are presented in Table VI-9 below.
---------------------------------------------------------------------------
\22\ Here, "monotonic PWL model" means a model producing a
monotonic exposure-response curve in the 0 to 2 μg/m3\ range.
Table VI-9--Excess Lung Cancer Risk per 1,000 [95% Confidence Interval] For Male Workers at Alternate PELs
[Based on Schubauer-Berigan et al., 2011]
----------------------------------------------------------------------------------------------------------------
Mean exposure
Exposure-response model -------------------------------------------------------------------------------
0.1 μg/m3\ 0.2 μg/m3\ 0.5 μg/m3\ 1 μg/m3\ 2 μg/m3\
----------------------------------------------------------------------------------------------------------------
Best monotonic PWL--all workers. 7.3 [2.0-13] 15 [3.3-29] 45 [9-98] 120 [20-340] 140 [29-370]
Best monotonic PWL--excluding 3.1 [<0-11] 6.4 [<0-23] 17 [<0-74] 39 [39-230] 61 [<0-280]
professional and asbestos
workers........................
Best categorical--all workers... 4.4 [1.3-8] 9 [2.7-17] 25 [6-48] 59 [13-130] 170 [29-530]
Best categorical--excluding 1.4 [<0-6.0] 2.7 [<0-12] 7.1 [<0-35] 15 [<0-87] 33 [<0-290]
professional and asbestos
workers........................
Power model--all workers........ 12 [6-19] 19 [9.3-29] 30 [15-48] 40 [19-66] 52 [23-88]
Power model--excluding 19 [8.6-31] 30 [13-50] 49 [21-87] 68 [27-130] 90 [34-180]
professional and asbestos
workers........................
----------------------------------------------------------------------------------------------------------------
Source: Schubauer-Berigan, Document ID 0521, pp. 6-10.
Schubauer-Berigan et al. (2011, Document ID 1265) discuss several
strengths, weaknesses, and uncertainties of their analysis. Strengths
include a long (>30 years) follow-up time and the extensive exposure
and work history data available for the development of exposure
estimates for workers in the cohort. Weaknesses and uncertainties of
the study include the limited information available on workers' smoking
habits: As mentioned above, smoking information was available only for
workers employed in 1968, about 25 percent of the cohort. Another
potential weakness was that the JEMs used did not account for possible
respirator use among workers in the cohort. The authors note that
workers' exposures may therefore have been overestimated, and that
overestimation may have been especially severe for workers with high
estimated exposures. They suggest that overestimation of exposures for
workers in highly exposed positions may have caused attenuation of the
exposure-response curve in some models at higher exposures. This could
cause the relationship between exposure level and lung cancer risk to
appear weaker than it would in the absence of this source of error in
the estimation of workers' beryllium exposures.
Schubauer-Berigan et al. (2011) did not discuss the reasons for
basing risk estimates on mean exposure rather than cumulative exposure,
which is more commonly used for lung cancer risk analysis. OSHA
believes the decision may involve the non-monotonic relationship the
authors observed between cancer risk and cumulative exposure level. As
discussed previously, workers from the Reading plant frequently had
very short tenures and high exposures, yielding lower cumulative
exposures compared to cohort workers from other plants with longer
employment. Despite the low estimated cumulative exposures among the
short-term Reading workers, they may have been at high risk of lung
cancer due to the tendency of beryllium to persist in the lung for long
periods. This could lead to the appearance of a non-monotonic
relationship between cumulative exposure and lung cancer risk. It is
possible that a dose-rate effect may exist for beryllium, such that the
risk from a cumulative exposure gained by long-term, low-level exposure
is not equivalent to the risk from a cumulative exposure gained by very
short-term, high-level exposure. In this case, mean exposure level may
better correlate with the risk of lung cancer than cumulative exposure
level. For these reasons, OSHA considers the authors' use of the mean
exposure metric to be appropriate and scientifically defensible for
this particular dataset.
Dr. Boffetta's comment, mentioned above, addressed the relevance of
the Schubauer-Berigan et al. (2011) cohort to determining whether
workers currently employed in the beryllium industry experience an
increased lung cancer hazard (Document ID 1659, pp. 1-2). His comment
also analyzed the methods and findings in Schubauer-Berigan et al.
(2011) (Document ID 1659, pp. 2-3). Notably, he stated that his own
study, Boffetta et al. (2015) provides better information for risk
assessment than does Schubauer-Berigan et al. (2011) (Document ID 1659,
pp. 1-2). As discussed above, OSHA cannot rely on a study for its QRA
(Boffetta et al., 2015) that has not been submitted to the record and
is not otherwise available to OSHA. However, in the discussion below,
OSHA addresses Dr. Boffetta's study to the extent it can given the
limited information available to the Agency. OSHA also responds to Dr.
Boffetta's comments on Schubauer-Berigan et al. (2011, Document ID
1265) and Boffetta et al. (2014, Document ID 0403), which Dr. Boffetta
asserts provides evidence that poorly soluble beryllium compounds are
not associated with lung cancer (Document ID 1659, p. 1).
Boffetta argued that the most informative study in the modern
(post-1965) beryllium industry is Boffetta et al. (2015, Document ID
1661, Attachment 1). According to Boffetta's comment, the study found
an SMR of 1.02 (95% CI 0.94-1.10, based on 672 deaths) for the overall
cohort and an SMR for lung cancer among workers exposed only to
insoluble beryllium of 0.93 (95% CI 0.79-1.08, based on 157 deaths).
Boffetta noted that his study was based on 23 percent more overall
deaths than the Schubauer-Berigan et al. cohort (Document ID 1659, pp.
1-2). As stated earlier, this study is unpublished and was not provided
to OSHA. The abstract provided by Materion (Document ID 1661,
Attachment 1) included very little information beyond the SMRs
reported; for example, it provided no information about the
manufacturing plants and distribution centers included, workers'
beryllium exposure levels, how the cohorts were defined, or how the
authors determined the solubility of the beryllium to which workers
were exposed. OSHA is therefore unable to evaluate the quality or
conclusions of this study.
Dr. Boffetta also commented that there is a lack of evidence of
increased lung cancer risk among workers exposed only to poorly soluble
beryllium compounds (Document ID 1659, p. 1). To support this
statement, he cited a study he published in 2014 of workers at four
"insoluble facilities" (Boffetta et al., 2014) and Schubauer-Berigan
et al.'s 2011 study, arguing that increased cancer risk in beryllium-
exposed workers in those two studies was only observed in workers
employed in Reading and Lorain prior to 1955. Workers employed at the
other plants and workers who were first employed in Reading and Lorain
after 1955, according to Dr. Boffetta, were exposed primarily to poorly
soluble forms of beryllium and did not experience an increased risk of
lung cancer. Dr. Boffetta further stated that his unpublished paper
(Boffetta et al., 2015) shows a similar result (Document ID 1659, p.
1).
OSHA carefully considered Dr. Boffetta's argument regarding the
status of poorly soluble beryllium compounds, and did not find
persuasive evidence showing that the solubility of the beryllium to
which the workers in the studies he cited were exposed accounts for the
lack of statistically significantly elevated risk in the Boffetta et
al. (2014) cohort or the Schubauer-Berigan et al. (2011) subcohort.
While it is true that the SMR for lung cancer was not statistically
significantly elevated in the Schubauer-Berigan et al. (2011) study
when workers hired before 1955 in the Reading and Lorain plants were
excluded from the study population, or in the study of four facilities
published by Boffetta et al. in 2014, there are various possible
reasons for these results that Dr. Boffetta did not consider in his
comment. As discussed below, OSHA finds that the type of beryllium
compounds to which these workers were exposed is not likely to explain
Dr. Boffetta's observations.
As discussed in Section V, Health Effects and in comments submitted
by NIOSH, animal toxicology evidence shows that poorly soluble
beryllium compounds can cause cancer. IARC determined that poorly
soluble forms of beryllium are carcinogenic to humans in its 2012
review of Group I carcinogens (see section V.E.5 of this preamble;
Document ID 1725, p. 9; IARC, 2012, Document ID 0650). NIOSH noted that
poorly soluble forms of beryllium remain in the lung for longer time
periods than soluble forms, and can therefore create prolonged exposure
of lung tissue to beryllium (Document ID 1725, p. 9). This prolonged
exposure may lead to the sustained tissue inflammation that causes many
forms of cancer and is believed to be one pathway for carcinogenesis
due to beryllium exposure (see Section V, Health Effects).
The comments from NIOSH also demonstrate that the available
information cannot distinguish between the effects of soluble and
poorly soluble beryllium. NIOSH submitted information on the solubility
of beryllium in the Schubauer-Berigan et al. (2011) cohort, stating
that operations typically involving both soluble and poorly soluble
beryllium were performed at all three of the beryllium plants included
in the study (Document ID 1725, p. 9; Ward et al., 1992, Document ID
1378). Based on evaluations of the JEMs and work histories of employees
in the cohort (which were not published in the 2011 Schubauer-Berigan
et al. paper), NIOSH stated that "the vast majority of beryllium work-
time at all three of these facilities was due to either insoluble or
mixed chemical forms. In fact, insoluble beryllium was the largest
single contributor to work-time (for beryllium exposure of known
solubility class) at the three facilities across most time periods"
(Document ID 1725, p. 9). NIOSH also provided figures showing the
contribution of insoluble beryllium to exposure over time in the
Schubauer-Berigan et al. (2011) study, as well as the relatively small
proportion of work years during which workers in the study were exposed
exclusively to either soluble or poorly soluble forms (Document ID
1725, pp. 10-11).
Boffetta et al. (2014, Document ID 0403) examined a population of
workers allegedly exposed exclusively to poorly soluble beryllium
compounds, in which overall SMR for lung cancer was not statistically
significantly elevated (SMR 96.0, 95% CI 80.0-114.3). Boffetta et al.
concluded, "[a]lthough a small risk for lung cancer is compatible with
our results, we can confidently exclude an excess greater than 20%" in
the study population (Boffetta et al., 2014, p. 592). Limitations of
the study include a lack of information on many workers' job titles, a
lack of any beryllium exposure measurements, and the very short-term
employment of most cohort members at the study facilities (less than 5
years for 72 percent of the workers) (Boffetta et al., 2014).
OSHA reviewed this study, and finds that it does not contradict the
findings of the Schubauer-Berigan et al. (2011) lung cancer risk
analysis for several reasons. First, as shown in Table VI-9 above, none
of the predictions of excess risk in the risk analysis exceed 20
percent (200 per 1,000 workers); most are well below this level, and
thus are well within the range that Boffetta et al. (2014) state they
cannot confidently exclude. Thus, the statement by Boffetta et al. that
the risk of excess lung cancer is no higher than 20 percent is actually
consistent with the risk findings from Schubauer-Berigan et al. (2011)
presented above. Second, the fact that most workers in the cohort were
employed for less than five years suggests that most workers'
cumulative exposures to beryllium were likely to be quite low, which
would explain the non-elevated SMR for lung cancer in the study
population regardless of the type of beryllium to which workers were
exposed. The SMR for workers employed in the study facilities for at
least 20 years was elevated (112.7, CI 66.8-178.1) (Boffetta et al.,
2014, Document ID 0403, Table 3),\23\ supporting OSHA's observation
that the lack of elevated SMR in the cohort overall may be due to
short-term
employment and low cumulative exposures.
---------------------------------------------------------------------------
\23\ This SMR was not statistically significantly elevated,
probably due to the small size of this subcohort (153 total deaths,
18 lung cancer deaths).
---------------------------------------------------------------------------
Finally, the approach of Boffetta et al. (2014), which relies on
SMR analyses, does not account for the healthy worker effect. SMRs are
calculated by comparing disease levels in the study population to
disease levels in the general population, using regional or national
reported disease rates. However, because working populations tend to
have lower disease rates than the overall population, SMRs can
underestimate excess risk of disease in those populations. The SMR in
Boffetta et al. (2014) for overall mortality in the study population
was statistically significantly reduced (94.7, 95 percent CI 89.9-
99.7), suggesting a possible healthy worker effect. The SMR for overall
mortality was even further reduced in the category of workers with at
least 20 years of employment (87.7, 95 percent CI 74.3-102.7), in which
an elevated SMR for lung cancer was observed. NIOSH commented that
"[i]n a modern industrial population, the expected SMR for lung cancer
would be approximately 0.93 [Park et al. (1991)]" (Document ID 1725,
p. 8). This is lower than the SMR for lung cancer (96) observed in
Boffetta et al. (2014) and much lower than the SMR for lung cancer in
the category of workers employed for at least 20 years (112.7), which
is the group most likely to have had sufficient exposure and latency to
show excess lung cancer (Boffetta et al., 2014, Document ID 0403,
Tables 2 and 3). Thus, it appears that the healthy worker effect is
another factor (in addition to low cumulative exposures) that may
account for the findings of Boffetta et al.'s 2014 study.
Taken together, OSHA finds that the animal toxicology evidence on
the carcinogenicity of poorly soluble beryllium forms, the long
residence of poorly soluble beryllium in the lung, the likelihood that
most workers in Schubauer-Berigan et al. (2011) were exposed to a
mixture of soluble and poorly soluble beryllium forms, and the points
raised above regarding Boffetta et al. (2014) rebut Boffetta's claim
that low solubility of beryllium compounds is the most likely
explanation for the lack of statistically significantly elevated SMR
results.
Dr. Boffetta's comment also raised technical questions regarding
the Schubauer-Berigan et al. (2011, Document ID 1265) risk analysis. He
noted that risk estimates at low exposures are dependent on choice of
model in their analysis; the authors' choice of a single "best" model
was based on purely statistical criteria, and the results of the
statistics used (AIC) were similar between the models" (Document ID
1659, p. 2). Therefore, according to Dr. Boffetta, "there is ample
uncertainty about the shape of the dose-response function in the low-
dose range" (Document ID 1659, p. 3).
OSHA agrees that it is difficult to distinguish a single "best"
model from the set of models presented by Schubauer-Berigan et al.
(2011), and that risk estimates at low exposure levels vary depending
on choice of model. That is one reason OSHA presented results from all
of the models (see Table VI-9). OSHA further agrees that there is
uncertainty in the lung cancer risk estimates, the estimation of which
(unlike for CBD) required extrapolation below beryllium exposure levels
experienced by workers in the Schubauer-Berigan et al. (2011) study.
However, the Schubauer-Berigan risk assessment's six best-fitting
models all support OSHA's significant risk determination, as they all
predict a significant risk of lung cancer at the preceding TWA PEL of 2
μg/m3\ (estimates ranging from 33 to 170 excess lung cancers per
1,000 workers) and a substantially reduced, though still significant,
risk of lung cancer at the new TWA PEL of 0.2 μg/m3\ (estimates
ranging from 3 to 30 excess lung cancers per 1,000 workers) (see Table
VI-9).
Dr. Boffetta also noted that the risk estimates provided by
Schubauer-Berigan et al. (2011, Document ID 1265) for OSHA's lung
cancer risk assessment depend on the background lung cancer rate used
in excess risk calculations, and that industrial workers may have a
different background lung cancer risk than the U.S. population as a
whole (Document ID 1659, p. 2). OSHA agrees that choice of background
risk could influence the number of excess lung cancers predicted by the
models the Agency relied on for its lung cancer risk estimates.
However, choice of background risk did not influence OSHA's finding
that excess lung cancer risks would be substantially reduced by a
decrease in exposure from the preceding TWA PEL to the final TWA PEL,
because the same background risk was factored into estimates of risk at
both levels. Furthermore, the Schubauer-Berigan et al. (2011) estimates
of excess lung cancer from exposure at the preceding PEL of 2 μg/
m3\ (ranging from 33 to 170 excess lung cancers per 1,000 workers,
depending on the model) are much higher than the level of 1 per 1,000
that OSHA finds to be clearly significant. Even at the final TWA PEL of
0.2 μg/m3\, the models demonstrate a range of risks of excess lung
cancers of 3 to 30 per 1,000 workers, estimates well above the
threshold for significant risk (see Section II, Pertinent Legal
Authority). Small variations in background risk across different
populations are highly unlikely to influence excess lung cancer risk
estimates sufficiently to influence OSHA's finding of significant risk
at the preceding TWA PEL, which is the finding OSHA relies on to
support the need for a new standard.
Finally, Dr. Boffetta noted that the models that exclude
professional and asbestos workers (the groups that Schubauer-Berigan et
al. believed could be affected by confounding from tobacco and asbestos
exposure) showed non-significant increases in lung cancer with
increasing beryllium exposure. According to Dr. Boffetta, this suggests
that confounding may contribute to the results of the models based on
the full population. He speculates that if more precise information on
confounding exposures were available, excess risk estimates might be
further reduced (Document ID 1659, p. 2).
OSHA agrees with Dr. Boffetta that there is uncertainty in the
Schubauer-Berigan et al. (2011) lung cancer risk estimates, including
uncertainty due to limited information on possible confounding from
associations between beryllium exposure level and workers' smoking
habits or occupational co-exposures. However, in the absence of
detailed smoking and co-exposure information, the models excluding
professional and asbestos workers are a reasonable approach to
addressing the possible effects of unmeasured confounding. OSHA's
decision to include these models in its preliminary and final QRAs
therefore represents the Agency's best available means of dealing with
this uncertainty.
E. Risk Assessment Conclusions
As described above, OSHA's risk assessment for beryllium
sensitization and CBD relied on two approaches: (1) Review of the
literature, and (2) analysis of a data set provided by NJH. OSHA has a
high level of confidence in its finding that the risks of sensitization
and CBD are above the benchmark of 1 in 1,000 at the preceding PEL, and
the Agency believes that a comprehensive standard requiring a
combination of more stringent controls on beryllium exposure will
reduce workers' risk of both sensitization and CBD. Programs that have
reduced median levels to below 0.1 μg/m3\ and tightly controlled
both respiratory exposure and dermal contact have substantially reduced
risk of sensitization within the first years of exposure. These
conclusions are supported by the results of several studies conducted
in facilities dealing
with a variety of production activities and physical forms of beryllium
that have reduced workers' exposures substantially by implementing
stringent exposure controls and PPE requirements since approximately
2000. In addition, these conclusions are supported by OSHA's analyses
of the NJH data set, which contains highly-detailed exposure and work
history information on several hundred beryllium workers.
Furthermore, OSHA believes that more stringent control of airborne
beryllium exposures will reduce beryllium-exposed workers' significant
risk of lung cancer. The risk estimates from the lung cancer study by
Schubauer-Berigan et al. (2011, Document ID 1265; 0521), described
above, range from 33 to 170 excess lung cancers per 1,000 workers
exposed at the preceding PEL of 2 μg/m3\, based on the study's six
best-fitting models. These models each predict substantial reductions
in risk with reduced exposure, ranging from 3 to 30 excess lung cancers
per 1,000 workers exposed at the final PEL of 0.2 μg/m3\. The
evidence of lung cancer risk from the Schubauer-Berigan et al. (2011)
risk assessment provides additional support for OSHA's conclusions
regarding the significance of risk of adverse health effects for
workers exposed to beryllium levels at and below the preceding PEL.
However, the lung cancer risks required a sizable low dose
extrapolation below beryllium exposure levels experienced by workers in
the Schubauer-Berigan et al. (2011) study. As a result, there is
greater uncertainty regarding the lung cancer risk estimates than there
is for the risk estimates for beryllium sensitization and CBD. The
conclusions with regard to significance of risk are presented and
further discussed in section VII of the preamble.
VII. Significance of Risk
In this section, OSHA discusses its findings that workers exposed
to beryllium at and below the preceding TWA PEL face a significant risk
of material impairment of health or functional capacity within the
meaning of the OSH Act, and that the new standards will substantially
reduce this risk. To make the significance of risk determination for a
new final or proposed standard, OSHA uses the best available scientific
evidence to identify material health impairments associated with
potentially hazardous occupational exposures and to evaluate exposed
workers' risk of these impairments assuming exposure over a working
lifetime. As discussed in section II, Pertinent Legal Authority, courts
have stated that OSHA should consider all forms and degrees of material
impairment--not just death or serious physical harm. To evaluate the
significance of the health risks that result from exposure to hazardous
chemical agents, OSHA relies on epidemiological, toxicological, and
experimental evidence. The Agency uses both qualitative and
quantitative methods to characterize the risk of disease resulting from
workers' exposure to a given hazard over a working lifetime (generally
45 years) at levels of exposure reflecting compliance with the
preceding standard and compliance with the new standards (see Section
II, Pertinent Legal Authority). When determining whether a significant
risk exists OSHA considers whether there is a risk of at least one-in-
a-thousand of developing a material health impairment from a working
lifetime of exposure. The Supreme Court has found that OSHA is not
required to support its finding of significant risk with scientific
certainty, but may instead rely on a body of reputable scientific
thought and may make conservative assumptions (i.e., err on the side of
protecting the worker) in its interpretation of the evidence (Section
II, Pertinent Legal Authority).
OSHA's findings in this section follow in part from the conclusions
of the preceding sections V, Health Effects, and VI, Risk Assessment.
In this preamble at section V, Health Effects, OSHA reviewed the
scientific evidence linking occupational beryllium exposure to a
variety of adverse health effects and determined that beryllium
exposure causes sensitization, CBD, and lung cancer, and is associated
with various other adverse health effects (see section V.D, V.E, and
V.F). In this preamble at section VI, Risk Assessment, OSHA found that
the available epidemiological data are sufficient to evaluate risk for
beryllium sensitization, CBD, and lung cancer among beryllium-exposed
workers. OSHA evaluated the risk of sensitization, CBD, and lung cancer
from levels of airborne beryllium exposure that were allowed under the
previous standard, as well as the expected impact of the new standards
on risk of these conditions. In this section of the preamble, OSHA
explains its determination that the risk of material impairments of
health, particularly CBD and lung cancer, from occupational exposures
allowable under the preceding TWA PEL of 2 μg/m3\ is significant,
and is substantially reduced but still significant at the new TWA PEL
of 0.2 μg/m3\. Furthermore, evidence reviewed in section VI, Risk
Assessment, shows that significant risk of CBD and lung cancer could
remain in workplaces with exposures as low as the new action level of
0.1 μg/m3\. OSHA also explains here that the new standards will
reduce the occurrence of sensitization.
In the NPRM, OSHA preliminarily determined that both CBD and lung
cancer are material impairments of health. OSHA also preliminarily
determined that a working lifetime (45 years) of exposure to airborne
beryllium at the preceding time-weighted average permissible exposure
limit (TWA PEL) of 2 μg/m3\ would pose a significant risk of both
CBD and lung cancer, and that this risk is substantially reduced but
still significant at the new TWA PEL of 0.2 μg/m3\. OSHA did not
make a preliminary determination as to whether beryllium sensitization
is a material impairment of health because, as the Agency explained in
the NPRM, it was not necessary to make such a determination. The
Agency's preliminary findings on CBD and lung cancer were sufficient to
support the promulgation of new beryllium standards.
Upon consideration of the entire rulemaking record, including the
comments and information submitted to the record in response to the
preliminary Health Effects, Risk Assessment, and Significance of Risk
analyses (NPRM Sections V, VI, and VIII), OSHA reaffirms its
preliminary findings that long-term exposure at the preceding TWA PEL
of 2 μg/m3\ poses a significant risk of material impairment of
workers' health, and that adoption of the new TWA PEL of 0.2 μg/m3\
and other provisions of the final standards will substantially reduce
this risk.
Material Impairment of Health
As discussed in Section V, Health Effects, CBD is a respiratory
disease caused by exposure to beryllium. CBD develops when the body's
immune system reacts to the presence of beryllium in the lung, causing
a progression of pathological changes including chronic inflammation
and tissue scarring. CBD can also impair other organs such as the
liver, skin, spleen, and kidneys and cause adverse health effects such
as granulomas of the skin and lymph nodes and cor pulmonale (i.e.,
enlargement of the heart) (Conradi et al., 1971 (Document ID 1319);
ACCP, 1965 (1286); Kriebel et al., 1988a (1292) and b (1473)).
In early, asymptomatic stages of CBD, small granulomatous lesions
and mild inflammation occur in the lungs. Over time, the granulomas can
spread and lead to lung fibrosis (scarring) and
moderate to severe loss of pulmonary function, with symptoms including
a persistent dry cough and shortness of breath (Saber and Dweik, 2000,
Document ID 1421). Fatigue, night sweats, chest and joint pain,
clubbing of fingers (due to impaired oxygen exchange), loss of
appetite, and unexplained weight loss may occur as the disease
progresses (Conradi et al., 1971, Document ID 1319; ACCP, 1965 (1286);
Kriebel et al., 1988 (1292); Kriebel et al., 1988 (1473)).
Dr. Lee Newman, speaking at the public hearing on behalf of the
American College of Occupational and Environmental Medicine (ACOEM),
testified on his experiences treating patients with CBD: "as a
physician who has spent most of my [practicing] career seeing patients
with exposure to beryllium, with beryllium sensitization, and with
chronic beryllium disease including those who have gone on to require
treatment and to die prematurely of this disease . . . [I've seen]
hundreds and hundreds, probably over a thousand individuals during my
career who have suffered from this condition" (Document ID 1756, Tr.
79). Dr. Newman further testified about his 30 years of experience
treating CBD in patients at various stages of the disease:
. . . some of them will go from being sensitized to developing
subclinical disease, meaning that they have no symptoms. As I
mentioned earlier, most of those will, if we actually do the tests
of their lung function and their oxygen levels in their blood, those
people are already demonstrating physiologic abnormality. They
already have disease affecting their health. They go on to develop
symptomatic disease and progress to the point where they require
treatment. And sometimes to the extent of even requiring a [lung]
transplant (Document ID 1756, Tr. 131).
Dr. Newman described one example of a patient who developed CBD
from his occupational beryllium exposure and "who went on to die
prematurely with a great deal of suffering along the way due to the
condition chronic beryllium disease" (Document ID 1756, Tr. 80).
During her testimony at the public hearing, Dr. Lisa Maier of
National Jewish Health (NJH) provided an example from her experience
with treating CBD patients. "This gentleman started to have a cough, a
dry cough in 2011 . . . His symptoms progressed and he developed
shortness of breath, wheezing, chills, night sweats, and fatigue. These
were so severe that he was eventually hospitalized" (Document ID 1756,
Tr. 105). Dr. Maier noted that this patient had no beryllium exposure
prior to 2006, and that his CBD had developed from beryllium exposure
in his job melting an aluminum alloy in a foundry casting airplane
parts (Document ID 1756, Tr. 105-106). She described how her patient
could no longer work because of his condition. "He requires oxygen and
systemic therapy . . . despite aggressive treatment [his] test findings
continue to demonstrate worsening of his disease and increased needs
for oxygen and medications as well as severe side effects from
medications. This patient may well need a lung transplant if this
disease continues to progress . . . " (Document ID 1756, Tr. 106-107).
The likelihood, speed, and severity of individuals' transition from
asymptomatic to symptomatic CBD is understood to vary widely, with some
individuals responding differently to exposure cessation and treatment
than others (Sood, 2009, Document ID 0456; Mroz et al., 2009 (1443)).
In the public hearing, Dr. Newman testified that the great majority of
individuals with very early stage CBD in a cross-sectional study he
published (Pappas and Newman, 1993) had physiologic impairment. Thus,
even before x-rays or CAT scans found evidence of CBD, the lung
functions of those individuals were abnormal (Document ID 1756, Tr.
112). Materion commented that the best available evidence on the
transition from asymptomatic to more severe CBD is a recent
longitudinal study by Mroz et al. (2009, Document ID 1443), which found
that 19.3 percent of individuals with CBD developed clinical
abnormalities requiring oral immunosuppressive therapy (Document ID
1661, pp. 5-6). The authors' overall conclusions in that study include
a finding that adverse physiological changes among initially
asymptomatic CBD patients progress over time, requiring many
individuals to be treated with corticosteroids, and that the patients'
levels of beryllium exposure may affect progression (Mroz et al.,
2009). Dr. Maier, a co-author of the study, testified that studies
"indicate that higher levels of exposure not only are risk factors for
[developing CBD in general] but also for more severe [CBD] (Document ID
1756, Tr. 111).\24\
---------------------------------------------------------------------------
\24\ The study by Mroz et al. (2009, Document ID 1443) included
all individuals who were clinically evaluated at NJH between 1982
and 2002 and were found to have CBD on baseline clinical evaluation.
All cohort members were identified by abnormal BeLPTs before
identification of symptoms, physiologic abnormalities, or
radiographic changes. All members were offered evaluation for
clinical abnormalities every 2 years through 2002, including
pulmonary function testing, exercise testing, chest radiograph with
International Labor Organization (ILO) B-reading, fiberoptic
bronchoscopy with bronchoalveolar lavage (BAL), and transbronchial
lung biopsies. Of 171 CBD cases, 33 (19.3%) developed clinical
abnormalities requiring oral immunosuppressive therapy, at an
average of 1.4 years after the initial diagnosis of CBD. To examine
the effect of beryllium exposure level on the progression of CBD,
Mroz et al. compared clinical manifestations of CBD among machinists
(the group of patients likely to have had the highest beryllium
exposures) to non- machinists, including only CBD patients who had
never smoked. Longitudinal analyses showed significant declines in
some clinical indicators over time since first exposure for
machinists (p <0.01) as well as faster development of illness (p <
0.05), compared to a control group of non-machinists.
---------------------------------------------------------------------------
Treatment of CBD using inhaled and systemic steroid therapy has
been shown to ease symptoms and slow or prevent some aspects of disease
progression. As explained below, these treatments can be most
effectively applied when CBD is diagnosed prior to development of
symptoms. In addition, the forms of treatment that can be used to
manage early-stage CBD have relatively minor side effects on patients,
while systemic steroid treatments required to treat later-stage CBD
often cause severe side effects.
In the public hearing, Dr. Newman and Dr. Maier testified about
their experiences treating patients with CBD at various stages of the
disease. Dr. Newman stated that patients' outcomes depend greatly on
how early they are diagnosed. "So there are those people who are
diagnosed very late in the course of disease where there's little that
we can do to intervene and they are going to die prematurely. There are
those people who may be detected with milder disease where there are
opportunities to intervene" (Document ID 1756, Tr. 132). Both Dr.
Maier and Dr. Newman emphasized the importance of early detection and
diagnosis, stating that removing the patient from exposure and
providing treatment early in the course of the disease can slow or even
halt progression of the disease (Document ID 1756, Tr. 111, 132).
Dr. Maier testified that inhaled steroids can be used to treat
relatively mild symptoms that may occur in early stages of the disease,
such as a cough during exercise (Document ID 1756, Tr. 139). Inhaled
steroids, she stated, are commonly used to treat other health
conditions and have fewer and milder side effects than forms of steroid
treatment that are used to treat more severe forms of CBD (Document ID
1756, Tr. 140). Early detection of CBD helps physicians to properly
treat early-onset symptoms, since appropriate forms of treatment for
early stage CBD can differ from treatments for conditions it is
commonly mistaken for, such as chronic obstructive pulmonary disease
(COPD) and asthma (Document ID 1756, Tr. 140-141).
CBD in later stages is often managed using systemic steroid
treatments such as corticosteroids. In workers with CBD whose beryllium
exposure has ceased, corticosteroid therapy has been shown to control
inflammation, ease symptoms (e.g., difficulty breathing, fever, cough,
and weight loss), and in some cases prevent the development of fibrosis
(Marchand-Adam et al., 2008, Document ID 0370). Thus, although there is
no cure for CBD, properly-timed treatment can lead to CBD regression in
some patients (Sood, 2004, Document ID 1331). Other patients have shown
short-term improvements from corticosteroid treatment, but then
developed serious fibrotic lesions (Marchand-Adam et al., 2008). Ms.
Peggy Mroz, of NJH, discussed the results of the Marchand-Adam et al.
study in the hearing, stating that treatment of CBD using steroids has
been most successful when treatment begins prior to the development of
lung fibrosis (Document ID 1756, Tr. 113). Once fibrosis has developed
in the lungs, corticosteroid treatment cannot reverse the damage (Sood,
2009, Document ID 0456). Persons with late-stage CBD experience severe
respiratory insufficiency and may require supplemental oxygen (Rossman,
1991, Document 1332). Historically, late-stage CBD often ended in death
(NAS, 2008, Document ID 1355). While the use of steroid treatments can
help to reduce the effects of CBD, OSHA is not aware of any studies
showing the effect of these treatments on the frequency of premature
death among patients with CBD.
Treatment with corticosteroids has severe side effects
(Trikudanathan and McMahon, 2008, Document ID 0366; Lipworth, 1999
(0371); Gibson et al., 1996 (1521); Zaki et al., 1987 (1374)). Adverse
effects associated with long-term corticosteroid use include, but are
not limited to: increased risk of opportunistic infections (Lionakis
and Kontoyiannis, 2003, Document ID 0372; Trikudanathan and McMahon,
2008 (0366)); accelerated bone loss or osteoporosis leading to
increased risk of fractures or breaks (Hamida et al., 2011, Document ID
0374; Lehouck et al., 2011 (0355); Silva et al., 2011 (0388); Sweiss et
al., 2011 (0367); Langhammer et al., 2009 (0373)); psychiatric effects
including depression, sleep disturbances, and psychosis (Warrington and
Bostwick, 2006, Document ID 0365; Brown, 2009 (0377)); adrenal
suppression (Lipworth, 1999, Document ID 0371; Frauman, 1996 (0356));
ocular effects including cataracts, ocular hypertension, and glaucoma
(Ballonzoli and Bourcier, 2010, Document ID 0391; Trikudanathan and
McMahon, 2008 (0366); Lipworth, 1999 (0371)); an increase in glucose
intolerance (Trikudanathan and McMahon, 2008, Document ID 0366);
excessive weight gain (McDonough et al., 2008, Document ID 0369; Torres
and Nowson, 2007 (0387); Dallman et al., 2007 (0357); Wolf, 2002
(0354); Cheskin et al., 1999 (0358)); increased risk of atherosclerosis
and other cardiovascular syndromes (Franchimont et al., 2002, Document
ID 0376); skin fragility (Lipworth, 1999, Document ID 0371); and poor
wound healing (de Silva and Fellows, 2010, Document ID 0390).
Based on the above, OSHA considers late-stage CBD to be a material
impairment of health, as it involves permanent damage to the pulmonary
system, causes additional serious adverse health effects, can have
adverse occupational and social consequences, requires treatment that
can cause severe and lasting side effects, and may in some cases cause
premature death.
Furthermore, OSHA has determined that early-stage CBD, an
asymptomatic period during which small lesions and inflammation appear
in the lungs, is also a material impairment of health. OSHA bases this
conclusion on evidence and expert testimony that early-stage CBD is a
measurable change in an individual's state of health that, with and
sometimes without continued exposure, can progress to symptomatic
disease (e.g., Mroz et al., 2009 (1443); 1756, Tr. 131). Thus,
prevention of the earliest stages of CBD will prevent development of
more serious disease. In OSHA's Lead standard, promulgated in 1978, the
Agency stated its position that a "subclinical" health effect may be
regarded as a material impairment of health. In the preamble to that
standard, the Agency said:
OSHA believes that while incapacitating illness and death
represent one extreme of a spectrum of responses, other biological
effects such as metabolic or physiological changes are precursors or
sentinels of disease which should be prevented. . . . Rather than
revealing the beginnings of illness the standard must be selected to
prevent an earlier point of measurable change in the state of health
which is the first significant indicator of possibly more severe ill
health in the future. The basis for this decision is twofold--first,
pathophysiologic changes are early stages in the disease process
which would grow worse with continued exposure and which may include
early effects which even at early stages are irreversible, and
therefore represent material impairment themselves. Secondly,
prevention of pathophysiologic changes will prevent the onset of the
more serious, irreversible and debilitating manifestations of
disease (43 FR 52952, 52954).
Since the Lead rulemaking, OSHA has also found other non-
symptomatic (or sub-clinical) health conditions to be material
impairments of health. In the Bloodborne Pathogens rulemaking, OSHA
maintained that material impairment includes not only workers with
clinically "active" hepatitis from the hepatitis B virus (HBV) but
also includes asymptomatic HBV "carriers" who remain infectious and
are able to put others at risk of serious disease through contact with
body fluids (e.g., blood, sexual contact) (56 FR 64004). OSHA stated:
"Becoming a carrier [of HBV] is a material impairment of health even
though the carrier may have no symptoms. This is because the carrier
will remain infectious, probably for the rest of his or her life, and
any person who is not immune to HBV who comes in contact with the
carrier's blood or certain other body fluids will be at risk of
becoming infected" (56 FR 64004, 64036).
OSHA finds that early-stage CBD is the type of asymptomatic health
effect the Agency determined to be a material impairment of health in
the Lead and Bloodborne Pathogens standards. Early stage CBD involves
lung tissue inflammation without symptoms that can worsen with--or
without--continued exposure. The lung pathology progresses over time
from a chronic inflammatory response to tissue scarring and fibrosis
accompanied by moderate to severe loss in pulmonary function. Early
stage CBD is clearly a precursor of advanced clinical disease,
prevention of which will prevent symptomatic disease. OSHA determined
in the Lead standard that such precursor effects should be considered
material health impairments in their own right, and that the Agency
should act to prevent them when it is feasible to do so. Therefore,
OSHA finds all stages of CBD to be material impairments of health
within the meaning of section 6(b)(5) of the OSH Act (29 U.S.C.
655(b)(5)).
In reviewing OSHA's Lead standard in United Steelworkers of
America, AFL-CIO v. Marshall, 647 F.2d 1189, 1252 (D.C. Cir. 1980)
(Lead I), the D.C. Circuit affirmed that the OSH Act "empowers OSHA to
set a PEL that prevents the subclinical effects of lead that lie on a
continuum shared with overt lead disease." See also AFL-CIO v.
Marshall, 617 F.2d 636, 654 n.83 (D.C. Cir. 1979) (upholding OSHA's
authority to prevent early symptoms of a disease, even if the effects
of the disease are, at that point, reversible). According to the Court,
OSHA only had to demonstrate,
on the basis of substantial evidence, that preventing the subclinical
effects would help prevent the clinical phase of disease (United
Steelworkers of America, AFL-CIO, 647 F.2d at 1252). Thus, OSHA has the
authority to regulate to prevent asymptomatic CBD whether or not it is
properly labeled as a material impairment of health.
OSHA has also determined that exposure to beryllium can cause
beryllium sensitization. Sensitization is a precursor to development of
CBD and an essential step for development of the disease. As discussed
in Section V, Health Effects, only sensitized individuals can develop
CBD (NAS, 2008, Document ID 1355).\25\ As explained above, OSHA has the
authority to promulgate regulations designed to prevent precursors to
material impairments of health. Therefore, OSHA's new beryllium
standards aim to prevent sensitization as well as the development of
CBD and lung cancer. OSHA's risk assessment for sensitization,
presented in section VI, informs the Agency's understanding of what
exposure control measures have been successful in preventing
sensitization, which in turn prevents development of CBD. Therefore,
OSHA addresses sensitization in this section on significance of risk.
---------------------------------------------------------------------------
\25\ In the NPRM, OSHA took no position on whether beryllium
sensitization by itself is a material impairment of health, stating
it was unnecessary to do so as part of this rulemaking. The only
comment on this issue came from Materion, which argued that "BeS
does not constitute a material impairment of health or functional
capacity" (document ID 1958). Because BeS is also a precursor to
CBD, OSHA finds it unnecessary to resolve this issue here.
---------------------------------------------------------------------------
Risk Assessment
As discussed in Section VI, Risk Assessment, the risk assessment
for beryllium sensitization and CBD relied on two approaches: (1)
OSHA's review of epidemiological studies of sensitization and CBD that
contain information on exposures in the range of interest to OSHA (2
μg/m3\ and below), and (2) OSHA's analysis of a NJH data set on
sensitization and CBD in a group of beryllium-exposed machinists in
Cullman, AL.
OSHA's review of the literature includes studies of beryllium-
exposed workers at a Tucson, AZ ceramics plant (Kreiss et al., 1996,
Document ID 1477; Henneberger et al., 2001 (1313); Cummings et al.,
2007 (1369)); a Reading, PA copper-beryllium processing plant (Schuler
et al., 2005, Document ID 0919; Thomas et al., 2009 (0590)); a Cullman,
AL beryllium machining plant (Newman et al., 2001, Document ID 1354;
Kelleher et al., 2001 (1363); Madl et al., 2007 (1056)); an Elmore, OH
metal, alloy, and oxide production plant (Kreiss et al., 1993 Document
ID 1478; Bailey et al., 2010 (0676); Schuler et al., 2012 (0473));
aluminum smelting facilities (Taiwo et al. 2008, Document ID 0621; 2010
(0583); Nilsen et al., 2010 (0460)); and nuclear facilities (Viet et
al., 2000, Document ID 1344; Arjomandi et al., 2010 (1275)).
The published literature on beryllium sensitization and CBD
discussed in section VI shows that the risk of both can be significant
in workplaces where exposures are at or below OSHA's preceding PEL of 2
μg/m3\ (e.g., Kreiss et al., 1996, Document ID 1477; Henneberger et
al., 2001 (1313); Newman et al., 2001 (1354); Schuler et al., 2005
(0919), 2012 (0473); Madl et al., 2007 (1056)). For example, in the
Tucson ceramics plant mentioned above, Kreiss et al. (1996) reported
that eight (5.9 percent) \26\ of the 136 workers tested in 1992 were
sensitized, six (4.4 percent) of whom were diagnosed with CBD. In
addition, of 77 Tucson workers hired prior to 1992 who were tested in
1998, eight (10.4 percent) were sensitized and seven of these (9.7
percent) were diagnosed with CBD (Henneberger et al., 2001, Document ID
1313). Full-shift area samples showed most airborne beryllium levels
below the preceding PEL: 76 percent of area samples collected between
1983 and 1992 were at or below 0.1 μg/m3\ and less than 1 percent
exceeded 2 μg/m3\; short-term breathing zone measurements collected
between 1981 and 1992 had a median of 0.3 μg/m3\; and personal
lapel samples collected at the plant beginning in 1991 had a median of
0.2 μg/m3\ (Kreiss et al., 1996).
---------------------------------------------------------------------------
\26\ Although OSHA reports percentages to indicate the risks of
sensitization and CBD in this section, the benchmark OSHA typically
uses to demonstrate significant risk, as discussed earlier, is
greater than or equal to 1 in 1,000 workers. One in 1,000 workers is
equivalent to 0.1 percent. Therefore, any value of 0.1 percent or
higher when reporting occurrence of a health effect is considered by
OSHA to indicate a significant risk.
---------------------------------------------------------------------------
Results from the Elmore, OH beryllium metal, alloy, and oxide
production plant and the Cullman, AL machining facility also showed
significant risk of sensitization and CBD among workers with exposures
below the preceding TWA PEL. Schuler et al. (2012, Document ID 0473)
found 17 cases of sensitization (8.6 percent) among Elmore, OH workers
within the first three quartiles of LTW average exposure (198 workers
with LTW average total mass exposures lower than 1.1 μg/m3\) and 4
cases of CBD (2.2 percent) within those quartiles of LTW average
exposure (183 workers with LTW average total mass exposures lower than
1.07 μg/m3\; note that follow-up time of up to 6 years for all
study participants was very short for development of CBD). At the
Cullman, AL machining facility, Newman et al. (2001, Document ID 1354)
reported 22 (9.4 percent) sensitized workers among 235 tested in 1995-
1999, 13 of whom were diagnosed with CBD within the study period.
Personal lapel samples collected between 1980 and 1999 indicate that
median exposures were generally well below the preceding PEL (<=0.35
μg/m3\ in all job titles except maintenance (median 3.1 μg/m3\
during 1980-1995) and gas bearings (1.05 μg/m3\ during 1980-1995)).
Although risk will be reduced by compliance with the new TWA PEL,
evidence in the epidemiological studies reviewed in section VI, Risk
Assessment, shows that significant risk of sensitization and CBD could
remain in workplaces with exposures as low as the new action level of
0.1 μg/m3\. For example, Schuler et al. (2005, Document ID 0919)
reported substantial prevalences of sensitization (6.5 percent) and CBD
(3.9 percent) among 152 workers at the Reading, PA facility screened
with the BeLPT in 2000. These results showed significant risk at this
facility, even though airborne exposures were primarily below both the
preceding and final TWA PELs due to the low percentage of beryllium in
the metal alloys used (median general area samples <=0.1 μg/m3\,
97% < 0.5 μg/m3\; 93% of personal lapel samples below the new TWA
PEL of 0.2 μg/m3\). The only group of workers with no cases of
sensitization or CBD, a group of 26 office administration workers, was
the group with exposures below the new action level of 0.1 μg/m3\
(median personal sample 0.01 μg/m3\, range <0.01-0.06 μg/m3\)
(Schuler et al., 2005). The Schuler et al. (2012, Document ID 0473)
study of short-term workers in the Elmore, OH facility found three
cases (4.6%) of sensitization among 66 workers with total mass LTW
average exposures below 0.1 μg/m3\. All three of these sensitized
workers had LTW average exposures of approximately 0.09 μg/m3\.
Furthermore, cases of sensitization and CBD continued to arise in
the Cullman, AL machining plant after control measures implemented
beginning in 1995 brought median airborne exposures below 0.2 μg/
m3\ (personal lapel samples between 1996 and 1999 in machining jobs
had a median of 0.16 μg/m3\ and the median was 0.08 μg/m3\ in
non-machining jobs)
(Madl et al., 2007, Document ID 1056, Table IV). At the time that
Newman et al. (2001, Document ID 1354) reviewed the results of BeLPT
screenings conducted in 1995-1999, a subset of 60 workers had been
employed at the plant for less than a year and had therefore benefitted
to some extent from the exposure reductions. Four (6.7 percent) of
these workers were found to be sensitized, of whom two were diagnosed
with CBD and one with probable CBD (Newman et al., 2001). A later study
by Madl. et al. (2007, Document ID 1056) reported seven sensitized
workers who had been hired between 1995 and 1999, of whom four had
developed CBD as of 2005 (Table II; total number of workers hired
between 1995 and 1999 not reported).
The enhanced industrial hygiene programs that have proven effective
in several facilities demonstrate the importance of minimizing both
airborne exposure and dermal contact to effectively reduce risk of
sensitization and CBD. Exposure control programs that have used a
combination of engineering controls, PPE, and stringent housekeeping
measures to reduce workers' airborne exposure and dermal contact have
substantially lowered risk of sensitization among newly-hired
workers.\27\ Of 97 workers hired between 2000 and 2004 in the Tucson,
AZ plant after the introduction of a comprehensive program which
included the use of respiratory protection (1999) and latex gloves
(2000), one case of sensitization was identified (1 percent) (Cummings
et al., 2007, Document ID 1369). In Elmore, OH, where all workers were
required to wear respirators and skin PPE in production areas beginning
in 2000-2001, the estimated prevalence of sensitization among workers
hired after these measures were put in place was around 2 percent
(Bailey et al., 2010, Document ID 0676). In the Reading, PA facility,
after workers' exposures were reduced to below 0.1 μg/m3\ and PPE
to prevent dermal contact was instituted, only one (2.2 percent) of 45
workers hired was sensitized (Thomas et al. 2009, Document ID 0590).
And, in the aluminum smelters discussed by Taiwo et al. (2008, Document
ID 0621), where available exposure samples from four plants indicated
median beryllium levels of about 0.1 μg/m3\ or below (measured as
an 8-hour TWA) and workers used respiratory and dermal protection,
confirmed cases of sensitization were rare (zero or one case per
location).
---------------------------------------------------------------------------
\27\ As discussed in Section V, Health Effects, beryllium
sensitization can occur from dermal contact with beryllium.
---------------------------------------------------------------------------
OSHA notes that the studies on recent programs to reduce workers'
risk of sensitization and CBD were conducted on populations with very
short exposure and follow-up time. Therefore, they could not adequately
address the question of how frequently workers who become sensitized in
environments with extremely low airborne exposures (median <0.1 μg/
m3\) develop CBD. Clinical evaluation for CBD was not reported for
sensitized workers identified in the studies examining the post-2000
worker cohorts with very low exposures in Tucson, Reading, and Elmore
(Cummings et al. 2007, Document ID 1369; Thomas et al. 2009, (0590);
Bailey et al. 2010, (0676)). In Cullman, however, two of the workers
with CBD had been employed for less than a year and worked in jobs with
very low exposures (median 8-hour personal sample values of 0.03-0.09
μg/m3\) (Madl et al., 2007, Document ID 1056, Table III). The body
of scientific literature on occupational beryllium disease also
includes case reports of workers with CBD who are known or believed to
have experienced minimal beryllium exposure, such as a worker employed
only in shipping at a copper-beryllium distribution center (Stanton et
al., 2006, Document ID 1070), and workers employed only in
administration at a beryllium ceramics facility (Kreiss et al., 1996,
Document ID 1477). Therefore, there is some evidence that cases of CBD
can occur in work environments where beryllium exposures are quite low.
In summary, the epidemiological literature on beryllium
sensitization and CBD that OSHA's risk assessment relied on show
sufficient occurrence of sensitization and CBD to be considered
significant within the meaning of the OSH Act. These demonstrated risks
are far in excess of 1 in 1,000 among workers who had full-shift
exposures well below the preceding TWA PEL of 2 μg/m3\ and workers
who had median full-shift exposures down to the new action level of 0.1
μg/m3\. These health effects occurred among populations of workers
whose follow-up time was much less than 45 years. As stated earlier,
OSHA is interested in the risk associated with a 45-year (i.e., working
lifetime) exposure. Because CBD often develops over the course of years
following sensitization, the risk of CBD that would result from 45
years of occupational exposure to airborne beryllium is likely to be
higher than the prevalence of CBD observed among these workers.\28\ In
either case, based on these studies, the risks to workers from long-
term exposure at the preceding TWA PEL and below are clearly
significant. OSHA's review of epidemiological studies further showed
that worker protection programs that effectively reduced the risk of
beryllium sensitization and CBD incorporated engineering controls, work
practice controls, and personal protective equipment (PPE) that reduce
workers' airborne beryllium exposure and dermal contact with beryllium.
OSHA has therefore determined that an effective worker protection
program should incorporate both airborne exposure reduction and dermal
protection provisions.
---------------------------------------------------------------------------
\28\ This point was emphasized by members of the scientific peer
review panel for OSHA's Preliminary Risk Assessment (see the NPRM
preamble at section VII).
---------------------------------------------------------------------------
OSHA's conclusions on significance of risk at the final PEL and
action level are further supported by its analysis of the data set
provided to OSHA by NJH from which OSHA derived additional information
on sensitization and CBD at exposure levels of interest. The data set
describes a population of 319 beryllium-exposed workers at a Cullman,
AL machining facility. It includes exposure samples collected between
1980 and 2005, and has updated work history and screening information
through 2003. Seven (2.2 percent) workers in the data set were reported
as sensitized only. Sixteen (5.0 percent) workers were listed as
sensitized and diagnosed with CBD upon initial clinical evaluation.
Three (0.9 percent) workers, first shown to be sensitized only, were
later diagnosed with CBD. The data set includes workers exposed at
airborne beryllium levels near the new TWA PEL of 0.2 μg/m3\, and
extensive exposure data collected in workers' breathing zones, as is
preferred by OSHA. Unlike the Tucson, Reading, and Elmore facilities
after 2000, respirator use was not generally required for workers at
the Cullman facility. Thus, analysis of this data set shows the risk
associated with varying levels of airborne exposure rather than
estimating exposure accounting for respirators. Also unlike the Tucson,
Elmore, and Reading facilities, glove use was not reported to be
mandatory in the Cullman facility. Therefore, OSHA believes reductions
in risk at the Cullman facility to be the result of airborne exposure
control, rather than the combination of airborne and dermal exposure
controls used at other facilities.
OSHA analyzed the prevalence of beryllium sensitization and CBD
among
workers at the Cullman facility who were exposed to airborne beryllium
levels at and below the preceding TWA PEL of 2 μg/m3\. In addition,
a statistical modeling analysis of the NJH Cullman data set was
conducted under contract with Dr. Roslyn Stone of the University of
Pittsburgh Graduate School of Public Heath, Department of
Biostatistics. OSHA summarizes these analyses briefly below, and in
more detail in section VI, Risk Assessment and in the background
document (Risk Analysis of the NJH Data Set from the Beryllium
Machining Facility in Cullman, Alabama--CBD and Sensitization, OSHA,
2016).
Tables VII-1 and VII-2 below present the prevalence of
sensitization and CBD cases across several categories of lifetime-
weighted (LTW) average and highest-exposed job (HEJ) exposure at the
Cullman facility. The HEJ exposure is the exposure level associated
with the highest-exposure job and time period experienced by each
worker. The columns "Total" and "Total percent" refer to all
sensitized workers in the data set, including workers with and without
a diagnosis of CBD.
Table VII-1--Prevalence of Sensitization and CBD by LTW Average Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized
LTW average exposure (μg/m3\) Group size only CBD Total Total (%) CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.080............................................... 91 1 1 2 2.2 1.0
0.081-0.18.............................................. 73 2 4 6 8.2 5.5
0.19-0.51............................................... 77 0 6 6 7.8 7.8
0.51-2.15............................................... 78 4 8 12 15.4 10.3
-----------------------------------------------------------------------------------------------
Total............................................... 319 7 19 26 8.2 6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.
Table VII-2--Prevalence of Sensitization and CBD by Highest-Exposed Job Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized
HEJ exposure (μg/m3\) Group size only CBD Total Total (%) CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.086............................................... 86 1 0 1 1.2 0.0
0.091-0.214............................................. 81 1 6 7 8.6 7.4
0.387-0.691............................................. 76 2 9 11 14.5 11.8
0.954-2.213............................................. 76 3 4 7 9.2 5.3
-----------------------------------------------------------------------------------------------
Total............................................... 319 7 19 26 8.2 6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.
The preceding PEL of 2 μg/m3\ is close to the upper bound of
the highest quartile of LTW average (0.51-2.15 μg/m3\) and HEJ
(0.954-2.213 μg/m3\) exposure levels. In the highest quartile of
LTW average exposure, there were 12 cases of sensitization (15.4
percent), including eight (10.3 percent) diagnosed with CBD. Notably,
the Cullman workers had been exposed to beryllium dust for considerably
less than 45 years at the time of testing. A high prevalence of
sensitization (9.2 percent) and CBD (5.3 percent) is seen in the top
quartile of HEJ exposure as well, with even higher prevalences in the
third quartile (0.387-0.691 μg/m3\).\29\
---------------------------------------------------------------------------
\29\ This exposure-response pattern, wherein higher rates of
response are seen in workers with lower exposures, is sometimes
attributed to a "healthy worker effect" or to exposure
misclassification, as discussed in this preamble at section VI, Risk
Assessment.
---------------------------------------------------------------------------
The new TWA PEL of 0.2 μg/m3\ is close to the upper bound of
the second quartile of LTW average (0.81-0.18 μg/m3\) and HEJ
(0.091-0.214 μg/m3\) exposure levels and to the lower bound of the
third quartile of LTW average (0.19-0.50 μg/m3\) exposures. The
second quartile of LTW average exposure shows a high prevalence of
beryllium-related health effects, with six workers sensitized (8.2
percent), of whom four (5.5 percent) were diagnosed with CBD. The
second quartile of HEJ exposure also shows a high prevalence of
beryllium-related health effects, with seven workers sensitized (8.6
percent), of whom six (7.4 percent) were diagnosed with CBD. Among six
sensitized workers in the third quartile of LTW average exposures, all
were diagnosed with CBD (7.8 percent). The prevalence of CBD among
workers in these quartiles was approximately 5-8 percent, and overall
sensitization (including workers with and without CBD) was about 8-9
percent. OSHA considers these rates to be evidence that the risks of
developing sensitization and CBD are significant among workers exposed
at and below the preceding TWA PEL, and even below the new TWA PEL.
These risks are much higher than the benchmark for significant risk of
1 in 1,000. Much lower prevalences of sensitization and CBD were found
among workers with exposure levels less than or equal to about 0.08
μg/m3\, although these risks are still significant. Two sensitized
workers (2.2 percent), including one case of CBD (1.0 percent), were
found among workers with LTW average exposure levels less than or equal
to 0.08 μg/m3\. One case of sensitization (1.2 percent) and no
cases of CBD were found among workers with HEJ exposures of at most
0.086 μg/m3\. Strict control of airborne exposure to levels below
0.1 μg/m3\ using engineering and work practice controls can,
therefore, substantially reduce risk of sensitization and CBD. Although
OSHA recognizes that maintaining exposure levels below 0.1 μg/m3\
may not be feasible in some operations (see this preamble at section
VIII, Summary of the Economic Analysis and Regulatory Flexibility
Analysis), the Agency finds that workers in facilities that meet the
action level of 0.1 μg/m3\ will face lower risks of sensitization
and CBD than workers in facilities that cannot meet the action level.
Table VII-3 below presents the prevalence of sensitization and CBD
cases across cumulative exposure quartiles, based on the same Cullman
data used to derive Tables 1 and 2. Cumulative exposure is the sum of a
worker's exposure across the duration of his or her employment.
Table VII-3--Prevalence of Sensitization and CBD by Cumulative Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sensitized
Cumulative exposure (μg/m3\-yrs) Group size only CBD Total Total % CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.147............................................... 81 2 2 4 4.9 2.5
0.148-1.467............................................. 79 0 2 2 2.5 2.5
1.468-7.008............................................. 79 3 8 11 13.9 8.0
7.009-61.86............................................. 80 2 7 9 11.3 8.8
-----------------------------------------------------------------------------------------------
Total............................................... 319 7 19 26 8.2 6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.
A 45-year working lifetime of occupational exposure at the
preceding PEL would result in 90 μg/m3\-years of exposure, a value
far higher than the cumulative exposures of workers in this data set,
who worked for periods of time less than 45 years and whose exposure
levels were mostly well below the previous PEL. Workers with 45 years
of exposure to the new TWA PEL of 0.2 μg/m3\ would have a
cumulative exposure (9 μg/m3\-years) in the highest quartile for
this worker population. As with the average and HEJ exposures, the
greatest risk of sensitization and CBD appears at the higher exposure
levels (<1.467 μg/m3\-years). The third cumulative quartile, at
which a sharp increase in sensitization and CBD appears, is bounded by
1.468 and 7.008 μg/m3\-years. This is equivalent to 0.73-3.50 years
of exposure at the preceding PEL of 2 μg/m3\, or 7.34-35.04 years
of exposure at the new TWA PEL of 0.2 μg/m3\. Prevalence of both
sensitization and CBD is substantially lower in the second cumulative
quartile (0.148-1.467 μg/m3\-years). This is equivalent to
approximately 0.7 to 7 years at the new TWA PEL of 0.2 μg/m3\, or
1.5 to 15 years at the action level of 0.1 μg/m3\. Risks at all
levels of cumulative exposure presented in Table 3 are significant.
These findings support OSHA's determination that maintaining exposure
levels below the new TWA PEL will help to protect workers against risk
of beryllium sensitization and CBD. Moreover, while OSHA finds that
significant risk remains at the PEL, OSHA's analysis shows that further
reductions of risk will ensue if employers are able to reduce exposure
to the action level or even below.
Lung Cancer
Lung cancer, a frequently fatal disease, is a well-recognized
material impairment of health. OSHA has determined that beryllium
causes lung cancer based on an extensive review of the scientific
literature regarding beryllium and cancer. This review included an
evaluation of the human epidemiological, animal cancer, and mechanistic
studies described in section V, Health Effects. OSHA's conclusion that
beryllium is carcinogenic is supported by the findings of expert public
health and governmental organizations such as the International Agency
for Research on Cancer (IARC), which has determined beryllium and its
compounds to be carcinogenic to humans (Group 1 category) (IARC, 2012,
Document ID 0650); the National Toxicology Program (NTP), which
classifies beryllium and its compounds as known carcinogens (NTP, 2014,
Document ID 0389); and the Environmental Protection Agency (EPA), which
considers beryllium to be a probable human carcinogen (EPA, 1998,
Document ID 0661).
OSHA's review of epidemiological studies of lung cancer mortality
among beryllium workers found that most of them did not characterize
exposure levels sufficiently to evaluate the risk of lung cancer at the
preceding and new TWA PELs. However, as discussed in this preamble at
section V, Health Effects and section VI, Risk Assessment, Schubauer-
Berigan et al. published a quantitative risk assessment based on
beryllium exposure and lung cancer mortality among 5,436 male workers
first employed at beryllium processing plants in Reading, PA, Elmore,
OH, and Hazleton, PA, prior to 1970 (Schubauer-Berigan et al., 2011,
Document ID 1265). This risk assessment addresses important sources of
uncertainty for previous lung cancer analyses, including the sole prior
exposure-response analysis for beryllium and lung cancer, conducted by
Sanderson et al. (2001) on workers from the Reading plant alone.
Workers from the Elmore and Hazleton plants who were added to the
analysis by Schubauer-Berigan et al. were, in general, exposed to lower
levels of beryllium than those at the Reading plant. The median worker
from Hazleton had a LTW average exposure of less than 1.5 μg/m3\,
while the median worker from Elmore had a LTW average exposure of less
than 1 μg/m3\. The Elmore and Hazleton worker populations also had
fewer short-term workers than the Reading population. Finally, the
updated cohorts followed the worker populations through 2005,
increasing the length of follow-up time compared to the previous
exposure-response analysis. For these reasons, OSHA based the
preliminary risk assessment for lung cancer on the Schubauer-Berigan
risk analysis.
Schubauer-Berigan et al. (2011, Document ID 1265) analyzed the data
set using a variety of exposure-response modeling approaches, described
in this preamble at section VI, Risk Assessment. The authors found that
lung cancer mortality risk was strongly and significantly correlated
with mean, cumulative, and maximum measures of workers' exposure to
beryllium (all of the models reported in the study). They selected the
best-fitting models to generate risk estimates for male workers with a
mean exposure of 0.5 μg/m3\ (the current NIOSH Recommended Exposure
Limit for beryllium). In addition, they estimated the daily weighted
average exposure that would be associated with an excess lung cancer
mortality risk of one in one thousand (.005 μg/m3\ to .07 μg/
m3\ depending on model choice). At OSHA's request, the authors also
estimated excess lifetime risks for workers with mean exposures at the
preceding TWA PEL of 2 μg/m3\ as well as at each of the alternate
TWA PELs that were under consideration: 1 μg/m3\, 0.2 μg/m3\,
and 0.1 μg/m3\. Table VII-4 presents the estimated excess risk of
lung cancer mortality associated with various levels of beryllium
exposure, based on the final models presented in Schubauer-Berigan et
al's risk assessment.\30\
---------------------------------------------------------------------------
\30\ The estimates for lung cancer represent "excess" risks in
the sense that they reflect the risk of dying from lung cancer over
and above the risk of dying from lung cancer faced by those who are
not occupationally exposed to beryllium.
Table VII-4--Excess Risk of Lung Cancer Mortality per 1,000 Male Workers at Alternate PELs (based on Schubauer-
Berigan et al., 2011)
----------------------------------------------------------------------------------------------------------------
Mean exposure
Exposure-response model -------------------------------------------------------------------------------
0.1 μg/m3\ 0.2 μg/m3\ 0.5 μg/m3\ 1 μg/m3\ 2 μg/m3\
----------------------------------------------------------------------------------------------------------------
Best monotonic PWL-all workers.. 7.3 15 45 120 140
Best monotonic PWL--excluding 3.1 6.4 17 39 61
professional and asbestos
workers........................
Best categorical--all workers... 4.4 9 25 59 170
Best categorical--excluding 1.4 2.7 7.1 15 33
professional and asbestos
workers........................
Power model--all workers........ 12 19 30 40 52
Power model--excluding 19 30 49 68 90
professional and asbestos
workers........................
----------------------------------------------------------------------------------------------------------------
Source: Schubauer-Berigan, Document ID 0521, pp. 6-10.
The lowest estimate of excess lung cancer deaths from the six final
models presented by Schubauer-Berigan et al. is 33 per 1,000 workers
exposed at a mean level of 2 μg/m3\, the preceding TWA PEL. Risk
estimates as high as 170 lung cancer deaths per 1,000 result from the
other five models presented. Regardless of the model chosen, the excess
risk of about 33 to 170 per 1,000 workers is clearly significant,
falling well above the level of risk the Supreme Court indicated a
reasonable person might consider acceptable (see Benzene, 448 U.S. at
655). The new PEL of 0.2 μg/m3\ is expected to reduce these risks
significantly, to somewhere between 2.7 and 30 excess lung cancer
deaths per 1,000 workers. At the new action level of 0.1 μg/m3\,
risk falls within the range of 1.4 to 19 excess lung cancer deaths.
These risk estimates still fall above the threshold of 1 in 1,000 that
OSHA considers clearly significant. However, the Agency believes the
lung cancer risks should be regarded as less certain than the risk
estimates for CBD and sensitization discussed previously. While the
risk estimates for CBD and sensitization at the preceding and new TWA
PELs were determined from exposure levels observed in occupational
studies, the lung cancer risks were extrapolated from much higher
exposure levels.
Conclusions
As discussed throughout this section, OSHA used the best available
scientific evidence to identify adverse health effects of occupational
beryllium exposure, and to evaluate exposed workers' risk of these
impairments. The Agency reviewed extensive epidemiological and
experimental research pertaining to adverse health effects of
occupational beryllium exposure, including lung cancer, CBD, and
beryllium sensitization, and has evaluated the risk of these effects
from exposures allowed under the preceding and new TWA PELs. The Agency
has, additionally, reviewed the medical literature, as well as previous
policy determinations and case law regarding material impairment of
health, and has determined that CBD, at all stages, and lung cancer
constitute material health impairments.
OSHA has determined that long-term exposure to beryllium at the
preceding TWA PEL would pose a risk of CBD and lung cancer greater than
the risk of 1 per 1,000 exposed workers the Agency considers clearly
significant, and that adoption of the new TWA PEL, action level, and
dermal protection requirements of the final standards will
substantially reduce this risk. OSHA believes substantial evidence
supports its determinations, including its choices of the best
available published studies on which to base its risk assessment, its
examination of the prevalence of sensitization and CBD among workers
with exposure levels comparable to the preceding TWA PEL and new TWA
PEL in the NJH data set, and its selection of the Schubauer-Berigan QRA
to form the basis for its lung cancer risk estimates. The previously-
described analyses demonstrate that workers with occupational exposure
to airborne beryllium at the preceding PEL face risks of developing CBD
and dying from lung cancer that far exceed the value of 1 in 1,000 used
by OSHA as a benchmark of clearly significant risk. Furthermore, OSHA's
risk assessment indicates that risk of CBD and lung cancer can be
significantly reduced by reduction of airborne exposure levels, and
that dermal protection measures will additionally help reduce risk of
sensitization and, therefore, of CBD.
OSHA's risk assessment also indicates that, despite the reduction
in risk expected with the new PEL, the risks of CBD and lung cancer to
workers with average exposure levels of 0.2 μg/m3\ are still
significant and could extend down to 0.1 μg/m3\, although there is
greater uncertainty in this finding for 0.1 μg/m3\ since there is
less information available on populations exposed at and below this
level. Although significant risk remains at the new TWA PEL, OSHA is
also required to consider the technological and economic feasibility of
the standard in determining exposure limits. As explained in Section
VIII, Summary of the Final Economic Analysis and Final Regulatory
Flexibility Analysis, OSHA determined that the new TWA PEL of 0.2
μg/m3\ is both technologically and economically feasible in the
general industry, construction, and shipyard sectors. OSHA was unable
to demonstrate, however, that a lower TWA PEL of 0.1 μg/m3\ would
be technologically feasible. Therefore, OSHA concludes that, in setting
a TWA PEL of 0.2 μg/m3\, the Agency is reducing the risk to the
extent feasible, as required by the OSH Act (see section II, Pertinent
Legal Authority). In this context, the Agency finds that the action
level of 0.1 μg/m3\, dermal protection requirements, and other
ancillary provisions of the final rule are critically important in
reducing the risk of sensitization, CBD, and lung cancer among workers
exposed to beryllium. Together, these provisions, along with the new
TWA PEL of 0.2 μg/m3\, will substantially reduce workers' risk of
material impairment of health from occupational beryllium exposure.
VIII. Summary of the Final Economic Analysis and Final Regulatory
Flexibility Analysis
A. Introduction
OSHA's Final Economic Analysis and Final Regulatory Flexibility
Analysis (FEA) addresses issues related to the costs, benefits,
technological and economic feasibility, and the economic impacts
(including impacts on small entities) of this final beryllium rule and
evaluates regulatory alternatives to the final rule. Executive Orders
13563 and
12866 direct agencies to assess all costs and benefits of available
regulatory alternatives and, if regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, and public health and safety effects;
distributive impacts; and equity). Executive Order 13563 emphasized the
importance of quantifying both costs and benefits, of reducing costs,
of harmonizing rules, and of promoting flexibility. The full FEA has
been placed in OSHA rulemaking docket OSHA-H005C-2006-0870. This rule
is an economically significant regulatory action under Sec. 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 the FEA 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 resulting from employers coming into
compliance with the final rule in terms of reductions in cases of lung
cancer, chronic beryllium disease;
Evaluate the costs and economic impacts that
establishments in the regulated community will incur to achieve
compliance with the final rule;
Assess the economic feasibility of the final rule for
affected industries; and
Assess the impact of the final rule on small entities
through a Final Regulatory Flexibility Analysis (FRFA), to include an
evaluation of significant regulatory alternatives to the final rule
that OSHA has considered.
Significant Changes to the FEA Between the Proposed Standards and the
Final Standards
OSHA made changes to the Preliminary Economic Analysis (PEA) for
several reasons:
Changes to the rule, summarized in Section I of the
preamble and discussed in detail in the Summary and Explanation;
Comments on the PEA;
Updates of economic data; and
Recognition of errors in the PEA.
OSHA revised its technological and economic analysis in response to
these changes and to comments received on the NPRM. The FEA contains
some costs that were not included in the PEA and updates data to use
more recent data sources and, in some cases, revised methodologies.
Detailed discussions of these changes are included in the relevant
sections throughout the FEA.
The Final Economic Analysis contains the following chapters:
Chapter I. Introduction
Chapter II. Market Failure and the Need for Regulation
Chapter III. Profile of Affected Industries
Chapter IV. Technological Feasibility
Chapter V. Costs of Compliance
Chapter VI. Economic Feasibility Analysis and Regulatory Flexibility
Determination
Chapter VII. Benefits and Net Benefits
Chapter VIII. Regulatory Alternatives
Chapter IX. Final Regulatory Flexibility Analysis
Table VIII-1 provides a summary of OSHA's best estimate of the
costs and benefits of the final rule using a discount rate of 3
percent. As shown, the final rule is estimated to prevent 90 fatalities
and 46 beryllium-related illnesses annually once it is fully effective,
and the estimated cost of the rule is $74 million annually. Also as
shown in Table VIII-1, the discounted monetized benefits of the final
rule are estimated to be $561 million annually, and the final rule is
estimated to generate net benefits of $487 million annually. Table
VIII-1 also presents the estimated costs and benefits of the final rule
using a discount rate of 7 percent.
Table VIII-1--Annualized Benefits, Costs and Net Benefits of OSHA's
Final Beryllium Standard
[3 Percent Discount Rate, 2015 dollars]
------------------------------------------------------------------------
------------------------------------------------------------------------
Annualized Costs:
Control Costs......................................... $12,269,190
Rule Familiarization.................................. 180,158
Exposure Assessment................................... 13,748,676
Regulated Areas....................................... 884,106
Beryllium Work Areas.................................. 129,648
Medical Surveillance.................................. 7,390,958
Medical Removal....................................... 1,151,058
Written Exposure Control Plan......................... 2,339,058
Protective Work Clothing & Equipment.................. 1,985,782
Hygiene Areas and Practices........................... 2,420,584
Housekeeping.......................................... 22,763,595
Training.............................................. 8,284,531
Respirators........................................... 320,885
---------------
Total Annualized Costs (Point Estimate)........... 73,868,230
Annual Benefits: Number of Cases Prevented:
Fatal Lung Cancers (Midpoint Estimate)................ 4
Fatal Chronic Beryllium Disease....................... 86
Beryllium-Related Mortality........................... 90
Beryllium Morbidity................................... 46
Monetized Annual Benefits (Midpoint Estimate)......... $560,873,424
Net Benefits:
Net Benefits.......................................... $487,005,194
------------------------------------------------------------------------
Sources: US DOL, OSHA, Directorate of Standards and Guidance, Office of
Regulatory Analysis
The remainder of this section (Section VIII) of the preamble is
organized as follows:
B. Market Failure and the Need for Regulation
C. Profile of Affected Industries
D. Technological Feasibility
E. Costs of Compliance
F. Economic Feasibility Analysis and Regulatory Flexibility
Determination
G. Benefits and Net Benefits
H. Regulatory Alternatives
I. Final Regulatory Flexibility Analysis.
B. Market Failure and the Need for Regulation
Employees in work environments addressed by the final beryllium
rule are exposed to a variety of significant hazards that can and do
cause serious injury and death. As described in Chapter II of the FEA
in support of the final rule, OSHA concludes there is a demonstrable
failure of private markets to protect workers from exposure to
unnecessarily high levels beryllium and that private markets, as well
as information dissemination programs, workers' compensation systems,
and tort liability options, each may fail to protect workers from
beryllium exposure, resulting in the need for a more protective OSHA
beryllium rule.
After carefully weighing the various potential advantages and
disadvantages of using a regulatory approach to improve upon the
current situation, OSHA concludes that, in the case of beryllium
exposure, the final mandatory standards represent the best choice for
reducing the risks to employees.
C. Profile of Affected Industries
Chapter III of the FEA presents profile data for industries
potentially affected by the final beryllium rule. This Chapter provides
the background data used throughout the remainder of the FEA including
estimates of what industries are affected, and their economic and
beryllium exposure characteristics. OSHA identified the following
application groups as affected by the standard:
Beryllium Production
Beryllium Oxide Ceramics and Composites
Nonferrous Foundries
Secondary Smelting, Refining, and Alloying
Precision Turned Products
Copper Rolling, Drawing, and Extruding
Fabrication of Beryllium Alloy Products
Welding
Dental Laboratories
Aluminum Production
Coal-Fired Electric Power Generation
Abrasive Blasting
Table VIII-3 shows the affected industries by application group and
selected economic characteristics of these affected industries. Table
VIII-4 provides industry-by-industry estimates of current exposure.
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D. Technological Feasibility of the Final Standard on Occupational
Exposure to Beryllium
The OSH Act requires OSHA to demonstrate that a proposed health
standard is technologically feasible (29 U.S.C. 655(b)(5)). As
described in the preamble to the final rule (see Section II, Pertinent
Legal Authority), technological feasibility has been interpreted
broadly to mean "capable of being done" (Am. Textile Mfrs. Inst. v.
Donovan, 452 U.S. 490, 509-510 (1981) ("Cotton Dust")). A standard is
technologically feasible if the protective measures it requires already
exist, can be brought into existence with available technology, or can
be created with technology that can reasonably be expected to be
developed, i.e., technology that "looms on today's horizon" (United
Steelworkers of Am., AFL-CIO-CLC v. Marshall, 647 F.2d 1189, 1272 (D.C.
Cir. 1980) ("Lead I"); Amer. Iron & Steel Inst. v. OSHA, 939 F.2d
975, 980 (D.C. Cir. 1991) ("Lead II"); AFL-CIO v. Brennan, 530 F.2
109, 121 (3rd Cir. 1975)). Courts have also interpreted technological
feasibility to mean that, for health standards, a typical firm in each
affected industry will reasonably be able to implement engineering and
work practice controls that can reduce workers' exposures to meet the
permissible exposure limit in most operations most of the time, without
reliance on respiratory protection (see Lead I, 647 F.2d at 1272; Lead
II, 939 F.2d at 990).
OSHA's technological feasibility analysis is presented in Chapter
IV of the FEA. The technological feasibility analysis identifies the
affected industries and application groups in which employees can
reasonably be expected to be exposed to beryllium, summarizes the
available air sampling data used to develop employee exposure profiles,
and provides descriptions of engineering controls and other measures
employers can take to reduce their employees' exposures to beryllium.
For each affected industry sector or application group, OSHA provides
an assessment of the technological feasibility of compliance with the
final permissible exposure limit (PEL) of 0.2 μg/m3\ as an 8-hour
TWA and a 15-minute short-term exposure limit (STEL) of 2.0 μg/m3\.
The technological feasibility analysis covers twelve application
groups that correspond to specific industries or production processes
that involve the potential for occupational exposures to materials
containing beryllium and that OSHA has determined fall within the scope
of this final beryllium standard. Within each of these application
groups, exposure profiles have been developed to characterize the
distribution of the available exposure measurements by job title or
group of jobs. Each section includes descriptions of existing, or
baseline, engineering controls for operations that generate beryllium
exposure. For those job groups in which current exposures were found to
exceed the final PEL, OSHA identifies and describes additional
engineering and work practice controls that can be implemented to
reduce exposure and achieve compliance with the final PEL. For each
application group or industry, a final determination is made regarding
the technological feasibility of achieving the proposed permissible
exposure limits based on the use of engineering and work practice
controls and without reliance on the use of respiratory protection. The
determination is made based on the legal standard of whether the PEL
can be achieved for most operations most of the time using such
controls. In a separate chapter on short-term exposures, OSHA also
analyzes the feasibility of achieving compliance with the Short-Term
Exposure Limit (STEL).
The analysis is based on the best evidence currently available to
OSHA, including a comprehensive review of the industrial hygiene
literature, National Institute for Occupational Safety and Health
(NIOSH) Health Hazard Evaluations and case studies of beryllium
exposure, site visits conducted by an OSHA contractor (Eastern Research
Group (ERG)), and inspection data from OSHA's Integrated Management
Information System (IMIS) and OSHA's Information System (OIS). OSHA
also obtained information on beryllium production processes, worker
exposures, and the effectiveness of existing control measures from
Materion Corporation, the primary beryllium producer in the United
States, interviews with industry experts, and comments submitted to the
rulemaking docket in response to the Notice of Proposed Rulemaking and
informal public hearings. All of this evidence is in the rulemaking
record.
The twelve application groups are:
Primary Beryllium Production,
Beryllium Oxide Ceramics and Composites,
Nonferrous Foundries,
Secondary Smelting, Refining, and Alloying, Including
Handling of Scrap and Recycled Materials,
Precision Turned Products,
Copper Rolling, Drawing, and Extruding,
Fabrication of Beryllium Alloy Products,
Welding,
Dental Laboratories,
Abrasive Blasting,
Coal-Fired Electric Power Generation,
Aluminum Production
For discussion purposes, the twelve application groups are divided
into four general categories based on the distribution of exposures in
the exposure profiles: (1) Application groups in which baseline
exposures for most jobs are already at or below the final PEL of 0.2
μg/m3\; (2) application groups in which baseline exposures for one
or more jobs exceed the final PEL of 0.2 μg/m3\, but additional
controls have been identified that could achieve exposures at or below
the final PEL for most of the operations most of the time; (3)
application groups in which exposures in one or more jobs routinely
exceed the preceding PEL of 2.0 μg/m3\, and therefore substantial
reductions in exposure would be required to achieve the final PEL; and
(4) application groups in which exposure to beryllium occurs due to
trace levels of beryllium found in dust or fumes that nonetheless can
result in exposures that exceed 0.1 μg/m3\ as an 8-hour TWA under
foreseeable conditions.
The application groups in category 1, where exposures for most jobs
are already at or below the final PEL of 0.2 μg/m3\, typically
handle beryllium alloys containing a low percentage of beryllium (<2
percent) using processes that do not result in significant airborne
exposures. These four application groups are (1) copper rolling,
drawing, and extruding; (2) fabrication of beryllium alloy products;
(3) welding; and (4) aluminum production. The handling of beryllium
alloys in solid form is not expected to result in exposures of concern.
For example, beryllium alloys used in copper rolling, drawing, and
extruding typically contain 2 percent beryllium by weight or less
(Document ID 0081, Attachment 1). One facility noted that the copper-
beryllium alloys it used contained as little as 0.1 percent beryllium
(Document ID 0081, Attachment 1). These processes, such as rolling
operations that consist of passing beryllium alloys through a rolling
press to conform to a desired thickness, tend to produce less
particulate and fume than high energy processes. Exposures can be
controlled using containment, exhaust ventilation, and work practices
that include rigorous housekeeping. In addition, the heating of metal
during welding operations results in the release of fume, but the
beryllium in the welding fume accounts for a relatively small
percentage of the beryllium exposure. Worker exposure to beryllium
during welding activities is largely attributable to flaking oxide
scale on the base metal, which can be reduced through chemically
stripping or pickling the beryllium alloy piece prior to welding on it,
and/or enhancing exhaust ventilation (Corbett, 2006; Kent, 2005;
Materion Information Meeting, 2012).
For application groups in category 2, where baseline exposures for
one or more jobs exceed the final PEL of 0.2 μg/m 3, but
additional controls have been identified that could achieve exposures
at or below the final PEL for most of the operations most of the time,
workers may encounter higher content beryllium (20 percent or more by
weight), or higher temperature processes (Document ID 1662, p. 4.) The
application groups in the second category are: (1) Precision turned
products and (2) secondary smelting, refining, and alloying. While the
median exposures for most jobs in these groups are below the preceding
PEL of 2.0 μg/m3\, the median exposures for some jobs in these
application groups exceed the final PEL of 0.2 μg/m3\ when not
adequately controlled. For these application groups, additional
exposure controls and work practices will be required to reduce
exposures to or below the final PEL for most operations most of the
time. For example, personal samples collected at a precision turned
products facility that machined pure beryllium metal and high beryllium
content materials (40-60 percent) measured exposures on two machinists
of 2.9 and 6.6 μg/m3 (ERG Beryllium Site 4, 2003). A second survey
at this same facility conducted after an upgrade to the ventilation
systems in the mill and lathe departments measured PBZ exposures for
these machinists of 1.1 and 2.3 μg/m3\ (ERG Beryllium Site 9,
2004), and it was noted that not all ventilation was optimally
positioned, indicating that further reduction in exposure could be
achieved. In 2007, the company reported that after the installation of
enclosures on milling machines and additional exhaust, average
exposures to mill and lathe operators were reduced to below 0.2
µg/m3\ (ICBD, 2007). For secondary smelting operations, several
surveys conducted at electronic recycling and precious metal recovery
operations indicate that exposures for mechanical processing operators
can be controlled to or below 0.2 µg/m3\. However, for furnace
operations in secondary smelting, the median value in the exposure
profile exceeds the preceding PEL. Furnace operations involve high
temperatures that produce significant amounts of fumes and particulate
that can be difficult to contain. Therefore, the reduction of 8-hour
average exposures to or below the final PEL may not be achievable for
most furnace operations involved with secondary smelting of beryllium
alloys. In these cases, the supplemental use of respiratory protection
for specific job tasks will be needed to adequately protect furnace
workers for operations where exposures are found to exceed 0.2 μg/
m3\ despite the implementation of all feasible engineering and work
practice controls.
The application groups in category 3 include application groups for
which the exposure profiles indicate that exposures in one or more jobs
routinely exceed the preceding PEL of 2.0 μg/m3\. The three
application groups in this category are: (1) Beryllium production, (2)
beryllium oxide ceramics production, and (3) nonferrous foundries. For
the job groups in which exposures have been found to routinely exceed
the preceding PEL, OSHA identifies additional exposure controls and
work practices that the Agency has determined can reduce exposures to
or below the final PEL, most of the time. For example, OSHA concluded
that exposures to beryllium resulting from material transfer, loading,
and spray drying of beryllium oxide powders can be reduced to or below
0.2 µg/m3 with process enclosures, ventilation hoods, and
diligent housekeeping for material preparation operators working in
beryllium oxide ceramics and composites facilities (FEA, Chapter IV-
04). However, for furnace operations in primary beryllium production
and nonferrous foundries, and shakeout operations at nonferrous
foundries, OSHA recognizes that even after installation of feasible
controls, supplemental use of respiratory protection may be needed to
protect workers adequately (FEA, Chapter IV-03 and IV-05). The evidence
in the rulemaking record is insufficient to conclude that these
operations would be able to reduce the majority of the exposure to
levels below 0.2 μg/m3\ most of the time, and therefore some
increased supplemental use of respiratory protection may be required
for certain tasks in these jobs.
Category 4 includes application groups that encounter exposure to
beryllium due to trace levels found in dust or fumes that nonetheless
can exceed 0.1 μg/m3\ as an 8-hour TWA under foreseeable
conditions. The application groups in this category are (1) coal-fired
power plants in which exposure to beryllium can occur due to trace
levels of beryllium in the fly ash during very dusty maintenance
operations, such as cleaning the air pollution control devices; (2)
aluminum production in which exposure to beryllium can occur due to
naturally occurring trace levels of beryllium found in bauxite ores
used to make aluminum; and (3) abrasive blasting using coal and copper
slag that can contain trace levels of beryllium. Workers who perform
abrasive blasting using either coal or copper slag abrasives are
potentially exposed to beryllium due to the high total exposure to the
blasting media. Due to the very small amounts of beryllium in these
materials, the final PEL for beryllium will be exceeded only during
operations that generate excessive amount of visible airborne dust, for
which engineering controls and respiratory protection are already
required. However, the other workers in the general vicinity do not
experience these high exposures if proper engineering controls and work
practices, such as temporary enclosures and maintaining appropriate
distance during the blasting or maintenance activities, are
implemented.
During the rulemaking process, OSHA requested and received comments
regarding the feasibility of the PEL of 0.2 μg/m3\, as well as the
proposed alternative PEL of 0.1 µg/m3\ (80 FR 47565, 47780 (Aug.
7, 2015)). OSHA did this because it recognizes that significant risk of
beryllium disease is not eliminated at an exposure level of 0.2 μg/
m3\. As discussed below, OSHA finds that the proposed PEL of 0.2
μg/m3\ can be achieved through engineering and work practice
controls in most operations most of the time in all the affected
industry sectors and application groups, and therefore is feasible for
these industries and application groups under the OSH Act. OSHA could
not find, however, that the proposed alternative PEL of 0.1 μg/m3\
is also feasible for all of the affected industry sectors and
application groups.
The majority of commenters, including stakeholders in labor and
industry, public health experts, and the general public, explicitly
supported the proposed PEL of 0.2 µg/m3\ (NIOSH, Document ID
1671, Attachment 1, p. 2; National Safety Council, 1612, p. 3;
Beryllium Health and Safety Committee Task Group, 1655, p. 2; Newport
News Shipbuilding, 1657, p. 1; National Jewish Health (NJH), 1664, p.
2; the Aluminum Association, 1666, p. 1; the Boeing Company, 1667, p.
1; American Industrial Hygiene Association, 1686, p. 2; United
Steelworkers (USW), 1681, p. 7; Andrew Brown, 1636, p. 6; Department of
Defense, 1684, p. 1). In addition, Materion Corporation, the sole
primary beryllium production company in the U.S., and USW, jointly
submitted a draft proposed rule that included an exposure limit of 0.2
μg/m3\ (Document ID 0754, p. 4). In its written comments, Materion
explained that it is feasible to control exposure to levels below 0.2
μg/m3\ through the use of engineering controls and work practices
in most, but not all, operations:
Based on many years' experience in controlling beryllium
exposures, its vigorous product stewardship program in affected
operations, and the judgment of its professional industrial hygiene
staff, Materion Brush believes that the 0.2 μg/m3\ PEL for
beryllium, based on median exposures, can be achieved in most
operations, most of the time. Materion Brush does recognize that it
is not feasible to reduce exposures to below the PEL in some
operations, and in particular, certain beryllium production
operations, solely through the use of engineering and work practice
controls (Document ID 1052).
On the other hand, the Nonferrous Founders' Society (NFFS) asserted
that OSHA had not demonstrated that the final PEL of 0.2 µg/m3\
was feasible for the nonferrous foundry industry (Document ID 1678, pp.
2-3). NFFS asserted that "OSHA has failed to meet its burden of proof
that a ten-fold reduction to the current two micrograms per cubic meter
limit is technologically or economically feasible in the non-ferrous
foundry industry" (Document ID 1678, pp. 2-3; 1756, Tr. 18). In
written testimony submitted as a hearing exhibit, NFFS claimed that
OSHA's supporting documentation in the PEA had no "concrete assurance
on technologic feasibility either by demonstration or technical
documentation" (Document ID 1732, Appendix A, p. 4).
However, contrary to the NFFS comments, which are addressed at
greater length in Section IV-5 of the FEA, OSHA's exposure profile is
based on the best available evidence for nonferrous foundries; the
exposure data are taken from NIOSH surveys, an ERG site visit, and the
California Cast Metals Association (Document ID 1217; 1185; 0341,
Attachment 6; 0899). Materion also submitted substantial amounts of
monitoring data, process descriptions and information of engineering
controls that have been implemented in its facilities to control
beryllium exposure effectively, including operations that involve the
production of beryllium alloys using the same types of furnace and
casting operations as those conducted at nonferrous foundries producing
beryllium alloys (Document ID 0719; 0720; 0723). Furthermore, Materion
submitted the above-referenced letter to the docket stating that, based
on its many years of experience controlling beryllium exposures, a PEL
of 0.2 μg/m3\ can be achieved in most operations, most of the time
(Document ID 1052). Materion's letter is consistent with the monitoring
data Materion submitted, and OSHA considers its statement regarding
feasibility at the final PEL relevant to nonferrous foundries because
Materion has similar operations in its facilities, such as beryllium
alloy production. As stated in Section IV-5 of the FEA, the size and
configuration of nonferrous foundries may vary, but they all use
similar processes; they melt and pour molten metal into the prepared
molds to produce a casting, and remove excess metal and blemishes from
the castings (NIOSH 85-116, 1985). While the design may vary, the basic
operations and worker job tasks are similar regardless of whether the
casting metal contains beryllium.
In the NPRM, OSHA requested that affected industries submit to the
record any available exposure monitoring data and comments regarding
the effectiveness of currently implemented control measures to inform
the Agency's final feasibility determinations. During the informal
public hearings, OSHA asked the NFFS panel to provide information on
current engineering controls or the personal protective equipment used
in foundries claiming to have difficulty complying with the preceding
PEL, but no additional information was provided (Document ID 1756; Tr.
24-25; 1785, p. 1). Thus, the NFFS did not provide any sampling data or
other evidence regarding current exposure levels or existing control
measures to support its assertion that a PEL of 0.2 μg/m3\ is not
feasible, and did not show that the data in the record are insufficient
to demonstrate technological feasibility for nonferrous foundry
industry.
In sum, while OSHA agrees that two of the operations in the
nonferrous foundry industry, furnace and shakeout operations, employing
a relatively small percentage of workers in the industry, may not be
able to achieve the final PEL of 0.2 μg/m3\ most of the time,
evidence in the record indicates that the final PEL is achievable in
the other six job categories in this industry. Therefore, in the FEA,
OSHA finds the PEL of 0.2 μg/m3\ is technologically feasible for
the nonferrous foundry industry.
OSHA also recognizes that engineering and work practice controls
may not be able to consistently reduce and maintain exposures to the
final PEL of 0.2 μg/m3\ in some job categories in other application
groups, due to the processing of materials containing high
concentrations of beryllium, which can result in the generation of
substantial amounts of fumes and particulate. For example, the final
PEL of 0.2 μg/m3\ cannot be achieved most of the time for furnace
operations in primary beryllium production and for some furnace
operation activities in secondary smelting, refining, and alloying
facilities engaged in beryllium recovery and alloying. Workers may need
supplementary respiratory protection during these high exposure
activities where exposures exceed the final PEL of 0.2 μg/m3\ or
STEL of 2.0 μg/m3\ with engineering and work practice controls. In
addition, OSHA has determined that workers who perform open-air
abrasive blasting using mineral grit (i.e., coal slag) will routinely
be exposed to levels above the final PEL (even after the installation
of feasible engineering and work practice controls), and therefore,
these workers will also be required to wear respiratory protection.
Overall, however, based on the information discussed above and the
other evidence in the record and described in Chapter IV of the FEA,
OSHA has determined that for the majority of the job groups evaluated
exposures are either already at or below the final PEL, or can be
adequately controlled to levels below the final PEL through the
implementation of additional engineering and work practice controls for
most operations most of the time. Therefore, OSHA concludes that the
final PEL of 0.2 μg/m3\ is technologically feasible.
In contrast, the record evidence does not show that it is feasible
for most operations in all affected industries and application groups
to achieve the alternative PEL of 0.1 μg/m3\ most of the time. As
discussed below, although a number of operations can achieve this
level, they may be interspersed with operations that cannot, and OSHA
sees value in having a uniform PEL that can be enforced consistently
for all operations, rather than enforcing different PELs for the same
contaminant in different operations.
Several commenters supported a PEL of 0.1 μg/m3\. Specifically,
Public Citizen; the American Federation of Labor and Congress of
Industrial Organizations (AFL-CIO); the International Union, United
Automobile, Aerospace, and Agriculture Implement Workers of America
(UAW); North America's Building Trades Unions (NABTU); and the American
College of Occupational and Environmental Medicine contended that OSHA
should adopt this lower level because of the residual risk at 0.2
μg/m3\
(Document ID 1689, p. 7; 1693, p. 3; 1670, p. 1; 1679, pp. 6-7; 1685,
p. 1; 1756, Tr. 167). Two of these commenters, Public Citizen and the
AFL-CIO, also contended that a TWA PEL of 0.1 μg/m3 is feasible
(Document ID 1756, Tr. 168-169, 197-198). Neither of those commenters,
however, submitted any additional evidence to the record that OSHA
could rely on to conclude that a PEL of 0.1 μg/m3\ is achievable.
On the other hand, the Beryllium Health and Safety Committee and
NJH specifically rejected a PEL of 0.1 μg/m3\ in their comments.
They explained that they believed the proposed PEL of 0.2 μg/m3\
and the ancillary provisions would reduce the prevalence of beryllium
sensitization and chronic beryllium disease (CBD) and be the best
overall combination for protecting workers when taking into
consideration the analytical chemistry capabilities and economic
considerations (Document ID 1655, p. 16; 1664, p. 2).
Based on the record evidence, OSHA cannot conclude that the
alternative PEL of 0.1 μg/m3\ is achievable most of the time for at
least one job category in 8 of the 12 application groups or industries
included in this analysis: Primary beryllium production; beryllium
oxide ceramics and composites; nonferrous foundries; secondary
smelting, refining, and alloying, including handling of scrap and
recycled materials; precision turned products; dental laboratories;
abrasive blasting; and coal-fired electric power generation. In
general, OSHA's review of the available sampling data indicates that
the alternative PEL of 0.1 μg/m3\ cannot be consistently achieved
with engineering and work practice controls in application groups that
use materials containing high percentages of beryllium or that involve
processes that result in the generation of substantial amounts of fumes
and particulate. Variability in processes and materials for operations
involving the heating or machining of beryllium alloys or beryllium
oxide ceramics also makes it difficult to conclude that exposures can
be routinely reduced to below 0.1 μg/m3\. For example, in the
precision turned products industry, OSHA has concluded that exposures
for machinists machining pure beryllium or high beryllium alloys can be
reduced to or below 0.2 μg/m3\, but not 0.1 μg/m3\.
Additionally, OSHA has determined that job categories that involve
high-energy operations will not be able to consistently achieve 0.1
μg/m3\ (e.g., abrasive blasting with coal slag in open-air). These
operations can cause workers to have elevated exposures even when
available engineering and work practice controls are used.
In other cases, paucity of data or other data issues prevent OSHA
from determining whether engineering and work practice controls can
reduce exposures to or below 0.1 μg/m3\ most of the time (see
Chapter IV of the FEA). A large portion of the sample results obtained
by OSHA for the dental laboratories industry and for two of the job
categories in the coal-fired electric power generation industry
(operations workers and routine maintenance workers) were below the
reported limit of detection (LOD). Because the LODs for many of these
samples were higher than 0.1 μg/m3\, OSHA could not assess whether
exposures were below 0.1 μg/m3\. For example, studies of dental
laboratories showed that use of well-controlled ventilation can
consistently reduce exposures to below the LOD of 0.2 μg/m3\.
However, without additional information, OSHA cannot conclude that
exposures can be reduced to or below 0.1 μg/m3\ most of the time.
Therefore, OSHA cannot determine if a PEL of 0.1 μg/m3\ would be
feasible for the dental laboratory industry.
The lack of available data has also prevented OSHA from determining
whether exposures at or below of 0.1 μg/m3\ can be consistently
achieved for machining operators in the beryllium oxide ceramics and
composites industry. As discussed in Section IV-4 of the FEA, the
exposure profile for dry (green) machining and lapping and plate
polishing (two tasks within the machining operator job category) is
based on 240 full-shift PBZ samples obtained over a 10-year period
(1994 to 2003). The median exposure levels in the exposure profile for
green machining and lapping and polishing are 0.16 μg/m3\ and 0.29
μg/m3\, respectively. While the record indicates that improvements
in exposure controls were implemented over time (Frigon, 2005, Document
ID 0825; Frigon, 2004 (Document ID 0826)), data showing to what extent
exposures have been reduced are not available. Nonetheless, because the
median exposures for green machining are already below 0.2 μg/m3\,
and the median exposures for lapping and polishing are only slightly
above the PEL of 0.2 μg/m3\, OSHA concluded that the controls that
have been implemented are sufficient to reduce exposures to at or below
0.2 μg/m3\ most of the time. However, without additional
information, OSHA cannot conclude that exposures could be reduced to or
below 0.1 μg/m3\ most of the time for these tasks.
Most importantly for this analysis, the available evidence
demonstrates that the alternative PEL of 0.1 μg/m3\ is not
achievable in five out of the eight job categories in the nonferrous
foundries industry: Furnace operator, shakeout operator, pouring
operator, material handler, and molder. As noted above, the first two
of these job categories, furnace operator and shakeout operator, which
together employ only a small fraction of the workers in this industry,
cannot achieve the final PEL of 0.2 μg/m3\ either, but evidence in
the record demonstrates that nonferrous foundries can reduce the
exposures of most of the rest of the workers in the other six job
categories to or below the final PEL of 0.2 μg/m3\, most of the
time. However, OSHA's feasibility determination for the pouring
operator, material handler, and molder job categories, which together
employ more than half the workers at these foundries, does not allow
the Agency to conclude that exposures for those jobs can be
consistently lowered to the alternative PEL of 0.1 μg/m3\. See
Section IV-5 of the FEA. Thus, OSHA cannot conclude that most
operations in the nonferrous foundries industry can achieve a PEL of
0.1 μg/m3\, most of the time. Accordingly, OSHA finds that the
alternative PEL of 0.1 μg/m3\ is not feasible for the nonferrous
foundries industry.
OSHA has also determined either that information in the rulemaking
record demonstrates that 0.1 μg/m3\ is not consistently achievable
in a number of operations in other affected industries or that the
information is insufficient to establish that engineering and work
practice controls can consistently reduce exposures to or below 0.1
μg/m3\. Therefore, OSHA finds that the proposed alternative PEL of
0.1 μg/m3\ is not appropriate, and the rule's final PEL of 0.2
μg/m3\ is the lowest exposure limit that can be found to be
technologically feasible through engineering and work practice controls
in all of the affected industries and application groups included in
this analysis.
Because of this inability to achieve 0.1 μg/m3\ in many
operations, if OSHA were to adopt a PEL of 0.1 μg/m3\, a
substantial number of employees would be required to wear respirators.
As discussed in the Summary and Explanation for paragraph (f), Methods
of Compliance, use of respirators in the workplace presents a number of
independent safety and health concerns. Workers wearing respirators may
experience diminished vision, and respirators can impair the ability of
employees to communicate with one another. Respirators can impose
physiological burdens on employees due to the weight of the respirator
and increased breathing resistance
experienced during operation. The level of physical work effort
required, the use of protective clothing, and environmental factors
such as temperature extremes and high humidity can interact with
respirator use to increase the physiological strain on employees.
Inability to cope with this strain as a result of medical conditions
such as cardiovascular and respiratory diseases, reduced pulmonary
function, neurological or musculoskeletal disorders, impaired sensory
function, or psychological conditions can place employees at increased
risk of illness, injury, and even death. The widespread, routine use of
respirators for extended periods of time that may be required by a PEL
of 0.1 μg/m3\ creates more significant concerns than the less
frequent respirator usage that is required by a PEL of 0.2 μg/m3\.
Furthermore, OSHA concludes that it would complicate both
compliance and enforcement of the rule if it were to set a PEL of 0.1
μg/m3\ for some industries or operations and a PEL of 0.2 μg/
m3\ for the remaining industries and operations where technological
feasibility at the lower PEL is either unattainable or unknown. OSHA
may exercise discretion to issue a uniform PEL if it determines that
the PEL is technologically feasible for all affected industries (if not
for all affected operations) and that a uniform PEL would constitute
better public policy. See Pertinent Legal Authority (discussing the
Chromium decision). In declining to lower the PEL to 0.1 μg/m3\ for
any segment of the affected industries, OSHA has made that
determination here. Therefore, OSHA has determined that the proposed
alternative PEL of 0.1 μg/m3\ is not appropriate.
OSHA also evaluated the technological feasibility of the final STEL
of 2.0 μg/m3\ and the alternative STEL of 1.0 μg/m3\. An
analysis of the available short-term exposure measurements presented in
Chapter IV, Section 15 of the FEA indicates that elevated exposures can
occur during short-term tasks such as those associated with the
operation and maintenance of furnaces at primary beryllium production
facilities, at nonferrous foundries, and at secondary smelting
operations. Peak exposures can also occur during the transfer and
handling of beryllium oxide powders. OSHA finds that in many cases, the
control of peak short-term exposures associated with these intermittent
tasks will be necessary to reduce workers' TWA exposures to or below
the final PEL. The short-term exposure data presented in the FEA show
that the majority (79%) of these exposures are already below 2.0 μg/
m3\.
A number of stakeholders submitted comments related to the proposed
and alternative STELs. Some of these stakeholders supported a STEL of
2.0 μg/m3\. Materion stated that a STEL of 2.0 μg/m3\ for
controlling the upper range of worker short term exposures is
sufficient to prevent CBD (Document ID 1661, p. 3). Other commenters
recommended a STEL of 1.0 μg/m3\ (Document ID 1661, p. 19; 1681, p.
7). However, no additional engineering controls capable of reducing
short term exposures to at or below 1.0 μg/m3\ were identified by
these commenters. OSHA provides a full discussion of the public
comments in the Summary and Explanation section of this preamble. OSHA
has determined that the implementation of engineering and work practice
controls required to maintain full shift exposures at or below a PEL of
0.2 μg/m3\ will reduce short term exposures to 2.0 μg/m3\ or
below, and that a STEL of 1.0 μg/m3\ would require additional
respirator use. Furthermore, OSHA notes that the combination of a PEL
of 0.2 μg/m3\ and a STEL of 2.0 μg/m3\ would, in most cases,
keep workers from being exposed to 15 minute intervals of 1.0 μg/
m3\. See Table IV.78 of Chapter IV of the FEA.
Therefore, OSHA concludes that the STEL of 2.0 μg/m3\ can be
achieved for most operations most of the time, given that most short-
term exposures are already below 2.0 μg/m3\. OSHA recognizes that
for a small number of tasks, short-term exposures may exceed the final
STEL, even after feasible control measures to reduce TWA exposure to or
below the final PEL have been implemented, and therefore, some limited
use of respiratory protection will continue to be required for short-
term tasks in which peak exposures cannot be reduced to less than 2.0
μg/m3\ through use of engineering controls.
After careful consideration of the record, including all available
data and stakeholder comments in the record, OSHA has determined that a
STEL of 2.0 μg/m3\ is technologically feasible. Thus, as explained
in the Summary and Explanation for paragraph (c), OSHA has retained the
proposed value of 2.0 μg/m3\ as the final STEL.
E. Costs of Compliance
In Chapter V, Costs of Compliance, OSHA assesses the costs to
general industry, maritime, and construction establishments in all
affected application groups of reducing worker exposures to beryllium
to an eight-hour time-weighted average (TWA) permissible exposure limit
(PEL) of 0.2 μg/m3\ and to the final short-term exposure limit
(STEL) of 2.0 μg/m3\, as well as of complying with the final
standard's ancillary provisions. These ancillary provisions encompass
the following requirements: Exposure monitoring, regulated areas (and
competent person in construction), a written exposure control plan,
protective work clothing, hygiene areas and practices, housekeeping,
medical surveillance, medical removal, familiarization, and worker
training. This final cost assessment is based in part on OSHA's
technological feasibility analysis presented in Chapter IV of the FEA;
analyses of the costs of the final standard conducted by OSHA's
contractor, Eastern Research Group (ERG); and the comments submitted to
the docket in response to the request for information (RFI) as part of
the Small Business Regulatory Enforcement Fairness Act (SBREFA)
process, comments submitted to the docket in response to the PEA,
comments during the hearings conducted in March 2016, and comments
submitted to the docket after the hearings concluded.
Table VIII-4 presents summary of the annualized costs. All costs in
this chapter are expressed in 2015 dollars and were annualized using a
discount rate of 3 percent. (Costs at other discount rates are
presented in the chapter itself). Annualization periods for
expenditures on equipment are based on equipment life, and one-time
costs are annualized over a 10-year period. Chapter V provides detailed
explanation of the basis for these cost estimates.
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F. Economic Feasibility and Regulatory Flexibility Determination
In Chapter VI, OSHA investigates the economic impacts of its final
beryllium rule on affected employers. This impact investigation has two
overriding objectives: (1) To establish whether the final rule is
economically feasible for all affected application groups/
industries,\31\ and (2) to determine if the Agency can certify that the
final rule will not have a significant economic impact on a substantial
number of small entities.
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\31\ As noted in the FEA, OSHA uses the umbrella term
"application group" to refer either to an industrial sector or to
a cross-industry group with a common process. In the industrial
profile chapter, because some of the discussion being presented has
historically been framed in the context of the economic feasibility
for an "industry," the Agency uses the term "application group"
and "industry" interchangeably.
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Table VIII-5 presents OSHA's screening analysis, which shows costs
as percentage of revenues and as a percentage of profits. The chapter
explains why these screening analysis
results can reasonably be viewed as economically feasible. Section
VIII.j shows similar results for small and very small entities.
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In Chapter VII, OSHA estimates the benefits and net benefits of the
final beryllium rule. The methodology for these estimates largely
remains the same as in the PEA. OSHA did not receive many comments
challenging any aspect
of the benefits analysis presented in the PEA. There are, however, a
few significant alterations, such as: Using an empirical turnover rate
as part of the estimation of exposure response functions, full analysis
of the population model with varying turnover (a model only briefly
presented in the PEA), and presentation of a statistical proportional
hazard model in response to comment. The other large change to the
benefits analysis is the result of the increase in the scope of the
rule to protect workers in the construction and ship-building
industries. In the proposed rule, coverage of these latter industries
was only presented as an alternative and therefore were not included in
the benefits in the PEA, but they are covered by the final rule.
This chapter proceeds in five steps. The first step estimates the
numbers of diseases and deaths prevented by comparing the current
(baseline) situation to a world in which the final PEL is adopted in a
final standard, and in which employees are exposed throughout their
working lives to either the baseline or the final PEL. The second step
also assumes that the final PEL is adopted, but uses the results from
the first step to estimate what would happen under a realistic scenario
in which new employees will not be exposed above the final PEL, while
employees already at work will experience a combination of exposures
below the final PEL and baseline exposures that exceed the final PEL
over their working lifetime. The comparison of these steps is given in
Table VIII-6. OSHA also presents in Chapter VII similar kinds of
results for a variety of other risk assessment and population models.
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The third step covers the monetization of benefits. Table VIII-7
presents the monetization of benefits at various interest rates and
monetization values.
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In the fourth step, OSHA estimates the net benefits of the final
rule by comparing the monetized benefits to the costs presented in
Chapter V of the FEA. These values are presented in Table VIII-8. The
table shows that benefits exceed costs for all situations except for
the low estimate of benefits using a 7 percent discount rate. The low
estimate of benefits reflects the assumption that the ancillary
provisions have no independent effect in reducing cases of CBD. OSHA
considers this assumption to be very unlikely, based on the available
evidence.
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In the fifth step, OSHA provides a sensitivity analysis to explore
the robustness of the estimates of net benefits with respect to many of
the assumptions made in developing and applying the underlying models.
This is done because the models underlying each step inevitably need to
make a variety of assumptions based on limited data. OSHA invited
comments on each aspect of the data and methods used in this chapter,
and received none specifically on the sensitivity analysis. Because
dental laboratories constituted a significant source of both costs and
benefits to the proposal, the PEA indicated that OSHA was particularly
interested in comments regarding the appropriateness of the model,
assumptions, and data for estimating the benefits to workers in that
industry. Although the Agency did not receive any comments on this
question directly, the American Dental Association's comments relevant
to the underlying use of beryllium alloys in dental labs are addressed
in Chapter III of the FEA. The Agency has not altered its main
estimates of the exposure profile for dental laboratory workers, but
provides sensitivity analyses in the FEA to examine the outcome if a
lower percentage of dental laboratories were to substitute materials
that do not contain beryllium for beryllium-containing materials. OSHA
also estimates net benefits with a variety of scenarios in which dental
laboratories are not included. All of these results are presented in
Chapter VII of the FEA.
H. Regulatory Alternatives
Chapter VIII presents the costs, benefits and net benefits of a
variety of regulatory alternatives.
I. Final Regulatory Flexibility Analysis
The Regulatory Flexibility Act, (RFA), Public Law 96-354, 94 Stat.
1164 (codified at 5 U.S.C. 601), requires Federal agencies to consider
the economic impact that a final rulemaking will have on small
entities. The RFA states that whenever an agency promulgates a final
rule that is required to conform to the notice-and-comment rulemaking
requirements of section 553 of the Administrative Procedure Act (APA),
the agency shall prepare a final regulatory flexibility analysis
(FRFA). 5 U.S.C. 604(a).
However, 5 U.S.C. 605(b) of the RFA states that Section 604 shall
not apply to any final rule if the head of the agency certifies that
the rule will not, if promulgated, have a significant economic impact
on a substantial number of small entities. As discussed in Chapter VI
of the FEA, OSHA was unable to so certify for the final beryllium rule.
For OSHA rulemakings, as required by 5 U.S.C. 604(a), the FRFA must
contain:
1. A statement of the need for, and objectives of, the rule;
2. a statement of the significant issues raised by the public
comments in response to the initial regulatory flexibility analysis, a
statement of the assessment of the agency of such issues, and a
statement of any changes made in the proposed rule as a result of such
comments;
3. the response of the agency to any comments filed by the Chief
Counsel for Advocacy of the Small Business Administration (SBA) in
response to the proposed rule, and a detailed statement of any change
made to the proposed rule in the final rule as a result of the
comments;
4. a description of and an estimate of the number of small entities
to which the rule will apply or an explanation of why no such estimate
is available;
5. a description of the projected reporting, recordkeeping and
other
compliance requirements of the rule, including an estimate of the
classes of small entities which will be subject to the requirement and
the type of professional skills necessary for preparation of the report
or record;
6. a description of the steps the agency has taken to minimize the
significant economic impact on small entities consistent with the
stated objectives of applicable statutes, including a statement of the
factual, policy, and legal reasons for selecting the alternative
adopted in the final rule and why each one of the other significant
alternatives to the rule considered by the agency which affect the
impact on small entities was rejected; and for a covered agency, as
defined in section 609(d)(2), a description of the steps the agency has
taken to minimize any additional cost of credit for small entities.
The Regulatory Flexibility Act further states that the required
elements of the FRFA may be performed in conjunction with or as part of
any other agenda or analysis required by any other law if such other
analysis satisfies the provisions of the FRFA. 5 U.S.C. 605(a).
In addition to these elements, OSHA also includes in this section
the recommendations from the Small Business Advocacy Review (SBAR)
Panel and OSHA's responses to those recommendations.
While a full understanding of OSHA's analysis and conclusions with
respect to costs and economic impacts on small entities requires a
reading of the complete FEA and its supporting materials, this FRFA
will summarize the key aspects of OSHA's analysis as they affect small
entities.
The Need for, and Objective of, the Rule
The objective of the final beryllium standard is to reduce the
number of fatalities and illnesses occurring among employees exposed to
beryllium. This objective will be achieved by requiring employers to
install engineering controls where appropriate and to provide employees
with the equipment, respirators, training, medical surveillance, and
other protective measures necessary to perform their jobs safely. The
legal basis for the rule is the responsibility given the U.S.
Department of Labor through the Occupational Safety and Health Act of
1970 (OSH Act). The OSH Act provides that, in promulgating health
standards dealing with toxic materials or harmful physical agents, 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.
655(b)(5). See Section II of the preamble for a more detailed
discussion.
Chronic beryllium disease (CBD) is a hypersensitivity, or allergic
reaction, to beryllium that leads to a chronic inflammatory disease of
the lungs. It takes months to years after final beryllium exposure
before signs and symptoms of CBD occur. Removing an employee with CBD
from the beryllium source does not always lead to recovery. In some
cases CBD continues to progress following removal from beryllium
exposure. CBD is not a chemical pneumonitis but an immune-mediated
granulomatous lung disease. OSHA's final risk assessment, presented in
Section VI of the preamble, indicates that there is significant risk of
beryllium sensitization and chronic beryllium disease from a 45-year
(working life) exposure to beryllium at the current TWA PEL of 2 μg/
m3\. The risk assessment further indicates that there is significant
risk of lung cancer to workers exposed to beryllium at the current TWA
PEL of 2 μg/m3\. The final standard, with a lower PEL of 0.2 μg/
m3\, will help to address these health concerns. See the Health
Effects and Risk Assessment sections of the preamble for further
discussion.
Summary of Significant Issues Raised by Comments on the
Initial Regulatory Flexibility Analysis (IRFA) and OSHA's Assessment
of, and Response to, Those Issues
This section of the FRFA focuses only on public comments concerning
significant issues raised on the Initial Regulatory Flexibility
Analysis (IRFA). OSHA received only one such comment.
The Non-Ferrous Founders' Society claimed that the costs of the
rule will disproportionately affect small employers and result in job
losses to foreign competition (Document ID 1678, p. 3). This comment is
addressed in the FEA in the section on International Trade Effects in
Chapter VI: Economic Feasibility Analysis and Regulatory Flexibility
Determination. The summary of OSHA's response is that, in general,
metalcasters in the U.S. have shortened lead times, improved
productivity through computer design and logistics management, expanded
design and development services to customers, and provided a higher
quality product than foundries in China and other nations where labor
costs are low (Document ID 1780, p. 3-12). All of these measures,
particularly the higher quality of many U.S. metalcasting products and
the ability of domestic foundries to fulfill orders quickly, are
substantial advantages for U.S. metalcasters that may outweigh the very
modest price increases that might occur due to the final rule. For a
more detailed response please see the section on International Trade
Effects in Chapter VI of the FEA.
Response to Comments by the Chief Counsel for Advocacy of the Small
Business Administration and OSHA'S Response to Those Comments
The Chief Counsel for Advocacy of the Small Business Administration
("Advocacy") did not provide OSHA with comments on this rule.
A Description of, and an Estimate of, the Number of Small
Entities To Which the Rule Will Apply
OSHA has analyzed the impacts associated with this final rule,
including the type and number of small entities to which the standard
will apply. In order to determine the number of small entities
potentially affected by this rulemaking, OSHA used the definitions of
small entities developed by the Small Business Administration (SBA) for
each industry.
OSHA estimates that approximately 6.600 small business entities
would be affected by the beryllium standard. Within these small
entities, 33,800 workers are exposed to beryllium and would be
protected by this final standard. A breakdown, by industry, of the
number of affected small entities is provided in Table III-14 in
Chapter III of the FEA.
OSHA estimates that approximately 5,280 very small entities--those
with fewer than 20 employees--would be affected by the beryllium
standard. Within these very small entities, 11,800 workers are exposed
to beryllium and would be protected by the standard. A breakdown, by
industry, of the number of affected very small entities is provided in
Table III-15 in Chapter III of the FEA.
A Description of the Projected Reporting, Recordkeeping, and Other
Compliance Requirements of the Rule
Tables VIII-9 and VIII-10 show the average costs of the beryllium
standard and the costs of compliance as a percentage of profits and
revenues by NAICS code for, respectively, small entities (classified as
small by SBA) and very small entities (those with fewer than 20
employees). The full derivation of these costs is presented in Chapter
V. The cost for SBA-defined small entities ranges from a low of $832
per entity for
entities in NAICS 339116a: Dental Laboratories, to a high of about
$599,836 for NAICS 331313: Alumina Refining and Primary Aluminum
Production.
The annualized cost for very small entities ranges from a low of
$542 for entities in NAICS 339116a: Dental Laboratories, to a high of
about $34,222 for entities in NAICS 331529b: Other Nonferrous Metal
Foundries (except Die-Casting).\32\
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\32\ The cost of $542 for NAICS 339116a is the sum of a $524
cost to substitute for a non-hazard material and $19 for cost of
ancillary provisions. The total cost of $34,222 for NAICS 331529b is
the sum of $22,601 for engineering controls, $186 for respirator
costs, and $11,435 for ancillary provisions.
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Description of the Steps OSHA Has Taken To Minimize the Significant
Economic Impact on Small Entities Consistent With the Stated Objectives
of Applicable Statutes and Statement of the Reasons For Selecting the
Alternative Adopted in the Final Rule
OSHA has made a number of changes in the final beryllium rule that
will serve to minimize significant impacts on small entities consistent
with the objectives of the OSH Act. These changes are explained in more
detail in Section XVI: Summary and Explanation in this preamble.
During the SBAR Panel, SERs requested a clearer definition of the
triggers for medical surveillance. This concern was rooted in the cost
of BeLPTs and the trigger of potential skin contact. For the final
rule, the Agency has removed skin contact as a trigger for medical
surveillance. OSHA has also reduced the frequency of medical
surveillance from annually (in the proposed rule) to biennially in the
final rule.
In the final rule, OSHA has added a performance option, as an
alternative to scheduled monitoring, to allow employers to comply with
exposure assessment requirements. This performance option should allow
employers more flexibility, and often lower cost, in complying with the
exposure assessment requirements.
Some SERs were already applying many of the protective controls and
practices that would be required by the ancillary provisions of the
standard. However, many SERs objected to the requirements regarding
hygiene facilities. For this final rule, OSHA has concluded that all
affected employers currently have hand washing facilities. OSHA has
also concluded that no affected employers will be required to install
showers. OSHA noted in the PEA that some facilities already have
showers. There were no comments challenging the Agency's preliminary
determinations regarding the existing availability of shower facilities
or the means of preventing contamination, so the Agency concludes that
all employers have showers where needed. Therefore, employers will not
need to provide any new shower facilities to comply with the
standard.\33\
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\33\ OSHA reached the same conclusion in the PEA (p. V-118). For
information purposes, OSHA estimated the initial cost of installing
portable showers at $39,687, with an annualized cost of $4,653 per
facility (Id.) and did not receive any comments suggesting that
shower costs should be included or regarding the cost of installing
them. The annual cost per employee for shower supplies, towels, and
time required for showering was estimated to be $1,519. However, as
indicated above in the text, the Agency believed that employers
would be able to comply with the standard by less costly means than
the installation of shower facilities.
---------------------------------------------------------------------------
Similarly, in the PEA the Agency included no additional costs for
readily accessible washing facilities, under the expectation that
employers already have such facilities in place (PEA p. IX-19).
Although the abrasive blasters exposed to beryllium in maritime and
construction work may not have been expressly addressed in the PEA,
OSHA notes that their employers are typically already required to
provide readily accessible washing facilities to comply with other OSHA
standards such as its sanitation standard at 29 CFR 1926.51(f)(1).\34\
In the absence of additional comment, OSHA is not including any costs
for washing facilities in the FEA.
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\34\ OSHA's shipyard standard at 29 CFR 1915.58(e) requires
handwashing facilities "at or adjacent to each toilet facility"
and "equipped with . . . running water and soap, or with waterless
skin-cleansing agents that are capable of . . . neutralizing the
contaminants to which the employee may be exposed." OSHA's
construction standard at 29 CFR 1926.51(f)(1) requires "adequate
washing facilities for employees engaged in . . . operations where
contaminants may be harmful to the employees. Such facilities shall
be in near proximity to the worksite and shall be so equipped as to
enable employees to remove such substances."
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OSHA's shipyard standard at 29 CFR 1915.58(e) requires handwashing
facilities "at or adjacent to each toilet facility" and "equipped
with . . . running water and soap, or with waterless skin-cleansing
agents that are capable of . . . neutralizing the contaminants to which
the employee may be exposed." OSHA's construction standard at 29 CFR
1926.51(f)(1) requires "adequate washing facilities for employees
engaged in . . . operations where contaminants may be harmful to the
employees. Such facilities shall be in near proximity to the worksite
and shall be so equipped as to enable employees to remove such
substances."
The Agency has determined that the long-term rental of modular
units was representative of costs for a range of reasonable approaches
to comply with the change room part of the provision. Alternatively,
employers could renovate and rearrange their work areas in order to
meet the requirements of this provision.
Finally, in the final rule, OSHA has extended the compliance
deadlines for change rooms from one year to two years and for
engineering controls from two years to three years.
Regulatory Alternatives
For the convenience of those persons interested only in OSHA's
regulatory flexibility analysis, this section repeats the discussion
presented in Chapter VIII of the FEA, but only for the regulatory
alternatives to the final OSHA beryllium standard that would have
lowered costs.
Each regulatory alternative presented here is described and
analyzed relative to the final rule. Where appropriate, the Agency
notes whether the regulatory alternative, to have been a legitimate
candidate for OSHA consideration, required evidence contrary to the
Agency's final findings of significant risk and feasibility. For this
chapter on the Final Regulatory Flexibility Analysis, the Agency is
only presenting regulatory alternatives that would have reduced costs
for small entities. (See Chapter VIII for the full list of all
alternatives analyzed.) There are 14 alternatives that would have
reduced costs for small entities (and for all businesses in total).
Using the numbering scheme from Chapter VIII of the FEA, these are
Regulatory Alternatives #1a, #2a, #2b, #5, #6, #7, #8, #9, #10, #11,
#12, #13, #15, #16, #18, and #22. OSHA has organized these 16 cost-
reducing alternatives (and a general discussion of considered phase-ins
of the rule) into four categories: (1) Scope; (2) exposure limits; (3)
methods of compliance; and (4) ancillary provisions.
(1) Scope Alternatives
The scope of the beryllium final rule applies to general industry
work, construction and maritime activities. In addition, the final rule
provides an exemption for those working with materials containing only
trace amounts of beryllium (less than 0.1% by weight) when the employer
has objective data that employee exposure to beryllium will remain
below the action level as an 8-hour TWA under any foreseeable
conditions.
The first set of regulatory alternatives would alter the scope of
the final standard by differing in coverage of groups of employees and
employers. Regulatory Alternatives #1a, #2a, and #2b would decrease the
scope of the final standard.
Regulatory Alternative #1a would exclude all operations where
beryllium exists only as a trace contaminant; that is, where the
materials used contain less than 0.1% beryllium by weight, with no
other conditions. OSHA has identified two industries with workers
engaged in general industry work that would be excluded under
Regulatory Alternative #1a: Primary aluminum production and coal-fired
power generation.
Table VIII-11 presents, for informational purposes, the estimated
costs, benefits, and net benefits of Regulatory Alternative #1a using
alternative discount rates of 3 percent and 7 percent. In addition,
this table presents the incremental costs, incremental benefits, and
incremental net benefits of this alternative relative to the final
rule. Table VIII-11 also breaks out costs by provision, and benefits by
type of disease and by morbidity/mortality prevented. (Note:
"morbidity" cases are cases where health effects are limited to non-
fatal illness; in these cases there is no further disease progression
to fatality).
As shown in Table VIII-11, Regulatory Alternative #1a would
decrease the annualized cost of the rule from $73.9 million to $64.6
million using a 3 percent discount rate and from $76.6 million to $67.0
million using a 7 percent discount rate. Annualized benefits in
monetized terms would decrease from $560.9 million to $515.7 million,
using a 3 percent discount rate, and from $249.1 million to $229.0
million using a 7 percent discount rate. Net benefits would decrease
from $487.0 million to $451.1 million using a 3 percent discount rate
and from $172.4 million to $162.0 million using a 7 percent discount
rate.
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Regulatory Alternative #2a would exclude construction and maritime
work from the scope of the final standard. For example, this
alternative would exclude abrasive blasters, pot tenders, and cleanup
staff working in
construction and shipyards who have the potential for airborne
beryllium exposure during blasting operations and during cleanup of
spent media.
Table VIII-12 presents the estimated costs, benefits, and net
benefits of Regulatory Alternative #2a using alternative discount rates
of 3 percent and 7 percent. In addition, this table presents the
incremental costs, incremental benefits, and incremental net benefits
of these alternatives relative to the final rule. Table VIII-12 also
breaks out costs by provision and benefits by type of disease and by
morbidity/mortality.
As shown in Table VIII-12, Regulatory Alternative #2a would
decrease costs from $73.9 million to $62.0 million, using a 3 percent
discount rate, and from $76.6 million to $64.4 million using a 7
percent discount rate. Annualized benefits would decrease from $560.9
million to $533.3 million, using a 3 percent discount rate, and from
$249.1 million to $236.8 million using a 7 percent discount rate. Net
benefits would change from $487.0 million to $471.3 million, using a 3
percent discount rate, and is essentially unchanged at a discount rate
of 7 percent, with the final rule having net benefits of $172.4 million
while the alternative has $172.5 million. Thus, at a 7 percent discount
rate, the costs exceed the benefits for this alternative by $0.1
million per year. However, OSHA believes that for these industries, the
cost estimate is severely overestimated because 45 percent of the costs
are for exposure monitoring assuming that employers use the periodic
monitoring option. Employers in this sector are far more likely to use
the performance based monitoring options at considerably reduced costs.
If this is the case, benefits would exceed costs even at a 7 percent
discount rate.
Regulatory Alternative #2b would eliminate the ancillary provisions
in the final rule for the shipyard and construction sectors and for any
operations where beryllium exists only as a trace contaminant.
Accordingly, only the final TWA PEL and STEL would apply to employers
in these sectors and operations (through 29 CFR 1910.1000 Tables Z-1
and Z-2, 1915.1000 Table Z, and 1926.55 Appendix A). Operations in
general industry where the ancillary provisions would be eliminated
under Regulatory Alternative #2b include aluminum smelting and
production and coal-powered utility facilities and any other operations
where beryllium is present only as a trace contaminant (in addition to
all operations in construction and shipyards).
As shown in Table VIII-13, Regulatory Alternative #2b would
decrease the annualized cost of the rule from $73.9 million to $53.5
million using a 3 percent discount rate, and from $76.6 to $55.6
million using a 7 percent discount rate. Annualized benefits would
decrease from $560.9 million to $493.3 million, using a 3 percent
discount rate, and from $249.1 million to $219.1 million, using a 7
percent discount rate. Net benefits would decrease from $487.0 million
to $439.8 million, using a 3 percent discount rate, and from $172.4
million to $163.5 million, using a 7 percent discount rate.
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(2) Exposure Limit (TWA PEL, STEL, and Action Level) Alternatives
Paragraph (c) of the three final standards establishes two PELs for
beryllium in all forms, compounds, and mixtures: An 8-hour TWA PEL of
0.2 μg/m3\ (paragraph (c)(1)), and a 15-minute short-term exposure
limit (STEL) of 2.0 μg/m3\ (paragraph (c)(2)). OSHA has defined the
action level for the final standard as an airborne concentration of
beryllium of 0.1 μg/m3\ calculated as an eight-hour TWA (paragraph
(b)). In this final rule, as in other standards, the action level has
been set at one half of the TWA PEL.
Regulatory Alternative #5 would set a higher TWA PEL at 0.5
µg/m3\ and an action level at 0.25 µg/m3\. This
alternative responds to an issue raised during the Small Business
Advocacy Review (SBAR) process conducted in 2007 to consider a draft
OSHA beryllium proposed rule that culminated in an SBAR Panel report
(SBAR, 2008). That report included a recommendation that OSHA consider
both the economic impact of a low TWA PEL and regulatory alternatives
that would ease cost burden for small entities. OSHA has provided a
full analysis of the economic impact of its final PELs (see Chapter VI
of the FEA), and Regulatory Alternative #5 was considered in response
to the second half of that recommendation. However, the higher 0.5
µg/m3\ TWA PEL is not consistent with the Agency's mandate under
the OSH Act to promulgate a lower PEL if it is feasible and could
prevent additional fatalities and non-fatal illnesses. The data
presented in Table VIII-14 below indicate that the final TWA PEL would
prevent additional fatalities and non-fatal illnesses relative to
Regulatory Alternative #5.
Table VIII-14 below presents, for informational purposes, the
estimated costs, benefits, and net benefits of the final rule under the
final TWA PEL of 0.2 μg/m3\ and for the regulatory alternative TWA
PEL of 0.5 μg/m3\ (Regulatory Alternative #5), using alternative
discount rates of 3 percent and 7 percent. In addition, the table
presents the incremental costs, the incremental benefits, and the
incremental net benefits of going from a TWA PEL of 0.5 μg/m3\ to
the final TWA PEL of 0.2 μg/m3\. Table VIII-14 also breaks out
costs by provision and benefits by type of disease and by morbidity/
mortality.
As Table VIII-14 shows, going from a TWA PEL of 0.5 μg/m3\ to a
TWA PEL of 0.2 μg/m3\ would prevent, annually, an additional 30
beryllium-related fatalities and an additional 16 non-fatal illnesses.
This is consistent with OSHA's final risk assessment, which indicates
significant risk to workers exposed at a TWA PEL of 0.5 μg/m3\;
furthermore, OSHA's final feasibility analysis indicates that a lower
TWA PEL than 0.5 μg/m3\ is feasible. Net benefits of this
regulatory alternative versus the final TWA PEL of 0.2 μg/m3\ would
decrease from $487.0 million to $376.5 million using a 3 percent
discount rate and from $172.4 million to $167.2 million using 7 percent
discount rate.
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Regulatory Alternative With Unchanged PEL But Full Ancillary Provisions
An Informational Analysis: This final regulation has the somewhat
unusual feature for an OSHA substance-specific health standard that
most of the quantified benefits that OSHA estimated would come from the
ancillary provisions rather than from meeting the PEL solely with
engineering controls (see Chapter VII of the FEA for a more detailed
discussion). OSHA decided to analyze for informational purposes the
effect of retaining the preceding PEL but applying all of the ancillary
provisions, including respiratory protection. Under this approach, the
TWA PEL would remain at 2.0 micrograms per cubic meter, but all of the
other final provisions (including respiratory protection) would be
required with their triggers remaining the same as in the final rule--
either the presence of airborne beryllium at any level (e.g., initial
monitoring, written exposure control plan), at certain kinds of dermal
exposure (PPE), at the action level of 0.1 µg/m3\ (e.g.,
periodic monitoring, medical removal), or at 0.2 µg/m3\ (e.g.,
regulated areas, respiratory protection, medical surveillance).
Given the record regarding beryllium exposures, this approach is
not one OSHA could legally adopt. The absence of engineering controls
would not be consistent with OSHA's application of the hierarchy of
controls, in which engineering controls are applied to eliminate or
control hazards, before administrative controls and personal protective
equipment are applied to address remaining exposures. Section 6(b)(5)
of the OSH Act requires OSHA 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 dealt with by such standard for the period of
his working life." For that reason, this additional analysis is
provided strictly for informational purposes. E.O. 12866 and E.O. 13563
direct agencies to identify approaches that maximize net benefits, and
this analysis is purely for the purpose of exploring whether this
approach would hold any real promise to maximize net benefits if it was
permissible under the OSH Act. It does not appear to hold such promise
because an ancillary-provisions-only approach would not be as
protective and thus offers fewer benefits than one that includes a
lower PEL and engineering controls. Also, OSHA estimates the costs
would be about the same (or slightly lower, depending on certain
assumptions) under that approach as under the traditional final
approach.
When examined on an industry-by-industry basis, OSHA found that
some industries would have lower costs if they could adopt the
ancillary-provision-only approach. Some employers would use engineering
controls where they are cheaper, even if they are not mandatory. OSHA
does not have sufficient information to do an analysis employer-by-
employer of when the ancillary-provisions-only approach might be
cheaper. In the majority of affected industries, the Agency estimates
there are no cost savings to the ancillary-provisions-only approach.
However, OSHA estimates an annualized total cost saving of $2.7 million
per year for entire industries where the ancillary-provisions-only
approach would be less expensive.
The above discussion does not account for the possibility that the
lack of engineering controls would result in higher beryllium exposures
for workers in adjacent (non-production) work areas due to the
increased level of beryllium in the air. Because of a lack of data, and
because the issue did not arise in the other regulatory alternatives
OSHA considered (all of which have a PEL of less than 2.0 µg/
m3\), OSHA did not examine exposure levels in non-production areas for
either cost or benefit purposes. To the extent such exposure levels
would be above the action level, there would be additional costs for
respiratory protection and medical surveillance.
If respirators were as effective as engineering controls, the
ancillary-provisions-only approach would have benefits comparable to
the benefits of the final rule. However, in this alternative most
exposed individuals would be required to use respirators, which OSHA
considers less effective than engineering controls in preventing
employee exposure to beryllium. OSHA also examined what the benefits
would be if respirators were not required, were not worn, or were
ineffective. OSHA found that, if all of the other aspects of the
benefits analysis remained the same, the annualized benefits would be
reduced by from $33.2 million using a discount rate of 3 percent, and
$22.4 using a discount rate of 7 percent, largely as a result of
failing to reduce deaths from lung cancer, which are unaffected by the
ancillary provisions. However, there are also other reasons to believe
that benefits may be even lower:
(1) As noted above, in the final rule OSHA did not consider
benefits caused by reductions in exposure in non-production areas.
Unless employers act to reduce exposures in the production areas, the
absence of a requirement for such controls would largely negate such
benefits from reductions in exposure in the non-productions areas.
(2) OSHA judges that the benefits of the ancillary provisions (a
midpoint estimate of eliminating 45 percent of all remaining cases of
CBD for all sectors except for abrasive blasting and coal-fired power
plants, and an estimate of 11.25 percent, or one fourth of the
percentage for other sectors, for abrasive blasting and coal-fired
power plants) would be partially or wholly negated in the absence of
engineering controls that would reduce both airborne and surface dust
levels. The Agency's high estimate (90 percent for all sectors except
abrasive blasting and coal fired power plants, 22.5 percent for
abrasive blasting and coal-fired power plants) of the proportion of
remaining CBD cases eliminable by ancillary provisions is based on data
from a facility with average exposure levels of less than 0.2 µg/
m3\.
Based on these considerations, OSHA finds that the ancillary-
provisions-only approach is not one that is likely to maximize net
benefits. The cost savings, if any, are estimated to be small, and the
difficult-to-measure declines in benefits could be substantial.
(2) A Method-of-Compliance Alternative
Paragraph (f)(2)(i) of the final standards contains requirements
for the implementation of engineering and work practice controls to
minimize beryllium exposures in general industry, maritime, and
construction. For each operation in a beryllium work area in general
industry or where exposures are or can reasonably be expected to be
above the action level in shipyards or construction, employers must
ensure that one or more of the following are in place to minimize
employee exposure: Material and/or process substitution; isolation,
such as ventilated partial or full enclosures; local exhaust
ventilation; or process controls, such as wet methods and automation.
Employers are exempt from using these methods only when they can show
that such methods are not feasible or where exposures are below the
action level based on two exposure samples taken at least seven days
apart.
OSHA believes that the methods outlined in paragraph (f)(2)(i)
provide the most reliable means to control variability in exposure
levels. However, OSHA also recognizes that the requirements of
paragraph (f)(2)(i) are not typical of OSHA standards, which usually
require engineering controls
only where exposures exceed the TWA PEL or STEL. The Agency therefore
also considered Regulatory Alternative #6, which would drop the
provisions of (f)(2)(i) from the final standard and make conforming
edits to paragraphs (f)(2)(ii) and (iii). This regulatory alternative
does not eliminate the need for engineering controls to comply with the
final TWA PEL and STEL, but does eliminate the requirement to use one
or more of the specified engineering or work practice controls where
exposures equal or exceed the action level. As shown in Table VIII-15,
Regulatory Alternative #6 would decrease the annualized cost of the
final rule by $606,706 using a discount rate of 3 percent and by
$638,100 using a discount rate of 7 percent.
In the PEA, OSHA had been unable to estimate the benefits of this
alternative and invited public comment. The Agency did not receive
public comment and therefore has not estimated the change in benefits
resulting from Regulatory Alternative #6.
[GRAPHIC] [TIFF OMITTED] TR09JA17.056
(4) Regulatory Alternatives That Affect Ancillary Provisions
The final standard contains several ancillary provisions
(provisions other than the exposure limits), including requirements for
exposure assessment, medical surveillance, medical removal, training,
competent person, and regulated areas or access control. As reported in
Chapter V of the FEA, these ancillary provisions account for $61.3
million (about 83 percent) of the total annualized costs of the rule
($73.4 million) using a 3 percent discount rate. The most expensive of
the ancillary provisions are the requirements for housekeeping and
exposure monitoring, with annualized costs of $22.8 million and $13.7
million, respectively, at a 3 percent discount rate.
OSHA's reasons for including each of the final ancillary provisions
are explained in Section XVI of the preamble, Summary and Explanation
of the Standards.
OSHA has examined a variety of regulatory alternatives involving
changes to one or more of the final ancillary provisions. The
incremental cost of each of these regulatory alternatives and its
impact on the total costs of the final rule are summarized in Table
VIII-16 at the end of this section. OSHA has determined that several of
these ancillary provisions will increase the benefits of the final
rule, for example, by helping to ensure the TWA PEL is not exceeded or
by lowering the risks to workers given the significant risk remaining
at the final TWA PEL. However, except for Regulatory Alternative #7
(involving the elimination of all ancillary provisions), OSHA did not
estimate changes in monetized benefits for the regulatory alternatives
that affect ancillary provisions. Two regulatory alternatives that
involve all ancillary provisions are presented below (#7 and #8),
followed by regulatory alternatives for exposure monitoring (#9, #10,
and #11), for regulated areas (#12), for personal protective clothing
and equipment (#13), for medical surveillance (#14 through #20), and
for medical removal protection (#22).
All Ancillary Provisions
The SBAR Panel recommended that OSHA analyze a PEL-only standard as
a regulatory alternative. The Panel also recommended that OSHA consider
not applying ancillary provisions of the standard where exposure levels
are low so as to minimize costs for small businesses (SBAR, 2008). In
response to these recommendations, OSHA analyzed Regulatory Alternative
#7, a PEL-only standard, and Regulatory Alternative #8, which would
apply ancillary provisions of the beryllium standard only where
exposures exceed the final TWA PEL of 0.2 μg/m3\ or the final STEL
of 2.0 μg/m3\.
Regulatory Alternative #7 would only update 1910.1000 Tables Z-1
and Z-2, so that the final TWA PEL and STEL would apply to all workers
in general industry, construction, and maritime. This alternative would
eliminate all of the ancillary provisions of the final rule, including
exposure assessment, medical surveillance, medical removal protection,
PPE, housekeeping, training, competent person, and regulated areas or
access control. Under this regulatory alternative, OSHA estimates that
the costs for the final ancillary provisions of the rule (estimated at
$61.4 million annually at a 3 percent discount rate) would be
eliminated. In order to meet the PELs, employers would still commonly
need to do monitoring, train workers on the use of controls, and set up
some kind of regulated areas to indicate where respirator use would be
required. It is also likely that, under this alternative, many
employers would follow the recommendations of Materion and the United
Steelworkers to provide medical surveillance, PPE, and other protective
measures for their workers (Materion and United Steelworkers, 2012).
OSHA has not attempted to estimate the extent to which these ancillary
provision costs would be incurred if they were not formally required or
whether any of
these costs under Regulatory Alternative #7 would reasonably be
attributable to the final rule. The total costs for this alternative
are $12.5 million at a 3% discount rate and $13.5 million at a 7%
discount rate.
OSHA has also estimated the effect of this regulatory alternative
on the benefits of the rule, presented in Table VIII-16. As a result of
eliminating all of the ancillary provisions, annualized benefits are
estimated to decrease 71 percent, relative to the final rule, from
$560.9 million to $211.9 million, using a 3 percent discount rate, and
from $249.1 million to $94.0 million using a 7 percent discount rate.
This estimate follows from OSHA's analysis of benefits in Chapter VII
of the FEA, which found that about 68 percent of the benefits of the
final rule, evaluated at their mid-point value, were attributable to
the combination of the ancillary provisions. As these estimates show,
OSHA expects that the benefits estimated under the final rule will not
be fully achieved if employers do not implement the ancillary
provisions of the final rule.
Both industry and worker groups have recognized that a
comprehensive standard is needed to protect workers exposed to
beryllium. The stakeholders' recommended standard--that representatives
of Materion, the primary beryllium producer, and the United
Steelworkers union provided to OSHA--confirms the importance of
ancillary provisions in protecting workers from the harmful effects of
beryllium exposure (Materion and United Steelworkers, 2012). Ancillary
provisions such as personal protective clothing and equipment,
regulated areas, medical surveillance, hygiene areas, housekeeping
requirements, and hazard communication all serve to reduce the risks to
beryllium-exposed workers beyond that which the final TWA PEL alone
could achieve.
Under Regulatory Alternative #8, several ancillary provisions that
the current final rule would require under a variety of exposure
conditions (e.g., dermal contact, any airborne exposure, exposure at or
above the action level) would instead only apply where exposure levels
exceed the TWA PEL or STEL.
Regulatory Alternative #8 affects the following provisions of the
final standard:
--Exposure monitoring: Whereas the scheduled monitoring option of the
final standards requires monitoring every six months when exposure
levels are at or above the action level and at or below the TWA PEL and
every three months when exposure levels exceed the TWA PEL, Regulatory
Alternative #8 would require annual exposure monitoring where exposure
levels exceed the TWA PEL or STEL;
[cir] Written exposure control plan: Whereas the final standards
require written exposure control plans to be maintained in any facility
covered by the standard, Regulatory Alternative #8 would require only
facilities with exposures above the TWA PEL or STEL to maintain a plan;
[cir] PPE: Whereas the final standards require PPE when airborne
exposure to beryllium exceeds, or can reasonably be expected to exceed,
the PEL or STEL, and where there is a reasonable expectation of dermal
contact with beryllium, Alternative #8 would require PPE only for
employees exposed above the TWA PEL or STEL;
[cir] Medical Surveillance: Whereas the final standard's medical
surveillance provisions require employers to offer medical surveillance
to employees exposed above the action level for 30 days per year,
showing signs or symptoms of CBD, exposed to beryllium in an emergency,
or when recommended by a medical opinion, Alternative #8 would require
surveillance only for those employees exposed above the TWA PEL or
STEL.
To estimate the cost savings for this alternative, OSHA re-
estimated the group of workers that would fall under the above
provisions, with results presented in Table VIII-16. Combining these
various adjustments along with associated unit costs, OSHA estimates
that, under this regulatory alternative, the costs for the final rule
would decline from $73.9 million to $35.8 million, using a 3 percent
discount rate, and from $76.6 million to $37.9 million, using a 7
percent discount rate.
The Agency has not quantified the impact of this alternative on the
benefits of the rule. However, ancillary provisions that offer
protective measures to workers exposed below the final TWA PEL, such as
personal protective clothing and equipment, beryllium work areas,
hygiene areas, housekeeping requirements, and hazard communication, all
serve to reduce the risks to beryllium-exposed workers beyond that
which the final TWA PEL and STEL could achieve.
The remainder of this chapter discusses additional regulatory
alternatives that apply to individual ancillary provisions.
Exposure Monitoring
Paragraph (d) of the final standard, Exposure Assessment, allows
employers to choose either the performance option or scheduled
monitoring. The scheduled monitoring option requires semi-annual
monitoring for those workers exposed at or above the action level but
at or below the PEL and quarterly exposure monitoring for those workers
exposed above the PEL. The rationale for this provision is provided in
the preamble discussion of paragraph (a) in Section XVI, Summary and
Explanation of the Standards.
OSHA has examined three regulatory alternatives that would modify
the requirements of periodic monitoring in the final rule. Under
Regulatory Alternative #9, employers would be required to perform
periodic exposure monitoring annually when exposures are at or above
the action level or above the STEL, but at or below the TWA PEL. As
shown in Table VIII-16, Regulatory Alternative #9 would decrease the
annualized cost of the final rule by about $4.3 million using either a
3 percent or 7 percent discount rate.
Under Regulatory Alternative #10, employers would be required to
perform periodic exposure monitoring annually when exposures are at or
above the action level. As shown in Table VIII-16, Regulatory
Alternative #10 would decrease the annualized cost of the final rule by
about $4.9 million using either a 3 percent or 7 percent discount rate.
Under Regulatory Alternative #11, employers would be required to
perform annual exposure monitoring where exposures are at or above the
action level but at or below the TWA PEL and STEL. When exposures are
above the TWA PEL, no periodic monitoring would be required. As shown
in Table VIII-16, Regulatory Alternative #11 would decrease the
annualized cost of the final rule by about $5.0 million using either a
3 percent or 7 percent discount rate. OSHA is unable to quantify the
effect of this change on benefits but has judged the alternative
adopted necessary and protective.
Regulated Areas
Final paragraph (e) for General Industry requires employers to
establish and maintain beryllium work areas in any work area containing
a process or operation that can release beryllium where employees are,
or can reasonably be expected to be, exposed to airborne beryllium at
any level or where there is the potential for dermal contact with
beryllium, and regulated areas wherever airborne concentrations of
beryllium exceed, or can reasonably be expected to
exceed, the TWA PEL or STEL. The Shipyards standard also requires
regulated areas. The Construction standard has a comparable competent
person requirement. Employers in General Industry and Shipyards are
required to demarcate regulated areas and limit access to regulated
areas to authorized persons.
The SBAR Panel report recommended that OSHA consider dropping or
limiting the provision for regulated areas (SBAR, 2008). In response to
this recommendation, OSHA examined Regulatory Alternative #12, which
would eliminate the requirement that employers establish regulated
areas in the General Industry and Maritime standards, and eliminate the
competent person requirement in the Construction standard. This
alternative would not eliminate the final requirement to establish
beryllium work areas, where required. As shown in Table VIII-16,
Regulatory Alternative #12 would decrease the annualized cost of the
final rule by about $1.0 million using either a 3 or 7 percent discount
rate.
Personal Protective Clothing and Equipment
Regulatory Alternative #13 would modify the requirements for
personal protective equipment (PPE) by eliminating the requirement for
appropriate PPE whenever there is potential for skin contact with
beryllium or beryllium-contaminated surfaces. This alternative would be
narrower, and thus less protective, than the PPE requirement in the
final standards, which require PPE to be used where airborne exposure
exceeds, or can reasonably be expected to exceed, the TWA PEL or STEL,
or where there is a reasonable expectation of dermal contact with
beryllium.
The economic analysis for the final standard already contains costs
for protective clothing, namely gloves, for all employees who can
reasonably be expected to be have dermal contact with beryllium; thus
OSHA estimated the cost of this alternative as the cost reduction from
not providing gloves under these circumstances. As shown in Table VIII-
16, Regulatory Alternative #13 would decrease the annualized cost of
the final rule by about $481,000 using either a 3 percent or 7 percent
discount rate.
Medical Surveillance
The final requirements for medical surveillance include: (1)
Medical examinations, including a test for beryllium sensitization, for
employees who are or are reasonably expected to be exposed to beryllium
at or above the action level for more than 30 days per year, who show
signs or symptoms of CBD or other beryllium-related health effects, are
exposed to beryllium in an emergency, or whose more recent written
medical opinion required by paragraph (k)(6) or (k)(7) recommends such
surveillance, and (2) low dose CT scans for employees when recommended
by the PLCHP. The final standards require biennial medical exams to be
provided for eligible employees. The standards also require tests for
beryllium sensitization to be provided to eligible employees
biennially.
OSHA estimated in Chapter V of the FEA that the medical
surveillance requirements would apply to 4,528 workers in general
industry, of whom 387 already receive medical surveillance.\35\ In
Chapter V of the FEA, OSHA estimated the costs of medical surveillance
for the remaining 4,141 workers who would now have such protection due
to the final standard. The Agency's final analysis indicates that 4
workers with beryllium sensitization and 6 workers with CBD will be
referred to a CBD diagnostic center annually as a result of this
medical surveillance. Medical surveillance is particularly important
for this rule because beryllium-exposed workers, including many workers
exposed below the final PELs, are at significant risk of illness.\36\
---------------------------------------------------------------------------
\35\ See baseline compliance rates for medical surveillance in
Chapter III of the FEA, Table III-20.
\36\ OSHA did not estimate, and the benefits analysis does not
include, monetized benefits resulting from early discovery of
illness.
---------------------------------------------------------------------------
OSHA has examined four regulatory alternatives (#15, #16, #18, and
#22) that would modify the final rule's requirements for employee
eligibility, the tests that must be offered, and the frequency of
periodic exams. Medical surveillance was a subject of special concern
to SERs during the SBAR Panel process, and the SBAR Panel offered many
comments and recommendations related to medical surveillance for OSHA's
consideration. Some of the Panel's concerns have been partially
addressed in this final rule, which was modified since the SBAR Panel
was convened (see the preamble at Section XVI, Summary and Explanation
of the Standards, for more detailed discussion). Regulatory Alternative
#16 also responds to recommendations by the SBAR Panel to reduce
burdens on small businesses by dropping or reducing the frequency of
medical surveillance requirements.
OSHA has determined that a significant risk of beryllium
sensitization, CBD, and lung cancer exists at exposure levels below the
final TWA PEL and that there is evidence that beryllium sensitization
can occur even from short-term exposures (see the preamble at Section
V, Health Effects, and Section VII, Significance of Risk). The Agency
therefore anticipates that more employees would develop adverse health
effects without receiving the benefits of early intervention in the
disease process because they are not eligible for medical surveillance
(see section XVI of this preamble, the Summary and Explanation for
paragraph (k)).
Regulatory Alternative #15 would decrease eligibility for medical
surveillance to employees who are exposed to beryllium above the final
PEL
To estimate the cost of Regulatory Alternative #15, OSHA assumed
that all workers exposed above the PEL before the final rule would
continue to be exposed after the standard is promulgated. Thus, this
alternative eliminates costs for medical exams for the number of
workers exposed between the action level and the TWA PEL. As shown in
Table VIII-16, Regulatory Alternative #15 would decrease the annualized
cost of the final rule by about $4.5 million using a discount rate of 3
percent, and by about $4.8 million using a discount rate of 7 percent.
In response to concerns raised during the SBAR Panel process about
testing requirements, OSHA considered two regulatory alternatives that
would provide greater flexibility in the program of tests provided as
part of an employer's medical surveillance program. Under Regulatory
Alternative #16, employers would not be required to offer employees
testing for beryllium sensitization. As shown in Table VIII-16, this
alternative would decrease the annualized cost of the final rule by
about $2.4 million using either a 3 percent or 7 percent discount rate.
Regulatory Alternative #18 would eliminate the CT scan requirement
from the final rule. This alternative would decrease the annualized
cost of the final rule by about $613,000 using a discount rate of 3
percent, and by about $643,000 using a discount rate of 7 percent.
Medical Removal
Under paragraph (l) of the final standard, Medical Removal,
employees in jobs with exposure at or above the action level become
eligible for medical removal when they provide their employers with a
written medical report indicating they are diagnosed with CBD or
confirmed positive for beryllium sensitization, or if a written medical
opinion recommends medical removal
in accordance with the medical surveillance paragraph of the standards.
When an employee chooses removal, the employer is required to remove
the employee to comparable work in an environment where beryllium
exposure is below the action level if such work is available and the
employee is either already qualified or can be trained within one
month. If comparable work is not available, the employer must place the
employee on paid leave for six months or until comparable work becomes
available (whichever comes first). Or, rather than choosing removal, an
eligible employee could choose to remain in a job with exposure at or
above the action level, in which case the employer would have to
provide, and the employee would have to use, a respirator.
The SBAR Panel report included a recommendation that OSHA give
careful consideration to the impacts that an MRP requirement could have
on small businesses (SBAR, 2008). In response to this recommendation,
OSHA analyzed Regulatory Alternative #22, which would remove the final
requirement that employers offer MRP. As shown in Table VIII-16, this
alternative would decrease the annualized cost of the final rule by
about $1.2 million using a discount rate of 3 percent, and by about
$1.3 million using a discount rate of 7 percent.
[GRAPHIC] [TIFF OMITTED] TR09JA17.057
SBAR Panel
Table VIII-17 lists all of the SBAR Panel recommendations and
OSHA's response to those recommendations.
Table VIII-17: SBAR Panel Recommendations and OSHA Responses
------------------------------------------------------------------------
Panel recommendation OSHA response
------------------------------------------------------------------------
The Panel recommends that OSHA evaluate OSHA has reviewed its cost
carefully the costs and technological estimates and the
feasibility of engineering controls at technological feasibility of
all PEL options, especially those at engineering controls at
the lowest levels. various PEL levels. These
issues are discussed in the
Regulatory Alternatives
Chapter.
The Panel recommends that OSHA consider OSHA has removed the initial
alternatives that would alleviate the exposure monitoring
need for monitoring in operations with requirement for workers likely
exposures far below the PEL. The Panel to be exposed to beryllium by
also recommends that OSHA consider skin or eye contact through
explaining more clearly how employers routine handling of beryllium
may use "objective data" to estimate powders or dusts or contact
exposures. Although the draft proposal with contaminated surfaces.
contains a provision allowing The periodic monitoring
employers to initially estimate requirement presented in the
exposures using "objective data" SBAR Panel report required
(e.g., data showing that the action monitoring every 6 months for
level is unlikely to be exceeded for airborne levels at or above
the kinds of process or operations an the action level but below the
employer has), the SERs did not appear PEL, and every 3 months for
to have fully understood how this exposures at or above the PEL.
alternative may be used. The final standard, in line
with OSHA's normal practice,
requires exposure monitoring
every three months for levels
above the PEL or STEL and
every six months for exposures
between the action level and
the PEL. In the preamble to
the final standard, OSHA
provides further explanation
on the use of objective data,
which would exempt employers
from the requirements of the
final rule.
These issues are discussed in
the preamble at Section XVI,
Summary and Explanation of the
Standards, (d): Exposure
Monitoring.
The Panel recommends that OSHA consider In the preamble to the final
providing some type of guidance to standards, OSHA discusses the
describe how to use objective data to issue of objective data. While
estimate exposures in lieu of OSHA recognizes that some
conducting personal sampling. establishments will have
Using objective data could provide objective data, for purposes
significant regulatory relief to of estimating the cost of this
several industries where airborne rule, the Agency is assuming
exposures are currently reported by that no establishments will
SERs to be well below even the lowest use objective data. The Agency
PEL option. In particular, since recognizes that this will
several ancillary provisions, which overestimate costs.
may have significant costs for small The use of objective data is
entities may be triggered by the PEL discussed in the preamble at
or an action level, OSHA should Section XVI, Summary and
consider encouraging and simplifying Explanation of the Standards,
the development of objective data from (d): Exposure Monitoring.
a variety of sources.
The Panel recommends that OSHA revisit SERs with very low exposure
its analysis of the costs of regulated levels or only occasional work
areas if a very low PEL is proposed. with beryllium will not be
Drop or limit the provision for required to have regulated
regulated areas: SERs with very low areas unless exposures are
exposure levels or only occasional above the final PEL of 0.2
work with beryllium questioned the μg/m3\.
need for separating areas of work by The final standards for general
exposure level. Segregating machines industry and maritime require
or operations, SERs said, would affect the employer to establish and
productivity and flexibility. Until maintain a regulated area
the health risks of beryllium are wherever employees are, or can
known in their industries, SERs be expected to be, exposed to
challenged the need for regulated airborne beryllium at levels
areas. above the PEL of 0.2 μg/
m3\. There is no regulated
area requirement in
Construction.
The Panel recommends that OSHA revisit In General industry employers
its cost model for hygiene areas to must ensure that employees who
reflect SERs' comments that estimated have dermal contact with
costs are too low and more carefully beryllium wash any exposed
consider the opportunity costs of skin at the end of the
using space for hygiene areas where activity, process, or work
SERs report they have no unused space shift and prior to eating,
in their physical plant for them. The drinking, smoking, chewing
Panel also recommends that OSHA tobacco or gum, applying
consider more clearly defining the cosmetics, or using the
triggers (skin exposure and toilet. In General Industry,
contaminated surfaces) for the hygiene although there is a shower
areas provisions. In addition, the requirement, OSHA has
Panel recommends that OSHA consider determined that establishments
alternative requirements for hygiene required to have showers will
areas dependent on airborne exposure already have them, and
levels or types of processes. Such employers will not have to
alternatives might include, for install showers to comply with
example, hand washing facilities in the beryllium standard (Please
lieu of showers in particular cases or see the Hygiene Areas and
different hygiene area triggers where Practices section in Chapter V
exposure levels are very low. of the FEA). In Construction
and Maritime, for each
employee required to use
personal protective clothing
or equipment, the employer
must ensure that employees who
have dermal contact with
beryllium wash any exposed
skin at the end of the
activity, process, or work
shift and prior to eating,
drinking, smoking, chewing
tobacco or gum, applying
cosmetics, or using the
toilet. For Construction and
Maritime, language involving
showers has been removed but
employers are still required
to provide change rooms. Where
personal protective clothing
or equipment must be used, the
employer must provide washing
facilities. The standards do
not require that eating and
drinking areas be provided,
but impose requirements when
the employer chooses to have
eating and drinking areas.
Change rooms have been costed
in general industry for
employees who work in a
beryllium work area and in
construction and maritime for
employees who required to use
personal protective clothing
or equipment. The Agency has
determined that the long-term
rental of modular units is
representative of costs for a
range of reasonable approaches
to comply with the change room
part of the provision.
Alternatively, employers could
renovate and rearrange their
work areas in order to meet
the requirements of this
provision.
The Panel recommends that OSHA consider In the preamble to the final
clearly explaining the purpose of the rule, OSHA has clarified the
housekeeping provision and describing purpose of the housekeeping
what affected employers must do to provision. However, due to the
achieve it. variety of work settings in
For example, OSHA should consider which beryllium is used, OSHA
explaining more specifically what has concluded that a highly
surfaces need to be cleaned and how specific directive in the
frequently they need to be cleaned. preamble on what surfaces need
The Panel recommends that the Agency to be cleaned, and how
consider providing guidance in some frequently, would not provide
form so that employers understand what effective guidance to
they must do. The Panel also businesses. Instead, at the
recommends that once the requirements suggestion of industry and
are clarified that the Agency re- union stakeholders (Materion
analyze its cost estimates. and USW, 2012), OSHA's final
The Panel also recommends that OSHA standards include a more
reconsider whether the risk and cost flexible requirement for
of all parts of the medical employers to develop a written
surveillance provisions are exposure control plan specific
appropriate where exposure levels are to their facilities. In
very low. In that context, the Panel general industry, the employer
recommends that OSHA should also must establish procedures to
consider the special problems and maintain all surfaces in
costs to small businesses that up beryllium work areas as free
until now may not have had to provide as practicable of beryllium as
or manage the various parts of an required by the written
occupational health standard or exposure control plan. Other
program. than requirements pertaining
to eating and drinking areas,
there are no requirements to
maintain surface cleanliness
in construction or maritime.
These issues are discussed in
the preamble at Section XVI,
Summary and Explanation of the
Standards, (f) Methods of
Compliance and (j)
Housekeeping. The adoption of
Regulatory Alternative #20 in
the PEA reduced the frequency
of physical examinations from
annual to biennial, matching
the frequency of BeLPT testing
in the final rule.
These alternatives for medical
surveillance are discussed in
the Regulatory Alternatives
Chapter, Chapter VIII and in
the preamble at section XVI,
Summary and Explanation of the
Standards, (k) Medical
Surveillance.
The Panel recommends that OSHA consider Under the final standards, skin
that small entities may lack the exposure is not a trigger for
flexibility and resources to provide medical removal (unlike the
alternative jobs to employees who test draft version used for the
positive for the BeLPT, and whether SBAR Panel). Employees are
medical removal protection (MRP) only eligible for medical
achieves its intended purpose given removal if they are in a job
the course of beryllium disease. The with airborne exposure at or
Panel also recommends that if MRP is above the action level and
implemented, that its effects on the provide the employer with a
viability of very small firms with a written medical report
sensitized employee be considered confirming that they are
carefully. sensitized or have been
diagnosed with CBD, or that
the physician recommends
removal, or if the employer
receives a written medical
opinion recommending removal
of the employee. After
becoming eligible for medical
removal an employee may choose
to remain in a job with
exposure at or above the
action level, provided that
the employer provides and the
employee wears a respirator in
accordance with the
Respiratory Protection
standard (29 CFR 1910.134). If
the employee chooses removal,
the employer is only required
to place the employee in
comparable work with exposure
below the action level if such
work is available; if such
work is not available, the
employer may place the
employee on paid leave for six
months or until such work
becomes available, whichever
comes first.
OSHA discusses the basis of the
provision in the preamble at
Section XVI, Summary and
Explanation of the Standards,
(l) Medical Removal
Protection. OSHA provides an
analysis of costs and economic
impacts of the provision in
the FEA in Chapter V and
Chapter VI, respectively.
The Panel recommends that OSHA consider As stated above, the triggers
more clearly defining the trigger for medical surveillance in
mechanisms for medical surveillance the final standard have
and also consider additional or changed from those presented
alternative triggers--such as limiting to the SBAR Panel. Whereas the
the BeLPT to a narrower range of draft standard presented at
exposure scenarios and reducing the the SBAR Panel required
frequency of BeLPT tests and physical medical surveillance for
exams. The Panel also recommends that employees with skin contact--
OSHA reconsider whether the risk and potentially applying to
cost of all parts of the medical employees with any level of
surveillance provisions are airborne exposure--the final
appropriate where exposure levels are standard ties medical
very low. In that context, the Panel surveillance to exposures at
recommends that OSHA should also or above the action level for
consider the special problems and more than 30 days per year (or
costs to small businesses that up signs or symptoms of beryllium-
until now may not have had to provide related health effects,
or manage the various parts of an emergency exposure, or a
occupational health standard or medical opinion recommending
program. medical surveillance on the
basis of a CBD or
sensitization diagnosis).
Thus, small businesses with
exposures below the final
action level would not need to
provide or manage medical
surveillance for their
employees unless employees
develop signs or symptoms of
beryllium-related health
effects or are exposed in
emergencies.
These issues are discussed in
the preamble at section XVI,
Summary and Explanation of the
Standards, (k) Medical
Surveillance.
The Panel recommends that the Agency, OSHA has reviewed the possible
in evaluating the economic feasibility effects of the final
of a potential regulation, consider regulation on market demand
not only the impacts of estimated and/or foreign production, in
costs on affected establishments, but addition to the Agency's usual
also the effects of the possible measures of economic impact
outcomes cited by SERs: Loss of market (costs as a fraction of
demand, the loss of market to foreign revenues and profits). This
competitors, and of U.S. production discussion can be found in
being moved abroad by U.S. firms. The Chapter VI of the FEA
Panel also recommends that OSHA (entitled Economic Feasibility
consider the potential burdens on Analysis and Regulatory
small businesses of dealing with Flexibility Determination).
employees who have a positive test
from the BeLPT. OSHA may wish to
address this issue by examining the
experience of small businesses that
currently provide the BeLPT test.
The Panel recommends that OSHA consider The provisions in the standard
seeking ways of minimizing costs for presented in the SBAR panel
small businesses where the exposure report applied to all
levels may be very low. Clarifying the employees, whereas the final
use of objective data, in particular, standard's ancillary
may allow industries and provisions are only applied to
establishments with very low exposures employees in work areas who
to reduce their costs and involvement are, or can reasonably be
with many provisions of a standard. expected to be, exposed to
The Panel also recommends that the airborne beryllium. In
Agency consider tiering the addition, the scope of the
application of ancillary provisions of final standard includes
the standard according to exposure several limitations. Whereas
levels and consider a more limited or the standard presented in the
narrowed scope of industries. SBAR panel report covered
beryllium in all forms and
compounds in general industry,
construction, and maritime,
the scope of the final
standard (1) does not apply to
beryllium-containing articles
that the employer does not
process; and (2) does not
apply to materials that
contain less than 0.1%
beryllium by weight if the
employer has objective data
demonstrating that employee
exposure to beryllium will
remain below the action level
as an 8-hour TWA under any
foreseeable conditions.
In the preamble to the final
standard, OSHA has clarified
the circumstances under which
an employer may use historical
and objective data in lieu of
initial monitoring (Section
XVI, Summary and Explanation
of the Standards, (d) Exposure
Monitoring).
OSHA also considered two
Regulatory Alternatives that
would reduce the impact of
ancillary alternatives on
employers, including small
businesses. Regulatory
Alternative #7, a PEL-only
standard, would drop all
ancillary provisions from the
standard. Regulatory
Alternative #8 would limit the
application of several
ancillary provisions,
including Exposure Monitoring,
the written exposure control
plan section of Method of
Compliance, PPE, Housekeeping,
and Medical Surveillance, to
operations or employees with
exposure levels exceeding the
TWA PEL or STEL.
These alternatives are
discussed in the Regulatory
Alternatives, Chapter VIII of
the FEA.
The Panel recommends that OSHA provide The explanation and analysis
an explanation and analysis for all for all health outcomes (and
health outcomes (and their scientific their scientific basis) are
basis) upon which it is regulating discussed in the preamble to
employee exposure to beryllium. The the final standard at Section
Panel also recommends that OSHA V, Health Effects, and Section
consider to what extent a very low PEL VI, Risk Assessment. They are
(and lower action level) may result in also reviewed in the preamble
increased costs of ancillary to the final standard at
provisions to small entities (without Section VII, Significance of
affecting airborne employee Risk, and the Benefits Chapter
exposures). Since in the draft of the FEA.
proposal the PEL and action level are As discussed above, OSHA
critical triggers, the Panel considered Regulatory
recommends that OSHA consider Alternatives #7 and #8, which
alternate action levels, including an would eliminate or reduce the
action level set at the PEL, if a very impact of ancillary provisions
low PEL is proposed. on employers, respectively.
These alternatives are
discussed in Chapter VIII of
the FEA.
The Panel recommends that OSHA consider OSHA has removed skin exposure
more clearly and thoroughly defining as a trigger for several
the triggers for ancillary provisions, ancillary provisions in the
particularly the skin exposure final standard, including
trigger. In addition, the Panel Exposure Assessment and
recommends that OSHA clearly explain Medical Surveillance. For each
the basis and need for small entities employee working in a
to comply with ancillary provisions. beryllium work area in general
The Panel also recommends that OSHA industry, and for each
consider narrowing the trigger related employee required to use
to skin and contamination to capture personal protective clothing
only those situations where surfaces or equipment in construction
and surface dust may contain beryllium and maritime, the employer
in a concentration that is significant must ensure that employees who
enough to pose any risk--or limiting have dermal contact with
the application of the trigger for beryllium wash any exposed
some ancillary provisions. skin at the end of the
activity, process, or work
shift and prior to eating,
drinking, smoking, chewing
tobacco or gum, applying
cosmetics, or using the
toilet. In addition, the
potential for dermal contact
with beryllium triggers
requirements related to
beryllium work areas, the
written exposure control plan,
washing facilities,
housekeeping and training: For
some ancillary provisions,
including PPE and
Housekeeping, the requirements
are triggered by visible
contamination with beryllium
or dermal contact with
beryllium.
In Construction and Maritime,
for each employee required to
use personal protective
clothing or equipment, the
employer must ensure that
employees who have dermal
contact with beryllium wash
any exposed skin at the end of
the activity, process, or work
shift and prior to eating,
drinking, smoking, chewing
tobacco or gum, applying
cosmetics, or using the
toilet. For Construction and
Maritime, language involving
showers has been removed and
employers are required to
provide change rooms for
employees required to use
personal protective clothing
or equipment and required to
remove their personal
clothing. Where dermal contact
occurs, employers must provide
washing facilities.
These requirements are
discussed in the preamble at
Section XVI, Summary and
Explanation of the Standards.
The Agency has also explained
the basis and need for
compliance with ancillary
provisions in the preamble at
Section XVI, Summary and
Explanation of the Standards.
Several SERs said that OSHA should In the Technological
first assume the burden of describing Feasibility Analysis presented
the exposure level in each industry in the FEA, OSHA has described
rather than employers doing so. Others the baseline exposure levels
said that the Agency should accept in each industry or
exposure determinations made on an application group.
industry-wide basis, especially where In the preamble to the final
exposures were far below the PEL standards, OSHA discusses the
options under consideration. issue of objective data. While
As noted above, the Panel recommends OSHA recognizes that some
that OSHA consider alternatives that establishments will have
would alleviate the need for objective data, for purposes
monitoring in operations or processes of the economic analysis, the
with exposures far below the PEL. The Agency is choosing to assume
use of objective data is a principal that no establishments will
method for industries with low use objective data. The Agency
exposures to satisfy compliance with a recognizes that this will
proposed standard. The Panel overestimate costs.
recommends that OSHA consider
providing some guidance to small
entities in the use of objective data.
The Panel recommends that OSHA consider OSHA has provided discussion of
more fully evaluating whether the the BeLPT in the preamble to
BeLPT is suitable as a test for the final rule at section V,
beryllium sensitization in an OSHA Health Effects; and in the
standard and respond to the points preamble at section XVI,
raised by the SERs about its efficacy. Summary and Explanation of the
In addition, the Agency should Standards, (b) Definitions and
consider the availability of other (k) Medical Surveillance. In
tests under development for detecting the regulatory text, OSHA has
beryllium sensitization and not limit clarified that a test for
either employers' choices or new beryllium sensitization other
science and technology in this area. than the BeLPT may be used in
Finally, the Panel recommends that lieu of the BeLPT if a more
OSHA re-consider the trigger for reliable and accurate
medical surveillance where exposures diagnostic test is developed.
are low and consider if there are As stated above, the triggers
appropriate alternatives. for medical surveillance in
the final standard have
changed from those presented
to the SBAR Panel. Whereas the
draft standard presented
during the SBREFA process
required medical surveillance
for employees with skin
contact--potentially applying
to employees with any level of
airborne exposure--the final
standard ties medical
surveillance to exposures
above the final action level
of 0.1 μg/m3\ (or signs or
symptoms of beryllium-related
health effects, emergency
exposure, or a medical opinion
recommending medical
surveillance on the basis of a
CBD or sensitization
diagnosis). The triggers for
medical surveillance are
discussed in the preamble at
section XVI, Summary and
Explanation of the Standards,
(k) Medical Surveillance.
OSHA has considered Regulatory
Alternative #16, where
employers would not be
required to offer employees a
BeLPT that tests for beryllium
sensitization. from the final
standard. This alternative is
discussed in the Regulatory
Alternatives Chapter and in in
the preamble at Section XVI,
Summary and Explanation of the
Final Standard, (k) Medical
Surveillance.
Seeking ways of minimizing costs to low- The standard presented in the
risk processes and operations: OSHA SBAR panel report had skin
should consider alternatives for exposure as a trigger. The
minimizing costs to industries, final standards require PPE
operations, or processes that have low when there is a reasonable
exposures. Such alternatives may expectation of dermal contact
include, but not be limited to: with beryllium. The employer
Encouraging the use of objective data must ensure that employees who
by such mechanisms as providing have dermal contact with
guidance for objective data; assuring beryllium wash any exposed
that triggers for skin exposure and skin at the end of the
surface contamination are clear and do activity, process, or work
not pull in low-risk operations; shift and prior to eating,
providing guidance on least-cost ways drinking, smoking, chewing
for low risk facilities to determine tobacco or gum, applying
what provisions of the standard they cosmetics, or using the
need to comply with; and considering toilet. OSHA uses an exposure
ways to limit the scope of the profile to determine which
standard if it can be ascertained that workers will be affected by
certain processes do not represent a the standards. As a result, in
significant risk. General Industry and Maritime,
the final standards require
regulated areas where
exposures can exceed the PEL
or STEL. In General Industry,
beryllium work areas must be
established in areas that
contain a process or operation
that can release beryllium
where employees are, or can
reasonably be expected to be,
exposed to airborne beryllium
at any level or where there is
the potential for dermal
contact with beryllium.
In Construction, the written
exposure control plan must
contain procedures used to
restrict access to work areas
when airborne exposures are,
or can reasonably be expected
to be, above the TWA PEL or
STEL, and the competent person
must implement the plan.
In addition, the scope of the
final standards includes
several limitations. Whereas
the standard presented in the
SBAR panel report covered
beryllium in all forms and
compounds in general industry,
construction, and maritime,
the scope of the final
standard (1) does not apply to
beryllium-containing articles
that the employer does not
process; and (2) does not
apply to materials that
contain less than 0.1%
beryllium by weight where the
employer has objective data
demonstrating that employee
exposure to beryllium will
remain below the action level
as an 8-hour TWA under any
foreseeable conditions. In the
preamble to the final
standards, OSHA discusses the
issue of objective data. While
OSHA recognizes that some
establishments will have
objective data, for purposes
of this rule, the Agency is
choosing to assume that no
establishments will use
objective data. The Agency
recognizes that this will
overestimate costs.
PEL-only standard: One SER recommended OSHA considered Regulatory
a PEL-only standard. This would Alternative #7, a PEL-only
protect employees from airborne standard. This alternative is
exposure risks while relieving the discussed in Chapter VIII of
beryllium industry of the cost of the the FEA.
ancillary provisions. The Panel
recommends that OSHA, consistent with
its statutory obligations, analyze
this alternative.
Alternative triggers for ancillary OSHA has removed skin exposure
provisions: The Panel recommends that as a trigger for several
OSHA clarify and consider eliminating ancillary provisions in the
or narrowing the triggers for final standard, including
ancillary provisions associated with Exposure Monitoring and
skin exposure or contamination. In Medical Surveillance. In
addition, the Panel recommends that General Industry, the employer
OSHA should consider trying ancillary must ensure that employees who
provisions dependent on exposure have dermal contact with
rather than have these provisions all beryllium wash any exposed
take effect with the same trigger. If skin at the end of the
OSHA does rely on a trigger related to activity, process, or work
skin exposure, OSHA should thoroughly shift and prior to eating,
explain and justify this approach drinking, smoking, chewing
based on an analysis of the scientific tobacco or gum, applying
or research literature that shows a cosmetics, or using the
risk of sensitization via exposure to toilet.
skin. If OSHA adopts a relatively low In Construction and Maritime,
PEL, OSHA should consider the effects for each employee required to
of alternative airborne action levels use personal protective
in pulling in many low risk facilities clothing or equipment, the
that may be unlikely to exceed the employer must ensure that
PEL--and consider using only the PEL employees who have dermal
as a trigger at very low levels. contact with beryllium wash
any exposed skin at the end of
the activity, process, or work
shift and prior to eating,
drinking, smoking, chewing
tobacco or gum, applying
cosmetics, or using the
toilet.
In addition, the language of
the final standard regarding
skin exposure has changed: For
some ancillary provisions,
including PPE and
Housekeeping, the requirements
are triggered by visible
contamination with beryllium
or skin contact with beryllium
compounds.
These requirements are
discussed in the preamble at
Section XVI, Summary and
Explanation of the Standards.
OSHA has explained the
scientific basis for
minimizing skin exposure to
beryllium in the preamble to
the final rule at Section V,
Health Effects, and explains
the basis for specific
ancillary provisions related
to skin exposure in the
preamble at Section XVI,
Summary and Explanation of the
Standards. In the final
standards, the application of
ancillary provisions is
dependent on exposure, and not
all provisions take effect
with the same trigger. A
number of requirements are
triggered by exposures (or a
reasonable expectation of
exposures) above the PEL or
action level (AL). As
discussed above, OSHA
considered Regulatory
Alternatives #7 and #8, which
would eliminate or reduce the
impact of ancillary provisions
on employers, respectively.
These alternatives are
discussed in Chapter VIII of
the FEA.
Revise the medical surveillance After considering comments from
provisions, including eliminating the SERs, OSHA has revised the
BeLPT: The BeLPT was the most common medical surveillance provision
complaint from SERs. The Panel and removed the skin exposure
recommends that OSHA carefully examine trigger for medical
the value of the BeLPT and consider surveillance. As a result,
whether it should be a requirement of OSHA estimates that the number
a medical surveillance program. The of small-business employees
Panel recommends that OSHA present the requiring a BELPT will be
scientific evidence that supports the substantially reduced.
use of the BeLPT as several SERs were OSHA has provided discussion of
doubtful of its reliability. The Panel the BeLPT in the preamble to
recommends that OSHA also consider the final rule at section V,
reducing the frequency of physicals Health Effects; and in the
and the BeLPT, if these provisions are preamble at section XVI,
included in a proposal. The Panel Summary and Explanation of the
recommends that OSHA also consider a Standards, (b) Definitions and
performance-based medical surveillance (k) Medical Surveillance. In
program, permitting employers in the regulatory text, OSHA has
consultation with physicians and clarified that a test for
health experts to develop appropriate beryllium sensitization other
tests and their frequency. than the BeLPT may be used in
lieu of the BeLPT if a more
reliable and accurate
diagnostic test is developed.
The frequency of periodic BeLPT
testing in the final standard
is biennial, whereas annual
testing was included in the
draft standard presented to
the SBAR Panel.
Regulatory Alternative #20
would reduce the frequency of
physical examinations from
biennial to annual, matching
the frequency of BeLPT testing
in the final rule.
In response to the suggestion
to allow performance-based
medical surveillance, OSHA
considered two regulatory
alternatives that would
provide greater flexibility in
the program of tests provided
as part of an employer's
medical surveillance program.
Regulatory Alternative #16
would eliminate BeLPT testing
requirements from the final
standard. Regulatory
Alternative #18 would
eliminate the CT scan
requirement from the final
standard. These alternatives
are discussed in the
Regulatory Alternatives
Chapter and in the preamble at
Section XVI, Summary and
Explanation of the Standards,
(k) Medical Surveillance.
No medical removal protection (MRP): The final standard includes an
OSHA's draft proposed standard did not MRP provision. OSHA discusses
include any provision for medical the basis of the provision in
removal protection, but OSHA did ask the preamble at Section XVI,
the SERs to comment on MRP as a Summary and Explanation of the
possibility. Based on the SER Standards, (l) Medical Removal
comments, the Panel recommends that if Protection. OSHA provides an
OSHA includes an MRP provision, the analysis of costs and economic
agency provide a thorough analysis of impacts of the provision in
why such a provision is needed, what the FEA in Chapter V and
it might accomplish, and what its full Chapter VI, respectively.
costs and economic impacts on those The Agency considered
small businesses that need to use it Alternative #22, which would
might be. eliminate the MRP requirement
from the standard. This
alternative is discussed in
the Regulatory Alternatives
Chapter and in the preamble at
section XVI, Summary and
Explanation of the Standards,
(l) Medical Removal
Protection.
------------------------------------------------------------------------
IX. OMB Review Under the Paperwork Reduction Act of 1995
Introduction
The three final beryllium standards (collectively "the
standards") for occupational exposure to beryllium--general industry
(29 CFR 1910.1024), construction (29 CFR 1926.1124), and shipyard (29
CFR 1915.1024)--contain 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), 44 U.S.C.
3501 et seq, and OMB's regulations at 5 CFR part 1320. The PRA requires
that agencies obtain approval from OMB before conducting any collection
of information (44 U.S.C. 3507). The PRA defines "collection of
information" to mean "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)).
In accordance with the PRA (44 U.S.C. 3506(c)(2)), OSHA solicited
public comments on the Beryllium Standard for General Industry (29 CFR
1910.1024), Information Collection Request (ICR) (paperwork burden hour
and cost analysis) for the proposed rule (80 FR 47555). The Department
submitted this ICR to OMB for review in accordance with 44 U.S.C.
3507(d) on August 7, 2015. A copy of this ICR is available to the
public at http://www.reginfo.gov/public/do/PRAOMBHistory?ombControlNumber=1218-0267).
On October 21, 2015, OMB issued a Notice of Action (NOA) assigning
Beryllium Standard for General Industry new OMB Control Number 1218-
0267 to use in future paperwork submissions involving this rulemaking.
OMB requested that, "Prior to publication of the final rule, the
agency should provide a summary of any comments related to the
information collection and their response, including any changes made
to the ICR as a result of comments. In addition, the agency must enter
the correct burden estimates."
The proposed rule invited the public to submit comments to OMB, in
addition to OSHA, on the proposed collections of information with
regard to the following:
Whether the proposed collections of information are
necessary for the proper performance of the Agency's functions,
including whether the information is useful;
The accuracy of OSHA's estimate of the burden (time and
cost) of the collections of information, including the validity of the
methodology and assumptions used;
The quality, utility, and clarity of the information
collected; and
Ways to minimize the compliance burden on employers, for
example, by using automated or other technological techniques for
collecting and transmitting information (78 FR 56438).
No public comments were received specifically in response to the
proposed ICR submitted to OMB for review. However, several public
comments submitted in response to the Notice of Proposed Rulemaking
(NPRM), described earlier in this preamble, substantively addressed
provisions containing collections of information and contained
information relevant to the burden hour and costs analysis. These
comments are addressed in the preamble, and OSHA considered them when
it developed the revised ICR associated with these final standards.
The Department of Labor submitted the final ICR January 9, 2017
containing a full analysis and description of the burden hours and
costs associated with the collections of information of the standards
to OMB for approval. A copy of the ICR is available to the public at
http://www.reginfo.gov. OSHA will publish a separate notice in the
Federal Register that will announce the results of OMB's review. That
notice will also include a list of OMB approved collections of
information and total burden hours and costs imposed by the new
standards.
Under the PRA, Federal agency cannot conduct or sponsor a
collection of information unless it is approved by OMB under the PRA,
and the collection of information notice displays a currently valid OMB
control number (44 U.S.C. 3507(a)(3)). Also, notwithstanding any other
provision of law, no employer shall be subject to penalty for failing
to comply with a collection of information if the collection of
information does not display a currently valid OMB control number (44
U.S.C. 3512). The major collections of information found in the
standards are listed below.
Summary of Information Collection Requirements
The Beryllium standards contain collection of information
requirements which are essential components of the occupational safety
and health standards that will assist both employers and their
employees in identifying the exposures to beryllium and beryllium
compounds, the medical effects of such exposures, and the means to
reduce the risk of overexposures to beryllium and beryllium compounds.
In the final ICR, OSHA has expanded its coverage to include the
construction and shipyard industries--in order to tailor the collection
of information requirements to the circumstances found in these
sectors. The decision to include standards for construction and
shipyards is based on information and comment submitted in response to
the NPRM request for comment, and during the informal public hearing.
1. Title: Beryllium (29 CFR 1910.1024; 29 CFR 1915.1024; 29 CFR
1926. 1124).
2. Type of Review: New.
3. OMB Control Number: 1218-0267.
4. Affected Public: Business or other for-profit. This standard
applies to employers in general industry, shipyard, and construction
who have employees that may have occupational exposures to any form of
beryllium, including compounds and mixtures, except those articles and
materials exempted by paragraphs (a)(2) and (a)(3) of the Final
standard.
5. Number of Respondents: 5,872 affected employers.
6. Frequency of Responses: On occasion; quarterly, semi-annually,
annual; biannual.
7. Number of Responses: 246,433.
8. Average Time per Response: Varies from 5 minutes (.08 hours) for
a clerical worker to generate and maintain an employee medical record,
to more than 8 hours for a human resource manager to develop and
implement a written exposure control plan.
9. Estimated Total Burden Hours: 196,894.
10. Estimated Cost (capital-operation and maintenance):
$46,158,266.
Discussion of Significant Changes in the Collections of Information
Requirements
Below is a summary of the collection of information requirements
contained in the final rule, and a brief description of the most
significant changes between the proposal and the final rule portions of
the regulatory text containing collection of information requirements.
One of the most significant changes between the NPRM and this final
rule is that OSHA extended the scope of the rule so that the most of
the provisions now also apply to construction and shipyard work. As a
result, while most of the provisions are identical across all three
standards (general industry, construction, and shipyards), there are
technically more collections of information. However, for purposes of
the review and explanation that follows, OSHA has focused on the
changes to the general industry provisions and has not separately
identified the additions to the construction and shipyard standard
unless they deviate from the requirements in the general industry
standard. A more detailed discussion of all the changes made to the
proposed rule, including the requirements that include identified
collection of information, is in Section XVIII: Summary and
Explanation. The impact on information collections is also discussed in
more detail in Item 8 of the ICR.
Exposure Assessment
Paragraph (d) sets forth requirements for assessing employee
exposures to beryllium. Consistent with the definition of "airborne
exposure" in paragraph (b) of these standards, exposure monitoring
results must reflect the exposure to airborne beryllium that would
occur if the employee were not using a respirator.
Proposed paragraph (d) used the term "Exposure monitoring." In
the final rule, this term was changed to "Exposure assessment"
throughout the paragraph. This change in the final standards was made
to align the provision's purpose with the broader concept of exposure
assessment beyond conducting air monitoring, including the use of
objective data.
OSHA added a paragraph (d)(2) as an alternative exposure assessment
method to the scheduled monitoring requirements in the proposed rule.
Under this option employers must assess 8-hour TWA exposure and the 15-
minute short term exposure for each employee using any combination of
air monitoring data and objective data sufficient to accurately
characterize airborne exposure to beryllium.
Proposed paragraph (d)(3), Periodic Exposure Monitoring, would have
required employers whose initial monitoring results indicated that
employee's exposures results are at or above the action level and at or
below the TWA PEL to conduct periodic exposure monitoring at least
annually. Final paragraph (d)(3), Scheduled Monitoring Option,
increased the frequency schedule for periodic monitoring and added a
requirement to perform periodic exposure monitoring when exposures are
above the PEL, paragraph (d)(3)(vi) and when exposures are above the
STEL in paragraph (d)(3)(viii).
Proposed paragraph (d)(4) would have required employers to conduct
exposure monitoring within 30 days after a change in production
processes, equipment, materials, personnel, work practices, or control
methods that could reasonably be expected to result in new or
additional exposures. OSHA changed the proposed requirement to require
that employers perform reassessment of exposures when there is a change
in "production, process, control equipment, personnel, or work
practices" that may reasonably be expected to result in new or
additional exposures at or above the action level or STEL. In addition,
OSHA added "at or above the action level or STEL" to final paragraph
(d)(4). In summary, the final rule requires that employers must perform
reassessment of exposures when there is a change in production,
process, control equipment, personnel, or work practices that may
reasonably be expected to result in new or additional exposures at or
above the action level or STEL.
Proposed paragraph (d)(5)(i), Employee Notification of Monitoring
Results, would have required employers in general industry to inform
their employees of results within 15 working days after receiving the
results of any exposure monitoring completed under this standard. Final
paragraph (d)(6), Employee Notification of Assessment Results, requires
that employers in general industry, construction and shipyards inform
their employees of results within 15 working days after completing an
exposure assessment.
Proposed paragraph (d)(5)(ii) (paragraph (d)(6)(ii) of the final
standards) would have required that whenever an exposure assessment
indicates that airborne exposure is above the TWA PEL or STEL, the
employer must include in the written notification the suspected or
known sources of exposure and the corrective action(s) the employer has
taken or will take to reduce exposure to or below the PELs, where
feasible corrective action exists but had not been implemented when the
monitoring was conducted. Final paragraph (d)(6)(ii) removes the
requirement that employers include suspected or known sources of
exposure in the written notification.
Methods of Compliance
Proposed paragraph (f)(1)(i) would have required employers to
establish, implement and maintain a written control plan for beryllium
work areas. OSHA has retained the requirement for a written exposure
control plan and incorporated most provisions of the proposed paragraph
(f)(1)(i) into the final standards for construction and shipyards, with
certain modifications due to the work processes and worksites
particular to these sectors.
Paragraph (f)(1)(i) differs from the proposal in that it requires a
written exposure control plan for each facility, whereas the proposal
would have required a written exposure control plan for beryllium work
areas within each facility. OSHA has modified the requirement of a list
of operations and job titles reasonably expected to have exposure to
include those operations and job titles that are reasonably expected to
have dermal contact with beryllium. Finally, OSHA modified the proposed
requirement to inventory engineering and work practice controls
required by paragraph (f)(2) of this standard to include respiratory
protection.
Paragraph (f)(1)(ii) of the final standards requires the employer
to review and evaluate the effectiveness of each written exposure
control plan at least annually and update it when: (A) Any change in
production processes, materials, equipment, personnel, work practices,
or control methods results or can reasonably be expected to result in
additional or new airborne exposure to beryllium; (B) the employer is
notified that an employee is eligible for medical removal in accordance
with paragraph
(l)(1) of this standard, referred for evaluation at a CBD Diagnostic
Center, or shows signs or symptoms associated with airborne exposure to
or dermal contact with beryllium; or (C) the employer has any reason to
believe that new or additional airborne exposure is occurring or will
occur.
OSHA made several changes to that paragraph. First, OSHA added a
requirement to review and evaluate the effectiveness of each written
exposure control plan at least annually. Second, OSHA changed the
proposed language of (f)(1)(ii)(B) to reflect other changes in the
standard, including a change to ensure that employers are not
automatically notified of cases of sensitization or CBD among their
employees. Third, OSHA modified (f)(1)(ii)(B) to clarify the Agency's
understanding that signs and symptoms of beryllium exposure may be
related to inhalation or dermal exposure. Finally, OSHA modified the
wording of (f)(1)(ii) to require the employer to update "each"
written exposure control plan rather than "the" written exposure
control plan, since an employer who operates multiple facilities is
required to establish, implement and maintain a written exposure
control plan for each facility.
Paragraph (f)(1)(iii) of the proposed rule would have required the
employer to make a copy of the exposure control plan accessible to each
employee who is or can reasonably be expected to be exposed to airborne
beryllium in accordance with OSHA's Access to Employee Exposure and
Medical Records (Records Access) standard (29 CFR 1910.1020(e)). OSHA
did not receive comments specific to this provision, and has retained
it in the final standard for general industry and included the
paragraph in the final standards for construction and shipyards.
Respiratory Protection
Proposed Paragraph (g) of the standard would have established the
requirements for the use of respiratory protection. OSHA added language
to paragraph (g) to clarify that both the selection and use of
respiratory protection must be in accordance with the Respiratory
Protection standard 29 CFR 1910.134, which is cross-referenced, and to
provide a powered air-purifying respirator (PAPR) when requested by an
employee. The Respiratory protection standard contains collection of
information requirements, include a written respiratory protection
program and fit-testing records (29 CFR 1910.134(c)). The collection of
information requirements contained in the Respiratory Protection
Program standard are approved under OMB Control Number 1218-0099.
Personal Protective Equipment
Final paragraph (h)(3)(iii), like proposed paragraph (h)(3),
requires employers to inform in writing the persons or the business
entities who launder, clean or repair the protective clothing or
equipment required by this standard of the potentially harmful effects
of exposure to airborne beryllium and contact with soluble beryllium
compounds and how the protective clothing and equipment must be handled
in accordance with the standard.
Housekeeping
Paragraph (j)(3) requires warning labels in accordance with the
requirements in paragraph (m) when employer transfer materials
containing beryllium. Medical Surveillance Final paragraph (k) sets
forth requirements for the medical surveillance provisions. The
paragraph specifies which employees must be offered medical
surveillance, as well as the frequency and content of medical
examinations. It also sets forth the information that the licensed
physician and CBD diagnostic center is to provide to the employee and
employer.
In paragraphs (k)(1)(i)(A)-(D) of the proposal, OSHA specified that
employers must make medical surveillance required by this paragraph
available for each employee: (1) Who has worked in a regulated area for
more than 30 days in the last 12 months; (2) showing symptoms or signs
of CBD, such as shortness of breath after a short walk or climbing
stairs, persistent dry cough, chest pain, or fatigue; or (3) exposed to
beryllium during an emergency; and (4) who was exposed to airborne
beryllium above .2 μg/m3\ for more than 30 days in a 12-month
period for 5 years or more, limited to the procedures described in
paragraph (k)(3)(ii)(F) of this section unless the employee also
qualifies for an examination under paragraph (k)(1)(i)(A), (B), or (C)
of this section. OSHA revised the first proposed medical surveillance
trigger to require the offering of medical surveillance based on
exposures at or above the action level, rather than the PEL. In
addition, OSHA revised the proposed trigger to require employers to
make medical surveillance available to each employee who is or is
reasonably expected to be exposed at or above the action level for more
than 30 days a year, rather than waiting for the 30th day of exposure
to occur.
Paragraph (k)(1)(i)(B) has been revised to include signs or
symptoms of other beryllium-related health effects.
Proposed paragraph (k)(1)(i)(C) required employers to offer medical
surveillance to employees exposed during an emergency. No revisions
were made to this paragraph.
OSHA added final paragraph (k)(1)(i)(D), which requires that
medical surveillance be made available when the most recent written
medical opinion to the employer recommends continued medical
surveillance. Under final paragraphs (k)(6) and (k)(7), the written
opinion must contain a recommendation for continued periodic medical
surveillance if the employee is confirmed positive or diagnosed with
CBD, and the employee provides written authorization.
Frequency: Proposed paragraph (k)(2) specified when and how
frequently medical examinations were to be offered to those employees
covered by the medical surveillance program. Under proposed paragraph
(k)(2)(i)(A), employers would have been required to provide each
employee with a medical examination within 30 days after making a
determination that the employee had worked in a regulated area for more
than 30 days in the past 12 months, unless the employee had received a
medical examination provided in accordance with this standard within
the previous 12 months. OSHA made several changes to this requirement.
First, OSHA revised the medical surveillance trigger of employees
working in a regulated area to a determination that employee is or is
reasonably expected to be exposed at or above the action level for more
than 30 days of year; or who shows signs or symptoms of CBD or other
beryllium-related health effects. Second, the Agency changed the
extended the length of time from within the last 12 months to within
the last two years.
Proposed paragraph (k)(2)(ii) required employers to provide an
examination annually (after the first examination is made available) to
employees who continue to meet the criteria of proposed paragraph
(k)(1)(i)(A) or (B). OSHA revised the paragraph to specify that medical
examinations were to be made available "at least" every two years and
to include employees who continue to meet the criteria of final
paragraph (k)(1)(i)(D), i.e., each employee whose most recent written
medical opinion required by paragraph (k)(6) or (k)(7) recommends
periodic medical surveillance. Under the final standards, employees
exposed in an
emergency, who are covered by paragraph (k)(1)(i)(C), are not included
in the biennial examination requirement unless they also meet the
criteria of paragraphs (k)(1)(i)(A) or (B) or (D). Final paragraph
(k)(2)(i)(A) also differs from the proposal in that in the proposed
paragraph the employer did not have to offer an examination if the
employee had received an equivalent examination within the last 12
months. In the final rule, this was increased to within two years to
align that provision with the frequency of periodic examinations, which
is every two years in the final rule.
Proposed paragraph (k)(2)(iii) required the employer to offer a
medical examination at the termination of employment, if the departing
employee met any of the criteria of proposed paragraphs (k)(1) at the
termination of employment for each employee who met the criteria of
paragraphs (k)(1)(i)(A), (B), or (C), unless an examination has been
provided in accordance with the standard during the 6 months prior to
the date of termination.
Final paragraph (k)(2)(iii) requires the employer to make a medical
examination available to each employee who meets the criteria of final
paragraph (k)(1)(i) at the termination of employment, unless the
employee received an exam meeting the requirements of the standards
within the last 6 months. OSHA extended the requirement to employees
who meet the criteria of final paragraph (k)(1)(i)(D).
Contents of Examination. Paragraph (k)(3) details the contents of
the examination. Paragraph (k)(3)(i) requires the employer to ensure
that the PLHCP advised the employee of the risks and benefits of
participating in the medical surveillance program and the employee's
right to opt out of any or all parts of the medical examination.
Paragraphs (k)(3)(ii)(A)-(D) detail the content of the medical
examination. The final rule made several changes to the content of the
employee medical examination including, but not limited to, revising
paragraphs: (k)(3)(ii)(A), to include emphasis on past and present
airborne exposure to or dermal contact with beryllium; (k)(3)(ii)(C) to
require a physical examination for skin rashes, rather than an
examination for breaks and wounds; (k)(3)(ii)(E) to require the BeLPT
test to be offered "at least" every two years, rather than every two
years; (k)(3)(ii)(F) to include an LDCT scan when recommended by the
PLHCP. With these changes, final paragraphs (k)(3)(ii)(A)-(D) require
the medical examination to include: (1) Medical and work history, with
emphasis on past and present airborne exposure to or dermal contact
with beryllium, any history of respiratory dysfunction and smoking
history, and; (2) a physical examination with emphasis on the
respiratory system; (3) a physical examination for skin rashes; and (4)
a pulmonary function test, performed in accordance with guidelines
established by the ATS including forced vital capacity (FVC) and a
forced expiratory volume in one second (FEV1). A more detailed
discussion regarding all of the changes to the content of the Medical
examinations may be found in section XVI, Summary and Explanation of
the Standards, under (k) Medical Surveillance.
Information Provided to the PLHCP
Proposed paragraph (k)(4) detailed which information must be
provided to the PHLCP. Specifically, the proposed standard required the
employer to provide to the examining PLHCP the following information,
if known to the employer: A description of the employee's former and
current duties that relate to the employee's occupational exposure
((k)(4)(i)); the employee's former and current levels of occupational
exposure ((k)(4)(ii)); a description of any personal protective
clothing and equipment, including respirators, used by the employee,
including when and for how long the employee has used that clothing and
equipment ((k)(4)(iii)); and information the employer has obtained from
previous medical examinations provided to the employee, that is
currently within the employer's control, if the employee provides a
medical release of the information ((k)(4)(iv)). OSHA made several
changes to this paragraph. First, OSHA updated paragraph (k)(4)(i) to
require the employer to provide a description of the employee's former
and current duties that relate to both the employee's airborne exposure
to and dermal contact with beryllium, instead of merely requiring the
provision of information related to occupational exposure. Second, OSHA
changed the requirement that the employer obtain a "medical release"
from the employee to "written consent" before providing the PLHCP
with information from records of employment-related medical
examinations. Third, OSHA revised the provision to require that the
employer ensure that the same information provided to the PLHCP is also
provided to the agreed-upon CBD diagnostic center, if an evaluation is
required under paragraph (k)(7) of the standard.
Licensed Physician's Written Medical Opinion
Paragraph (k)(5) of the proposed standard provided for the licensed
physician to give a written medical opinion to the employer, but relied
on the employer to give the employee a copy of that opinion; thus,
there was no difference between information the employer and employee
received. The final standards differentiate the types of information
the employer and employee receive by including two separate paragraphs
within the medical surveillance section that require a written medical
report to go to the employee, and a more limited written medical
opinion to go to the employer. The requirement to provide the medical
opinion to the employee is in paragraph (k)(5) of the final standards;
the requirement for providing documentation to the employer is in
paragraph (k)(6) of the final standards. Most significantly, OSHA
removed the requirement that the medical opinion pass through the
employer to the employee.
Licensed Physician's Written Medical Report for the Employee
Final paragraphs (k)(5)(i)-(v) provide the contents of the licensed
physician's written medical report for the employee. They include: The
results of the medical examination, including any medical condition(s),
such as CBD or beryllium sensitization (i.e., the employee is confirmed
positive, as is defined in paragraph (b) of the standard), that may
place the employee at increased risk from further airborne exposure;
any medical conditions related to airborne exposure that require
further evaluation or treatment (this requirement was not expressly
included in the proposal); any recommendations on the employee's use of
respirators, protective clothing, or equipment; and any recommended
limitations on airborne beryllium exposure.
Paragraph (k)(5) also provides that if the employee is confirmed
positive or diagnosed with CBD, or if the physician otherwise deems it
appropriate, the written medical report must also contain a referral to
a CBD diagnostic center, a recommendation for continued medical
surveillance, and a recommendation for medical removal from airborne
beryllium exposures above the action level, as described in paragraph
(l) of the standard. Proposed paragraph (k)(6) also addressed
information provided to employees who were confirmed positive or
diagnosed with CBD, but simply required a consultation with the
physician.
Licensed Physician's Written Medical Opinion for the Employer
Paragraph (k)(6)(i) requires employers to obtain a written medical
opinion from the licensed physician within 45 days of the medical
examination (including any follow-up BeLPT required under
(k)(3)(ii)(E)). In proposed (k)(5), the physician would have been
required to share most of the information identified now provided
directly to the employee per final (k)(5) with the employer, but in the
final rule OSHA limited the information that could be shared with the
employer. In final (k)(6) the written medical opinion for the employer
must contain only the date of the examination, a statement that the
examination has met the requirements of this standard, and any
recommended limitations on the employee's use of respirators,
protective clothing, and equipment; and a statement that the PLHCP
explained the results of the examination to the employee, including any
tests conducted, any medical conditions related to airborne exposure
that require further evaluation or treatment, and any special
provisions for use of personal protective clothing or equipment.
Paragraph (k)(6)(ii) states that if the employee provides written
authorization, the written medical opinion for the employer must also
contain any recommended limitations on the employee's airborne exposure
to beryllium. The requirement for written authorization was not in the
proposal. Paragraphs (k)(6)(iii)-(v) state that if an employee is
confirmed positive or diagnosed with CBD and the employee provides
written authorization, the written opinion must also contain a referral
for evaluation at a CBD diagnostic center and recommendations for
continued medical surveillance and medical removal from airborne
exposure to beryllium as described in paragraph (l).
Paragraph (k)(6)(vi) requires the employer to ensure that employees
receive a copy of the written medical opinion for the employer within
45 days of any medical examination (including any follow-up BeLPT
required under paragraph (k)(3)(ii)(E) of this standard) performed for
that employee. A similar requirement was included in proposed
(k)(5)(iii), but the time period was two weeks.
Beryllium Sensitization Test Results Research (Removed)
Proposed paragraph (k)(7) would have required employers to convey
the results of beryllium sensitization tests to OSHA for evaluation and
analysis at the request of OSHA. Based on comments received during the
comment period, OSHA decided not to include the proposed paragraph
(k)(7) in the final standard.
Referral to a Diagnostic Center
Final paragraph (k)(7) requires that if the employee wants a
clinical evaluation at a CBD diagnostic center, the employer must
provide the examination at no cost to the employee. OSHA made several
changes to final paragraph (k)(7) as compared to similar provisions in
paragraph (k)(6) of the proposal. First, OSHA changed the trigger for
referral to a CBD diagnostic center to include both confirmed positive
and a CBD diagnosis for consistency with final paragraphs (k)(5)(iii)
and (k)(6)(iii). Second, OSHA removed the requirement for a
consultation between the physician and employee. However, final
paragraph (k)(7)(i) requires that employers provide a no-cost
evaluation at a CBD-diagnostic center that is mutually agreed upon by
the employee and employer.
Final paragraph (k)(7) requires the employer to ensure that the
employee receives a written medical report form the CBD diagnostic
center that contains all the information required in paragraph
(k)(5)(i), (ii), (iv) and (v) and that the PLHCP explains the results
of the examination of the employee within 30 days of the examination.
Communication of Hazards
Proposed paragraph (m)(1)(i) required chemical manufacturers,
importers, distributors, and employers to comply with all applicable
requirements of the HCS (29 CFR 1910.1200) for beryllium. No
substantive changes were made to this paragraph.
Proposed paragraph (m)(1)(ii) would have required employers to
address at least the following, in classifying the hazards of
beryllium: Cancer; lung effects (chronic beryllium disease and acute
beryllium disease); beryllium sensitization; skin sensitization; and
skin, eye, and respiratory tract irritation. According to the HCS,
employers must classify hazards if they do not rely on the
classifications of chemical manufacturers, importers, and distributors
(see 29 CFR 1910.1200(d)(1)). OSHA revised the language to bring it
into conformity with other substance specific standards so it is clear
that chemical manufacturers, importers, and distributors are among the
entities required to classify the hazards of beryllium. OSHA has chosen
not to include an equivalent requirement in the final standards for
construction and shipyards since employers in construction and
shipyards are generally downstream users of beryllium products
(blasting media) and would not therefore be classifying chemicals.
Proposed paragraph (m)(1)(iii) would have required employers to
include beryllium in the hazard communication program established to
comply with the HCS, and ensure that each employee has access to labels
on containers and safety data sheets for beryllium and is trained in
accordance with the HCS and the training paragraph of the standard. The
final paragraph (m)(1)(iii) applies to the general industry, shipyards,
and construction. The final provisions are substantively unchanged from
the proposal.
Recordkeeping
Paragraph (n) of the final standards sets forth the employer's
obligation to comply with requirements to maintain records of air
monitoring data, objective data, medical surveillance, and training.
Proposed paragraph (n)(1)(i) required employers to maintain records
of all measurements taken to monitor employee exposure to beryllium as
required by paragraph (d) of the standard. OSHA made one minor
modification in the final standard: OSHA added the words "make and"
prior to "maintain" in order to clarify that the employer's
obligation is to create and preserve such records.
Proposed paragraph (n)(1)(ii) required that records of all
measurements taken to monitor employee exposure include at least the
following information: The date of measurement for each sample taken;
the operation being monitored; the sampling and analytical methods used
and evidence of their accuracy; the number, duration, and results of
samples taken; the type of personal protective clothing and equipment,
including respirators, worn by monitored employees at the time of
monitoring; and the name, social security number, and job
classification of each employee represented by the monitoring,
indicating which employees were actually monitored. OSHA has made one
editorial modification to paragraph (n)(1)(ii)(B), which is to change
"operation" to "task." Proposed paragraph (n)(1)(iii) required
employers to maintain employee exposure monitoring records in
accordance with 29 CFR 1910.1020(d)(1)(ii). OSHA has changed the
requirement that the employer "maintain this record as required by"
OSHA's Records Access standard to "ensure that exposure records are
maintained and made available in accordance with" that standard.
Proposed Paragraph (n)(2) Historical Monitoring Data (Removed)
Proposed paragraph (n)(2) contained the requirement to retain
records of any historical monitoring data used to satisfy the proposed
standard's the initial monitoring requirements. OSHA deleted the
separate recordkeeping requirement for historical data.
Final (n)(2)(i), (ii), and (iii) Objective Data
As a result of deleting paragraph (n)(2) Historical Data, OSHA has
included proposed paragraph (n)(3) as paragraph (n)(2) in the final
standards, with minor alterations. Paragraph (n)(2) contains the
requirements to keep accurate records of objective data. Paragraph
(n)(2)(i) requires employers to establish and maintain accurate records
of the objective data relied upon to satisfy the requirement for
initial monitoring in paragraph (d)(2). Under paragraph (n)(2)(ii), the
record is required to contain at least the following information: (A)
The data relied upon; (B) the beryllium-containing material in
question; (C) source of the data; (D) description of the process, task,
or activity on which the objective data were based; (E) other data
relevant to the process, task, activity, material, or airborne exposure
on which the objective data were based. These requirements included
minor changes in the description of the last two changes, but were not
substantively different.
Paragraph (n)(2)(iii) of the final standard (paragraph (n)(3)(iii)
in the proposal) requires the employer to maintain a record of
objective data relied upon as required by the Records Access standard,
which specifies that exposure records must be maintained for 30 years
(29 CFR 1910.1020(d)(1)(ii)).
Paragraph (n)(3)(i), (ii), & (iii) Medical Surveillance Records
Paragraph (n)(3) of the final standards (paragraph (n)(4) in the
proposal), addresses medical surveillance records. Employers must
establish and maintain medical surveillance records for each employee
covered by the medical surveillance requirements in paragraph (k).
Paragraph (n)(3)(ii) lists the categories of information that an
employer was required to record: The employee's name, social security
number, and job classification; a copy of all licensed physicians'
written medical opinions; and a copy of the information provided to the
PLHCP. OSHA has moved the requirement that the record include copies of
all licensed physicians' written opinions from proposed paragraph
(n)(4)(ii)(B) to paragraph (n)(3)(ii)(B) of the final standards.
Proposed paragraph (n)(4)(iii) required the employer to maintain
employee medical records in accordance with OSHA's Records Access
Standard at 29 CFR 1910.1020. OSHA has added "and made available"
after "maintained" in final paragraph (n)(3)(iii) of the standards,
but the requirement is otherwise unchanged.
Paragraph (n)(4)(i) and (ii) Training Records
Paragraph (n)(4) of the final standards (paragraph (n)(5) of the
proposal) requires employers to preserve training records, including
records of annual retraining or additional training, for a period of
three years after the completion of the training. At the completion of
training, the employer is required to prepare a record that includes
the name, social security number, and job classification of each
employee trained; the date the training was completed; and the topic of
the training. This record maintenance requirement also applied to
records of annual retraining or additional training as described in
paragraph (m)(4). This paragraph is substantively unchanged from the
proposal.
Paragraph (n)(5) Access to Records
Paragraph (n)(5) of the final standards (paragraph (n)(6) of the
proposal), requires employers to make all records mandated by these
standards available for examination and copying to the Assistant
Secretary, the Director of NIOSH, each employee, and each employee's
designated representative as stipulated by OSHA's Records Access
standard (29 CFR 1910.1020). This paragraph is substantively unchanged
from the proposal.
Paragraph (n)(6) Training Records
Paragraph (n)(6) of the final standards (paragraph (n)(6) in the
proposal), requires that employers comply with the Records Access
standard regarding the transfer of records, 29 CFR 1910.1020(h), which
instructs employers either to transfer records to successor employers
or, if there is no successor employer, to inform employees of their
access rights at least three months before the cessation of the
employer's business. This paragraph is substantively unchanged from the
proposal.
X. Federalism
OSHA reviewed the final beryllium rule according to the most recent
Executive Order ("E.O.") on Federalism, E.O. 13132, 64 FR 43255 (Aug.
10, 1999). The E.O. requires that Federal agencies, to the extent
possible, refrain from limiting State policy options, consult with
States before taking actions that would restrict States' policy
options, and take such actions only when clear constitutional authority
exists and the problem is of national scope. The E.O. 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"), 29 U.S.C. 667, Congress expressly provides
that States may adopt, with Federal approval, a plan for the
development and enforcement of occupational safety and health
standards. OSHA refers to States that obtain Federal approval for such
plans as "State-Plan States." 29 U.S.C. 667. Occupational safety and
health standards developed by State-Plan States must be at least as
effective in providing safe and healthful employment and places of
employment as the Federal standards. Subject to these requirements,
State-Plan States are free to develop and enforce their own
occupational safety and health standards.
While OSHA wrote this final rule to protect employees in every
State, Section 18(c)(2) of the OSH Act permits State-Plan States to
develop and enforce their own standards, provided those standards
require workplaces to be at least as safe and healthful as this final
rule requires. Additionally, standards promulgated under the OSH Act do
not apply to any worker whose employer is a state or local government.
29 U.S.C. 652(5).
This final rule complies with E.O. 13132. In States without OSHA-
approved State plans, Congress expressly provides for OSHA standards to
preempt State occupational safety and health standards in areas
addressed by the Federal standards. In these States, this rule limits
State policy options in the same manner as every standard promulgated
by the Agency. In States with OSHA-approved State plans, this
rulemaking does not significantly limit State policy options to adopt
stricter standards.
XI. State-Plan States
When Federal OSHA promulgates a new standard or a more stringent
amendment to an existing standard, the States and U.S. territories with
their own OSHA-approved occupational safety and health plans ("State-
Plan
States") must revise their standards to reflect the new standard or
amendment. The State standard must be at least as effective as the
Federal standard or amendment, and must be promulgated within six
months of the publication date of the final Federal rule. 29 CFR
1953.5(a). Currently, there are 28 State-Plan States.
A State-Plan State may demonstrate that a standard change is not
necessary because the State standard is already the same as or at least
as effective as the new or amended Federal standard. In order to avoid
delays in worker protection, the effective date of the State standard
and any of its delayed provisions must be the date of State
promulgation or the Federal effective date, whichever is later. The
Assistant Secretary may permit a longer time period if the State makes
a timely demonstration that good cause exists for extending the time
limitation. 29 CFR 1953.5(a).
Of the 28 States and territories with OSHA-approved State plans, 22
cover public and private-sector employees: Alaska, Arizona, California,
Hawaii, Indiana, Iowa, Kentucky, Maryland, Michigan, Minnesota, Nevada,
New Mexico, North Carolina, Oregon, Puerto Rico, South Carolina,
Tennessee, Utah, Vermont, Virginia, Washington, and Wyoming. The
remaining six states and territories cover only public-sector
employees: Connecticut, Illinois, New Jersey, Maine, New York, and the
Virgin Islands.
This beryllium rule applies to general industry, construction, and
shipyards. This rule requires that all State-Plan States revise their
standards appropriately within six months of the date of this notice.
XII. Unfunded Mandates Reform Act
Under Section 202 of the Unfunded Mandates Reform Act of 1995
("UMRA"), 2 U.S.C. 1532, an agency must prepare a written
"qualitative and quantitative assessment" of any regulation creating
a mandate that "may result in the expenditure by the State, local, and
tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation)" in any one
year before promulgating a final rule. OSHA's rule does not place a
mandate on State or local governments, for purposes of the UMRA,
because OSHA cannot enforce its regulations or standards on State or
local governments. 29 U.S.C. 652(5). Under voluntary agreement with
OSHA, some States require public sector entities to comply with State
standards, and these agreements specify that these State standards must
be at least as protective as OSHA standards. The OSH Act does not cover
tribal governments in the performance of traditional governmental
functions, though it does cover tribal governments when they engage in
commercial activity. However, the final rule will not require tribal
governments to expend, in the aggregate, $100,000,000 or more in any
one year for their commercial activities. Thus, the final rule does not
trigger the requirements of UMRA based on its impact on State, local,
or tribal governments.
Based on the analysis presented in the Final Economic Analysis (see
Section VIII above), OSHA concludes that the rule would not impose a
Federal mandate on the private sector in excess of $100 million
(adjusted annually for inflation) in expenditures in any one year. As
noted below, OSHA also reviewed this final rule in accordance with E.O.
13175 on Consultation and Coordination with Indian Tribal Governments,
65 FR 67249 (Nov. 9, 2000), and determined that it does not have
"tribal implications" as defined in that Order.
XIII. Protecting Children From Environmental Health and Safety Risks
E.O. 13045, 66 FR 19931 (Apr. 23, 2003), requires that Federal
agencies submitting covered regulatory actions to OMB's Office of
Information and Regulatory Affairs ("OIRA") for review pursuant to
E.O. 12866, 58 FR 51735 (Oct. 4, 1993), 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. E.O. 13045
defines "covered regulatory actions" as rules that may (1) be
economically significant under E.O. 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, or product use).
The final beryllium rule is economically significant under E.O.
12866 (see Section IX of this preamble). However, after reviewing the
rule, OSHA has determined that it will not impose environmental health
or safety risks to children as set forth in E.O. 13045. The final rule
will require employers to limit employee exposure to beryllium and take
other precautions to protect employees from adverse health effects
associated with exposure to beryllium. OSHA is not aware of any studies
showing that exposure to beryllium in workplaces disproportionately
affects children, who typically are not allowed in workplaces where
such exposure exists. OSHA is also not aware that there are a
significant number of employees under 18 years of age who may be
exposed to beryllium, or that employees of that age are
disproportionately affected by such exposure. One commenter, Kimberly-
Clark Professional, noted that children may be subject to secondary
beryllium exposure due to beryllium particles being carried home on
their parents' work clothing, shoes, and hair (Document ID 1962, p. 2).
Commenter Evan Shoemaker also noted that "beryllium can collect on
surfaces such as shoes, clothing, and hair as well as vehicles leading
to contamination of the family and friends of workers exposed to
beryllium" (Document ID 1658, p. 3). However, OSHA does not believe
beryllium exposure disproportionately affects children or that
beryllium particles brought home on work clothing, shoes, and hair
result in exposures at or near the action level. Furthermore, Kimberly-
Clark Professional also noted that potential secondary exposures can be
controlled through the use of personal protective equipment in the
workplace (Document ID 1676, p. 2). The final standards contain
ancillary provisions, such as personal protective clothing and hygiene
areas, which are specifically designed to minimize the amount of
beryllium leaving the workplace. Therefore, OSHA believes that the
final beryllium rule does not constitute a covered regulatory action as
defined by E.O. 13045.
XIV. Environmental Impacts
OSHA has reviewed the final beryllium rule according to the
National Environmental Policy Act of 1969 (NEPA) (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). OSHA made a preliminary determination that the proposed
standard would have no significant impact on air, water, or soil
quality; plant or animal life; the use of land or aspects of the
external environment. No comments to the record questioned this
determination, nor has the Agency found other evidence to invalidate
it. Therefore, OSHA concludes that the final beryllium standard will
have no significant environmental impacts.
XV. Consultation and Coordination With Indian Tribal Governments
OSHA reviewed this final rule in accordance with E.O. 13175 on
Consultation and Coordination with Indian Tribal Governments, 65 FR
67249 (Nov. 9, 2000), and determined that it does not have "tribal
implications" as defined in that order. The OSH Act does not cover
tribal governments in the performance of traditional governmental
functions, so the rule will not have substantial direct effects on one
or more Indian tribes in their sovereign capacity, on the relationship
between the Federal government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
government and Indian tribes. On the other hand, employees in
commercial businesses owned by tribes or tribal members will receive
the same protections and benefits of the standard as all other covered
employees.
XVI. Summary and Explanation of the Standards
OSHA proposed a standard for occupational exposure to beryllium and
beryllium compounds in general industry and proposed regulatory
alternatives to address beryllium exposures in the construction and
maritime industries. The proposed standard for general industry was
structured according to OSHA's traditional approach, with permissible
exposure limits, and ancillary provisions such as exposure assessment,
methods of compliance, and medical surveillance. As discussed below,
OSHA based the proposal substantively on a joint industry and labor
stakeholders' draft occupational health standard developed and
submitted to OSHA by Materion Corporation (Materion) and the United
Steelworkers (USW). The final rule, however, is based on the entirety
of the rulemaking record.
In the final rule, OSHA is expanding coverage to include the
construction and shipyard industries and establishing separate final
standards for occupational exposure to beryllium in general industry,
construction, and shipyards. In the NPRM, OSHA discussed Regulatory
Alternative 2a to include both the construction and shipyard industries
in the final rule (80 FR 47732-47734), presented estimated costs and
benefits associated with extending the scope of the final rule, and
requested comment on the alternative. The decision to include standards
for construction and shipyards is based on information and comment
submitted in response to this request for comment and evaluated by OSHA
during the public comment periods and the informal public hearing. OSHA
decided to issue three separate standards because there are some
variations in the standards for each industry, although the structure
of the final standards for general industry, construction, and
shipyards remains generally consistent with other OSHA health
standards. The most significant change is in the standard for
construction where paragraph (e) Competent person, replaces paragraph
(e) Beryllium work areas and regulated areas in general industry and
paragraph (e) Regulated areas in shipyards.
All three final standards have a provision for methods of
compliance, although in the standard for construction this provision
has an additional requirement to describe procedures used by the
designated competent person to restrict access to work areas, when
necessary, to minimize the number of employees exposed to airborne
beryllium above the PEL or STEL. This requirement allows the competent
person to perform essentially the same role as the requirement
governing regulated areas in general industry and shipyards, which is
to regulate and minimize the number of workers exposed to hazardous
levels of beryllium. OSHA decided to include a competent person
provision in the final standard for construction because of the
industry's familiarity with this concept and its past successful use in
many OSHA construction standards and documents. "Competent person" is
defined in OSHA's Safety and Health Regulations for Construction (29
CFR 1926.32(f)) as being a person who is capable of identifying
existing and predictable hazards in the surroundings or working
conditions which are unsanitary, hazardous, or dangerous to employees,
and who has authorization to take prompt corrective measures to
eliminate them. This generally applicable definition corresponds well
with the definition for "competent person" in the standard for
construction: In this context, "competent person" means an individual
who is capable of identifying existing and foreseeable beryllium
hazards in the workplace and who has authorization to take prompt
corrective measures to eliminate or minimize them. The competent person
must have the knowledge, ability, and authority necessary to fulfill
the responsibilities set forth in paragraph (e) of this standard.
OSHA has retained, in modified form, the scope exemption from the
proposed standard for materials containing less than 0.1 percent
beryllium by weight in the standard for general industry and included
it in the standards for construction and shipyards. The scope exemption
has been modified in the final standards with the additional
requirement that the employer must have objective data demonstrating
that employee exposure to beryllium will remain below the action level
as an 8-hour TWA under any foreseeable conditions. The 0.1 percent
exemption was generally supported by commenters from general industry
and shipyards; construction employers did not comment. Other
commenters, especially those representing workers or public health
organizations, expressed concern that these materials, in some cases,
could expose workers to hazardous levels of beryllium. As discussed in
more detail in the summary and explanation for Scope and application,
the objective data requirement addresses these concerns and ensures the
protection of workers who experience significant exposures from
materials containing trace amounts of beryllium. Employers who have
objective data showing that employees will not be exposed at or above
the action level under any foreseeable conditions when processing
materials containing less than 0.1 percent beryllium by weight are
exempt from the standard.
OSHA decided to add a performance option in paragraph (d), Exposure
assessment, as an alternative exposure assessment method to the
scheduled monitoring requirements in the proposed rule, based on public
comment received from industry and labor. OSHA believes the performance
option, which encompasses either exposure monitoring or assessments
based on objective data, gives employers flexibility in determining
employee exposure to beryllium based on to their unique workplace
circumstances. OSHA has provided this performance option in recent
health standards such as respirable crystalline silica (29 CFR
1910.1053(d)(2)) and chromium VI (29 CFR 1910.1026(d)(3)).
OSHA also received comments about other provisions in the proposed
standard, and in some cases, OSHA responded with changes from the
proposed rule that were based on the evidence provided in the record.
Any changes made to the provisions in the final standards are described
in detail in their specific summary and explanation sections.
Although details of the final standards for general industry,
construction, and shipyards differ slightly, most of the requirements
are the same or similar in all three standards. Therefore, the summary
and explanation is organized according to the main requirements of the
standards, but includes paragraph references to the standards for
general industry, construction, and shipyards. The summary and
explanation uses the term "standards" or "final standards" when
referring to all three standards. Generally, when the summary and
explanation refers to the term "standards," it is referring to the
final standards. To avoid confusion, the term "final rule" is
sometimes used when making a comparison to or clarifying a change from
the proposed rule.
The proposed rule applied to occupational exposure to beryllium in
all forms, compounds, and mixtures in general industry, except those
articles and materials exempted by proposed paragraphs (a)(2) and
(a)(3) of the proposed standard. The final standards are identical in
their application to occupational exposures to beryllium. In the
summary and explanation sections, OSHA has changed "beryllium and
beryllium compounds" or anything specifying soluble beryllium to just
"beryllium." OSHA intends the term "beryllium" to cover all forms
of beryllium, including compounds and mixtures, both soluble and poorly
soluble, throughout the summary and explanation sections. Other global
changes in the regulatory text include changing "shall" to "must"
to make it clear when a provision is a requirement and adding
"personal" to "protective clothing or equipment" and "protective
clothing and equipment" consistently. OSHA has changed "exposure" to
"airborne exposure" to make it clear when referring to just airborne
exposure, and specifically noting when OSHA intends to cover dermal
contact.
As noted above, OSHA's proposed rule was based, in part, upon a
draft occupational health standard submitted to the Agency by Materion,
the leading producer of beryllium and beryllium products in the United
States, and USW, an international labor union representing workers who
manufacture beryllium alloys and beryllium-containing products in a
number of industries (Document ID 0754). Materion and USW worked
together to craft a model beryllium standard that OSHA could adopt and
that would have support from both labor and industry. They submitted
their joint draft standard to OSHA in February 2012.
Like the proposal, many of the provisions in the final rules are
identical or substantively similar to those contained in Materion and
USW's draft standard. For example, the final rule for general industry
and the Materion/USW draft standard both include an exclusion for
materials containing less than 0.1 percent beryllium; both contain many
similar definitions; both contain a time weighted average (TWA) PEL of
0.2 μg/m3\; both include exposure monitoring provisions, including
provisions for scheduled monitoring, employee notification of results,
methods of sample analysis, and observation of monitoring; both contain
similar requirements for beryllium work areas and regulated areas; both
mandate a written exposure control plan and engineering and work
practice controls that follow OSHA's traditional hierarchy of controls;
and both include similar provisions related to respiratory protection,
protective clothing and equipment, hygiene areas and practices,
housekeeping, medical surveillance, medical removal protection,
training and communication of hazards, recordkeeping, and compliance
dates.
(a) Scope and Application
Separate standards for general industry, construction, and
shipyards. OSHA proposed a standard addressing occupational exposure to
beryllium in general industry and regulatory alternatives to address
exposures in the construction and maritime industries.\37\ The proposal
was modeled on a suggested rule that was crafted by two major
stakeholders in general industry, Materion Corporation (Materion) and
the United Steelworkers (USW) (Document ID 0754). Materion and USW
provided OSHA with data on exposure and control measures and
information on their experiences with handling beryllium in general
industry settings (80 FR 47774). At the time, the information available
to OSHA on beryllium exposures outside of general industry was limited.
Therefore, the Agency preliminarily decided to limit the scope of its
beryllium rule proposal to general industry but propose regulatory
alternatives that would expand the scope of the proposed standard to
also include employers in construction and maritime if it turned out
the record evidence warranted it. Specifically, OSHA requested comment
on Regulatory Alternative #2a, which would expand the scope of the
proposed standard to also include employers in construction and
maritime, and Regulatory Alternative #2b, which would update 29 CFR
1910.1000 Tables Z-1 and Z-2, 1915.1000 Table Z, and 1926.55 Appendix A
so that the proposed TWA PEL and STEL would apply to all employers and
employees in general industry, shipyards, and construction, including
occupations where beryllium exists only as a trace contaminant. OSHA
also requested stakeholder comment and data on employees in
construction or maritime, or in general industry, not covered in the
scope of the proposed standard, who deal with beryllium only as a trace
contaminant, who may be at significant risk from occupational beryllium
exposures.
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\37\ The proposed rule did not cover agricultural employers
because OSHA had not found any evidence indicating that beryllium is
used or handled in agriculture in a way that might result in
beryllium exposure. OSHA's authority is also restricted in this
area; since 1976, an annual rider in the Agency's Congressional
appropriations bill has limited OSHA's use of funds with respect to
farming operations that employ fewer than ten employees
(Consolidated Appropriations Act, 1976, 94, 90 Stat. 1420, 1421
(1976) (and subsequent appropriations acts)). In the Notice of
Proposed Rulemaking (NPRM), the Agency requested information on
whether employees in the agricultural sector are exposed to
beryllium in any form and, if so, their levels of exposure and what
types of exposure controls are currently in place (80 FR 47565,
47775). OSHA did not receive comment on beryllium and the
agriculture industry or information that would support coverage of
agricultural operations. Therefore, agriculture employers and
operations are not covered by the rule.
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OSHA did not receive any additional exposure data for construction
or shipyards in response to OSHA's request in the NPRM. However, since
the proposal, OSHA reviewed its OIS compliance exposure database and
identified personal exposure sample results on beryllium for abrasive
blasting workers in construction, general industry and maritime, which
can be found broken out by sector in FEA Table IV.68.
The vast majority of stakeholders who submitted comments on this
issue supported extending the scope of the proposed rule to cover
workers in the construction and maritime industries who are exposed to
beryllium (e.g., Document ID 1592; 1625, p. 3; 1655, p. 15; 1658, p. 5;
1664, pp. 1-2; 1670, p. 7; 1671, Attachment 1, p. 5; 1672, p. 1; 1675,
p. 2; 1676, p. 1; 1677, p. 1; 1679, p. 2; 1681, pp. 5, 16; 1683, p. 2;
1684, Attachment 2, p. 3; 1685, p. 2; 1686, p. 2; 1689, p. 6; 1690, p.
2; 1693, p. 3; 1703, p. 2; 1705, p. 1). For example, the National
Council for Occupational Safety and Health (National COSH) urged that
OSHA should ensure greater
protections to beryllium exposed workers by extending the scope of the
proposed standard to workers in the construction and maritime
industries. National COSH explained: "In the proposed preamble, OSHA
recognizes that these workers are exposed to beryllium during abrasive
blasting and clean-up of spent material. The risks that construction
and maritime workers face when exposed to beryllium particulate is the
same as the risk faced at similar exposures by general industry
workers" (Document ID 1690, p. 2). The American Federation of Labor
and Congress of Industrial Organizations (AFL-CIO) agreed, adding that
"[a]vailable data in the construction and maritime sector shows that
there is a significant risk of sensitization and CBD among these
workers" (Document ID 1689, p. 6). Similarly, the American Industrial
Hygiene Association (AIHA) warned that the "[p]otential for exposure,
especially in the construction industry, is very high" (Document ID
1686, p. 2).
OSHA also heard testimony during the public hearing from Dr. Lee
Newman of the American College of Occupational and Environmental
Medicine (ACOEM), Peggy Mroz of National Jewish Health (NJH), Emily
Gardner of Public Citizen, Mary Kathryn Fletcher of AFL-CIO, and Mike
Wright of the USW that supported covering workers in the construction
and maritime industries (Document ID 1756, Tr. 81; 1756, Tr. 97-98;
1756, Tr. 172-175; 1756, Tr. 198-199; 1755, Tr. 181). Peggy Mroz of NJH
testified that "[b]ased on the data presented, [NJH] support[s]
expanding the scope of the proposed standard to include . . . employers
in construction and maritime" (Document ID 1756, Tr. 98). Emily
Gardner of Public Citizen argued that "the updated standard cannot
leave construction and shipyard workers vulnerable to the devastating
effects of beryllium" (Document ID 1756, Tr. 175). She added that
"Public Citizen urges OSHA to revise the proposed rule to cover these
workers" (Document ID 1756, Tr. 175).
Several commenters specifically supported Regulatory Alternative
#2a. For example, the International Union, United Automobile,
Aerospace, and Agriculture Implement Workers of America (UAW) indicated
its support for this alternative (Document ID 1693, p. 3 (pdf)). UAW
added that Alternative #2a would cover abrasive blasters, pot tenders,
and cleanup staff working in construction and shipyards who have the
potential for airborne beryllium exposure during blasting operations
and during cleanup of spent media (Document ID 1693, p. 3 (pdf)).
Kimberly-Clark Professional (KCP) similarly indicated that it favored
the adoption of this alternative (Document ID 1676, p. 1). KCP
explained that "[h]azardous exposures are equally dangerous to workers
regardless of whether the worker is in a factory or on a construction
site, and the worker protection provided by OSHA regulations should
also be equal" (Document ID 1676, p. 1). In addition, 3M Company also
observed that Regulatory Alternative #2a is a more protective
alternative (Document ID 1625, p. 3 (pdf)).
However, other commenters argued in favor of keeping the proposed
scope unchanged (e.g., Document ID 1583; 1661, Attachment 2, pp. 6-7;
1673, pp. 12-23). Some of these stakeholders contended that adding
construction and maritime was not necessary (e.g., Document ID 1673,
pp. 20-22). For example, Materion opined that "the requirements of [29
CFR] 1910.94 provide sufficient protections for the construction and
maritime industries and accordingly, [Materion and USW] did not include
construction and maritime within [their] assessment of technological
feasibility or the scope of the standard" (Document ID 1661,
Attachment 2, p. 7). Materion added that "it is [its] understanding
that in the absence of a specific maritime standard, OSHA applies
general industry standards to the maritime industries" (Document ID
1661, Attachment 2, p. 7). While this may be the general practice of
the industry, OSHA does not enforce general industry standards where
the shipyard standards apply unless they are specifically cross
referenced in the shipyard standards.
Some of these commenters offered specific concerns with covering
the construction and maritime industries, or with covering abrasive
blasting in general. For instance, Jack Allen, Inc. argued against
extending the proposed rule to cover the use of coal slag in the
sandblasting industry because the industry already has processes and
controls in place to prevent exposures to all dusts during operations
(Document ID 1582). The Abrasive Blasting Manufacturers Alliance (ABMA)
presented a number of arguments against the coverage of abrasive
blasting. ABMA argued that regulating the trace amounts of beryllium in
abrasive blasting will increase the use of silica-based blasting agents
"despite OSHA's longstanding recommendation of substitution for
silica-based materials" (Document ID 1673, p. 14). ABMA added that
scoping in abrasive blasting would increase the amount of coal slag
materials "going to landfills rather than being used for beneficial
purpose" (Document ID 1673, p. 14). ABMA also cited to technological
feasibility issues in sampling and analysis, noted that the proposed
standard was not appropriately tailored to construction and maritime
worksites, and argued that it is not appropriate to regulate abrasive
blasting on a chemical-by-chemical basis (Document ID 1673, pp. 8, 21-
23).
After careful consideration of these comments and those relating to
Regulatory #2b discussed below, OSHA has decided to adopt Regulatory
Alternative #2a to expand the proposal's scope to cover construction
and shipyards. As noted by commenters like the AFL-CIO, record evidence
shows that exposures above the new action level and PEL, primarily from
abrasive blasting operations, occur in both the construction and
shipyard industries (see Chapter IV of the Final Economic Analysis and
Regulatory Flexibility Analysis (FEA)). As discussed in Section V,
Health Effects, and Section VII, Significance of Risk, employees
exposed to airborne beryllium at these levels are at significant risk
of developing adverse health effects, primarily chronic beryllium
disease (CBD) and lung cancer. And under the OSH Act, and specifically
section 6(b)(5), the Agency is required to set health standards which
most adequately assure, to the extent feasible, 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
standards for the period of his working life. Therefore, OSHA finds it
would be inappropriate to exclude construction and shipyard employers
from coverage under this rule.
OSHA disagrees with Materion's assertion that existing standards
render it unnecessary to have this standard cover construction and
shipyard employers whose employees are exposed to beryllium during
abrasive blasting operations. The OSHA Ventilation standard referenced
by Materion (29 CFR 1910.94) applies only to general industry and does
not cover construction and shipyard workers. The OSHA Ventilation
standard in construction (1926.57) and Mechanical paint removers
standard in shipyards (1915.34) provide some general protections for
abrasive blasting workers but do not provide the level of protection
provided by the ancillary provisions contained in the final standards
such as medical surveillance, personal protective clothing and
equipment, and beryllium-specific training.
OSHA also disagreed with Jack Allen, Inc.'s assertion that the
employers conducting abrasive blasting already have sufficient
processes and controls in place to prevent exposures to all dusts
during operations. OSHA's examination of the record identifies data on
beryllium exposure in the abrasive blasting industry showing beryllium
exposure above the action level and TWA PEL when beryllium-containing
slags are used (e,g., Document ID 1166; 1815, Attachment 35; 1880). And
even in abrasive blasting operations where all available controls and
work processes to reduce beryllium exposure are used, additional
ancillary provisions are still as necessary to protect workers from the
harmful effects of exposure to beryllium as in general industry. OSHA
also finds unsubstantiated ABMA's assertion that regulating the trace
amounts of beryllium in abrasive blasting will increase the use of
silica-based blasting agents and result in an increase in the amount of
coal slag materials going to landfills. OSHA has identified several
controls for abrasive blasting in its technological feasibility
analysis (see Chapter IV of the FEA). OSHA also noted that substitution
is not always feasible and employers should be cautious to not
introduce additional hazards when switching to an alternate media. The
Agency is certainly not encouraging employers to increase the use of
silica sand as a blasting media. However, workers using silica-based
blasting materials are protected under a new comprehensive silica
standard (29 CFR 1910.1053, 29 CFR 1926.1153). Employers are in the
best position to determine which blasting material to use and how to
weigh the costs of compliance with the two rules. A 1998 NIOSH-funded
study on substitute materials for silica sand in abrasive blasting
provides comprehensive information on alternative media and can be used
by employers seeking to identify appropriate abrasive blasting media
alternatives (Document ID 1815, Attachment 85-87). In fact, exploring
the use of alternative media for safer abrasive blasting media is
already underway (Document ID 1741, p. 2). OSHA anticipates that the
amount of slag material being deposited in landfills will remain
constant regardless of its use prior to disposal, as the spent slag
material used in abrasive blasting will still need to be disposed of.
OSHA is also not persuaded by ABMA's technological feasibility argument
that regulating trace amounts of beryllium would require testing below
the limit of detection and that it is not technologically feasible to
measure beryllium exposures in abrasive blasting. As explained in
sections 2 and 12 of Chapter IV of the Final Economic Analysis, there
are a number of available sampling and analytical methods that are
capable of detecting beryllium at air concentrations below the action
level of 0.1 μg/m3\, as well as existing exposure data for
beryllium in abrasive blasting operations. And finally, OSHA disagrees
with ABMA's assertion that regulating abrasive blasting on a chemical-
by-chemical basis is inappropriate. The beryllium rule is typical of
OSHA substance-specific health standards that have been promulgated for
the construction and shipyard industries and include abrasive blasting
operations, such as the Lead standard for construction (1926.62) and
the Lead standard for general industry (1910.1025), which applies to
the shipyard industry.
However, OSHA does agree with ABMA's observation that many of the
conditions in the construction and shipyard industries are distinct
from those in general industry, and agrees that the standard as
proposed was not tailored to construction and shipyard worksites. The
Agency has long recognized a distinction between the construction and
general industry sectors and has issued standards specifically
applicable to construction and shipyard work under 29 CFR part 1926 and
29 CFR part 1915, respectively. OSHA's understanding of the differences
between these industries is why OSHA specifically asked stakeholders
with experience and knowledge of the construction or shipyard
industries to opine on whether coverage of those industries is
appropriate and, if so, how the proposal should be revised to best
protect workers in those industries. As discussed throughout the rest
of this Summary and Explanation section, many stakeholders responded to
OSHA's request.
After careful consideration of the record, OSHA finds that the
unique needs of, conditions in, and challenges posed by the
construction and maritime sectors, particularly concerning abrasive
blasting operations at construction sites and shipyards, warrant
different requirements from general industry. Therefore, OSHA is
issuing three separate standards--one for each of these sectors. OSHA
judges that the primary source of beryllium exposure at construction
worksites and in shipyards is from abrasive blasting operations when
using abrasives that contain trace amounts beryllium.
Abrasive blasters and their helpers are exposed to beryllium from
coal slag and other abrasive blasting material like copper slag that
may contain beryllium as a trace contaminant. The most commonly used
abrasives in the construction industry include coal slag and steel
grit, which are used to remove old coatings and etch the surfaces of
outdoor structures, such as bridges, prior to painting (Document ID
1815, Attachment 93, p. 80). Shipyards are large users of mineral slag
abrasives. In a recent survey conducted for the Navy, the use of coal
slag abrasives accounted for 68 percent and copper slag accounted for
20 percent of abrasive media usage as reported by 26 U.S. shipyards and
boatyards (Document ID 0767). The use of coal and copper slag abrasives
has increased in recent years as industries have sought substitutes for
silica sand blasting abrasives to avoid health risks associated with
respirable crystalline silica (Document ID 1671, Attachment 3; 1681,
Attachment 1, pp. 1-2).
OSHA's exposure profile for abrasive blasters, pot tenders/helpers,
and abrasive material cleanup workers is found in Section 12 of Chapter
IV in the FEA. The exposure profile for abrasive blasters shows a
median of 0.2 μg/m3\, a mean of 2.18 μg/m3\, and a range from
0.004 μg/m3\ to 66.5 μg/m3\. The mean level of 2.18 µg/
m3\ is above the preceding PEL for beryllium. For pot tenders/helpers,
the exposure profile shows a median of 0.09 μg/m3\, a mean of 0.10
μg/m3\, and a range from 0.04 to 0.20 μg/m3\. Beryllium
exposure for workers engaged in abrasive material cleanup shows a
median of 0.18 μg/m3\, a mean of 1.76 μg/m3\, and a range from
0.04 μg/m3\ to 7.4 μg/m3\ (see Section 12 of Chapter IV in the
FEA). OSHA concludes that abrasive blasters, pot tenders/helpers, and
cleanup workers have the potential for significant airborne beryllium
exposure during abrasive blasting operations and during cleanup of
spent abrasive material. Accordingly, these workers require protection
under the beryllium standards. To address high concentrations of
various hazardous chemicals in abrasive blasting, employers are already
required to use engineering and work practice controls to limit
workers' exposures and supplement these controls with respiratory
protection when necessary. For example, abrasive blasters in the
construction industry fall under the protection of the Ventilation
standard (29 CFR 1926.57). The Ventilation standard includes an
abrasive blasting subsection (29 CFR 1926.57(f)), which requires that
abrasive blasting respirators be worn by all abrasive
blasting operators when working inside blast-cleaning rooms (29 CFR
1926.57(f)(5)(ii)(A)), when using silica sand in manual blasting
operations where the nozzle and blast are not physically separated from
the operator in an exhaust-ventilated enclosure (29 CFR
1926.57(f)(5)(ii)(B)), or when needed to protect workers from exposures
to hazardous substances in excess of the limits set in Sec. 1926.55
(29 CFR 1926.57(f)(5)(ii)(C)). For the shipyard industry, paragraph (c)
of the Mechanical paint removers standard (29 CFR 1915.34) also has
respiratory protection requirements for abrasive blasting operations.
Because of these requirements, OSHA believes that employers already
have those controls in place and provide respiratory protection during
abrasive blasting operations. Nonetheless, the construction and
shipyard standards' new ancillary provisions such as medical
surveillance, personal protective clothing and equipment, housekeeping,
and beryllium-specific training will provide increased protections to
workers in these industries.
OSHA also received comment and heard testimony on potential
beryllium exposure from other sources. NIOSH commented that
construction workers may be exposed to beryllium when demolishing
buildings or building equipment, based on a study of workers
demolishing oil-fired boilers (Document ID 1671, Attachment 1, pp. 5,
15; 1671, Attachment 21). Peggy Mroz of NJH testified that "[n]umerous
studies have documented beryllium exposure sensitization and chronic
beryllium disease in construction industries, demolition and
decommissioning, and among workers who use non-sparking tools"
(Document ID 1756, Tr. 98). Many such cases were discovered among trade
workers at Department of Energy sites from the National Supplemental
Screening Program (Document ID 1756, Tr. 81-82). Ashlee Fitch from the
USW testified that in addition to abrasive blasting using beryllium-
contaminated slags, workers in the maritime industry use non-sparking
tools that are composed of beryllium alloys. Ms. Fitch stated that
these tools can create beryllium particulate when they are dressed
(e.g., sharpening, grinding, straightening). She also noted that
shipyards may use beryllium for other tasks in the future. Ms. Fitch
alluded to a 2000 Navy survey of potential exposure to beryllium in
shipyards which identified potential beryllium sources in welding,
abrasive blasting, and metal machining (Document ID 1756, Tr. 242-243).
Mr. Wright of the USW testified that shipyard management told a USW
representative "that most of the beryllium that they're aware of comes
in in the form of articles . . . . That is to say, it might be part of
some assembly . . . [a]nd it comes in and it's sealed and closed"
(Document ID 1756, Tr. 270). However, Mr. Wright stated that beryllium
is a high-tech material and that "there is nothing more high-tech than
an aircraft carrier or a nuclear submarine" so exposure from
beryllium-containing alloys cannot be ruled out in these operations
(Document ID 1756, Tr. 270).
Despite requesting information both in the NPRM and during the
public hearing, OSHA does not have sufficient data on beryllium
exposures in the construction and shipyard industries to characterize
exposures of workers in application groups other than abrasive blasting
with beryllium-containing slags. OSHA could not develop exposure
profiles for construction and shipyard workers engaged in activities
involving non-sparking tools, demolition of beryllium-contaminated
buildings or equipment, and working with beryllium-containing alloys.
However, OSHA acknowledges the USW's concerns about future beryllium
use and recognizes that there is potential for exposure to beryllium in
construction and shipyard operations other than abrasive blasting. As
such, workers engaged in such operations are exposed to the same hazard
of developing CBD and other beryllium-related disease, and therefore
deserve the same level of protection as do workers who are engaged in
abrasive blasting or covered in the general industry final rule.
Therefore, although at this time OSHA cannot specifically quantify
exposures in construction or shipyard operations outside of abrasive
blasting, OSHA has determined that it is necessary for the final
standards for construction and maritime to cover all occupational
exposures to beryllium in those industries in order to ensure that the
standard is broadly effective and addresses all potential harmful
exposures.
Three commenters representing the maritime industry supported
Regulatory Alternative #2b--adopting the new PELs for construction and
maritime by updating the existing Z tables to incorporate them, but not
applying the other ancillary provisions of this standard to
construction and maritime (Document ID 1595, p. 2; 1618, p. 2; 1657. p.
1). The Shipbuilders Council of America (SCA) supported lowering the
PEL for beryllium from 2.0 μ/m3\ to 0.2 μ/m3\ in 29 CFR
1915.1000 Table Z, but argued that a new beryllium standard would prove
to be redundant. SCA contended that many shipyards maintain a
comprehensive industrial hygiene program focused on exposure
assessments and protective measures for a variety of metals in shipyard
tasks, and that shipyards encounter beryllium only at trace contaminant
levels in materials involved in the welding and abrasive blasting
processes. SCA stated that the potential hazards inherent in and unique
to abrasive blasting in shipyards are already effectively controlled
through existing regulations (Document ID 1618, pp. 2-4). General
Dynamics' Bath Iron Works expressed similar views in their comments on
this issue, as did Newport News Shipbuilding (Document 1595, p. 2;
1657, p. 1).
In addition to the commenters representing the maritime industry,
Ameren, an electric and natural gas public utility, also supported
applying the proposed TWA PEL and STEL to all employers in general
industry, construction, and maritime even where beryllium exists only
as a trace contaminant (Document ID 1675, p. 3). However, not all
commenters endorsed Alternative #2b. The Department of Energy's
National Supplemental Screening Program (NSSP) did not support this
alternative because the other provisions of the standard would only
cover employers and employees within the scope of the proposed general
industry rule (Document ID 1677, p. 2). Furthermore, many commenters
supported extending the full protections of the standard to the
construction and maritime industries as set forth in Regulatory
Alternative #2a, discussed earlier, which implicitly rejects Regulatory
Alternative #2b (see, e.g., Document ID 1756, Tr. 81; 1756, Tr. 97-98;
1756, Tr. 172-175; 1756, Tr. 198-199; 1755, Tr. 181).
OSHA is not persuaded by the maritime industry commenters'
assertions that the ancillary provisions of the beryllium standard
would be redundant. While OSHA acknowledges that shipyards encounter
beryllium only at trace levels in materials involved in the welding and
abrasive blasting processes, OSHA disagrees with their contention that
updating the PEL and STEL will provide adequate protection to shipyard
workers. OSHA agrees with NSSP and all the commenters supporting
Regulatory Alternative #2a that a comprehensive standard specific to
beryllium will provide the important protection of ancillary
provisions, such as medical surveillance and medical removal
protection. OSHA intends to
ensure that workers exposed to beryllium in the construction and
shipyard industries are provided with protection that is comparable to
the protection afforded workers in general industry. Therefore, OSHA
has set an identical PEL and STEL and, where no meaningful distinctions
are identified in the record, included substantially the same or
approximately equivalent ancillary provisions in all three standards.
For further discussion of the differences among the standards, see the
provision-specific sections included in this Summary and Explanation.
Therefore, OSHA declines to adopt Regulatory Alternative #2b,
which, as noted above, would have updated 29 CFR 1910.1000 Tables Z-1
and Z-2, 29 CFR 1915.1000 Table Z, and 29 CFR 1926.55 Appendix A so
that the new TWA PEL and STEL, but not the standard's ancillary
provisions, would apply to all employers and employees in general
industry, shipyards, and construction, including occupations where
beryllium exists only as a trace contaminant. The Agency intends for
employers that are exempt from the scope of these comprehensive
standards in accordance with paragraph (a) to comply with the preceding
TWA PEL and STEL in 29 CFR 1910.1000 Table Z-2, 29 CFR 1915.1000 Table
Z, and 29 CFR 1926.55 Appendix A, as applicable. Given that the Agency
is issuing separate beryllium standards for the construction and
shipyard industries, OSHA is also adding to these tables a cross-
reference to the new standards and clarifying that if the new standards
are stayed or otherwise not in effect, the preceding PEL and short-term
ceiling limit apply.
Paragraph (a)(1). Proposed paragraph (a)(1) applied the standard to
occupational exposures to beryllium in all forms, compounds, and
mixtures in general industry, except those articles and materials
exempted by paragraphs (a)(2) and (a)(3) of the standards. As OSHA
explained in the proposal, the Agency preliminarily chose to treat
beryllium generally, instead of individually addressing specific
compounds, forms, and mixtures. This decision was based on the Agency's
preliminary determination that the toxicological effects of beryllium
exposure on the human body are similar regardless of the form of
beryllium (80 FR 47774).
Several commenters offered opinions on this approach. The Non-
Ferrous Founders' Society (NFFS) expressed concern that beryllium metal
was being treated the same as soluble beryllium compounds, such as
salts, even though NFFS believes these soluble compounds are more
hazardous and suggested that OSHA establish a bifurcated standard for
insoluble beryllium versus soluble beryllium compounds (Document ID
1732, p. 3; 1678, p. 2; 1756, Tr. 18). In related testimony, NIOSH's
Dr. Aleks Stefaniak discussed the dermal exposure mechanisms of poorly
soluble beryllium through particle penetration and particle dissolving
(Document ID 1755, pp. 35-39). Dr. Stefaniak testified that while
"intact skin naturally has a barrier . . . [v]ery few people actually
have fully intact skin, especially in an industrial environment"
(Document ID 1755, p. 36). He added:
in fact, beryllium particles, beryllium oxide, beryllium metal,
beryllium alloys, all these sort of what we call insoluble forms
actually do in fact dissolve very readily in analog of human sweat.
And once beryllium is in an ionic form on the skin, it's actually
very easy for it to cross the skin barrier (Document ID 1755, pp.
36-37).
NIOSH also provided additional information on beryllium solubility and
the development of CBD in its post-hearing brief, labeling as untrue
NFFS's assertion that insoluble beryllium does not cause CBD (Document
ID 1960, Attachment 2, pp. 8-10), citing studies showing that workers
exposed to insoluble forms of beryllium have developed sensitization
and CBD (Kreiss, et al., 1997, Document ID 1360; Schuler et al., 2005
(1349); Schuler et al., 2008 (1291); Wegner et al., 2000, (1960,
Attachment 7)).
After careful consideration of the various comments on this issue,
OSHA is not persuaded that there are differences in workers' health
risks that justify treating poorly soluble beryllium differently than
soluble compounds. The Agency is persuaded by NIOSH that poorly soluble
beryllium presents a significant risk of beryllium-related disease to
workers and discusses this topic further in Section V of this preamble,
Health Effects. OSHA has determined that the toxicological effects of
beryllium exposure on the human body are similar regardless of the form
of beryllium. Therefore, the Agency concludes that the record supports
issuing standards that apply to beryllium in all forms, compounds, and
mixtures. Final paragraph (a)(1) is therefore substantively unchanged
from the proposal in all three standards.
Paragraph (a)(2). Proposed paragraph (a)(2) excluded from the
standard's scope articles, as defined in the Hazard Communication
standard (HCS) (29 CFR 1910.1200(c)), that contain beryllium and that
the employer does not process. As OSHA explained in the proposal (80 FR
47775), the HCS defines an "article" as
a manufactured item other than a fluid or particle: (i) Which is
formed to a specific shape or design during manufacture; (ii) which
has end use function(s) dependent in whole or in part upon its shape
or design during end use; and (iii) which under normal conditions of
use does not release more than very small quantities, e.g., minute
or trace amounts of a hazardous chemical . . ., and does not pose a
physical hazard or health risk to employees.
OSHA preliminarily found that items or parts containing beryllium that
employers assemble where the physical integrity of the item is not
compromised are unlikely to release beryllium that would pose a
physical or health hazard for workers. Therefore, OSHA proposed to
exempt such articles from the scope of the standard. This proposed
provision was intended to ease the burden on employers by exempting
items from coverage where they are unlikely to pose a risk to
employees.
Commenters generally supported this proposed exemption. For
example, NFFS stated that the exemption was "important and practical"
(Document ID 1678, p. 2; Document ID 1756, Tr. 35-36)). However, two
commenters requested minor amendments to the exemption. First, ORCHSE
Strategies (ORCHSE) asked OSHA to "clarify" that proposed paragraph
(a)(2) "exempts `articles' even if they are processed, unless the
processing releases beryllium to an extent that negates the definition
of an `article' " (Document ID 1691, Attachment 1, p. 16). ORCHSE
asserted that the standard should not apply in a workplace when "the
item actually meets OSHA's definition of an article" and that OSHA
should change the regulation's language accordingly (Document ID 1691,
Attachment 1, pp. 16-17). Second, the American Dental Association (ADA)
asked that OSHA clarify the article exemption, specifically that
employers who use but do not process articles are fully exempt from all
requirements of the proposed rule, including those established for
recordkeeping (Document ID 1597, p. 1).
In contrast, Public Citizen objected to the inclusion of this
exemption because exempting articles that are not processed does not
take into consideration dermal exposure from handling articles
containing beryllium (Document ID 1670, p. 7). Public Citizen pointed
to OSHA's proposed rule in which OSHA acknowledged that beryllium
absorbed through the skin can induce a sensitization response that is a
necessary first step toward CBD and that there is evidence that the
risk is not limited to soluble forms. However, during follow-up
questioning at the beryllium public hearings, Dr. Almashat
of Public Citizen was unable to provide any examples of dermal exposure
from articles through their handling, as opposed to when processing
beryllium materials (Document ID 1756, Tr. 178-180). And, in its post-
hearing comments, Public Citizen did not provide evidence of dermal
exposure to workers handling beryllium materials that would fall under
the definition of article (Document ID 1964). In the final standard,
OSHA has decided not to alter the proposed exemption of articles. OSHA
is not persuaded by ORCHSE's argument that OSHA should change the
regulation's language to exempt articles even if they are processed,
unless the processing releases beryllium to an extent that negates the
definition of an article. The HCS defines an article as
a manufactured item other than a fluid or particle: (i) Which is
formed to a specific shape or design during manufacture; (ii) which
has end use function(s) dependent in whole or in part upon its shape
or design during end use; and (iii) which under normal conditions of
use does not release more than very small quantities, e.g., minute
or trace amounts of a hazardous chemical (as determined under
paragraph (d) of this section), and does not pose a physical hazard
or health risk to employees. (29 CFR 1910.1200(c)).
Whether a particular item is an "article" under the HCS depends on
the physical properties and intended use of that item. However,
employers may use and process beryllium-containing items in ways not
necessarily intended by the manufacturer. Therefore, OSHA has decided
not to link the processing limitation to the definition of an
"article" and is retaining the language of proposed (a)(2) to comport
with the intention of the exemption.
In response to the ADA's request for clarification that employers
who use but do not process articles are fully exempt from all
requirements of the rule, OSHA notes that paragraph (a)(2) of the final
standards states that the "standard does not apply" to those
articles. Furthermore, the recordkeeping requirement for objective data
in paragraph (n)(2) of the standards states that it applies to
objective data used to satisfy exposure assessment requirements, but
does not mention any data used to determine coverage under paragraph
(a). Therefore, OSHA has determined that no further clarification in
the regulatory text is necessary.
In response to the comment from Public Citizen, OSHA did not
receive any evidence on the issue of beryllium exposure through dermal
contact with unprocessed articles. Therefore, OSHA cannot find that
such contact poses a risk.
Paragraph (a)(2) of the final standards therefore remains unchanged
from the proposed standard. The final standards do not apply to
articles, as defined in the Hazard Communication standard (HCS) (29 CFR
1910.1200(c)), that contain beryllium and that the employer does not
process.
Paragraph (a)(3). Proposed paragraph (a)(3) exempted from coverage
materials containing less than 0.1 percent beryllium by weight.
Requesting comment on this exemption (80 FR 47776), OSHA presented
Regulatory Alternative #1a, which would have eliminated the proposal's
exemption for materials containing less than 0.1 percent beryllium by
weight, and #1b, which would have exempted operations where the
employer can show that employees' exposures will not meet or exceed the
action level or exceed the STEL. The Agency asked whether it is
appropriate to include an exemption for operations where beryllium
exists only as a trace contaminant, but some workers can nevertheless
be significantly exposed. And the Agency asked whether it should
consider dropping the exemption, or limiting it to operations where
exposures are below the proposed action level and STEL. In addition,
OSHA requested additional data describing the levels of airborne
beryllium in workplaces that fall under this exemption. Some
stakeholders supported keeping the 0.1 percent exemption as proposed
(Document ID 1661, p. 6; 1666, p. 2; 1668, p. 2; 1673, p. 8; 1674, p.
3; 1687, Attachment 2, p. 8; 1691, Attachment 1, p. 3; 1756, Tr. 35-36,
63). For example, the Edison Electric Institute (EEI) strongly
supported the exemption and asserted "that abandoning the exemption
would result in no additional benefits from a reduction in the
beryllium permissible exposure limit (PEL) or from ancillary provisions
similar to those already in place for the arsenic and other standards"
(Document ID 1674, p. 3). Mr. Weaver of NFFS also opposed eliminating
the exemption, testifying that without the 0.1 percent exemption, 900
to 1,100 foundries would come under the scope of the rule (Document ID
1756, Tr. 55-56).
ABMA also supported the proposed 0.1 percent exemption, suggesting
that there is a lack of evidence of significant risk from working with
material containing beryllium in trace amounts and that OSHA needs
substantial evidence that it is "at least more likely than not" that
exposure to beryllium in trace amounts presents significant risk of
harm, under court decisions concerning the Benzene rule (Document ID
1673, pp. 8-9). ABMA further argued that significant risk does not
exist even below the previous PEL of 2.0 μg/m3\ (Document ID 1673,
pp. 8-9, 11). ABMA added that its members collectively have over 200
years of experience producing coal and/or copper slag abrasive material
and have employed thousands of employees in this production process.
ABMA explained:
Through the years, Alliance members have worked with and put to
beneficial use over 100 million tons of slag material that would
otherwise have been landfilled. Despite this extensive history, the
Alliance members have no history of employees with beryllium
sensitization or beryllium-related illnesses. Indeed, the Alliance
members are not aware of a single documented case of beryllium
sensitization or beryllium-related illness associated with coal or
copper slag abrasive production among their employees, or their
customers' employees working with the products of Alliance members
(Document ID 1673, p. 9).
OSHA is not persuaded by these arguments. The lack of anecdotal
evidence of sensitization or beryllium-related illness does not mean
these workers are not at risk. As noted by Representative Robert C.
"Bobby" Scott, Ranking Member of the U.S. House of Representatives
Committee on Education and the Workforce the U.S. House of
Representatives, "medical surveillance has not been required for
beryllium-exposed workers outside of the U.S. Department of Energy. The
absence of evidence is not evidence of absence" (Document ID 1672). As
discussed in Section II of this preamble, Pertinent Legal Authority,
courts have not required OSHA "to support its finding that a
significant risk exists with anything approaching scientific
certainty" (Benzene, 448 U.S. 607, 656 (1980)). Rather, OSHA may rely
on "a body of reputable scientific thought" to which "conservative
assumptions in interpreting the data . . ." may be applied, "risking
error on the side of overprotection" (Benzene, 448 U.S. at 656). OSHA
may thus act with a "pronounced bias towards worker safety" in making
its risk determinations (Bldg & Constr. Trades Dep't v. Brock, 838 F.2d
1258, 1266 (D.C. Cir. 1988). Where, as here, the Agency has evidence
indicating that a certain operation can result in exposure levels that
the Agency knows can pose a significant risk--such as evidence that
workers that have been exposed to beryllium at the final PEL of 0.2
μg/m3\ in primary beryllium production and beryllium machining
operations have developed CBD (see this preamble at section V, Risk
assessment)--OSHA need not wait until it has specific evidence that
employees in that
particular industry are suffering. A number of commenters supported
Regulatory Alternative #1a, proposing to eliminate the proposal's
exemption for materials containing less than 0.1 percent beryllium by
weight (Document ID 1655, p. 15; 1664, p. 2; 1670, p. 7; 1671,
Attachment 1, p. 5; 1672, pp. 4-5; 1683, p. 2; 1686, p. 2; 1689, pp. 6-
7; 1690, p. 3; 1693, p. 3; 1720, pp. 1, 4). Public Citizen expressed
concern with the proposed exemption and pointed out that OSHA
identified studies in its proposal unequivocally demonstrating that
beryllium sensitization and CBD occur in multiple industries utilizing
products containing trace amounts of beryllium and that such an
exemption would expose workers in such industries to the risks of
beryllium toxicity (Document ID 1670, p. 7). The American Association
for Justice, the AFL-CIO, and the UAW were all concerned that the
proposed standard's 0.1 percent exemption would result in workers being
exposed to significant amounts of beryllium from abrasive blasting
(Document ID 1683, p. 2; 1689, pp. 6-7, 10-11; 1693, p. 3). Both Dr.
Sammy Almashat and Emily Gardner of Public Citizen testified that they
support inclusion of work processes that involve materials containing
less than 0.1 percent of beryllium because the beryllium can become
concentrated in air, even when using materials with only trace amounts
(Document ID 1756, Tr. 174, 177-178, 185-186). Similarly, the AFL-CIO
stated that "there are known over-exposures among industries that use
materials with less than 0.1% beryllium by weight, including an
estimated 1,665 workers in primary aluminum production and 14,859 coal-
fired electric power generation workers" (Document ID 1689, p. 7).
Mary Kathryn Fletcher of the AFL-CIO further explained that the AFL-CIO
supported eliminating the exemption because these employees are at
significant risk for developing sensitization, chronic beryllium
disease (CBD), and lung cancer (Document ID 1756, Tr. 198-199). The
Sampling and Analysis Subcommittee Task Group of the Beryllium Health
and Safety Committee (BHSC Task Group) recommended that OSHA remove the
exemption (Document ID 1655, p. 15). AIHA also recommended eliminating
or reducing the percentage content exemption until data is available to
demonstrate that materials with very low beryllium content will not
result in potential exposure above the proposed PEL (Document ID 1686,
p. 2).
Both NIOSH and North America's Building Trades Unions (NABTU)
expressed concern that the 0.1 percent exemption would expose
construction and shipyard workers conducting abrasive blasting with
coal slags to beryllium in concentrations above the final PEL. NIOSH
and NABTU cited a study by the Center for Construction Research and
Training, and NIOSH also cited one of its exposure assessment studies
of a coal slag blaster showing beryllium air concentrations exceeding
the preceding OSHA PEL (Document ID 1671, Attachment 1, p. 5; 1679, pp.
3-4). In addition, NIOSH points out that although the abrasive blasting
workers may use personal protective equipment that limits exposure,
supervisors and other bystanders may be exposed. NIOSH gave other
examples where the 0.1 percent exemption could result in workers being
exposed to beryllium, such as building or building equipment demolition
and work in dental offices that fabricate or modify beryllium-
containing dental alloys, but did not provide reference material or
exposure data for these examples (Document ID 1671, pp. 5-6). In its
post-hearing brief, NIOSH also specifically disagreed with EEI's
contention that compliance with the arsenic and asbestos standards
satisfies the proposed regulatory requirements of the beryllium rule.
NIOSH argued that, unlike arsenic and lead, beryllium is a sensitizer,
and as such, necessary and sufficient controls are required to protect
workers from life-long risk of beryllium sensitization and disease
(Document ID 1960, Attachment 2, p. 6).
OSHA also received comment and heard testimony from Dr. Weissman of
NIOSH recommending that the scope of the standard be based on employee
exposures and not the concentration of beryllium in the material
(Document ID 1671, pp. 5-6; Document ID 1755, Tr. 17-18). NIOSH
identified coal-fired electric power generation and primary aluminum
production as industries that could fall under the 0.1 percent
exemption (Document ID 1671, Attachment 1, p. 6). Stating it was not
aware of any medical screening of utility workers exposed to fly ash,
NIOSH recommended that OSHA include coal-fired electric power
generation in the scope of the standard unless and until available data
can demonstrate that there is no risk of sensitization to those workers
(Document ID 1671, p. 6). NIOSH did not offer specifics on the
magnitude of beryllium exposure in the aluminum production industry. In
its post-hearing brief, NIOSH recommended that OSHA remove the 0.1
percent exemption from the rule, allowing the rule to cover a broad
range of construction, shipyard, and electric utility power generation
activities that are associated with beryllium exposure, such as
abrasive blasting with coal or copper slag, repairing and maintaining
structures contaminated with fly ash, and remediation or demolition
(Document ID 1960, Attachment 2, p. 2). And Peggy Mroz of NJH testified
that beryllium sensitization and CBD have been reported in the aluminum
industry and that NJH has continued to see cases of severe CBD in
workers exposed to beryllium through medical recycling and metal
reclamation (Document ID 1756, Tr. 98-99).
Other commenters suggested limiting the exemption, as OSHA proposed
in Regulatory Alternative #1b, to require employers to demonstrate,
using objective data, that the materials, when processed or handled,
cannot release beryllium in concentrations at or above the action level
as an 8-hour TWA under any foreseeable conditions (Document ID 1597, p.
1; 1681, pp. 5-6). For example, the Materion-USW proposed standard
included the 0.1 percent exemption unless objective data or initial
monitoring showed exposures could exceed the action level or STEL. USW
asserted that not including this requirement in the rule would be a
mistake (Document ID 1681, pp. 5-6). The AFL-CIO also supported the
joint USW-Materion scope provision (Document ID 1756, Tr. 212). Mike
Wright of the USW asserted that maintaining the 0.1 percent exemption
would leave thousands of workers unprotected, including those
performing abrasive blasting operations in general industry, ship
building, and construction (Document ID 1755, Tr. 111-114). Mr. Wright
argued that in the 1,3 Butadiene standard OSHA recognized that the 0.1
percent exemption would not protect some workers and therefore included
additional language limiting the exemption where objective data showed
"that airborne concentrations generated by such mixtures can exceed
the action level or STEL under reasonably predictable conditions of
processing, use or handling that will cause the greatest possible
release" (Document ID 1755, Tr. 113; 29 CFR 1910.1051(a)(2)(ii)). Mr.
Wright urged OSHA to include similar language in the beryllium standard
(Document ID 1755, Tr. 113-114).
Some commenters endorsed a modified version of Alternative #1b. For
example, the Department of Defense (DOD) supported Alternative #1b, but
also suggested limiting the exemption if exposures "could present a
health risk
to employees" (Document ID 1684, Attachment 2, pp. 1, 3). Boeing
suggested adding a different exemption to the scope of the standard:
where the employer has objective data demonstrating that a material
containing beryllium or a specific process, operation, or activity
involving beryllium cannot release dusts, fumes, or mists of
beryllium in concentrations at or above 0.02 μg/m3\ as an 8-hour
time-weighted average (TWA) or at or above 0.2 μg/m3\ as
determined over a sampling period of 15 minutes under any expected
conditions of use (Document ID 1667, p. 12).
Other commenters, like ABMA, criticized Regulatory Alternative #1b,
insisting that the rulemaking record contained no evidence to support
expanding the scope, but that if the scope was expanded to cover trace
beryllium, a significant exemption would be needed. ABMA argued that
such an exemption would need to go considerably beyond that of using
the action level or STEL because of the substantial costs, particularly
on small businesses, that would be incurred where there is no evidence
of benefit. However, ABMA did not specify what such an exemption would
look like (Document ID 1673, p. 11). Similarly, the National Rural
Electric Cooperative Association (NRECA) objected to Regulatory
Alternative #1b as being unnecessary to protect employees from CBD in
coal fired power plants (Document ID 1687, p. 2).
Ameren did not agree with the objective data requirement in
Regulatory Alternative #1b because it would be difficult to perform
sampling in a timely manner for the many different maintenance
operations that occur infrequently. This would include in the scope of
the rule activities for which exposures are difficult to measure, but
are less likely to cause exposure than other operations (Document ID
1675, p. 2). The NSSP also does not support Regulatory Alternative #1b
because without first expanding the scope of the rule to cover the
construction and maritime sectors, employers in construction and
maritime would still be excluded (Document ID 1677, p. 1).
OSHA agrees with the many commenters and testimony expressing
concern that materials containing trace amounts of beryllium (less than
0.1 percent by weight) can result in hazardous exposures to beryllium.
We disagree, however, with those who supported completely eliminating
the exemption because this could have unintended consequences of
expanding the scope to cover minute amounts of naturally occurring
beryllium (Ex 1756 Tr. 55). Instead, we believe that alternative #1b--
essentially as proposed by Materion and USW and acknowledging that
workers can have significant beryllium exposures even with materials
containing less than 0.1%--is the most appropriate approach. Therefore,
in the final standard, it is exempting from the standard's application
materials containing less than 0.1% beryllium by weight only where the
employer has objective data demonstrating that employee exposure to
beryllium will remain below the action level as an 8-hour TWA under any
foreseeable conditions.
As noted by NIOSH, NABTU, and the AFL-CIO, and discussed in Chapter
IV of the FEA, workers in abrasive blasting operations using materials
that contain less than 0.1 percent beryllium still have the potential
for significant airborne beryllium exposure during abrasive blasting
operations and during cleanup of spent abrasive material. NIOSH and the
AFL-CIO also identified coal-fired electric power generation and
primary aluminum production as industries that could fall under the 0.1
percent exemption but still have significant worker exposure to
beryllium. Furthermore, OSHA agrees with NIOSH that the Agency should
regulate based on the potential for employee exposures and not the
concentration of beryllium in the material being handled. However, OSHA
acknowledges the concerns expressed by ABMA and EEI that processing
materials with trace amounts of beryllium may not necessarily cause
significant exposures to beryllium. OSHA does not have evidence that
all materials containing less than 0.1 percent beryllium by weight can
result in significant exposure to beryllium, but the record contains
ample evidence that there are significant exposures in operations using
materials with trace amounts of beryllium, such as abrasive blasting,
coal-fired power generation, and primary aluminum production. As
discussed in Section VII of this preamble, Significance of Risk,
preventing airborne exposures at or above the action level reduces the
risk of beryllium-related health effects to workers. OSHA is also not
persuaded by comments that claim obtaining this exposure data is too
difficult for infrequent or short-term tasks because employers must be
able to establish their eligibility for the exemption before being able
to take advantage of it. If an employer cannot establish by objective
data, including actual monitoring data, that exposures will not exceed
the action level, then the beryllium standards apply to protect that
employer's workers.
As pointed out by commenters such as the USW, similar exemptions
are included in other OSHA standards, including Benzene (29 CFR
1910.1028), Methylenedianiline (MDA) (29 CFR 1910.1050), and 1,3-
Butadiene (BD) (29 CFR 1910.1051). These exemptions were established
because workers in the exempted industries or workplaces were not
exposed to the subject chemical substances at levels of significant
risk. In the preamble to the MDA standard, OSHA states that the Agency
relied on data showing that worker exposure to mixtures or materials of
MDA containing less than 0.1 percent MDA did not create any hazards
other than those expected from worker exposure beneath the action level
(57 FR 35630, 35645-46). The exemption in the BD standard does not
apply where airborne concentrations generated by mixtures containing
less than 0.1 percent BD by volume can exceed the action level or STEL
(29 CFR 1910.1051(a)(2)(ii)). The exemption in the Benzene standard was
based on indications that exposures resulting from substances
containing trace amounts of benzene would generally be below the
exposure limit and on OSHA's determination that the exemption would
encourage employers to reduce the concentration of benzene in certain
substances (43 FR 27962, 27968).
OSHA's decision to maintain the 0.1 percent exemption and require
employers to demonstrate, using objective data, that the materials,
when processed or handled, cannot release beryllium in concentrations
at or above the action level as an 8-hour TWA under any foreseeable
conditions, is a change from proposed paragraph (a)(3) that specified
only that the standard did not apply to materials containing less than
0.1 percent beryllium by weight. This is also a change from Regulatory
Alternative #1b in another respect, insofar as it proposed requiring
objective data demonstrating that employee exposure to beryllium will
remain below both the proposed action level and STEL. OSHA removed the
STEL requirement as largely redundant because if exposures exceed the
STEL of 2.0 µg/m3\ for more than one 15-minute period per 8-hour
shift, even if exposures are non-detectable for the remainder of the
shift, the 8-hour TWA would exceed the action level of 0.1 μg/m3\.
Further, OSHA added the phrase "under any foreseeable conditions"
to paragraph (a)(3) of the final standards to make clear that limited
sampling results indicating exposures are below the
action level would be insufficient to take advantage of this exemption.
When using the phrase "any foreseeable conditions," OSHA is referring
to situations that can reasonably be anticipated. For example, annual
maintenance of equipment during which exposures could exceed the action
level would be a situation that is generally foreseeable.
In sum, the proposed standard covered occupational exposures to
beryllium in all forms, compounds, and mixtures in general industry. It
did not apply to articles, as defined by the HCS, or to materials
containing less than 0.1 percent beryllium by weight. After a thorough
review of the record, OSHA has decided to adopt Regulatory Alternative
#2a and include the construction and shipyard sectors within the scope
of the final rule. This decision was in response to the majority of
comments recommending that OSHA protect workers in these sectors under
the final rule and the exposure data in these sectors contained in the
record. OSHA has also decided to adopt a modified version of Regulatory
Alternative #1b and limit the 0.1 percent exemption to those employers
who have objective data demonstrating that employee exposure to
beryllium will remain below the action level as an 8-hour TWA under any
foreseeable conditions.
Therefore, the final rule contains three standards--one each for
general industry, construction, and shipyard. The article exemption has
remained unchanged, and the 0.1 percent exemption has been limited to
protect workers with significant exposures despite working with
materials with trace amounts of beryllium.
(b) Definitions
Paragraph (b) includes definitions of key terms used in the
standard. To the extent possible, OSHA uses the same terms and
definitions in the standard as the Agency has used in other OSHA health
standards. Using similar terms across health standards, when possible,
makes them more understandable and easier for employers to follow. In
addition, using similar terms and definitions helps to facilitate
uniformity of interpretation and enforcement.
Action level means a concentration of airborne beryllium of 0.1
micrograms per cubic meter of air (μg/m3\) calculated as an 8-hour
time-weighted average (TWA). Exposures at or above the action level
trigger requirements for periodic exposure monitoring when the employer
is following the scheduled monitoring option (see paragraph (d)(3)). In
addition, paragraph (f)(1)(i)(B) requires employers to list as part of
their written exposure control plan the operations and job titles
reasonably expected to have exposure at or above the action level.
Paragraph (f)(2) requires employers to ensure that at least one of the
controls listed in paragraph (f)(2)(i) is in place unless employers can
demonstrate for each operation or process either that such controls are
not feasible, or that employee exposures are below the action level
based on at least two representative personal breathing zone samples
taken at least seven days apart. In addition, under paragraph
(k)(1)(i)(A), employee exposure at or above the action level for more
than 30 days per year triggers requirements for medical surveillance.
The medical surveillance provision triggered by the action level allows
employees to receive exams at least every two years at no cost to the
employee. The action level is also relevant to the medical removal
requirements. Employees eligible for removal can choose to remain in
environments with exposures at or above the action level, provided they
wear respirators (paragraph (l)(2)(ii)). These employees may also
choose to be transferred to comparable work in environments with
exposures below the action level (if comparable work is not available,
the employer must maintain the employee's earnings and benefits for six
months or until comparable work becomes available (paragraph (l)(3)).
OSHA's risk assessment indicates that significant risk remains at
and below the TWA PEL (see this preamble at section VII, Significance
of Risk). When there is significant risk remaining at the PEL, the
courts have ruled that OSHA has the legal authority to impose
additional requirements, such as action levels, on employers to further
reduce risk when those requirements will result in a greater than
minimal incremental benefit to workers' health (Asbestos II, 838 F.2d
at 1274). OSHA concludes that an action level for beryllium exposure
will result in a further reduction in risk beyond that provided by the
PEL alone.
Another important reason to set an action level involves the
variable nature of employee exposures to beryllium. Because of this
fact, OSHA concludes that maintaining exposures below the action level
provides reasonable assurance that employees will not be exposed to
beryllium above the TWA PEL on days when no exposure measurements are
made. This consideration is discussed later in this section of the
preamble regarding paragraph (d)(3).
The United Steelworkers (USW) commented in support of the action
level, noting that it is typical in OSHA standards to have an action
level at one half of the PEL (Document ID 1681, p. 11). The USW also
commented that the "action level will further reduce exposure to
beryllium by workers and will incentivize employers to implement best
practice controls keeping exposures at a minimum as well as reducing
costs of monitoring and assessments" (Document ID 1681, p. 11).
National Jewish Health (NJH) also supported OSHA's proposal for a more
comprehensive standard and noted that the action level in the
Department of Energy's beryllium standard has been "very effective at
reducing exposures and rates of beryllium sensitization and chronic
beryllium disease in those facilities" (Document ID 1756, p. 90).
As noted by the commenters, OSHA's decision to set an action level
of one-half of the TWA PEL is consistent with previous standards,
including those for inorganic arsenic (29 CFR 1910.1018), chromium (VI)
(29 CFR 1910.1026), benzene (29 CFR 1910.1028), ethylene oxide (29 CFR
1910.1047), methylene chloride (29 CFR 1910.1052), and respirable
crystalline silica (29 CFR 1910.1053).
The definition of "action level" is therefore unchanged from the
proposal. Some of the ancillary provisions triggered by the action
level have changed since the proposal. Those changes are discussed in
more detail in the Summary and Explanation sections for those
provisions.
Airborne exposure and airborne exposure to beryllium mean the
exposure to airborne beryllium that would occur if the employee were
not using a respirator.
OSHA included a definition for the terms "exposure" and
"exposure to beryllium" in the proposed rule, and defined the terms
to mean "the exposure to airborne beryllium that would occur if the
employee were not using a respirator." In the final rule, the word
"airborne" is added to the terms to make clear that they refer only
to airborne beryllium, and not to dermal contact with beryllium. The
modified terms replace "exposure" and "exposure to beryllium" in
the rule, and the terms "exposure" and "exposure to beryllium" are
no longer defined.
Assistant Secretary means the Assistant Secretary of Labor for
Occupational Safety and Health, United States Department of Labor, or
designee. OSHA received no comments on this definition, and it is
unchanged from the proposal.
Beryllium lymphocyte proliferation test (BeLPT) means the
measurement of blood lymphocyte proliferation in a
laboratory test when lymphocytes are challenged with a soluble
beryllium salt. For additional explanation of the BeLPT, see the Health
Effects section of this preamble (section V). Under paragraph
(f)(1)(ii)(B), an employer must review and evaluate its written
exposure control plan when an employee is confirmed positive. The BeLPT
could be used to determine whether an employee is confirmed positive
(see definition of "confirmed positive" in paragraph (b) of this
standard). Paragraph (k)(3)(ii)(E) requires the BeLPT unless a more
reliable and accurate test becomes available.
NJH supported OSHA's definition of the BeLPT in the NPRM (Document
ID 1664, p. 5). However, OSHA has made one change from the proposed
definition of the BeLPT in the NPRM to the final definition to provide
greater clarity. The Agency has moved the characterization of a
confirmed positive result from the BeLPT definition to the "confirmed
positive" definition because it was more appropriate there.
Beryllium work area means any work area containing a process or
operation that can release beryllium where employees are, or can
reasonably be expected to be, exposed to airborne beryllium at any
level or where there is potential for dermal contact with beryllium.
The definition of "beryllium work area" has been changed from the
proposed definition to reflect stakeholder concerns regarding the
overlap between a beryllium work area and regulated area, and to
include the potential for dermal exposure. The definition only appears
in the general industry standard because the requirement for a
beryllium work area only applies to the general industry standard.
Beryllium work areas are areas where employees are or can reasonably be
expected to be exposed to airborne beryllium at any level, whereas an
area is a regulated area only if employees are or can reasonably be
expected to be exposed above the TWA PEL or STEL; the regulated area,
therefore, is either a subset of the beryllium work area or, less
likely, identical to it, depending on the configuration and
circumstances of the worksite. Dermal exposure has also been included
in the final definition to address the potential for sensitization from
dermal contact. Therefore, while not all beryllium work areas are
regulated areas, all regulated areas are beryllium work areas because
they are areas with employee exposure to beryllium. Accordingly, all
requirements for beryllium work areas also apply in all regulated
areas, but requirements specific to regulated areas apply only to
regulated areas and not to beryllium work areas where exposures do not
exceed the TWA PEL or STEL. For further discussion, see this section of
the preamble regarding paragraph (e), Beryllium work areas and
regulated areas.
The presence of a beryllium work area triggers a number of the
requirements in the general industry standard. Under paragraph
(d)(3)(i), employers must determine exposures for each beryllium work
area. Paragraphs (e)(1)(i) and (e)(2)(i) require employers to
establish, maintain, identify, and demarcate the boundaries of each
beryllium work area. Under paragraph (f)(1)(i)(D), employers must
minimize cross-contamination by preventing the transfer of beryllium
between surfaces, equipment, clothing, materials, and articles within a
beryllium work area. Paragraph (f)(1)(i)(F) states that employers must
minimize migration of beryllium from the beryllium work area to other
locations within and outside the workplace. Paragraph (f)(2) requires
employers to implement at least one of the controls listed in
(f)(2)(i)(A) through (D) for each operation in a beryllium work area
unless one of the exemptions in (f)(2)(ii) applies. Paragraph (i)(1)
requires employers to provide readily accessible washing facilities to
employees working in a beryllium work area, and to ensure that
employees who have dermal contact with beryllium wash any exposed skin
at the end of the activity, process, or work shift and prior to eating,
drinking, smoking, chewing tobacco or gum, applying cosmetics, or using
the toilet. In addition employers must ensure that these areas comply
with the Sanitation standard (29 CFR 1910.141) (paragraph (i)(4)).
Employers must maintain surfaces in all beryllium work areas as free as
practicable of beryllium (paragraph (j)(1)(i)). Paragraph (j)(2)
requires certain practices and prohibits other practices for cleaning
surfaces in beryllium work areas. Under paragraph (m)(4)(ii)(B),
employers must ensure workers demonstrate knowledge of the written
exposure control plan with emphasis on the location(s) of beryllium
work areas.
CBD diagnostic center means a medical diagnostic center that has an
on-site pulmonary specialist and on-site facilities to perform a
clinical evaluation for the presence of chronic beryllium disease
(CBD). This evaluation must include pulmonary function testing (as
outlined by the American Thoracic Society criteria), bronchoalveolar
lavage (BAL), and transbronchial biopsy. The CBD diagnostic center must
also have the capacity to transfer BAL samples to a laboratory for
appropriate diagnostic testing within 24 hours. The on-site pulmonary
specialist must be able to interpret the biopsy pathology and the BAL
diagnostic test results. For purposes of these standards, the term
"CBD diagnostic center" refers to any medical facility that meets
these criteria, whether or not the medical facility formally refers to
itself as a CBD diagnostic center. For example, if a hospital has all
of the capabilities required by this standard for CBD diagnostic
centers, the hospital would be considered a CBD diagnostic center for
purposes of these standards.
OSHA received comments from NJH and ORCHSE Strategies (ORCHSE)
regarding the definition of the "CBD diagnostic center." NJH
commented that CBD diagnostic centers do not need to be able to perform
the BeLPT but should be able to process the BAL appropriately and ship
samples within 24 hours to a facility that can perform the BeLPT. NJH
also indicated that CBD diagnostic centers should be able to perform CT
scans, pulmonary function tests with DLCO (diffusing capacity of the
lungs for carbon monoxide), and measure gas exchange abnormalities. NJH
further indicated that CBD diagnostic centers should have a medical
doctor who has experience and expertise, or is willing to obtain such
expertise, in the diagnosis and treatment of chronic beryllium disease
(Document ID 1664, pp. 5-6). ORCHSE argued that CBD diagnostic centers
should be allowed to rely on off-site interpretation of transbronchial
biopsy pathology, reasoning that this change would broaden the
accessibility of CBD diagnostic centers to more affected employees
(Document ID 1691, p. 3).
OSHA evaluated these recommendations and included the language
regarding sample processing and removed the proposal's requirement that
BeLPTs be performed on-site. The Agency also changed the requirement
that pulmonary specialist perform testing as outlined in the proposal
to the final definition which requires that a pulmonary specialist be
on-site. This requirement addresses the concerns ORCHSE raised about
accessibility of CBD diagnostic centers by increasing the number of
facilities that would qualify as centers. This also preserves the
expertise required to diagnose and treat CBD as stated by NJH (Document
1664, p. 6).
Paragraph (k)(7) includes provisions providing for an employee who
has been confirmed positive to receive an initial clinical evaluation
and subsequent medical examinations at a CBD diagnostic center.
Chronic beryllium disease (CBD) means a chronic lung disease
associated
with exposure to airborne beryllium. The Health Effects section of this
preamble, section V, contains more information on CBD. CBD is relevant
to several provisions of this standard. Under paragraph (k)(1)(i)(B),
employers must make medical surveillance available at no cost to
employees who show signs and symptoms of CBD. Paragraph (k)(3)(ii)(B)
requires medical examinations conducted under this standard to include
a physical examination with emphasis on the respiratory system, in
order to identify respiratory conditions such as CBD. Under paragraph
(k)(5)(i)(A), the licensed physician's report must advise the employee
on whether or not the employee has any detected medical condition that
would place the employee at an increased risk of CBD from further
exposure to beryllium. Furthermore, CBD is a criterion for medical
removal under paragraph (l)(1). Under paragraph (m)(1)(ii), employers
must address CBD in classifying beryllium hazards under the hazard
communication standard (HCS) (29 CFR 1910.1200). Employers must also
train employees on the signs and symptoms of CBD (see paragraph
(m)(4)(ii)(A) of the general industry and shipyard standards and
paragraph (m)(3)(ii)(A) of the construction standard).
Competent person means an individual on a construction site who is
capable of identifying existing and foreseeable beryllium hazards in
the workplace and who has authorization to take prompt corrective
measures to eliminate or minimize them. The competent person must have
the knowledge, ability, and authority necessary to fulfill the
responsibilities set forth in paragraph (e) of the standard for
construction. This definition appears only in the standard for
construction.
The competent person concept has been broadly used in OSHA
construction standards (e.g., 29 CFR 1926.32(f) and 1926.20(b)(2)),
including in the recent health standard for respirable crystalline
silica (29 CFR 1926.1153). Under 29 CFR 1926.32(f), competent person is
defined as "one capable of identifying existing and predictable
hazards in the surroundings or working conditions that are unsanitary,
hazardous, or dangerous to employees and who is authorized to take
prompt corrective measures to eliminate them." OSHA has adapted this
definition for the beryllium construction standard by specifying
"foreseeable beryllium hazards in the workplace" instead of
"predictable hazards in the surroundings or working conditions that
are unsanitary, hazardous, or dangerous to employees." The Agency also
replaced the word "one" with "an individual." The Agency revised
the phrase "to eliminate them" to read "to eliminate or minimize
them" to denote there may be cases where complete elimination would
not be feasible. The definition of competent person also indicates that
the competent person must have the knowledge, ability, and authority
necessary to fulfill the responsibilities set forth in paragraph (e) of
the construction standard, in order to ensure that the competent has
appropriate training, education, or experience. See the discussion of
"competent person" in the summary and explanation of paragraphs (e),
Beryllium work areas and regulated areas, and (f), Methods of
compliance, in this section.
Confirmed positive means the person tested has beryllium
sensitization, as indicated by two (either consecutive or non-
consecutive) abnormal BeLPT test results, an abnormal and borderline
test result, or three borderline test results. The definition of
"confirmed positive" also includes a single result of a more reliable
and accurate test indicating that a person has been identified as
sensitized to beryllium if the test has been validated by repeat
testing to have more accurate and precise diagnostic capabilities
within a single test result than the BeLPT. OSHA recognizes that
diagnostic tests for beryllium sensitization could eventually be
developed that would not require a second test to confirm
sensitization. Alternative test results would need to have comparable
or increased sensitivity, specificity and positive predictive value
(PPV) in order to replace the BeLPT as an acceptable test to evaluate
beryllium sensitization (see section V.D.5.b of this preamble).
OSHA received comments from NJH, the American Thoracic Society
(ATS) and ORCHSE regarding the requirement for consecutive test results
within a two year time frame, and the inclusion of borderline test
results (Document ID 1664, p.5; 1668, p. 2; 1691, p. 20). NJH and ATS
submitted similar comments regarding the requirement of two abnormal
BeLPT test results to be consecutive and within two years. According to
NJH, "the definition of `confirmed positive' [should] include two
abnormals, an abnormal and a borderline test result, and/or three
borderline tests. This recommendation is based on studies of Middleton
et al. (2008, and 2011), which showed that these other two combinations
result in a PPV similar to two abnormal test results and are an equal
predictor of CBD." (Document ID 1664, p. 5). In addition, the ATS
stated:
These test results need not be from consecutive BeLPTs or from a
second abnormal BeLPT result within a two-year period of the first
abnormal result. These recommendations are based on the many studies
cited in the docket, as well as those of Middleton, et al. (2006,
2008, and 2011), which showed that an abnormal and a borderline
result provide a positive predictive value (PPV) similar to that of
two abnormal test results for the identification of both beryllium
sensitization and for CBD (Document ID 1668, p. 2).
Materion Corporation (Materion) opposed changing the requirement
for two abnormal BeLPT results and opposed allowing two or three
borderline results to determine sensitization (Document ID 1808, p. 4).
Without providing scientific studies or other bases for its position,
Materion argued that "[m]aking a positive BeS determination for an
individual without any confirmed abnormal test result is not warranted
and clearly is not justifiable from a scientific, policy or legal
perspective" (Document ID 1808, p. 4).
OSHA evaluated these comments and modified the definition of
"confirmed positive" accordingly for reasons described more fully
within the Health Effects section of this preamble, V.D.5.b, including
reliance on the Middleton studies (2008, 2011). The original definition
for "confirmed positive" in the proposed standard was adapted from
the model standard submitted to OSHA by Materion and the USW in 2012.
Having carefully considered all these comments and their supporting
evidence, where provided, the Agency finds the arguments from NJH, ATS,
and ORCHSE persuasive. In particular ATS points out the Middleton et
al. studies ". . . showed that an abnormal and a borderline result
provide a positive predictive value (PPV) similar to that of two
abnormal test results for the identification of both beryllium
sensitization and for CBD." (Document ID. 1688 p. 3). Therefore, the
Agency recognizes that a borderline BeLPT test result when accompanied
by an abnormal test result, or three separate borderline test results,
should also be considered "confirmed positive."
In addition, ORCHSE commented on the use of a single test result
from a more reliable and accurate test (Document ID 1691, p. 20).
Specifically, ORCHSE recommended revising the language to include "the
result of a more reliable and accurate test such that beryllium
sensitization can be confirmed after one test, indicating a person has
been identified as having beryllium sensitization" (Document ID 1691,
p. 20). In response to the comment from ORCHSE, the Agency has included
additional language regarding the results from an alternative test
(Document ID 1691, p. 20). OSHA inserted additional language clarifying
that the alternative test has to be validated by repeat testing
indicating that it has comparable or increased sensitivity, specificity
and PPV than the BeLPT. The Agency finds that this language provides
more precise direction for acceptance of an alternative test.
Director means the Director of the National Institute for
Occupational Safety and Health (NIOSH), U.S. Department of Health and
Human Services, or designee. The recordkeeping requirements mandate
that, upon request, employers make all records required by this
standard available to the Director (as well as the Assistant Secretary)
for examination and copying (see paragraph (n)(6)). Typically, the
Assistant Secretary sends representatives to review workplace safety
and health records. However, the Director may also review these records
while conducting studies such as Health Hazard Evaluations of
workplaces, or for other purposes. OSHA received no comments on this
definition, and it is unchanged from the proposal.
Emergency means any uncontrolled release of airborne beryllium. An
emergency could result from equipment failure, rupture of containers,
or failure of control equipment, among other causes.
An emergency triggers several requirements of this standard. Under
paragraph (g)(1)(iv), respiratory protection is required during
emergencies to protect employees from potential overexposures.
Emergencies also trigger clean-up requirements under paragraph
(j)(1)(ii), and medical surveillance under paragraph (k)(1)(i)(C). In
addition, under paragraph (m)(4)(ii)(D) of the standards for general
industry and shipyards and paragraph (m)(3)(ii)(D) of the standard for
construction, employers must train employees in applicable emergency
procedures.
High-efficiency particulate air (HEPA) filter means a filter that
is at least 99.97 percent effective in removing particles 0.3
micrometers in diameter (see Department of Energy Technical Standard
DOE-STD-3020-2005). HEPA filtration is an effective means of removing
hazardous beryllium particles from the air. The standard requires
beryllium-contaminated surfaces to be cleaned by HEPA vacuuming or
other methods that minimize the likelihood of exposure (see paragraphs
(j)(2)(i) and (ii)). OSHA received no comments on this definition, and
it is unchanged from the proposal.
Objective data means information, such as air monitoring data from
industry-wide surveys or calculations based on the composition of a
substance, demonstrating airborne exposure to beryllium associated with
a particular product or material or a specific process, task, or
activity. The data must reflect workplace conditions closely resembling
or with a higher airborne exposure potential than the processes, types
of material, control methods, work practices, and environmental
conditions in the employer's current operations.
OSHA did not include a definition of "objective data" in the
proposed rule. Use of objective data was limited in the proposed rule,
and applied only to an exception from initial monitoring requirements
in proposed paragraph (d)(2). Proposed paragraph (d)(2)(ii) included
criteria for objective data.
The final rule allows for expanded use of objective data. Paragraph
(a)(3) allows for use of objective data to support an exception from
the scope of the standards. Paragraph (d)(2) allows for use of
objective data as part of the performance option for exposure
assessment. OSHA is therefore including a definition of "objective
data" in paragraph (b) of the standards. The definition is generally
consistent with the criteria included in proposed paragraph (d)(2)(ii),
and with the use of this term in other OSHA substance-specific health
standards such as the standards addressing exposure to cadmium (29 CFR
1910.1027), chromium (VI) (29 CFR 1010.1026), and respirable
crystalline silica (29 CFR 1910.1053).
Physician or other licensed health care professional (PLHCP) means
an individual whose legally permitted scope of practice, such as
license, registration, or certification, allows the person to
independently provide or be delegated the responsibility to provide
some or all of the health care services required in paragraph (k). The
Agency recognizes that personnel qualified to provide medical
surveillance may vary from State to State, depending on State licensing
requirements. Whereas all licensed physicians would meet this
definition of PLHCP, not all PLHCPs must be physicians.
Under paragraph (k)(5) of the standards, the written medical report
for the employee must be completed by a licensed physician. Under
paragraph (k)(6) of the standard, the written medical opinion for the
employer must also be completed by a licensed physician. However, other
requirements of paragraph (k) may be performed by a PLHCP under the
supervision of a licensed physician (see paragraphs (k)(1)(ii),
(k)(3)(i), (k)(3)(ii)(F), (k)(3)(ii)(G), and (k)(5)(iii)). The standard
also identifies what information the employer must give to the PLHCP
providing the services listed in this standard, and requires that
employers maintain a record of this information for each employee (see
paragraphs (k)(4) and (n)(3)(ii)(C), and the summary and explanation of
paragraphs (k), Medical surveillance, in this section).
Allowing a PLHCP to provide some of the services required under
this rule is consistent with other recent OSHA health standards, such
as bloodborne pathogens (29 CFR 1910.1030), respiratory protection (29
CFR 1910.134), methylene chloride (29 CFR 1910.1052), and respirable
crystalline silica (29 CFR 1910.1053). OSHA received no comments on
this definition, and it is unchanged from the proposal.
Regulated area means an area, including temporary work areas where
maintenance or non-routine tasks are performed, where an employee's
airborne exposure exceeds, or can reasonably be expected to exceed,
either the TWA PEL or STEL. For an explanation of the distinction and
overlap between beryllium work areas and regulated areas, see the
definition of "beryllium work area" earlier in this section of the
preamble and the summary and explanation for paragraph (e), Beryllium
work areas and regulated areas. Regulated areas appear only in the
general industry and shipyard standards, and they trigger several other
requirements.
Paragraphs (e)(1)(ii) and (e)(2)(ii) require employers to establish
and demarcate regulated areas. Note that the demarcation requirements
for regulated areas are more specific than those for other beryllium
work areas (see also paragraph (m)(2) of the standards for general
industry and shipyards). Paragraph (e)(3) requires employers to
restrict access to regulated areas to authorized persons, and paragraph
(e)(4) requires employers to provide all employees in regulated areas
appropriate respiratory protection and personal protective clothing and
equipment, and to ensure that these employees use the required
respiratory protection and protective clothing and equipment. Paragraph
(i)(5)(i) prohibits employers from allowing employees to eat, drink,
smoke, chew tobacco or gum, or apply cosmetics in regulated areas.
Paragraph (m)(2) requires warning signs associated with regulated areas
to meet
certain specifications. Paragraph (m)(4)(ii)(B) requires employers to
train employees on the written exposure control plan required by
paragraph (f)(1), including the location of regulated areas and the
specific nature of operations that could result in airborne exposure.
In the proposed rule, OSHA included in the definition of the term
"regulated area" that it was "an area that the employer must
demarcate." Because the requirement to demarcate regulated areas is
presented elsewhere in the standards, the reference in the definition
to "an area that the employer must demarcate" is redundant, and has
been removed from the final definition of the term.
This definition of regulated areas is consistent with other
substance-specific health standards that apply to general industry and
shipyards, such as the standards addressing occupational exposure to
cadmium (29 CFR 1910.1027 and 29 CFR 1915.1027), benzene (29 CFR
1910.1028 and 29 CFR 1915.1028), and methylene chloride (29 CFR
1910.1052 and 29 CFR 1915.1052).
This standard means the beryllium standard in which it appears. In
the general industry standard, it refers to 29 CFR 1910.1024. In the
shipyard standard, it refers to 29 CFR 1915.1024. In the construction
standard, it refers to 29 CFR 1926.1124. This definition elicited no
comments and differs from the proposal only in that it appears in the
three separate standards.
(c) Permissible Exposure Limits (PELs)
Paragraph (c) of the standards establishes two permissible exposure
limits (PELs) for beryllium in all forms, compounds, and mixtures: An
8-hour time-weighted average (TWA) PEL of 0.2 μg/m3\ (paragraph
(c)(1)), and a 15-minute short-term exposure limit (STEL) of 2.0 μg/
m3\ (paragraph (c)(2)). The TWA PEL section of the standards requires
employers to ensure that no employee's exposure to beryllium, averaged
over the course of an 8-hour work shift, exceeds 0.2 μg/m3\. The
STEL section of the standards requires employers to ensure that no
employee's exposure, sampled over any 15-minute period during the work
shift, exceeds 2.0 μg/m3\. While the proposed rule contained
slightly different language in paragraph (c), i.e. requiring that
"each employee's airborne exposure does not exceed" the TWA PEL and
STEL, the final language was chosen by OSHA to remain consistent with
prior OSHA health standards and to clarify that OSHA did not intend a
different interpretation of the PELs in this standard. The same PELs
apply to general industry, construction, and shipyards.
TWA PEL. OSHA proposed a new TWA PEL of 0.2 μg/m3\ of
beryllium--one-tenth the preceding TWA PEL of 2 μg/m3\--because
OSHA preliminarily found that occupational exposure to beryllium at and
below the preceding TWA PEL of 2 μg/m3\ poses a significant risk of
material impairment of health to exposed workers. As with several other
provisions of these standards, OSHA's proposed TWA PEL followed the
draft recommended standard submitted to the Agency by Materion
Corporation (Materion) and the United Steelworkers (USW) (see this
preamble at section III, Events Leading to the Standards).
After evaluating the record, including published studies and more
recent exposure data from industrial facilities involved in beryllium
work, OSHA is adopting the proposed TWA PEL of 0.2 μg/m3\. OSHA has
made a final determination that occupational exposure to a variety of
beryllium compounds at levels below the preceding PELs poses a
significant risk to workers (see this preamble at section VII,
Significance of Risk). OSHA's risk assessment, presented in section VI
of this preamble, indicates that there is significant risk of beryllium
sensitization,\38\ CBD, and lung cancer from a 45-year (working life)
exposure to beryllium at the preceding TWA PEL of 2 μg/m3\. The
risk assessment further indicates that, although the risk is much
reduced, significant risk remains at the new TWA PEL of 0.2 μg/m3\.
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\38\ As discussed in section VII of this preamble, Significance
of Risk, beryllium sensitization is a necessary precursor to
developing CBD.
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OSHA has determined that the new TWA PEL is feasible across all
affected industry sectors (see section VIII.D of this preamble,
Technological Feasibility) and that compliance with the new PEL will
substantially reduce employees' risks of beryllium sensitization,
Chronic Beryllium Disease (CBD), and lung cancer (see section VI of
this preamble, Risk Assessment). OSHA's conclusion about feasibility is
supported both by the results of the Agency's feasibility analysis and
by the recommendation of the PEL of 0.2 μg/m3\ by Materion and the
USW.
Materion is the sole beryllium producer in the U.S., and its
facilities include some of the processes where OSHA expects it will be
most challenging to control beryllium exposures. Although OSHA also
found that there is significant risk at the proposed alternative TWA
PEL of 0.1 μg/m3\, OSHA did not adopt that alternative because the
Agency could not demonstrate technological feasibility at that level
(see section VIII.D of this preamble, Technological Feasibility).
The TWA PEL was the subject of numerous comments in the rulemaking
record. Comments from stakeholders in labor and industry, public health
experts, and the general public supported OSHA's selection of 0.2
μg/m3\ as the final PEL (NIOSH, Document ID 1671, Attachment 1, p.
2; National Safety Council, 1612, p. 3; The Sampling and Analysis
Subcommittee Task Group of the Beryllium Health and Safety Committee of
the Department of Energy's National Nuclear Security Administration
Lawrence Livermore National Lab (BHSC Task Group), 1655, p. 2; Newport
News Shipbuilding, 1657, p. 1; National Jewish Health (NJH),1664, p. 2;
The Aluminum Association, 1666, p. 1; The Boeing Company (Boeing),
1667, p. 1; American Industrial Hygiene Association (AIHA), 1686, p. 2;
United Steelworkers (USW), 1681, p. 7; Andrew Brown, 1636, p. 6;
Department of Defense, 1684, p. 1). Materion stated that the record
does not support the feasibility of any limit lower than 0.2 μg/m3\
(Document ID 1808, p. 2). OSHA also received comments supporting
selection of a lower TWA PEL of 0.1 μg/m3\ from Public Citizen, the
AFL-CIO, the United Automobile, Aerospace & Agricultural Implement
Workers of America (UAW), North America's Building Trades Unions
(NABTU), and the American College of Occupational and Environmental
Medicine (ACOEM) (Document ID 1689, p. 7; 1693, p. 3; 1670, p. 1; 1679,
pp. 6-7; 1685, p. 1; 1756, Tr. 167). These commenters based their
recommendations on the significant risk of material health impairment
from exposure at the TWA PEL of 0.2 μg/m3\ and below, which OSHA
acknowledges.
In addition to their concerns about risk, Public Citizen and the
American Federation of Labor and Congress of Industrial Organizations
(AFL-CIO) argued that a TWA PEL of 0.1 μg/m3\ is feasible (Document
ID 1756, Tr. 168-169, 197-198). As discussed further below, however,
OSHA's selection of the TWA PEL in this case was limited by the
findings of its technological feasibility analysis. No commenter
provided information that would permit OSHA to show the feasibility of
a TWA PEL of 0.1 μg/m3\ in industries where OSHA did not have
sufficient information to make this determination at the proposal
stage. Public Citizen instead argued that insufficient evidence that
engineering and work practice controls can maintain exposures at or
below a TWA PEL of 0.1
μg/m3\ should not preclude OSHA from establishing such a PEL; and
that workplaces unable to achieve a TWA PEL of 0.1 μg/m3\ should be
required to reduce airborne exposures as much as possible using
engineering and work practice controls, supplemented with a respiratory
protection program (Document ID 1670, p. 5).
OSHA has determined that Public Citizen's claim that the Agency
should find a PEL of 0.1 μg/m3\ technologically feasible is
inconsistent with the test for feasibility as described by the courts
as well as the evidence in the rulemaking record. OSHA bears the
evidentiary burden of establishing feasibility in a rulemaking
challenge. The D.C. Circuit, in its decision on OSHA's Lead standard
(United Steelworkers of America v. Marshall, 647 F.2d 1189 (D.C. Cir.
1981) ("Lead")), explained that in order to establish that a standard
is technologically feasible, "OSHA must prove a reasonable possibility
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" (Lead, 647 F.2d at 1272). "The effect of such proof,"
the court continued, "is to establish a presumption that industry can
meet the PEL without relying on respirators" (Lead, 647 F.2d at 1272).
The court's definition of technological feasibility thus recognizes
that, for a standard based on a hierarchy of controls prioritizing
engineering and work practice controls over respirators, a particular
PEL is not technologically feasible simply because it can be achieved
through the widespread use of respirators (see Lead, 647 F.2d at 1272).
OSHA's long-held policy of avoiding requirements that will result in
extensive respirator use is consistent with this legal standard.
In consi