What is CBD?
Chronic Beryllium Disease, sometimes called berylliosis, is a chronic granulomatous lung disease caused by an immunological response from exposure to beryllium. CBD can progress to a serious and life-threatening disease if left undiagnosed and beryllium exposure continues.
Exposure to beryllium via inhalation of airborne beryllium or skin contact with beryllium-containing dust, fume, mist, or solutions can cause health effects. Under OSHA’s beryllium standards (29 CFR 1910.1024; 29 CFR 1915.1024; 29 CFR 1926.1024) employers must reduce exposures to airborne beryllium to or below the beryllium PELs through engineering controls to the extent feasible, supplemented by respirators where all feasible controls are not sufficient to reduce exposures to or below the PELs. In addition, personal protective clothing and equipment (PPE) (e.g. gloves, shoe covers) is required when airborne exposures can exceed the PEL or STEL or there is the potential for skin exposure.
OSHA also requires employers provide workers with detailed training on the health effects of beryllium. Training must include, among other things: information on the health hazards associated with airborne exposure to and dermal contact with beryllium, including the signs and symptoms of CBD; information on the purpose, proper selection, fitting, proper use, and limitations of personal protective clothing and equipment, including respirators; any protective measures workers can take to protect themselves from airborne or skin exposure to beryllium (including personal hygiene practices); and the purpose and description of the medical surveillance program and medical removal protection.
The following information describes the primary health effects associated with exposure to beryllium, medical testing and surveillance requirements, and possible treatment for beryllium-related health effects.
Primary Health Effects Associated with Exposure to Beryllium
The most common health effects associated with overexposure to beryllium in the workplace include: beryllium sensitization, chronic beryllium disease (CBD), and lung cancer.
Beryllium Sensitization - Beryllium sensitization is the activation of the body’s immune response to beryllium. Beryllium sensitization can result from inhalation or skin exposure to beryllium dust, fume, mist, or solutions. While no clinical symptoms may be associated with sensitization, a sensitized worker is at risk of developing CBD when inhalation exposure to beryllium has occurred.
Chronic Beryllium Disease - CBD is a chronic granulomatous lung disease caused by inhaling airborne beryllium after becoming sensitized to beryllium. Some common symptoms of CBD are shortness of breath, unexplained coughing, fatigue, weight loss, fever, and night sweats. CBD can result from inhalation exposure to beryllium at levels below the current OSHA PEL (0.2 μg/m3). Progression of CBD can vary among individuals. For instance, after initial exposure to beryllium, some workers may quickly develop signs and severe symptoms of CBD. Others may not experience signs and symptoms until months or years after initial exposure. The symptoms can sometimes worsen even after the worker has been removed from exposure. CBD can progress to a chronic obstructive lung disorder, resulting in loss of quality of life and the potential for decreased life expectancy (for additional information see section on Treatment below).
CBD shares many signs and symptoms with pulmonary sarcoidosis, a granulomatous lung disease of unknown cause or origin. Without appropriate diagnosis, CBD may be difficult to distinguish from sarcoidosis.
Lung cancer - Based on numerous studies in occupational settings, OSHA has determined that occupational exposure to beryllium causes lung cancer in humans. In addition, the International Agency for Research on Cancer (IARC) classifies beryllium as a Group 1 carcinogen (carcinogenic to humans), and the National Toxicology Program (NTP) lists beryllium as a known human carcinogen.
Acute Beryllium Disease (ABD) - Acute beryllium disease (ABD) is a rapid onset form of chemical pneumonia that results from breathing high airborne concentrations of beryllium. ABD is generally associated with exposure to beryllium levels at or above 100 μg/m3 and may be fatal in 10 percent of cases. ABD is extremely rare in the workplace today due to more stringent exposure controls implemented following occupational and environmental standards set in the 1970s.
The purpose of medical surveillance is to detect and eliminate the underlying causes of observed health effects from hazards. Medical surveillance programs can contribute to the success of workplace health and safety programs by identifying potential problem areas and verifying the effectiveness of existing control and prevention programs.
Under the beryllium standards (29 CFR 1910.1024; 29 CFR 1915.1024; 29 CFR 1926.1024), OSHA requires employers to offer medical surveillance to workers within 30 days of determining that the worker meets one of the following conditions: is or is reasonably expected to be exposed above the action level of 0.1 µg/m3 for 30 days in a year; show signs or symptoms of CBD; were exposed to beryllium during an emergency; or have received a recommendation for continued medical surveillance from a physician or other licensed health care professional (PLHCP) from the most recent exam (see Beryllium Standard: Guidance on Medical Surveillance for Beryllium Exposed Workers). Employees may opt out of the medical surveillance program if they so choose. The medical surveillance requirements within the beryllium standards include the following provisions:
Employers must offer medical surveillance to a worker within 30 days of meeting the criteria set forth in paragraph (k)(2)(i), and at least every two years thereafter for those who continue to meet the criteria in paragraph (k)(1). The standards also specify medical examination at the termination of employment (see paragraph (k)(2)(iii) in the standards).
The medical examination must include:
- Medical and work history with emphasis on past and present airborne exposure to or dermal contact with beryllium, smoking history, and any history of respiratory system dysfunction
- Physical examination with emphasis on the respiratory system
- Physical examination for skin rashes
- Pulmonary function tests
- BeLPT2 (or other equivalent test)
- Any other test deemed appropriate by the PLHCP (including low-dose CT scan3)
OSHA requires that employers provide certain information to the PLHCP. This information includes:
- A copy of the standard
- A description of the employee’s former and current duties that relate to the employee’s airborne exposure to and dermal contact with beryllium
- The employee’s former and current levels of airborne exposure
- A description of any personal protective clothing and equipment (PPE), including respirators, used by the employee, including when and how long these were used
- Information from records of employment-related medical examinations previously provided to the employee, currently within the control of the employer, after obtaining written consent from the employee
OSHA requires the employer to ensure that the employee receives a written medical opinion from the licensed physician within 30 days of the medical examination. The written opinion must include:
- The results of the medical examination (including whether the employee has any detected medical condition 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)
- Any recommendations on the employee’s use of PPE or respirators
- Any limitations on the employee’s airborne beryllium exposure
- Any recommendation for referral to a CBD diagnostic center, continued medical surveillance, or medical removal
OSHA also requires the employer receive a medical opinion form the licensed physician. The written medical opinion must include:
- The date of the examination
- Statements that the results of the examination were explained to the worker4 and that the examination met the requirements of the beryllium standard
- Any recommended limitations on the worker’s use of respirators, protective clothing, or equipment
- If the employee provides written authorization, the written opinion must also contain any recommended limitations on the worker’s airborne exposure to beryllium
If the worker is either confirmed positive for beryllium sensitization or CBD or a licensed physician has determined it appropriate, and the worker provides written authorization, OSHA requires employers to provide:
- A referral to a CBD Diagnostic Center5
- Continued medical surveillance
- Medical removal (upon request by worker)
The BeLPT - Beryllium sensitization may be detected with the beryllium lymphocyte proliferation test (BeLPT), a blood test for measuring the immune response to beryllium. The observation of beryllium-specific lymphocyte proliferation in an individual peripheral blood sample indicates an abnormal response and may indicate beryllium sensitization. There is some concern about the accuracy of the BeLPT. A single BeLPT has been reported to have a false-positive rate of about 1% (Middleton et al., 2008). Many programs therefore rely on a second test to confirm a positive result (NAS, 2008), which has been reported to reduce the false-positive rate to about 0.02% (Middleton et al., 2008).
Another way to measure the accuracy of a test such as the BeLPT is to measure its positive predictive value (PPV). The PPV is the probability that a person with a positive result has the disease or condition being measured. To address some criticism regarding the PPV of the BeLPT, Middleton et al. (2011) conducted another study to evaluate borderline results from BeLPT testing. Table 1 below shows the PPV for the BeLPT using either 2 abnormal results, 1 borderline and 1 abnormal result, or 3 borderline results (Middleton et al., 2008 and 2011):
|1 abnormal result||2 abnormal results||1 abnormal + 1 borderline||3 borderline results|
|PPV at 1% prevalence||38.3%||96.8%||89.3%||83.7%|
|PPV at 2% prevalence||89.3%||98.4%||94.4%.||91.2%|
Based on this information OSHA considers a worker positive for sensitization with either 2 abnormal results, 1 abnormal and 1 borderline, or 3 borderline results. CBD is generally confirmed when it can be shown there is a history of beryllium exposure; positive histopathology findings in the lung (e.g. fiber-optic bronchoscopy, X-ray, CT scan, lung biopsy); and beryllium sensitization.
Workers found to be sensitized to beryllium are at risk for developing CBD and in need of continuing medical follow-up. OSHA requires employers to offer sensitized workers a physical examination every 2 years performed under the direction of a licensed physician.
For more information see OSHA's Safety and Health Topics page on medical screening and surveillance.
There is no cure for CBD. Treatment for CBD can vary for each patient, depending on the severity of the disease. Treatment may include corticosteroids, oxygen, and other means to ease symptoms or slow the disease progression.
For more information, see the National Institute for Occupational Safety and Health Workplace Safety and Topics – Beryllium webpage; National Jewish Medical and Research Center Chronic Beryllium Disease Treatment webpage; the Agency for Toxic Substance and Disease Registry ToxFAQs for Beryllium webpage; and the Department of Energy Chronic Beryllium Disease Prevention Program webpage.
The following webpages provide additional information on the health effects of beryllium.
- Beryllium: Guidance on Medical Surveillance for Beryllium Exposed Workers. OSHA Publication 4116, (May 2021).
- Beryllium Medical Surveillance Information for Workers. OSHA QuickCard® (Publication 4115), (May 2021).
- Beryllium: Worker Information on the BeLPT. OSHA QuickCard® (Publication 4114), (May 2021).
- Beryllium. National Institute for Occupational Safety and Health (NIOSH) Workplace Safety and Health Topic. Provides links to sources of information on a variety of topics relating to beryllium.
- Report on Carcinogens (ROC). U.S. Department of Health and Human Services (DHHS), National Toxicology Program (NTP). Identifies and discusses agents, substances, mixtures, or exposure circumstances that may pose a health hazard due to their carcinogenicity. The listing of substances in the RoC only indicates a potential hazard and does not establish the exposure conditions that would pose cancer risks to individuals.
- Beryllium and Beryllium Compounds. NTP classification: Known to be human carcinogens
- International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks for Humans. World Health Organization (WHO).
- Toxicological Profile for Beryllium. Agency for Toxic Substances and Disease Registry (ATSDR), (September 2002). Provides exposure risks, exposure limits, and health effects for beryllium.
- ToxFAQs - Beryllium. Agency for Toxic Substances and Disease Registry (ATSDR), (September 2002). Answers the most frequently asked health questions about beryllium.
- Chronic Beryllium Disease Prevention Program. U.S. Department of Energy (DOE), (December 8, 1999). Provides links to DOE policies, guidance, and training regarding beryllium.
- Chronic Beryllium Disease: Overview. National Jewish Medical and Research Center, (2010). Describes the health effects of beryllium.
- Health Effects of Beryllium. National Academy of Sciences, (2007). Summarizes the health effects literature on beryllium.
- Managing Health Effects of Beryllium Exposure. National Academy of Sciences, (2008). Provides information on clinical studies of beryllium sensitization and CBD. Includes information on designing a beryllium exposure and disease management program for Air Force workers.
A list of journal articles related to the health effects of exposure to beryllium:
- Balkissoon, R.C. and Newman, L.S. (1999). Beryllium Copper Alloy (2%) Causes Chronic Beryllium Disease. J. Occup. Environ. Med. 41(4): 304-8.
- Balmes JR, Abraham JL, Dweik RA, Fireman E, Fontenot AP, Maier LA, Muller-Quernheim J, Ostiguy G, Pepper LD, Saltini C, Schuler CR, Takaro TK, Wambach PF; ATS Ad Hoc Committee on Beryllium Sensitivity and Chronic Beryllium Disease. An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med. 2014 Nov 15;190(10):e34-59.
- Belman S. (1969) Beryllium Binding of Epidermal Constituents. J Occup Med 99(4): 175-183.
- Berlin J.M. et al. (2003). Beryllium Dermatitis. J. Am. Acad. Dermatol. 49(5): 939-41.
- Cummings, K.J. et al. (2009). A Reconsideration of Acute Beryllium Disease. Environmental Health Perspectives. 117(8): 1250-6.
- Curtis G. (1951) Cutaneous Hypersensitivity due to Beryllium; A Study of Thirteen Cases. AMA Archives Dermatol Syphil 64 (4): 470-482.
- Dai S, Falta MT, Bowerman NA, McKee AS, Fontenot AP. T cell recognition of beryllium. Curr Opin Immunol. 2013 Dec; 25(6):775-80.
- Epstein, WL (1991). Cutaneous effects of beryllium. Beryllium biomedical and environmental aspects.
- Day GA, Hoover MD, Stefaniak AB, Dickerson RM, Peterson EJ, Esmen NA. (2007) Bioavailabilty of Beryllium Oxide Particles: An In Vitro Study in the Murine J774A.1 Macrophage Cell Line Model. Exp Lung Research 31: 341-360.
- Delic J. (1992) Toxicity Review 27 (Part 2). Beryllium and beryllium compounds. London, Her Majesty’s Stationary Office (ISBN 0 11 886343 6).
- De Nardi JM, Van Orstrand HS, Curtis GH, Zielinski J. (1953) Berylliosis: Summary and survey of all clinical types observed in a twelve-year period. American Medical Association archives of industrial hygiene and occupational medicine, 8:1–24
- Deubner DC, Lowney YW, Paustenbach DJ, Warmerdam J. (2001) Contribution of Indicidental Exposure Pathways to total Beryllium Exposures. Appl Occup Environ Hyg 16 (5): 568-578.
- Epstein (1991)
- Harber P, Su J, Alongi G. (2014). Beryllium BioBank2: Lymphocyte Proliferation Testing. J Occup Environ Med. 56 (8); 857-860.
- Harber P, Su J. (2014). Beryllium BioBank 3: Considerations for Improving Chronic Beryllium Disease Screening. J Occup Environ Med. 56 (8); 861-866.
- Hines SE, Pacheco K, Maier LA. The role of lymphocyte proliferation tests in assessing occupational sensitization and disease. Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):102-10.
- Kirshen C, Pratt M. Dental allergic contact dermatitis: an interesting case series and review of the literature. Dermatitis. 2012 Sep-Oct;23(5):222-6.
- Kreis, K, et al. (1993). Epidemiology of Beryllium Sensitization and Disease in Nuclear Workers. Am. Rev. Respir. Dis. 148(4 Pt 1): 985-91.
- Lang, L. (1994). Beryllium: A Chronic Problem. Environmental Health Perspectives 102(6-7): 526-531.
- Lederer H and Savage J. (1954) Beryllium Granuloma of the Skin. Br J Ind Med. 11(1): 45-48
- Maier, L A et al. (2008). Recent Chronic Beryllium Disease in Residents Surrounding a Beryllium Facility. Am. J. Respir. Crit. Care Med. 177(9): 1012-7.
- Mayer AS, Hamzeh N, Maier LA. Sarcoidosis and chronic beryllium disease: similarities and differences. Semin Respir Crit Care Med. 2014 Jun;35(3):316-29.
- Martin SC, Larivière C. Community health risk assessment of primary aluminum smelter emissions. J Occup Environ Med. 2014 May;56(5 Suppl):S33-9.
- Middleton D, Kowalski P. Advances in identifying beryllium sensitization and disease. Int J Environ Res Public Health. 2010 Jan;7(1):115-24
- Middleton, D.C. (1998). Chronic Beryllium Disease: Uncommon Disease, Less Common Diagnosis. Environmental Health Perspectives 106 (12):765-767.
- Newman, L.S., et al. (1996). The Natural History of Beryllium Sensitization and Chronic Beryllium Disease. Environmental Health Perspectives 104(Supplement 5): 937-943Newman, L. S., Mroz, M. M., Balkissoon, R., & Maier, L. A. (2005). Beryllium sensitization progresses to chronic beryllium disease: a longitudinal study of disease risk. American journal of respiratory and critical care medicine, 171(1), 54-60
- Nishimura M. (1966) Clinical and experimental studies on acute beryllium disease. Nagoya J Med Sci. Nov; 29(1):17-44Pappas, G. P., & Newman, L. S. (1993). Early pulmonary physiologic abnormalities in beryllium disease. American review of respiratory disease, 148, 661-661.
- Rossman MD, Preuss OP, Powers MB, eds. (1991) Beryllium: Biomedical and Environmental Aspects. Baltimore, MD: Williams and Wilkins
- Schubauer-Berigan MK, Deddens JA, Couch JR, Petersen MR. Risk of lung cancer associated with quantitative beryllium exposure metrics within an occupational cohort. Occup Environ Med. 2011 May;68(5):354-60.
- Seidler A, Euler U, Müller-Quernheim J, Gaede KI, Latza U, Groneberg D, Letzel S. Systematic review: Progression of beryllium sensitization to chronic beryllium disease. Occup Med (Lond). 2012 Oct;62(7):506-13.
- Skaugset, N.P. et al. (2012). Occupational Exposure to Beryllium in Primary Aluminum Production. J. Environ. Monit. 14(2): 353-9.
- Stanton, M. L. et al. (2006). Sensitization and Chronic Beryllium Disease Among Workers in Copper-Beryllium Distribution Centers. J. Occup. Environ. Med. 48(2): 204-11.
- Thomas, C. A.et al. (2013). Long-Term Efficacy of a Program to Prevent Beryllium Disease. Am. J. Ind. Med. 56(7): 733-41.
- Tinkle SS, Antonini JM, Rich BA, Roberts JR, Salmen R, DePree K, Adkins EJ. (2003) Skin as a route of exposure and sensitization in chronic beryllium disease. Environ Health Perspect. Jul; 111(9):1202-8
- Toledo , F., Silvestre, J. F., Cuesta, L., Latorre, N., & Monteagudo, A. (2011). Contact allergy to beryllium chloride: report of 12 cases. Contact dermatitis, 64(2), 104-109.
- VanOrdstrand HS, Hughes R, DeNardi JM, et al. (1945). Beryllium poisoning. J Am Med Assoc129:1084-1090
1 PELs: 0.2 micrograms of beryllium per cubic meter of air (µg/m3), as an 8-hour time-weighted average and a Short Term Exposure Limit of 2.0 μg/m3 determined over a sampling period of 15 minutes.
2 The BeLPT is a recognized diagnostic test for measuring the immune response to beryllium (i.e. beryllium sensitization).
3 The Low-dose CT scan is generally used for diagnosing lung cancer.
4 This includes any recommendation for use of PPE or respirator.
5 A CBD Diagnostic Center is any medical diagnostic center that has an on-site pulmonary specialist and on-site facilities to perform a clinical evaluation for 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 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.