Health Effects of Beryllium Exposure
A Literature Review
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This project was supported by Contract W81K04-06-D-0023 between the National Academy of Sciences and the U.S. Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
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COMMITTEE ON BERYLLIUM ALLOY EXPOSURES
Members
CHARLES H. HOBBS (Chair),
Lovelace Respiratory Research Institute, Albuquerque, NM
PATRICK N. BREYSSE,
Johns Hopkins University School of Public Health, Baltimore, MD
SCOTT BURCHIEL,
University of New Mexico, Albuquerque
LUNG CHI CHEN,
New York University School of Medicine, Tuxedo, NY
DAVID DIAZ-SANCHEZ,
University of California, Los Angeles
DAVID G. HOEL,
Medical University of South Carolina, Charleston
LOREN D. KOLLER,
Loren Koller & Associates, Corvallis, OR
DAVID KRIEBEL,
University of Massachusetts, Lowell
MICHAEL J. MCCABE, JR.,
University of Rochester School of Medicine, Rochester, NY
CARRIE A. REDLICH,
Yale University School of Medicine, New Haven, CT
ROSALIND A. SCHOOF,
Integral Consulting, Mercer Island, WA
NANCY L. SPRINCE,
University of Iowa, Iowa City
SUSAN M. TARLO,
University of Toronto, Ontario, Canada
LAURA S. WELCH,
Center to Protect Workers’ Rights, Silver Spring, MD
Staff
SUSAN N. J. MARTEL, Project Director
NORMAN GROSSBLAT, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager,
Technical Information Center
TAMARA DAWSON, Senior Program Assistant
Sponsor
U.S. DEPARTMENT OF DEFENSE
COMMITTEE ON TOXICOLOGY
Members
WILLIAM E. HALPERIN (Chair),
UMDNJ–New Jersey Medical School, Newark
LAWRENCE S. BETTS,
Eastern Virginia Medical School, Norfolk
EDWARD C. BISHOP,
HDR Engineering, Inc., Omaha, NE
JAMES V. BRUCKNER,
University of Georgia, Athens
GARY P. CARLSON,
Purdue University, West Lafayette, IN
MARION F. EHRICH,
Virginia Polytechnic Institute and State University, Blacksburg
SIDNEY GREEN,
Howard University, Washington, DC
MERYL H. KAROL,
University of Pittsburgh, Pittsburgh, PA
JAMES N. MCDOUGAL,
Wright State University School of Medicine, Dayton, OH
ROGER G. MCINTOSH,
Science Applications International Corporation, Abingdon, MD
GERALD N. WOGAN,
Massachusetts Institute of Technology, Cambridge
Staff
SUSAN N. J. MARTEL, Senior Program Officer for Toxicology
EILEEN N. ABT, Senior Program Officer for Risk Analysis
KULBIR S. BAKSHI, Senior Program Officer
ELLEN K. MANTUS, Senior Program Officer
JENNIFER SAUNDERS, Associate Program Officer
AIDA NEEL, Program Associate
MIRSADA KARALIC-LONCAREVIC, Manager,
Technical Information Center
TAMARA DAWSON, Senior Program Assistant
RADIAH A. ROSE, Senior Editorial Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1
Members
JONATHAN M. SAMET (Chair),
Johns Hopkins University, Baltimore, MD
RAMÓN ALVAREZ,
Environmental Defense, Austin, TX
JOHN M. BALBUS,
Environmental Defense, Washington, DC
DALLAS BURTRAW,
Resources for the Future, Washington, DC
JAMES S. BUS,
Dow Chemical Company, Midland, MI
RUTH DEFRIES,
University of Maryland, College Park
COSTEL D. DENSON,
University of Delaware, Newark
E. DONALD ELLIOTT,
Willkie Farr & Gallagher LLP, Washington, DC
MARY R. ENGLISH,
University of Tennessee, Knoxville
J. PAUL GILMAN,
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
SHERRI W. GOODMAN,
Center for Naval Analyses, Alexandria, VA
JUDITH A. GRAHAM,
American Chemistry Council, Arlington, VA
WILLIAM P. HORN,
Birch, Horton, Bittner and Cherot, Washington, DC
WILLIAM M. LEWIS, JR.,
University of Colorado, Boulder
JUDITH L. MEYER,
University of Georgia, Athens
DENNIS D. MURPHY,
University of Nevada, Reno
PATRICK Y. O’BRIEN,
ChevronTexaco Energy Technology Company, Richmond, CA
DOROTHY E. PATTON (retired),
Chicago, IL
DANNY D. REIBLE,
University of Texas, Austin
JOSEPH V. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEAD G. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERT F. SAWYER,
University of California, Berkeley
KIMBERLY M. THOMPSON,
Massachusetts Institute of Technology, Cambridge
MONICA G. TURNER,
University of Wisconsin, Madison
MARK J. UTELL,
University of Rochester Medical Center, Rochester, NY
CHRIS G. WHIPPLE,
ENVIRON International Corporation, Emeryville, CA
LAUREN ZEISE,
California Environmental Protection Agency, Oakland
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Sciences and Engineering
EILEEN N. ABT, Senior Program Officer for Risk Analysis
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
KULBIR BAKSHI, Senior Program Officer
KARL E. GUSTAVSON, Senior Program Officer
ELLEN K. MANTUS, Senior Program Officer
STEVEN K. GIBB, Program Officer for Strategic Communications
RUTH E. CROSSGROVE, Senior Editor
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Models in Environmental Regulatory Decision Making (2007)
Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)
Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)
Environmental Impacts of Wind-Energy Projects (2007)
Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)
Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)
New Source Review for Stationary Sources of Air Pollution (2006)
Human Biomonitoring for Environmental Chemicals (2006)
Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)
Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)
State and Federal Standards for Mobile-Source Emissions (2006)
Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)
Health Implications of Perchlorate Ingestion (2005)
Air Quality Management in the United States (2004)
Endangered and Threatened Species of the Platte River (2004)
Atlantic Salmon in Maine (2004)
Endangered and Threatened Fishes in the Klamath River Basin (2004)
Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)
Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)
Biosolids Applied to Land: Advancing Standards and Practices (2002)
The Airliner Cabin Environment and Health of Passengers and Crew (2002)
Arsenic in Drinking Water: 2001 Update (2001)
Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)
Compensating for Wetland Losses Under the Clean Water Act (2001)
A Risk-Management Strategy for PCB-Contaminated Sediments (2001)
Acute Exposure Guideline Levels for Selected Airborne Chemicals (five volumes, 2000-2007)
Toxicological Effects of Methylmercury (2000)
Strengthening Science at the U.S. Environmental Protection Agency (2000)
Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)
Ecological Indicators for the Nation (2000)
Waste Incineration and Public Health (2000)
Hormonally Active Agents in the Environment (1999)
Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)
The National Research Council’s Committee on Toxicology: The First 50 Years (1997)
Carcinogens and Anticarcinogens in the Human Diet (1996)
Upstream: Salmon and Society in the Pacific Northwest (1996)
Science and the Endangered Species Act (1995)
Wetlands: Characteristics and Boundaries (1995)
Biologic Markers (five volumes, 1989-1995)
Review of EPA's Environmental Monitoring and Assessment Program (three volumes, 1994-1995)
Science and Judgment in Risk Assessment (1994)
Pesticides in the Diets of Infants and Children (1993)
Dolphins and the Tuna Industry (1992)
Science and the National Parks (1992)
Human Exposure Assessment for Airborne Pollutants (1991)
Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)
Decline of the Sea Turtles (1990)
Copies of these reports may be ordered from the National Academies Press
(800) 624-6242 or (202) 334-3313
OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, Volume 1 (2007)
Review of the Department of Defense Research Program on Low-Level Exposures to Chemical Warfare Agents (2005)
Review of the Army's Technical Guides on Assessing and Managing Chemical Hazards to Deployed Personnel (2004)
Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 1 (2004), Volume 2 (2007)
Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)
Review of Submarine Escape Action Levels for Selected Chemicals (2002)
Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals (2001)
Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity (2001)
Acute Exposure Guideline Levels for Selected Airborne Contaminants, Volume 1 (2000), Volume 2 (2002), Volume 3 (2003), Volume 4 (2004), Volume 5 (2007)
Review of the US Navy’s Human Health Risk Assessment of the Naval Air Facility at Atsugi, Japan (2000)
Methods for Developing Spacecraft Water Exposure Guidelines (2000)
Review of the U.S. Navy Environmental Health Center’s Health-Hazard Assessment Process (2000)
Review of the U.S. Navy’s Exposure Standard for Manufactured Vitreous Fibers (2000)
Re-Evaluation of Drinking-Water Guidelines for Diisopropyl Methylphosphonate (2000)
Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23, and HFC-404a (2000)
Review of the U.S. Army’s Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999)
Toxicity of Military Smokes and Obscurants, Volume 1(1997), Volume 2 (1999), Volume 3 (1999)
Assessment of Exposure-Response Functions for Rocket-Emission Toxicants (1998)
Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (1996)
Permissible Exposure Levels for Selected Military Fuel Vapors (1996)
Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994), Volume 2 (1996), Volume 3 (1996), Volume 4 (2000)
Preface
Beryllium is a light-weight metal that is used for its exceptional strength and high heat-absorbing capability. Beryllium and its alloys can be found in many important technologies of the defense and aeronautics industries, including electro-optical targeting and infrared countermeasure devices, missile systems, radar systems, nuclear devices, satellite systems, rocket propellants, and navigational systems.
Pulmonary disease associated with exposure to beryllium has been recognized and studied since the early 1940s, and an occupational guideline for limiting exposure to beryllium has been in place since 1949. Over the last few decades, much has been learned about chronic beryllium disease and factors that contribute to its occurrence in exposed people. In addition, beryllium has been classified as a likely human carcinogen by several agencies (e.g., the International Agency for Research on Cancer, the National Toxicology Program, and the U.S. Environmental Protection Agency). Those developments have led to debates about the adequacy of the long-standing occupational exposure limit for protecting worker health. To help determine the steps necessary to protect its workforce from the effects of beryllium used in military aerospace applications, the U.S. Air Force asked the Committee on Toxicology of the National Research Council to conduct an independent review of the scientific literature on beryllium and to estimate chronic inhalation exposure levels that are unlikely to produce adverse health effects in military personnel and civilian contractors.
In response to the agency’s request, the National Research Council convened the Committee on Beryllium Alloy Exposures, which prepared this report. The members of the committee were selected for their expertise in pulmonary and occupational medicine, epidemiology, industrial hygiene, inhalation toxicology, immunotoxicology, pathology, biostatistics, and risk assessment (see Appendix for biographic information on the members).
The committee was asked to produce two reports. The first is to provide a review of the scientific literature on beryllium, and the second will expand more critically on that review in considering the maximum chronic inhalation exposure levels that are unlikely to produce adverse health effects, estimating carcinogenic risks, and developing guidance on testing methods for surveillance and monitoring of worker populations. In this, its first report, the committee identifies the scientific literature that will help to form the basis of its recommendations in the second report. The review focuses on the most important health risks: beryllium sensitization, chronic beryllium disease, and cancer.
To help the committee in its review, two data-gathering meetings were held in early 2007. The committee is grateful to the people who gave presentations on their research in and experience with beryllium exposure and disease. They include John Balmes, of the University of California, San Francisco; David DeCamp, of the Air Force Institute of Operational Health; Terry Gordon, of the New York University School of Medicine; Kathleen Kreiss, of the National Institute for Occupational Safety and Health; David Louis, of the Air Force Materiel Command; Lisa Maier, of the National Jewish Medical and Research Center; Aleksandr Stefaniak, of the National Institute for Occupational Safety and Health; and Paul Wambach, of the U.S. Department of Energy.
This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report
Review Committee. The purpose of the independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following for their review of this report: Scott Bartell, University of California at Irvine; David Deubner, Brush Wellman, Inc.; Meryl Karol, University of Pittsburgh; Kathleen Kreiss, National Institute for Occupational Safety and Health; Joseph Landolph, Jr., University of Southern California; and Lisa Maier, National Jewish Medical and Research Center.
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Frank Speizer, Harvard Medical School. Appointed by the National Research Council, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the author committee and the institution.
The committee is grateful for the assistance of National Research Council staff in preparing the report. It particularly wishes to acknowledge the support of Project Director Susan Martel, who coordinated the project and contributed to the committee’s report. Other staff members who contributed to this effort are James Reisa, director of the Board on Environmental Studies and Toxicology; Tamara Dawson, senior program assistant; Norman Grossblat, senior editor; and Mirsada Karalic-Loncarevic, manager of the Technical Information Center.
Finally, I thank all the members of the committee for their efforts throughout the development of this report.
Charles H. Hobbs, DVM
Chair, Committee on Beryllium Alloy Exposures
BOX
S-1 |
Statement of Task for the Committee on Beryllium Alloy Exposures, |
FIGURE
3-1 |
Immune Response to Beryllium, |
TABLES
1-1 |
Selected Exposure Guidelines and Actions Taken on Beryllium, |
|||
2-1 |
Anthropogenic and Natural Emissions of Beryllium and Beryllium Compounds to the Atmosphere, |
|||
2-2 |
Releases of Beryllium Metal to the Environment for Facilities that Produce, Process, or Use Beryllium, |
|||
2-3 |
Releases of Beryllium Compounds to the Environment from Facilities that Produce, Process, or Use Them, |
|||
2-4 |
Industries that Use Beryllium, |
|||
2-5 |
Summary of Beryllium Airborne Exposure Studies, |
|||
2-6 |
Summary of Beryllium Skin and Surface Exposure Studies, |
|||
2-7 |
Summary of Beryllium Biomonitoring Exposure Studies, |
|||
2-8 |
Physical and Chemical Properties of Beryllium and Beryllium Compounds, |
|||
2-9 |
Comparison of Beryllium Concentrations and Particle Size Obtained with Different Operators in a Precision Machining Plant, |
|||
3-1 |
Summary of Recent Epidemiologic Studies of Chronic Beryllium Disease, |
|||
3-2 |
Summary of Association Studies on HLA-DPB1 Glu69 and TNF-α as Susceptibility Factors in Chronic Beryllium Disease and Beryllium Sensitization, |
|||
4-1 |
Genotoxicity Studies of Beryllium Compounds, |
|||
4-2 |
Inhalation Carcinogenicity Studies of Beryllium, |
Abbreviations
ACGIH American Conference of Governmental Industrial Hygienists
AEC Atomic Energy Commission
ATSDR Agency for Toxic Substances and Disease Registry
BAL bronchoalveolar lavage
BeLPT beryllium lymphocyte proliferation test
BeS beryllium sensitization
CBD chronic beryllium disease
CI confidence interval
COT Committee on Toxicology
DLCO carbon monoxide diffusing capacity
DLCO/VA carbon monoxide diffusing capacity per liter of alveolar volume
DOE U.S. Department of Energy
EPA U.S. Environmental Protection Agency
HLA human leukocyte antigen
HRCT high resolution computed tomography
IARC International Agency for Research on Cancer
LANL Los Alamos National Laboratory
LOAEL lowest-observed-adverse-effect level
MHC major histocompatability complex
MIF migration inhibitory factor
MMAD mass median aerodynamic diameter
MOUDI micro-orifice uniform deposition impactor
NIOSH National Institutes of Occupational Safety and Health
NRC National Research Council
NTP National Toxicology Program
OEL occupational exposure limit
OR odds ratio
OSHA Occupational Safety and Health Administration
PPE personal protective equipment
PPV positive predictive value
RfD reference dose
SMR standardized mortality ratio
SSA specific surface area
SUF serum ultrafiltrate
TGF transforming growth factor
TLV Threshold Limit Value
TRI Toxic Release Inventory
TWA time-weighted average
VD/VT ratio of dead space to tidal volume