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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 Nos. DAMD17-89-C-9086 and DAMD17-99-C-9049 between the National Academy of Sciences and U.S. Army. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
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THE NATIONAL ACADEMIES
National Academy of Sciences
National Academy of Engineering
Institute of Medicine
National Research Council
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. Bruce M. Alberts is president of the National Academy of Sciences.
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Subcommittee on Toxicological Hazard and Risk Assessment
ROGENE HENDERSON (CHAIR),
Lovelace Respiratory Research Institute, Albuquerque, New Mexico
GERMAINE M. BUCK,
University at Buffalo, State of New York
JACK H. DEAN,
Sanofi-Synthelabo, Inc., Malvern, Pennsylvania
KEVIN E. DRISCOLL,
Proctor and Gamble Pharmaceuticals, Cincinnati, Ohio
DAVID W. GAYLOR,
U.S. Food and Drug Administration, Jefferson, Arkansas
JUDITH A. GRAHAM,
U.S. Environmental Protection Agency, Research Triangle Park, North Carolina
JOHN L. O'DONOGHUE,
Eastman Kodak Company, Rochester, New York
ROBERT SNYDER,
Rutgers University, Piscataway, New Jersey
BERNARD M. WAGNER, Consultant,
Short Hills, New Jersey
ANNETTA P. WATSON,
Oak Ridge National Laboratory, Oak Ridge, Tennessee
HANSPETER R. WITSCHI,
University of California, Davis, California
Staff
KULBIR S. BAKSHI, Project Director
ROBERT J. CROSSGROVE, Editor
MIRSADA KARALIC-LONCAREVIC, Information Specialist
TANYA LEE, Acting Project Assistant
Sponsor
U.S. DEPARTMENTOF DEFENSE
COMMITTEE ON TOXICOLOGY
BAILUS WALKER, JR. (Chair),
Howard University Medical Center and American Public Health Association, Washington, D.C.
MELVIN E. ANDERSEN,
Colorado State University, Denver, Colorado
GERMAINE M. BUCK,
University at Buffalo, State of New York
ROBERT E. FORSTER II,
University of Pennsylvania, Philadelphia, Pennsylvania
PAUL M.D. FOSTER,
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina
WILLIAM E. HALPERIN,
National Institute for Occupational Safety and Health, Cincinnati, Ohio
CHARLES H. HOBBS,
Lovelace Respiratory Research Institute and Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico
SAM KACEW,
Department of Pharmacology Faculty of Medicine and University of Ottawa, Ontario,Canada
NANCY KERKVLIET,
Oregon State University, Agricultural and Life Sciences, Corvallis, Oregon
FLORENCE K. KINOSHITA,
Hercules Incorporated, Wilmington, Delaware
MICHAEL J. KOSNETT,
University of Colorado Health Sciences Center, Denver, Colorado
MORTON LIPPMANN,
New York University School of Medicine, Tuxedo, New York
ERNEST E. MCCONNELL,
ToxPath, Inc., Raleigh, North Carolina
THOMAS E. MCKONE,
Lawrence Berkeley National Laboratory and University of California, Berkeley, California
HARIHARA MEHENDALE,
The University of Louisiana at Monroe, Monroe, Louisiana
DAVID H. MOORE,
Battelle Memorial Institute, Bel Air, Maryland
GÜNTER OBERDÖRSTER,
University of Rochester, Rochester, New York
JOHN L. O'DONOGHUE,
Eastman Kodak Company, Rochester, New York
GEORGE M. RUSCH,
AlliedSignal, Inc., Morristown, New Jersey
MARY E. VORE,
University of Kentucky, Lexington, Kentucky
ANNETTA P. WATSON,
Oak Ridge National Laboratory, Oak Ridge, Tennessee
LAUREN ZEISE,
Office of Environmental Health Hazard Assessment, Oakland, California
Staff
KULBIR S. BAKSHI, Program Director
SUSAN N.J. PANG, Program Officer
ABIGAIL E. STACK, Program Officer
KATHRINE J. IVERSON, Manager,
Toxicology Information Center
TANYA LEE, Acting Project Assistant
EMILY SMAIL, Project Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
GORDON ORIANS (Chair),
University of Washington, Seattle, Washington
DONALD MATTISON (Vice Chair),
March of Dimes, White Plains, New York
DAVID ALLEN,
University of Texas, Austin, Texas
INGRID C. BURKE,
Colorado State University, Fort Collins, Colorado
WILLIAM L CHAMEIDES,
Georgia Institute of Technology, Atlanta, Georgia
JOHN DOULL,
University of Kansas Medical Center, Kansas City, Kansas
CHRISTOPHER B. FIELD,
Carnegie Institute of Washington, Stanford, California
JOHN GERHART,
University of California, Berkeley, California
J. PAUL GILMAN,
Celera Genomics, Rockville, Maryland
BRUCE D. HAMMOCK,
University of California, Davis, California
MARK HARWELL,
University of Miami, Miami, Florida
ROGENE HENDERSON,
Lovelace Respiratory Research Institute, Albuquerque, New Mexico
CAROL HENRY,
Chemical Manufacturers Association, Arlington, Virginia
BARBARA HULKA,
University of North Carolina, Chapel Hill, North Carolina
JAMES F. KITCHELL,
University of Wisconsin, Madison, Wisconsin
DANIEL KREWSKI,
University of Ottawa, Ottawa, Ontario
JAMES A. MACMAHON,
Utah State University, Logan, Utah
MARIO J. MOLINA,
Massachusetts Institute of Technology, Cambridge, Massachusetts
CHARLES O'MELIA,
Johns Hopkins University, Baltimore, Maryland
WILLEM F. PASSCHIER,
Health Council of the Netherlands
KIRK SMITH,
University of California, Berkeley, California
MARGARET STRAND,
Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C.
TERRY F. YOSIE,
Chemical Manufacturers Association, Arlington, Virginia
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Associate Director and Senior Program Director for Applied Ecology
CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment
RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and Engineering
KULBIR BAKSHI, Program Director for the Committee on Toxicology
LEE R. PAULSON, Program Director for Resource Management
ROBERTA M. WEDGE, Program Director for Risk Analysis
COMMISSION ON LIFE SCIENCES
MICHAEL T. CLEGG (Chair),
University of California, Riverside, California
PAUL BERG (Vice Chair),
Stanford University, Stanford, California
FREDERICK R. ANDERSON,
Cadwalader, Wickersham & Taft, Washington, D.C.
JOANNA BURGER,
Rutgers University, Piscataway, New Jersey
JAMES E. CLEAVER,
University of California, San Francisco, California
DAVID S. EISENBERG,
University of California, Los Angeles, California
JOHN L. EMMERSON,
Fishers, Indiana
NEAL L. FIRST,
University of Wisconsin, Madison, Wisconsin
DAVID J. GALAS,
Keck Graduate Institute of Applied Life Science, Claremont, California
DAVID V. GOEDDEL,
Tularik, Inc., South San Francisco, California
ARTURO GOMEZ-POMPA,
University of California, Riverside, California
COREY S. GOODMAN,
University of California, Berkeley, California
JON W. GORDON,
Mount Sinai School of Medicine, New York, New York
DAVID G. HOEL,
Medical University of South Carolina, Charleston, South Carolina
BARBARA S. HULKA,
University of North Carolina, Chapel Hill, North Carolina
CYNTHIA J. KENYON,
University of California, San Francisco, California
BRUCE R. LEVIN,
Emory University, Atlanta, Georgia
DAVID M. LIVINGSTON,
Dana-Farber Cancer Institute, Boston, Massachusetts
DONALD R. MATTISON,
March of Dimes, White Plains, New York
ELLIOT M. MEYEROWITZ,
California Institute of Technology, Pasadena, California
ROBERT T. PAINE,
University of Washington, Seattle, Washington
RONALD R. SEDEROFF,
North Carolina State University, Raleigh, North Carolina
ROBERT R. SOKAL,
State University of New York, Stony Brook, New York
CHARLES F. STEVENS,
The Salk Institute for Biological Studies, La Jolla, California
SHIRLEY M. TILGHMAN,
Princeton University, Princeton, New Jersey
RAYMOND L. WHITE,
University of Utah, Salt Lake City, Utah
Staff
WARREN R. MUIR, Executive Director
JACQUELINE K. PRINCE, Financial Officer
BARBARA B. SMITH, Administrative Associate
LAURA T. HOLLIDAY, Senior Program Assistant
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Strengthening Science at the U.S. Environmental Protection Agency: Research Management and Peer Review Practice (2000)
Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)
Modeling Mobile-Source Emissions (2000)
Copper in Drinking Water (2000)
Ecological Indicators for the Nation (2000)
Waste Incineration and Public Health (1999)
Hormonally Active Agents in the Environment (1999)
Research Priorities for Airborne Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); II. Evaluating Research Progress and Updating the Portfolio (1999)
Ozone-Forming Potential of Reformulated Gasoline (1999)
Risk-Based Waste Classification in California (1999)
Arsenic in Drinking Water (1999)
Brucellosis in the Greater Yellowstone Area (1998)
The National Research Council's Committee on Toxicology: The First 50 Years (1997)
Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (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 (5 reports, 1989-1995)
Review of EPA's Environmental Monitoring and Assessment Program (3 reports, 1994-1995)
Science and Judgment in Risk Assessment (1994)
Ranking Hazardous Waste Sites for Remedial Action (1994)
Pesticides in the Diets of Infants and Children (1993)
Issues in Risk Assessment (1993)
Setting Priorities for Land Conservation (1993)
Protecting Visibility in National Parks and Wilderness Areas (1993)
Dolphins and the Tuna Industry (1992)
Hazardous Materials on the Public Lands (1992)
Science and the National Parks (1992)
Animals as Sentinels of Environmental Health Hazards (1991)
Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993)
Human Exposure Assessment for Airborne Pollutants (1991)
Monitoring Human Tissues for Toxic Substances (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 Academy Press
(800) 624-6242 or (202) 334-3313
OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers (2000)
Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23, and HFC-404a (2000)
Health Risk Assessment of Selected Flame-Retardant Chemicals (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)
Review of a Screening Level Risk Assessment for the Naval Air Facility at Atsugi, Japan (Letter Report) (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, Vol. 1 (1994), Vol. 2 (1996), Vol. 3 (1996), Vol. 4 (2000)
Preface
THE U.S. NAVY Environmental Health Center (NEHC) supports the preventive medicine program of the Navy, especially in the areas of occupational health and public health. NEHC receives numerous requests to evaluate potential health hazards associated with materials used by the Navy and Marine Corps. In response to such requests, NEHC develops and reviews toxicological and related data and makes recommendations of acceptable exposures to these materials based on their potential to produce toxic effects in humans.
As part of its efforts to protect Navy personnel and their families from exposures to toxic chemicals, the Navy's Office of the Surgeon General asked the National Research Council (NRC) to independently review the adequacy of the NEHC health- hazard assessment (HHA) process. The NRC assigned this task to the Committee on Toxicology (COT) of the Board on Environmental Studies and Toxicology. The COT established the Subcommittee on Toxicological Hazard Evaluation, which prepared this report.
The subcommittee was asked to assess the validity and effectiveness of NEHC's HHA process; to determine whether the process as implemented provides the Navy with state-of-the-art, comprehensive, and defensible evaluations of toxicological hazards; and to identify any program elements that require improvement. This report is intended to provide NEHC with recommendations that will improve and strengthen the HHA process and aid the Navy's efforts related to preventive medicine.
The subcommittee gratefully acknowledges Capt. David Macys, Capt.
Richard Buck, Commander William Luttrell, Capt. George Kramer, Capt. Kenneth Still, James Crawl, Gerald Drewyer, Andrea Lunsford, Vera Wang, Charles Gross, Steven Sorgen (all from the U.S. Navy), and Dr. Ronald Wolff (Lilly Research Laboratories) for providing background information and for making presentations to the subcommittee.
This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise in accordance with procedures for reviewing NRC reports approved by the NRC's Report Review Committee. The purpose of this independent review was to provide candid and critical comments to assist the NRC in making the published report as sound as possible and to ensure that the report meets institutional standards for 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 wish to thank the following individuals, who are neither officials nor employees of the NRC, for their participation in the review of this report: Sidney Green, Howard University; George Rusch, AlliedSignal, Inc.; Donald Gardner, Inhalation Toxicology Associates; Joseph Barzelleca, Virginia Commonwealth University, and John Doull, University of Kansas Medical Center.
The individuals listed above have provided many constructive comments and suggestions. It may be emphasized, however, that responsibility for the final content of this report rests entirely with the authoring committee and the NRC.
The subcommittee was ably guided and assisted by staff of the NRC 's Board on Environmental Studies and Toxicology, especially Kulbir S. Bakshi (project director), Robert Crossgrove (editor), Evelyn Simeon, and Pamela Friedman (project administrative assistants). These staff members merit special recognition for their thoughtful contributions and extraordinary efforts in producing the report.
Finally, we would like to express my thanks and admiration to the members of the subcommittee for their dedicated efforts throughout the development of the report.
Rogene Henderson, Chair
Subcommittee on Toxicological Hazard and Risk Assessment
Bailus Walker, Chair
Committee on Toxicology
Abbreviations
AAALAC
American Association for the Accreditation of Laboratory Animal Care
ACGIH
American Conference of Governmental Industrial Hygienists
AEGL
acute exposure guideline level
AEHA
U.S. Army Environmental Hygiene Agency (now known as CHPPM)
AIHA
American Industrial Hygiene Association
ATSDR
Agency for Toxic Substances and Disease Registry
BUMED
Bureau of Medicine and Surgery
CEGL
continuous exposure guidance level
CHPPM
U.S. Army Center for Health Promotion and Preventive Medicine
CNO
Chief of Naval Operations
COT
Committee on Toxicology
DOD
Department of Defense
DON
Department of the Navy
DTIC
Defense Technical Information Center
EEGL
emergency exposure guidance level
EPA
U.S. Environmental Protection Agency
GLP
good laboratory practice
HCS
hazard communication standard
HEAST
health effects assessment summary table
HHA
health hazard assessment
HMD
Hazardous Materials Department
HSDB
Hazardous Substances Data Base
IARC
International Agency for Research on Cancer
IERA
Institute for Environment, Safety, and Occupational Health Risk Analysis
IH
industrial hygiene
IPCS
International Program on Chemical Safety
IRIS
Integrated Risk Information System
ISO
International Organization for Standardization
LCA
life-cycle assessment
MSDS
Material Safety Data Sheet
NAVOSH
Navy Occupational Safety and Health
NEHC
Navy Environmental Health Center
NHRC
Naval Health Research Center
NIOSH
National Institute for Occupational Safety and Health
NHRC/TD
Naval Health Research Center's Toxicology Detachment
NRC
National Research Council
ORNL
Oak Ridge National Laboratory
OSHA
Occupational Safety and Health Administration
QA/QC
quality assurance/quality control
QAO
Quality Assurance Office
RTECS
Registry of Toxic Effects
SOP
standard operating procedure
SECNAV
Secretary of the Navy
SMAC
spacecraft maximum allowable concentration
WPAFB
Wright-Patterson Air Force Base
