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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 the 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.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A.Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I.Shine is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M.Alberts and Dr. William A.Wulf are chairman and vice chairman, respectively, of the National Research Council.
SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS
DANIEL KREWSKI, (Chair),
University of Ottawa, Ottawa, Ontario
EDWARD C.BISHOP,
Parsons Engineering Science, Inc., Fairfax, Virginia
JAMES V.BRUCKNER,
University of Georgia, Athens
JOHN DOULL,
University of Kansas Medical Center, Kansas City
DONALD E.GARDNER,
Inhalation Toxicology Associates, Inc., Raleigh, North Carolina
DAVID W.GAYLOR,
U.S. Food and Drug Administration, Jefferson, Arkansas
FLORENCE K.KINOSHITA,
Hercules Incorporated, Wilmington, Delaware
STEPHEN U.LESTER,
Center for Health, Environment and Justice, Falls Church, Virginia
HARIHARA MEHENDALE,
University of Louisiana, Monroe
RICHARD B.SCHLESINGER,
New York University School of Medicine, Tuxedo
CALVIN C.WILLHITE,
State of California, Berkeley
Staff
KULBIR S.BAKSHI, Project Director
RUTH E.CROSSGROVE, Editor
AIDA NEEL, Administrative Assistant
Sponsor: U.S. Department of 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
GERMAINE M.BUCK,
National Institute of Health, Washington, D.C.
ROBERT E.FORSTER II,
University of Pennsylvania, Philadelphia
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,
University of Ottawa, Ottawa, Ontario
NANCY KERKVLIET,
Oregon State University, Corvallis
MICHAEL J.KOSNETT,
University of Colorado Health Sciences Center, Denver
MORTON LIPPMANN,
New York University School of Medicine, Tuxedo
ERNEST E.MCCONNELL,
ToxPath, Inc., Raleigh, North Carolina
THOMAS E.MCKONE,
Lawrence Berkeley National Laboratory and University of California, Berkeley
HARIHARA MEHENDALE,
University of Louisiana, Monroe
DAVID H.MOORE,
Battelle Memorial Institute, Bel Air, Maryland
LAUREN ZEISE,
California Environmental Protection Agency, Oakland
Staff
KULBIR S.BAKSHI, Program Director
SUSAN N.J.MARTEL, Program Officer
ABIGAIL E.STACK, Program Officer
RUTH E.CROSSGROVE, Publications Manager
AIDA NEEL, Administrative Assistant
JESSICA BROCK, Project Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
GORDON ORIANS (Chair),
University of Washington, Seattle
JOHN DOULL,
University of Kansas Medical Center, Kansas City
DAVID ALLEN,
University of Texas, Austin
INGRID C.BURKE,
Colorado State University, Fort Collins
THOMAS BURKE,
Johns Hopkins University, Baltimore, Maryland
GLEN R.CASS,
Georgia Institute of Technology, Atlanta
WILLIAM L.CHAMEIDES,
Georgia Institute of Technology, Atlanta
CHRISTOPHER B.FIELD,
Carnegie Institute of Washington, Stanford, California
JOHN GERHART,
University of California, Berkeley
J.PAUL GILMAN,
Celera Genomics, Rockville, Maryland
DANIEL S.GREENBAUM,
Health Effects Institute, Cambridge, Massachusetts
BRUCE D.HAMMOCK,
University of California, Davis
ROGENE HENDERSON,
Lovelace Respiratory Research Institute, Albuquerque, New Mexico
CAROL HENRY,
American Chemistry Council, Arlington, Virginia
ROBERT HUGGETT,
Michigan State University, East Lansing
JAMES F.KITCHELL,
University of Wisconsin, Madison
DANIEL KREWSKI,
University of Ottawa, Ottawa, Ontario
JAMES A.MACMAHON,
Utah State University, Logan
CHARLES O’MELIA,
Johns Hopkins University, Baltimore, Maryland
WILLEM F.PASSCHIER,
Health Council of the Netherlands, The Hague
ANN POWERS,
Pace University School of Law, White Plains, New York
KIRK SMITH,
University of California, Berkeley
TERRY F.YOSIE,
American Chemistry Council, Arlington, Virginia
Senior Staff
JAMES J.REISA, Director
DAVID J.POLICANSKY, Associate Director and Senior Program Director for Applied Ecology
RAYMOND A.WASSEL, Senior Program Director for Environmental Sciences and Engineering
KULBIR BAKSHI, Program Director for the
Committee on Toxicology
ROBERTA M.WEDGE, Program Director for Risk Analysis
JOHN HOLMES, Senior Staff Officer
COMMISSION ON LIFE SCIENCES
MICHAEL T.CLEGG (Chair),
University of California, Riverside
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
DAVID S.EISENBERG,
University of California, Los Angeles
NEAL L.FIRST,
University of Wisconsin, Madison
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
COREY S.GOODMAN,
University of California, Berkeley
JON W.GORDON,
Mount Sinai School of Medicine, New York
DAVID G.HOEL,
Medical University of South Carolina, Charleston
BARBARA S.HULKA,
University of North Carolina, Chapel Hill
CYNTHIA J.KENYON,
University of California, San Francisco
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
ROBERT T.PAINE,
University of Washington, Seattle
RONALD R.SEDEROFF,
North Carolina State University, Raleigh
ROBERT R.SOKAL,
State University of New York, Stony Brook
CHARLES F. STEVENS,
The Salk Institute for Biological Studies, La Jolla, California
SHIRLEY M.TILGHMAN,
Princeton University, Princeton, New Jersey
RAYMOND L.WHITE,
DNA Sciences, Inc., Mountain View, California
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
A Risk-Management Strategy for PCB-Contaminated Sediments (2001)
Toxicological Effects of Methylmercury (2000)
Strengthening Science at the U.S. Environmental Protection Agency: Research-Management and Peer-Review Practices (2000)
Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)
Modeling Mobile-Source Emissions (2000)
Toxicological Risks of Selected Flame-Retardant Chemicals (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
(202) 334–3313
OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity (2001)
Acute Exposure Guideline Levels for Selected Airborne Contaminants, Volume 1 (2000)
Review of the U.S. 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
Extremely hazardous substances (EHSs)1 can be released accidentally as a result of chemical spills, industrial explosions, fires, or accidents involving railroad cars and trucks transporting EHSs. The people in communities surrounding industrial facilities where EHSs are manufactured, used, or stored and in communities along the nation’s railways and highways are potentially at risk of being exposed to airborne EHSs during accidental releases. Pursuant to the Superfund Amendments and Reauthorization Act of 1986, the U.S. Environmental Protection Agency (EPA) has identified approximately 400 EHSs on the basis of acute lethality data in rodents.
As part of its efforts to develop acute exposure guideline levels for EHSs, EPA and the Agency for Toxic Substances and Disease Registry (ATSDR) requested that the National Research Council (NRC) in 1991 develop guidelines for establishing such levels. In response to that request, the NRC published Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances in 1993.
Using the 1993 NRC guidelines report, the National Advisory Committee (NAC) on Acute Exposure Guideline Levels for Hazardous Substances—consisting of members from EPA, the Department of Defense (DOD), the Department of Energy (DOE), the Department of Transportation, other federal and state governments, the chemical industry, academia, and other organizations from the private sector—has developed acute exposure guideline levels (AEGLs) for approximately 80 EHSs.
In 1998, EPA and DOD requested that the NRC independently review the AEGLs developed by NAC. In response to that request, the NRC organized within its Committee on Toxicology the Subcommittee on Acute Exposure Guideline Levels, which prepared this report. This report evaluates the NAC’s Standing Operating Procedures (SOP) document for its scientific validity, completeness, and for conformance to the 1993 NRC guidelines report. The report will be useful to EPA, DOD, ATSDR, and other federal, state, and local agencies, and industry in developing toxicologic risk assessments for hazardous chemicals.
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC’s Report Review Committee. The purpose of this 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 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 for their review of this report: Gary Carlson (Purdue University), Charles Feigley (University of South Carolina), and Ralph Kodell (National Center for Toxicological Research).
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 Mary Vore (University of Kentucky), appointed by the Commission on Life Sciences, who 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 authoring committee and the institution.
The subcommittee gratefully acknowledges the valuable assistance provided by the following persons: Roger Garrett, Paul Tobin, and Ernest Falke (all from EPA); George Rusch (Honeywell, Inc.); Po Yung Lu, Sylvia Talmage, Robert Young, and Cheryl Bast (all from Oak Ridge National Laboratory), and Karl Rozman (University of Kansas Medical Center). Aida Neel was the project assistant. Ruth Crossgrove edited the report. We are grateful to James J.Reisa, director of the Board on Environmental Studies and Toxicology (BEST), and David Policansky, associate director of BEST, for their helpful comments. The subcommittee particularly acknowledges Kulbir Bakshi, project director for the subcommittee, for bringing the report to
LIST OF TABLES
TABLE 2–1 |
Values of n from Ten Berge et al. (1986) |
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TABLE 3–1 |
Grouping Data into Categories for Plotting |
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TABLE A-1 |
Priority List of Chemicals |
LIST OF FIGURES