NATIONAL ACADEMY PRESS
2101 Constitution Ave., N.W. Washington, D.C. 20418
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.
International Standard Book Number 0-309-07294-8
Additional copies of this report are available from:
National Academy Press
2101 Constitution Ave., NW Box 285 Washington, DC 20055 800–624–6242 202–334–3313 (in the Washington metropolitan area) http://www.nap.edu
Copyright 2000 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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.
DANIELKREWSKI,(Chair),
University of Ottawa, Ottawa, Ontario, Canada
EDWARDC.BISHOP,
Parsons Engineering Science, Inc., Fairfax, Virginia
JAMESV.BRUCKNER,
University of Georgia, Athens, Georgia
JOHNDOULL,
University of Kansas Medical Center, Kansas City, Kansas
DONALDE.GARDNER,
Inhalation Toxicology Associates, Inc., Raleigh, North Carolina
DAVIDW.GAYLOR,
U.S. Food and Drug Administration, Jefferson, Arkansas
HARIHARAMEHENDALE,
University of Louisiana, Monroe, Louisiana
FLORENCEK.KINOSHITA,
Hercules Incorporated, Wilmington, Delaware
STEPHENU.LESTER,
Center for Health, Environment and Justice, Falls Church, Virginia
RICHARDB.SCHLESINGER,
New York University School of Medicine, Tuxedo, New York
CALVINC.WILLHITE,
State of California, Berkeley, California
KULBIRS.BAKSHI, Project Director
RUTHE.CROSSGROVE, Editor
AIDA NEEL, Administrative Assistant
Sponsor: U.S. Department of Defense
BAILUSWALKER, JR. (Chair),
Howard University Medical Center and American Public Health Association, Washington, D.C.
MELVINE.ANDERSEN,
Colorado State University, Denver, Colorado
GERMAINEM.BUCK,
National Institute of Health, Washington, D.C.
ROBERTE.FORSTERII,
University of Pennsylvania, Philadelphia, Pennsylvania
WILLIAME.HALPERIN,
National Institute for Occupational Safety and Health, Cincinnati, Ohio
CHARLESH.HOBBS,
Lovelace Respiratory Research Institute and Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico
SAMKACEW,
Department of Pharmacology Faculty of Medicine and University of Ottawa, Ontario, Canada
NANCYKERKVLIET,
Oregon State University, Agricultural and Life Sciences, Corvallis, Oregon
MICHAELJ.KOSNETT,
University of Colorado Health Sciences Center, Denver, Colorado
MORTONLIPPMANN,
New York University School of Medicine, Tuxedo, New York
ERNESTE.MCCONNELL,
ToxPath, Inc., Raleigh, North Carolina
THOMASE.MCKONE,
Lawrence Berkeley National Laboratory and University of California, Berkeley, California
HARIHARAMEHENDALE,
The University of Louisiana at Monroe, Monroe, Louisiana
DAVIDH.MOORE,
Battelle Memorial Institute, Bel Air, Maryland
LAURENZEISE,
California Environmental Protection Agency, Oakland, California
KULBIRS.BAKSHI, Program Director
SUSANN.J.MARTEL, Program Officer
ABIGAILE.STACK, Program Officer
RUTHE.CROSSGROVE, Publications Manager
KATHYIVERSON, Manager,
Toxicology Information Center
AIDANEEL, Administrative Assistant
EMILYSMAIL, Project Assistant
GORDONORIANS(Chair),
University of Washington, Seattle, Washington
JOHNDOULL,
University of Kansas Medical Center, Kansas City, Kansas
DAVIDALLEN,
University of Texas, Austin, Texas
INGRIDC.BURKE,
Colorado State University, Fort Collins, Colorado
THOMASBURKE,
Johns Hopkins University, Baltimore, Maryland
GLENR.CASS,
Georgia Institute of Technology, Atlanta, Georgia
WILLIAML.CHAMEIDES,
Georgia Institute of Technology, Atlanta, Georgia
CHRISTOPHERB.FIELD,
Carnegie Institute of Washington, Stanford, California
JOHNGERHART,
University of California, Berkeley, California
J.PAULGILMAN,
Celera Genomics, Rockville, Maryland
DANIELS.GREENBAUM,
Health Effects Institute, Cambridge, Massachusetts
BRUCED.HAMMOCK,
University of California, Davis, California
ROGENEHENDERSON,
Lovelace Respiratory Research Institute, Albuquerque, New Mexico
CAROLHENRY,
American Chemistry Council, Arlington, Virginia
ROBERTHUGGETT,
Michigan State University, East Lansing, Michigan
JAMESF.KITCHELL,
University of Wisconsin, Madison, Wisconsin
DANIELKREWSKI,
University of Ottawa, Ottawa, Ontario
JAMESA.MACMAHON,
Utah State University, Logan, Utah
CHARLESO’MELIA,
Johns Hopkins University, Baltimore, Maryland
WILLEMF.PASSCHIER,
Health Council of the Netherlands, The Hague
ANNPOWERS,
Pace University School of Law, White Plains, New York
KIRKSMITH,
University of California, Berkeley, California
TERRYF.YOSIE,
American Chemistry Council, Arlington, Virginia
JAMESJ.REISA, Director
DAVIDJ.POLICANSKY, Associate Director and Senior Program Director for Applied Ecology
RAYMONDA.WASSEL, Senior Program Director for Environmental Sciences and Engineering
KULBIRBAKSHI, Program Director for the Committee on Toxicology
LEER.PAULSON, Program Director for Resource Management
ROBERTAM.WEDGE, Program Director for Risk Analysis
MICHAELT.CLEGG(Chair),
University of California, Riverside, California
PAULBERG(Vice Chair),
Stanford University, Stanford, California
FREDERICKR.ANDERSON,
Cadwalader, Wickersham & Taft, Washington, D.C.
JOANNABURGER,
Rutgers University, Piscataway, New Jersey
JAMESE.CLEAVER,
University of California, San Francisco, California
DAVIDS.EISENBERG,
University of California, Los Angeles, California
JOHNL.EMMERSON,
Fishers, Indiana
NEALL.FIRST,
University of Wisconsin, Madison, Wisconsin
DAVIDJ.GALAS,
Keck Graduate Institute of Applied Life Science, Claremont, California
DAVIDV.GOEDDEL,
Tularik, Inc., South San Francisco, California
ARTUROGOMEZ-POMPA,
University of California, Riverside, California
COREYS.GOODMAN,
University of California, Berkeley, California
JONW.GORDON,
Mount Sinai School of Medicine, New York, New York
DAVIDG.HOEL,
Medical University of South Carolina, Charleston, South Carolina
BARBARAS.HULKA,
University of North Carolina, Chapel Hill, North Carolina
CYNTHIAJ.KENYON,
University of California, San Francisco, California
BRUCER.LEVIN,
Emory University, Atlanta, Georgia
DAVIDM.LIVINGSTON,
Dana-Farber Cancer Institute, Boston, Massachusetts
DONALDR.MATTISON,
March of Dimes, White Plains, New York
ELLIOTM.MEYEROWITZ,
California Institute of Technology, Pasadena, California
ROBERTT.PAINE,
University of Washington, Seattle, Washington
RONALDR.SEDEROFF,
North Carolina State University, Raleigh, North Carolina
ROBERTR.SOKAL,
State University of New York, Stony Brook, New York
CHARLESF.STEVENS,
The Salk Institute for Biological Studies, La Jolla, California
SHIRLEYM.TILGHMAN,
Princeton University, Princeton, New Jersey
RAYMONDL.WHITE,
University of Utah, Salt Lake City, Utah
WARRENR.MUIR, Executive Director
JACQUELINEK.PRINCE, Financial Officer
BARBARAB.SMITH, Administrative Associate
LAURAT.HOLLIDAY, Senior Program Assistant
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
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)
Space"craft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994), Volume 2 (1996), Volume 3 (1996), Volume 4 (2000)
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 organiza-
tions 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 is the first volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals. It reviews the appropriateness of the AEGLs for four chemicals for their scientific validity, completeness, and consistency with the NRC guideline reports.
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 Carolson, Purdue University; Charles Feigley, University of South Carolina, Charleston; 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, 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 Sylvia Milanez (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 completion. Finally, we would like to