Acute Exposure Guideline Levels for Selected Airborne Chemicals

VOLUME 4

Subcommittee on Acute Exposure Guideline Levels

Committee on Toxicology

Board on Environmental Studies and Toxicology

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 Acute Exposure Guideline Levels for Selected Airborne Chemicals VOLUME 4 Subcommittee on Acute Exposure Guideline Levels Committee on Toxicology Board on Environmental Studies and Toxicology Division on Earth and Life Studies NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 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 0-309-09147-0 (Book) International Standard Book Number 0-309-53013-X (PDF) Additional copies of this report are available from: The National Academies Press 500 Fifth Street., NW Box 285 Washington, DC 20055 800–624–6242 202–334–3313 (in the Washington metropolitan area) http://www.nap.edu Copyright 2004 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine 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. Wm.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. Harvey V.Fineberg 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. Wm.A.Wulf are chair and vice chair, respectively, of the National Research Council www.national-academies.org

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS Members DANIEL KREWSKI (Chair), University of Ottawa, Ottawa, Ontario, Canada EDWARD C.BISHOP, Parsons Corporation, Pasadena, CA JAMES V.BRUCKNER, University of Georgia, Athens DAVID P.KELLY, Dupont Company, Newark, DE KANNAN KRISHNAN, University of Montreal, Montreal, Quebec, Canada STEPHEN U.LESTER, Center for Health, Environment and Justice, Falls Church, VA JUDITH MACGREGOR, Toxicology Consulting Services, Arnold, MD PATRICIA MCGINNIS, Syracuse Research Corporation, Ft. Washington, PA FRANZ OESCH, University of Mainz, Mainz, Germany RICHARD B.SCHLESINGER, Pace University, Pleasantville, NY CALVIN C.WILLHITE, Department of Toxic Substances, State of California, Berkeley FREDERIK A.DE WOLFF, Leiden University, Leiden, The Netherlands Staff KULBIR S.BAKSHI, Program Director KELLY CLARK, Editor AIDA C.NEEL, Senior Project Assistant

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 COMMITTEE ON TOXICOLOGY Members BAILUS WALKER, JR. (Chair), Howard University Medical Center and American Public Health Association, Washington, DC MELVIN E.ANDERSEN, CIIT-Centers for Health Research, Research Triangle Park, NC EDWARD C.BISHOP, Parsons Corporation, Pasadena, CA GARY P.CARLSON, Purdue University, West Lafayette, IN JANICE E.CHAMBERS, Mississippi State University, Mississippi State LEONARD CHIAZZE, JR., Georgetown University, Washington, DC JUDITH A.GRAHAM, American Chemistry Council, Arlington, VA SIDNEY GREEN, Howard University, Washington, DC MERYL KAROL, University of Pittsburgh, Pittsburgh, PA STEPHEN U.LESTER, Center for Health Environment and Justice, Falls Church, VA DAVID H.MOORE, Battelle Memorial Institute, Bel Air, MD CALVIN C.WILLHITE, Department of Toxic Substances, State of California, Berkeley GERALD WOGAN, Massachusetts Institute of Technology, Cambridge Staff KULBIR S.BAKSHI, Program Director for Toxicology ROBERTA M.WEDGE, Program Director for Risk Analysis SUSAN N.J.MARTEL, Senior Staff Officer ELLEN K.MANTUS, Senior Staff Officer KELLY CLARK, Assistant Editor AIDA C.NEEL, Senior Project Assistant TAMARA DAWSON, Project Assistant

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members JONATHAN SAMET (Chair), Johns Hopkins University, Baltimore, MD DAVID ALLEN, University of Texas, Austin, Texas THOMAS BURKE, Johns Hopkins University, Baltimore, MD JUDITH C.CHOW, Desert Research Institute, Reno, NV COSTEL D.DENSON, University of Delaware, Newark E.DONALD ELLIOTT, Willkie, Farr & Gallagher, LLP, Washington, DC CRISTOPHER B.FIELD, Carnegie Institute of Washington, Stanford, CA WILLIAM H.GLAZE, Oregon Health and Sciences University, Beaverton SHERRI W.GOODMAN, Center for Naval Analyses Corporation, Alexandria, VA DANIEL S.GREENBAUM, Health Effects Institute, Cambridge, MA ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, NM CAROL HENRY, American Chemistry Council, Arlington, VA ROBERT HUGGETT, Michigan State University, East Lansing BARRY L.JOHNSON, Emory University, Atlanta, GA JAMES H.JOHNSON, Howard University, Washington, DC JUDITH L.MEYER, University of Georgia, Athens PATRICK V.O’BRIEN, Chevron Research and Technology, Richmond, CA DOROTHY E.PATTON, International Life Sciences Institute, Washington, DC STEWARD T.A.PICKETT, Institute of Ecosystems Studies, Millbrook, NY ARMISTEAD G.RUSSELL, Georgia Institute of Technology, Atlanta LOUISE M.RYAN, Harvard University, Boston, MA KIRK SMITH, University of California, Berkeley LISA SPEER, Natural Resources Defense Council, New York, NY G.DAVID TILMAN, University of Minnesota, St. Paul CHRIS G.WHIPPLE, Environ, Inc., Emeryville, CA LAUREEN A.ZEISE, California Environmental Protection Agency, Oakland Senior Staff JAMES J.REISA, Director DAVID J.POLICANSKY, Associate Director RAYMOND A.WASSEL, Senior Program Director for Environmental Sciences and Engineering KULBIR BAKSHI, Program Director for Toxicology ROBERTA M.WEDGE, Program Director for Risk Analysis K.JOHN HOLMES, Senior Staff Officer SUSAN N.J.MARTEL, Senior Staff Officer SUZANNE VAN DRUNICK, Senior Staff Officer EILEEN N.ABT, Senior Staff Officer ELLEN K.MANTUS, Senior Staff Officer RUTH E.CROSSGROVE, Managing Editor 1   This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY Air Quality Management in the United States (2004) Endangered and Threatened Fishes in the Klamath River Basin: Causes of Decline and Strategies for Recovery (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 (4 volumes, 2000–2004) 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 (1999) Hormonally Active Agents in the Environment (1999) Research Priorities for Airborne Particulate Matter (4 volumes, 1998–2003) Arsenic in Drinking Water (1999) 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 (5 volumes, 1989–1995) Review of EPA’s Environmental Monitoring and Assessment Program (3 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 www.nap.edu

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 1 (2004) 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) 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)

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 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 potentially are 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) in 1991 requested that the National Research Council (NRC) 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, academe, and other 1   As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986.

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 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 is the fourth volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals. It reviews the AEGLs for chlorine, hydrogen chloride, hydrogen fluoride, toluene 2,4- and 2,6-diisocyanate, and uranium hexafluoride for scientific accuracy, completeness, and consistency with the NRC guideline reports. This report was reviewed in draft by individuals selected 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: David H.Moore of Battelle Memorial Institute; Sam Kacew of University of Ottawa; and Rakesh Dixit of Merck and Company, Inc. 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 Janice E.Chambers of Mississippi State University, appointed by the Division on Earth and Life Studies, 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 people: Ernest Falke and Paul Tobin, EPA; George Rusch, Honeywell, Inc.; Sylvia Talmage, Cheryl Bast, and Carol Wood, Oak Ridge National Laboratory; and Aida Neel, senior project assistant for the Board on Environmental Studies and Toxicology. Kelly Clark edited the report. We are grateful to James J.Reisa, director of the Board on Environmental Studies and Toxicology, for his helpful comments. The subcommittee particularly acknowledges Kulbir Bakshi, project director for

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 the subcommittee, for bringing the report to completion. Finally, we would like to thank all members of the subcommittee for their expertise and dedicated effort throughout the development of this report. Daniel Krewski, Chair Subcommittee on Acute Exposure Guideline Levels Bailus Walker, Chair Committee on Toxicology

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Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4 Contents     Introduction   1     Roster of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances   7     Appendixes         1   Chlorine: Acute Exposure Guideline Levels   13     2   Hydrogen Chloride: Acute Exposure Guideline Levels   77     3   Hydrogen Fluoride: Acute Exposure Guideline Levels   123     4   Toluene 2,4- and 2,6-Diisocyanate: Acute Exposure Guideline Levels   198     5   Uranium Hexafluoride: Acute Exposure Guideline Levels   250

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