VOLUME 5
THE NATIONAL ACADEMIES PRESS
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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 ap¬propriate balance.
This project was supported by Contract No. DAMD17-99-C-9049 between the National Academy of Sciences and the U.S. Department of Defense and Contract No. 68-C-03-081 between the National Academy of Sciences and the U.S. Environmental Protection Agency. 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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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. Ralph J. Cicerone 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. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.
DONALDE. GARDNER(Chair),
Inhalation Toxicology Associates, Raleigh, NC
DANIELKREWSKI(past Chair),
University of Ottawa, Ontario, Canada
EDWARDC. BISHOP,
HDR Engineering, Inc., Omaha, NE
JAMESV. BRUCKNER(past member),
University of Georgia, Athens
RAKESHDIXIT,
MedImmune, Inc., Gaithersburg, MD
JOHNDOULL (past member),
University of Kansas Medical Center, Kansas City
JEFFREYW. FISHER,
University of Georgia, Athens
DAVIDW. GAYLOR(past member),
Gaylor and Associates, LLC, Eureka Springs, AR
KANNANKRISHNAN(past member),
University of Montreal, Quebec, Canada
DAVIDP. KELLY,
Dupont Company, Newark, DE
STEPHENU. LESTER(past member),
Center for Health, Environment, and Justice, Falls Church, VA
JUDITHMACGREGOR(past member),
Toxicology Consulting Services, Arnold, MD
PATRICIAM. MCGINNIS (past member),
Syracuse Research Corporation, Ft. Washington, PA
DAVIDA. MACYS,
Island County Health Department, Coupeville, WA
FRANZOESCH,
University of Mainz, Mainz, Germany
RICHARDB. SCHLESINGER,
Pace University, New York, NY
CALVINC. WILLHITE(past member),
California Department of Toxic Substances Control, Berkeley
FREDERIKA.DEWOLFF,
Leiden University Medical Center, Leiden, Netherlands
KULBIRS. BAKSHI, Project Director
RUTHE. CROSSGROVE, Senior Editor
AIDAC. NEEL, Program Associate
MIRSADAKARALIC-LONCAREVIC, Research Associate
RADIAHA. ROSE, Senior Editorial Assistant
U.S. Department of Defense
U.S. Environmental Protection Agency
WILLIAME. HALPERIN(Chair),
New Jersey Medical School, Newark
LAWRENCES. BETTS,
Eastern Virginia Medical School, Norfolk
EDWARDC. BISHOP,
HDR Engineering, Inc., Omaha, NE
JAMESV. BRUCKNER,
University of Georgia, Athens
GARYP. CARLSON,
Purdue University, West Lafayette, IN
JANICEE. CHAMBERS,
Mississippi State University, Mississippi State
MARIONEHRICH,
College of Veterinary Medicine, Blacksburg, VA
SIDNEYGREEN,
Howard University, Washington, DC
MERYLKAROL,
University of Pittsburgh, Pittsburgh, PA
JAMESMCDOUGAL,
Wright State University School of Medicine, Dayton, OH
ROGERMCINTOSH,
Science Applications International Corporation, Abingdon, MD
GERALDN. WOGAN,
Massachusetts Institute of Technology, Cambridge
KULBIRS. BAKSHI, Senior Program Officer for Toxicology
EILEENN. ABT, Senior Program Officer for Risk Analysis
ELLENK. MANTUS, Senior Program Officer
SUSANN. J. MARTEL, Senior Program Officer
JENNIFERSAUNDERS, Associate Program Officer
AIDANEEL, Program Associate
MIRSADAKARALIC-LONCAREVIC, Research Associate
TAMARADAWSON, Senior Program Assistant
RADIAHA. ROSE, Senior Editorial Assistant
JONATHANM. SAMET (Chair),
Johns Hopkins University, Baltimore, MD
RAMÓNALVAREZ,
Environmental Defense, Austin, TX
JOHNM. BALBUS,
Environmental Defense, Washington, DC
DALLASBURTRAW,
Resources for the Future, Washington, DC
JAMESS. BUS,
Dow Chemical Company, Midland, MI
COSTELD. DENSON,
University of Delaware, Newark
E. DONALDELLIOTT,
Willkie Farr & Gallagher LLP, Washington, DC
MARYR. ENGLISH,
University of Tennessee, Knoxville
J. PAULGILMAN,
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
SHERRIW. GOODMAN,
Center for Naval Analyses, Alexandria, VA
JUDITHA. GRAHAM,
American Chemistry Council, Arlington, VA
WILLIAMP. HORN,
Birch, Horton, Bittner and Cherot, Washington, DC
JAMESH. JOHNSONJR.,
Howard University, Washington, DC
WILLIAMM. LEWIS, JR.,
University of Colorado, Boulder
JUDITHL. MEYER,
University of Georgia, Athens
DENNISD. MURPHY,
University of Nevada, Reno
PATRICKY. O’BRIEN,
ChevronTexaco Energy Technology Company, Richmond, CA
DOROTHYE. PATTON (retired),
Chicago, IL
DANNYD. REIBLE,
University of Texas, Austin
JOSEPHV. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEADG. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERTF. SAWYER,
University of California, Berkeley
LISASPEER,
Natural Resources Defense Council, New York, NY
KIMBERLYM. THOMPSON,
Massachusetts Institute of Technology, Cambridge
MONICAG. TURNER,
University of Wisconsin, Madison
MARKJ. UTELL,
University of Rochester Medical Center, Rochester, NY
CHRISG. WHIPPLE,
ENVIRON International Corporation, Emeryville, CA
LAURENZEISE,
California Environmental Protection Agency, Oakland
JAMESJ. REISA, Director
DAVIDJ. POLICANSKY, Scholar
RAYMONDA. WASSEL, Senior Program Officer for Environmental Sciences and Engineering
KULBIRBAKSHI, Senior Program Officer for Toxicology
EILEENN. ABT, Senior Program Officer for Risk Analysis
KARLE. GUSTAVSON, Senior Program Officer
K. JOHNHOLMES, Senior Program Officer
ELLENK. MANTUS, Senior Program Officer
SUSANN.J. MARTEL, Senior Program Officer
SUZANNE VANDRUNICK, Senior Program Officer
STEVENK. GIBB, Program Officer for Strategic Communications
RUTHE. CROSSGROVE, Senior Editor
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 (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, 1998-2004)
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 (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
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)
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, Volume 1 (2004)
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)
Copies of these reports may be ordered from the National Academies Press
(800) 624-6242 or (202) 334-3313
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. Workers and residents 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 or intentional releases by terrorists. 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 indus-
try, academia, and other organizations from the private sector—has developed acute exposure guideline levels (AEGLs) for approximately 185 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 Committee on Acute Exposure Guideline Levels, which prepared this report. This report is the fifth volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals. It reviews the AEGLs for chlorine dioxide, chlorine trifluoride, cyclohexylamine, ethylenediamine, hydrofluoroether-7100 (HFE-7100), and tetranitromethane 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: Sidney Green, Jr., Howard University; Loren Koller, Independent Consultant; Ramesh Gupta, Murray State University; Harihara Mehendale, University of Louisana at Monroe; and Deepak Bhalla, Wayne State University.
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 Robert Goyer, University of Western Ontario, 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 committee gratefully acknowledges the valuable assistance provided by the following persons: Ernest Falke, Marquea D. King, Iris A. Camacho, and Paul Tobin (all from EPA); George Rusch (Honeywell, Inc.); Cheryl Bast, Sylvia Talmage, Robert Young, and Sylvia Milanez (all from Oak Ridge National Laboratory), Aida Neel (project associate),
and Radiah Rose (senior editorial assistant). We are grateful to James J. Reisa, director of the Board on Environmental Studies and Toxicology (BEST), for his helpful comments. The committee particularly acknowledges Kulbir Bakshi, project director for the committee, for bringing the report to completion. Finally, we would like to thank all members of the committee for their expertise and dedicated effort throughout the development of this report.
Donald E. Gardner, Chair
Committee on Acute Exposure Guideline Levels
William E. Halperin, Chair
Committee on Toxicology