Acute Exposure Guideline Levels for Selected Airborne Chemicals
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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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. 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.
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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.
COMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS
Members
DONALD E. GARDNER (Chair),
Inhalation Toxicology Associates, Raleigh, NC
DANIEL KREWSKI (past Chair),
University of Ottawa, Ontario, Canada
EDWARD C. BISHOP,
HDR Engineering, Inc., Omaha, NE
JAMES V. BRUCKNER (past member),
University of Georgia, Athens
RAKESH DIXIT,
MedImmune, Inc., Gaithersburg, MD
JOHN DOULL (past member),
University of Kansas Medical Center, Kansas City
JEFFREY W. FISHER,
University of Georgia, Athens
DAVID W. GAYLOR (past member),
Gaylor and Associates, LLC, Eureka Springs, AR
KANNAN KRISHNAN (past member),
University of Montreal, Quebec, Canada
DAVID P. KELLY,
Dupont Company, Newark, DE
STEPHEN U. LESTER (past member),
Center for Health, Environment, and Justice, Falls Church, VA
JUDITH MACGREGOR (past member),
Toxicology Consulting Services, Arnold, MD
PATRICIA M. MCGINNIS (past member),
Syracuse Research Corporation, Ft. Washington, PA
DAVID A. MACYS,
Island County Health Department, Coupeville, WA
FRANZ OESCH,
University of Mainz, Mainz, Germany
RICHARD B. SCHLESINGER,
Pace University, New York, NY
CALVIN C. WILLHITE (past member),
California Department of Toxic Substances Control, Berkeley
FREDERIK A. DE WOLFF,
Leiden University Medical Center, Leiden, Netherlands
Staff
KULBIR S. BAKSHI, Project Director
RUTH E. CROSSGROVE, Senior Editor
AIDA C. NEEL, Program Associate
MIRSADA KARALIC-LONCAREVIC, Research Associate
RADIAH A. ROSE, Senior Editorial Assistant
Sponsors
U.S. Department of Defense
U.S. Environmental Protection Agency
COMMITTEE ON TOXICOLOGY
Members
WILLIAM E. HALPERIN (Chair),
New Jersey Medical School, Newark
LAWRENCE S. BETTS,
Eastern Virginia Medical School, Norfolk
EDWARD C. BISHOP,
HDR Engineering, Inc., Omaha, NE
JAMES V. BRUCKNER,
University of Georgia, Athens
GARY P. CARLSON,
Purdue University, West Lafayette, IN
JANICE E. CHAMBERS,
Mississippi State University, Mississippi State
MARION EHRICH,
College of Veterinary Medicine, Blacksburg, VA
SIDNEY GREEN,
Howard University, Washington, DC
MERYL KAROL,
University of Pittsburgh, Pittsburgh, PA
JAMES MCDOUGAL,
Wright State University School of Medicine, Dayton, OH
ROGER MCINTOSH,
Science Applications International Corporation, Abingdon, MD
GERALD N. WOGAN,
Massachusetts Institute of Technology, Cambridge
Staff
KULBIR S. BAKSHI, Senior Program Officer for Toxicology
EILEEN N. ABT, Senior Program Officer for Risk Analysis
ELLEN K. MANTUS, Senior Program Officer
SUSAN N. J. MARTEL, Senior Program Officer
JENNIFER SAUNDERS, Associate Program Officer
AIDA NEEL, Program Associate
MIRSADA KARALIC-LONCAREVIC, Research Associate
TAMARA DAWSON, Senior Program Assistant
RADIAH A. ROSE, Senior Editorial Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1
Members
JONATHAN M. SAMET (Chair),
Johns Hopkins University, Baltimore, MD
RAMÓN ALVAREZ,
Environmental Defense, Austin, TX
JOHN M. BALBUS,
Environmental Defense, Washington, DC
DALLAS BURTRAW,
Resources for the Future, Washington, DC
JAMES S. BUS,
Dow Chemical Company, Midland, MI
COSTEL D. DENSON,
University of Delaware, Newark
E. DONALD ELLIOTT,
Willkie Farr & Gallagher LLP, Washington, DC
MARY R. ENGLISH,
University of Tennessee, Knoxville
J. PAUL GILMAN,
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
SHERRI W. GOODMAN,
Center for Naval Analyses, Alexandria, VA
JUDITH A. GRAHAM,
American Chemistry Council, Arlington, VA
WILLIAM P. HORN,
Birch, Horton, Bittner and Cherot, Washington, DC
JAMES H. JOHNSON JR.,
Howard University, Washington, DC
WILLIAM M. LEWIS, JR.,
University of Colorado, Boulder
JUDITH L. MEYER,
University of Georgia, Athens
DENNIS D. MURPHY,
University of Nevada, Reno
PATRICK Y. O’BRIEN,
ChevronTexaco Energy Technology Company, Richmond, CA
DOROTHY E. PATTON (retired),
Chicago, IL
DANNY D. REIBLE,
University of Texas, Austin
JOSEPH V. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEAD G. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERT F. SAWYER,
University of California, Berkeley
LISA SPEER,
Natural Resources Defense Council, New York, NY
KIMBERLY M. THOMPSON,
Massachusetts Institute of Technology, Cambridge
MONICA G. TURNER,
University of Wisconsin, Madison
MARK J. UTELL,
University of Rochester Medical Center, Rochester, NY
CHRIS G. WHIPPLE,
ENVIRON International Corporation, Emeryville, CA
LAUREN ZEISE,
California Environmental Protection Agency, Oakland
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Sciences and Engineering
KULBIR BAKSHI, Senior Program Officer for Toxicology
EILEEN N. ABT, Senior Program Officer for Risk Analysis
KARL E. GUSTAVSON, Senior Program Officer
K. JOHN HOLMES, Senior Program Officer
ELLEN K. MANTUS, Senior Program Officer
SUSAN N.J. MARTEL, Senior Program Officer
SUZANNE VAN DRUNICK, Senior Program Officer
STEVEN K. GIBB, Program Officer for Strategic Communications
RUTH E. CROSSGROVE, Senior Editor
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
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
OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
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
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. 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