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Committee on Acute Exposure Guideline Levels
Committee on Toxicology
Board on Environmental Studies and Toxicology
Division on Earth and Life Studies
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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 Insti-
tute 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 No. W81K04-06-D-0023 and EP-W-09-007 be-
tween the National Academy of Sciences and the U.S. Department of Defense and the
U.S. Environmental Protection Agency. Any opinions, findings, conclusions, or recom-
mendations 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-13: 978-0-309-21987-7
International Standard Book Number-10: 0-309-21987-6
Additional copies of this report are available from
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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
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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. Charles M. Vest is president of the National Academy of
Engineering.
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tional Academy of Engineering in providing services to the government, the public, and
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Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest
are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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COMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS
Members
DONALD E. GARDNER (Chair), Inhalation Toxicology Associates,
Savannah, GA
EDWARD C. BISHOP, The Parsons Corporation, Council Bluffs, IA
LUNG CHI CHEN, New York University, Tuxedo
RAKESH DIXIT, MedImmune/AstraZeneca Biologics, Inc., Gaithersburg, MD
KATHLEEN L. GABRIELSON, Johns Hopkins School of Medicine,
Baltimore, MD
GUNNAR JOHANSON, Karolinska Institute, Stockholm, Sweden
DAVID P. KELLY, Dupont Company (retired), Newark, DE
MARGARET M. MACDONELL, Argonne National Laboratory, Argonne, IL
DAVID A. MACYS, U.S. Department of the Navy (retired), Oak Harbor, WA
MARIA T. MORANDI, University of Montana, Missoula
FRANZ OESCH, University of Mainz (retired), Mainz, Germany
NU-MAY RUBY REED, California Environmental Protection Agency
(retired), Davis
GEORGE C. RODGERS, University of Louisville, Louisville, KY
RICHARD B. SCHLESINGER, Pace University, Pleasantville, NY
ROBERT SNYDER, Rutgers University, Piscataway, NJ
KENNETH R. STILL, Occupational Toxicology Associates, Inc., Hillsboro, OR
Staff
KEEGAN SAWYER, Associate Program Officer
RUTH CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
Sponsors
U.S. DEPARTMENT OF DEFENSE
U.S. ENVIRONMENTAL PROTECTION AGENCY
v
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COMMITTEE ON TOXICOLOGY
Members
GARY P. CARLSON (Chair), Purdue University (retired), West Lafayette, IN
LAWRENCE S. BETTS, Eastern Virginia Medical School, Norfolk
DEEPAK K. BHALLA, Wayne State University, Detroit, MI
EDWARD C. BISHOP, The Parsons Corporation, Council Bluffs, IA
JAMES V. BRUCKNER, University of Georgia, Athens
DEBORAH A. CORY-SLECHTA, University of Rochester School of Medicine
and Dentistry, Rochester, NY
MARY E. DAVIS, West Virginia University, Morgantown
DAVID C. DORMAN, North Carolina State University, Raleigh
MARION F. EHRICH, Virginia Polytechnic Institute and State University,
Blacksburg
WILLIAM E. HALPERIN, UMDNJ–New Jersey Medical School, Newark
JAMES N. MCDOUGAL, Wright State University School of Medicine,
Dayton, OH
JOYCE S. TSUJI, Exponent, Inc., Bellevue, WA
Staff
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
RUTH E. CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
TAMARA DAWSON, Program Associate
vi
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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1
Members
ROGENE F. HENDERSON (Chair), Lovelace Respiratory Research Institute,
Albuquerque, NM
PRAVEEN AMAR, Clean Air Task Force, Boston, MA
TINA BAHADORI, American Chemistry Council, Washington, DC
MICHAEL J. BRADLEY, M.J. Bradley & Associates, Concord, MA
DALLAS BURTRAW, Resources for the Future, Washington, DC
JONATHAN Z. CANNON, University of Virginia, Charlottesville
GAIL CHARNLEY, HealthRisk Strategies, Washington, DC
FRANK W. DAVIS, University of California, Santa Barbara
RICHARD A. DENISON, Environmental Defense Fund, Washington, DC
CHARLES T. DRISCOLL, JR., Syracuse University, New York
H. CHRISTOPHER FREY, North Carolina State University, Raleigh
RICHARD M. GOLD, Holland & Knight, LLP, Washington, DC
LYNN R. GOLDMAN, George Washington University, Washington, DC
LINDA E. GREER, Natural Resources Defense Council, Washington, DC
WILLIAM E. HALPERIN, University of Medicine and Dentistry of New
Jersey, Newark
PHILIP K. HOPKE, Clarkson University, Potsdam, NY
HOWARD HU, University of Michigan, Ann Arbor
SAMUEL KACEW, University of Ottawa, Ontario
ROGER E. KASPERSON, Clark University, Worcester, MA
THOMAS E. MCKONE, University of California, Berkeley
TERRY L. MEDLEY, E.I. du Pont de Nemours & Company, Wilmington, DE
JANA MILFORD, University of Colorado at Boulder, Boulder
FRANK O’DONNELL, Clean Air Watch, Washington, DC
RICHARD L. POIROT, Vermont Department of Environmental Conservation, Waterbury
KATHRYN G. SESSIONS, Health and Environmental Funders Network,
Bethesda, MD
JOYCE S. TSUJI, Exponent Environmental Group, Bellevue, WA
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
ELLEN K. MANTUS, Senior Program Officer for Risk Analysis
EILEEN N. ABT, Senior Program Officer
RUTH E. CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
1
This study was planned, overseen, and supported by the Board on Environmental
Studies and Toxicology.
vii
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OTHER REPORTS OF THE
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
A Risk-Characterization Framework for Decision-Making at the Food and Drug
Administration (2011)
Review of the Environmental Protection Agency’s Draft IRIS Assessment of
Formaldehyde (2011)
Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change (2010)
The Use of Title 42 Authority at the U.S. Environmental Protection Agency (2010)
Review of the Environmental Protection Agency’s Draft IRIS Assessment of
Tetrachloroethylene (2010)
Hidden Costs of Energy: Unpriced Consequences of Energy Production and Use (2009)
Contaminated Water Supplies at Camp Lejeune—Assessing Potential Health
Effects (2009)
Review of the Federal Strategy for Nanotechnology-Related Environmental, Health,
and Safety Research (2009)
Science and Decisions: Advancing Risk Assessment (2009)
Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)
Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone
Air Pollution (2008)
Respiratory Diseases Research at NIOSH (2008)
Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)
Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)
Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk
Assessment (2007)
Models in Environmental Regulatory Decision Making (2007)
Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)
Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)
Environmental Impacts of Wind-Energy Projects (2007)
Scientific Review of the Proposed Risk Assessment Bulletin from the Office of
Management and Budget (2007)
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)
viii
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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 (nine volumes,
2000-2010)
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 (2000)
Hormonally Active Agents in the Environment (1999)
Research Priorities for Airborne Particulate Matter (four 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 (five volumes, 1989-1995)
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
ix
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OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
Review of the Department of Defense Enhanced Particulate Matter Surveillance
Program Report (2010)
Evaluation of the Health and Safety Risks of the New USAMRIID High-Containment
Facilities at Fort Detrick, Maryland (2010)
Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations:
Final Report (2008)
Managing Health Effects of Beryllium Exposure (2008)
Review of Toxicologic and Radiologic Risks to Military Personnel from Exposures to
Depleted Uranium (2008)
Emergency and Continuous Exposure Guidance Levels for Selected Submarine
Contaminants, Volume 1 (2007), Volume 2 (2008)
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)
Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 1 (2004),
Volume 2 (2007), Volume 3 (2008)
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), Volume 5 (2007),
Volume 6 (2008), Volume 7 (2009), Volume 8 (2009), Volume 9 (2010)
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),
Volume 5 (2008)
x
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Preface
Extremely hazardous substances (EHSs)2 can be released accidentally as a
result of chemical spills, industrial explosions, fires, or accidents involving rail-
road 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 Reauthoriza-
tion Act of 1986, the U.S. Environmental Protection Agency (EPA) has identi-
fied 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 Hazard-
ous Substances in 1993. Subsequently, Standard Operating Procedures for De-
veloping Acute Exposure Guideline Levels for Hazardous Substances was pub-
lished in 2001, providing updated procedures, methodologies, and other
guidelines used by the National Advisory Committee (NAC) on Acute Exposure
Guideline Levels for Hazardous Substances and the Committee on Acute Expo-
sure Guideline Levels (AEGLs) in developing the AEGL values.
Using the 1993 and 2001 NRC guidelines reports, the NAC—consisting of
members from EPA, the Department of Defense (DOD), the Department of En-
ergy (DOE), the Department of Transportation (DOT), other federal and state
governments, the chemical industry, academia, and other organizations from the
private sector—has developed AEGLs for approximately 200 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 (COT) the Committee on Acute Exposure
Guideline Levels, which prepared this report. This report is the tenth volume in
that series. AEGL documents for N,N-dimethylformamide, jet propellant fuels 5
2
As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986.
xi
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xii Preface
and 8, methyl ethyl ketone, perchloromethyl mercaptan, phosphorus oxychlo-
ride, phosphorus trichloride, and sulfuryl chloride are each published as an ap-
pendix in this report. The committee concludes that the AEGLs developed in these
appendixes are scientifically valid conclusions based on the data reviewed by
NAC and are consistent with the NRC guideline reports. AEGL reports for addi-
tional chemicals will be presented in subsequent volumes.
The committee’s review of the AEGL documents involved both oral and
written presentations to the committee by the NAC authors of the documents.
The committee examined the draft documents and provided comments and rec-
ommendations for how they could be improved in a series of interim reports.
The authors revised the draft AEGL documents based on the advice in the in-
terim reports and presented them for reexamination by the committee as many
times as necessary until the committee was satisfied that the AEGLs were scien-
tifically justified and consistent with the 1993 and 2001 NRC guideline reports.
After these determinations have been made for an AEGL document, it is pub-
lished as an appendix in a volume such as this one.
The six interim reports of the committee that led to this report were re-
viewed in draft form by individuals selected for their diverse perspectives and
technical expertise, in accordance with procedures approved by the NRC’s Re-
port Review Committee. The purpose of this independent review is to provide
candid and critical comments that will assist the institution in making its pub-
lished report as sound as possible and to ensure that the report meets institu-
tional standards for objectivity, evidence, and responsiveness to the study
charge. The review comments and draft manuscript remain confidential to pro-
tect the integrity of the deliberative process. We wish to thank the following
individuals for their review of the six committee interim reports, which summa-
rize the committee’s conclusions and recommendations for improving NAC’s
AEGL documents for N,N-dimethylformamide (fourteenth interim report, 2006),
jet propellant fuels 5 and 8 (seventeenth interim report, 2010), methyl ethyl ke-
tone (twelfth and fifteenth interim reports, 2005 and 2008, respectively), per-
chloromethyl mercaptan (fifteenth interim report, 2008), phosphorus oxychlo-
ride (eleventh and fifteenth interim reports, 2004 and 2008, respectively),
phosphorus trichloride (eleventh and fifteenth interim reports, 2004 and 2008,
respectively), and sulfuryl chloride (sixteenth interim report, 2009): Deepak
Bhalla (Wayne State University), Harvey Clewell (The Hamner Institutes for
Health Sciences), David Gaylor (Gaylor and Associates, LLC), Sidney Green,
Jr. (Howard University), A. Wallace Hayes (Harvard School of Public Health),
Rogene Henderson (Lovelace Respiratory Research Institute [retired]), Sam
Kacew (University of Ottawa), Charles Reinhardt (DuPont Haskell Laboratory
[retired]), Kenneth Still (Occupational Toxicology Associates, Inc.), and Ber-
nard M. Wagner (New York University Medical Center [retired]).
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 this volume before its re-
lease. The review of the eleventh interim report was overseen by Rakesh Dixit
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xiii
Preface
(MedImmune/AstraZeneca Biologics), and the twelfth interim report was over-
seen by David Gaylor (Gaylor and Associates, LLC). The review of the four-
teenth, fifteenth, sixteenth, and seventeenth interim reports was overseen by
Robert Goyer, University of Western Ontario (retired). Appointed by the NRC,
they were responsible for making certain that an independent examination of the
interim reports 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 institu-
tion.
The committee gratefully acknowledges the valuable assistance provided
by the following persons: Ernest Falke and Iris A. Camacho (both from EPA)
and George Rusch (Honeywell, Inc.). The committee also acknowledges Keegan
Sawyer, the project director for her work this project. Other staff members who
contributed to this effort are James J. Reisa (director of the Board on Environ-
mental Studies and Toxicology), Susan Martel (senior program officer for toxi-
cology), Ruth Crossgrove (senior editor), Radiah Rose (manager of editorial
projects), Mirsada Karalic-Loncarevic (manager of the Technical Information
Center), Orin Luke (senior program assistant), and Tamara Dawson (program
associate). Finally, I 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
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Dedication
The subcommittee dedicates this series of reports to our late colleague
and co-founder of the Acute Exposure Guideline Levels program,
Dr. Paul Tobin,
whose 31 years of distinguished service with the
U.S. Environmental Protection Agency in the fields of chemistry,
toxicology and health-risk assessment contributed significantly to scientific
knowledge, to the development of the Acute Exposure Guideline Levels
program, and to the protection of public health and safety.
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Contents
NATIONAL RESEARCH COUNCIL COMMITTEE REVIEW
OF ACUTE EXPOSURE GUIDELINE LEVELS OF SELECTED
AIRBORNE CHEMICALS ............................................................................................. 3
ROSTER OF THE NATIONAL ADVISORY COMMITTEE FOR ACUTE
EXPOSURE GUIDELINE LEVELS FOR HAZARDOUS SUBSTANCES ............... 9
APPENDIXES
1 N,N-DIMETHYLFORMAMIDE ....................................................................... 13
Acute Exposure Guideline Levels
2 JET PROPELLANT FUELS 5 AND 8 .............................................................. 72
Acute Exposure Guideline Levels
3 METHYL ETHYL KETONE........................................................................... 140
Acute Exposure Guideline Levels
4 PERCHLOROMETHYL MERCAPTAN ....................................................... 198
Acute Exposure Guideline Levels
5 PHOSPHORUS OXYCHLORIDE .................................................................. 227
Acute Exposure Guideline Levels
6 PHOSPHORUS TRICHLORIDE .................................................................... 250
Acute Exposure Guideline Levels
7 SULFURYL CHLORIDE ................................................................................. 282
Acute Exposure Guideline Levels
xv
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