Acute Exposure Guideline Levels for
Selected Airborne Chemicals
VOLUME 13
Committee on Acute Exposure Guideline Levels
Committee on Toxicology
Board on Environmental Studies and Toxicology
Division on Earth and Life Studies
NATIONAL RESEARCH COUNCIL
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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 appropriate balance.
This project was supported by Contract No. W81K04-11-D-0017 and EP-W-09-007 between the National Academy of Sciences and the U.S. Department of Defense 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.
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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. Charles M. Vest 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, Savannah, GA
DEEPAK K. BHALLA, Wayne State University, Detroit, MI
LUNG CHI CHEN, New York University, Tuxedo
KATHLEEN L. GABRIELSON, Johns Hopkins School of Medicine, Baltimore, MD
GUNNAR JOHANSON, Karolinska Institute, Stockholm, Sweden
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
LEENA A. NYLANDER-FRENCH, University of North Carolina, Chapel Hill, NC
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
ROBERT SNYDER, Rutgers University, Piscataway, NJ
FRANK E. SPEIZER, Harvard University, Boston, MA
KENNETH R. STILL, Portland State University, Portland, OR
Staff
SUSAN N.J. MARTEL, Senior Program Officer
TAMARA DAWSON, Program Associate
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
Sponsors
U.S. DEPARTMENT OF DEFENSE
U.S. ENVIRONMENTAL PROTECTION AGENCY
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
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
WAYNE M. LEDNAR, E.I. du Pont de Nemours and Company, Wilmington, DE
MARGARET M. MACDONELL, Argonne National Laboratory, Argonne, IL
IVAN RUSYN, University of North Carolina, Chapel Hill, NC
KENNETH R. STILL, Portland State University, Portland, OR
JOYCE S. TSUJI, Exponent, Inc., Bellevue, WA
Staff
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
TAMARA DAWSON, Program Associate
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
MICHAEL J. BRADLEY, M.J. Bradley & Associates, Concord, MA
JONATHAN Z. CANNON, University of Virginia, Charlottesville
GAIL CHARNLEY, HealthRisk Strategies, Washington, DC
FRANK W. DAVIS, University of California, Santa Barbara
CHARLES T. DRISCOLL, JR., Syracuse University, New York
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
STEVEN P. HAMBURG, Environmental Defense Fund, New York, NY
ROBERT A. HIATT, University of California, San Francisco
PHILIP K. HOPKE, Clarkson University, Potsdam, NY
SAMUEL KACEW, University of Ottawa, Ontario
H. SCOTT MATTHEWS, Carnegie Mellon University, Pittsburgh, PA
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
RICHARD L. POIROT, Vermont Department of Environmental Conservation, Waterbury
MARK A. RATNER, Northwestern University, Evanston, IL
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
ELLEN K. MANTUS, Senior Program Officer for Risk Analysis
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
EILEEN N. ABT, Senior Program Officer
MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center
RADIAH ROSE, Manager, Editorial Projects
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1This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Science for Environmental Protection: The Road Ahead (2012)
Exposure Science in the 21st Century: A Vision and A Strategy (2012)
A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials (2012)
Macondo Well–Deepwater Horizon Blowout: Lessons for Improving Offshore Drilling Safety (2012)
Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops (2011)
Improving Health in the United States: The Role of Health Impact Assessment (2011)
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)
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 (twelve volumes, 2000-2012)
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
OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY
Potential Health Risks to DOD Firing-Range Personnel from Recurrent Lead Exposure (2012)
Review of Studies of Possible Toxic Effects from Past Environmental Contamination at Fork Detrick: A Letter Report (2012)
Review of Risk Assessment Work Plan for the Medical Countermeasures Test and Evaluation Facility at Fort Detrick, A Letter Report (2011)
Assistance to the U.S. Army Medical Research and Materiel Command with Preparation of a Risk Assessment for the Medical Countermeasures Test and Evaluation (MCMT&E) Facility at Fort Detrick, Maryland, A Letter Report (2011)
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), Volume 10 (2011), Volume 11 (2012), Volume 12 (2012)
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)
Preface
Extremely hazardous substances (EHSs)2 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. Subsequently, Standard Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Substances was published 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 Exposure 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 Energy (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 more than 270 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 thirteenth volume in that series. AEGL documents for boron trifluoride, bromoacetone, chloroacetone, hexa-
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2As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986.
fluoroacetone, perchloryl fluoride, piperidine, propargyl alcohol, trimethoxysilane and tetramethoxysilane, and trimethylbenzenes are each published as an appendix 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 additional 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 authors of the documents. The committee examined the draft documents and provided comments and recommendations 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 interim reports and presented them for reexamination by the committee as many times as necessary until the committee was satisfied that the AEGLs were scientifically justified and consistent with the 1993 and 2001 NRC guideline reports. After these determinations have been made for an AEGL document, it is published as an appendix in a volume such as this one.
The six interim reports of the committee that led to this report were reviewed in draft form 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 the committee interim reports, which summarize the committee’s conclusions and recommendations for improving NAC’s AEGL documents for boron trifluoride (interim reports 8 and 15), bromoacetone (interim report 20a), chloroacetone (interim reports 16, 19a, and 20a), hexafluoroacetone (interim reports 16 and 19a), perchloryl fluoride (interim report 20a), piperidine (interim reports 18 and 20a), propargyl alcohol (interim reports 16 and 19a), trimethoxysilane and tetramethoxysilane (interim reports 19a and 20a), and trimethylbenzenes (interim reports 16, 18, and 19a): Harvey Clewell (The Hamner Institutes for Health Sciences), Jeffrey Fisher (U.S. Food and Drug Administration), A. Wallace Hayes (Harvard School of Public Health), Rogene Henderson (Lovelace Respiratory Research Institute [retired]), Sam Kacew (University of Ottawa), Florence Kinoshita (Hercules Incorporated [retired]), James McDougal (Wright State University [retired]), Kenneth Poirier (Kendle International, Inc.), Charles Reinhardt (DuPont Haskell Laboratory [retired]), Andrew Salmon (California Environmental Protection Agency), Joyce Tsuji (Exponent, Inc.), and Judith Zelikoff (New York 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 this volume before its release. The review of interim report 8 was overseen by David Moore (Battelle
Memorial Institute), and the reviews of interim reports 15, 16, 18, 19a, and 20a 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 institution.
The committee gratefully acknowledges the valuable assistance provided by Ernest Falke and Iris A. Camacho from EPA. The committee also acknowledges Susan Martel, 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 Environmental Studies and Toxicology), Radiah Rose (manager of editorial projects), Mirsada Karalic-Loncarevic (manager of the Technical Information Center), 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 |