Acute Exposure Guideline Levels for
Selected Airborne Chemicals

VOLUME 14

Committee 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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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. W81K04-11-D-0017 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: 978-0-309-28308-3 International Standard Book Number-10: 0-309-28308-6 Additional copies of this report are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334- 3313; http://www.nap.edu/. Copyright 2013 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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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 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. Charles M. Vest 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 re- sponsibility 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 Nation- al 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. www.national-academies.org

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COMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS Members EDWARD C. BISOHP (Chair), HDR Engineering, Inc., Omaha, NE DONALD E. GARDNER (Chair until November 2012), 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 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 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 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 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 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 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 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 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) viii

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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 (thirteen volumes, 2000-2013) 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 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 13 (2013) 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) x

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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) xi

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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 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 fourteenth vol- ume in that series. AEGL documents for BZ (2-quinuclidinyl benzilate), ethyl 2 As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986. xiii

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xiv Preface phosphorodichloridate, hexane, methanesulfonyl chloride, nitric acid, propargyl alcohol, and vinyl acetate monomer are each published as an appendix in this re- port. The committee concludes that the AEGLs developed in these appendixes are scientifically valid conclusions based on the data reviewed by NAC and are con- sistent 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 recom- mendations 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 scientifical- ly 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 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 com- ments 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 BZ (interim reports 19a, 20a, and 21a), ethyl phosphorodichloridate (interim reports 20a and 21a), hexane (interim reports 17 and 21a), methanesulfonyl chloride (interim reports 20a and 21a), nitric acid (interim reports 15, 18, and 21a), propargyl al- cohol (interim reports 16 and 19a), and vinyl acetate monomer (interim reports 18 and 21a): Harvey Clewell (The Hamner Institutes for Health Sciences), Jef- frey Fisher (U.S. Food and Drug Administration), Sam Kacew (University of Ottawa), A. Wallace Hayes (Harvard School of Public Health), Rogene Hender- son (Lovelace Respiratory Research Institute [retired]), James McDougal (Wright State University [retired], Charles Reinhardt (DuPont Haskell Laborato- ry [retired]), Andrew Salmon (California Environmental Protection Agency), Kenneth Still, Occupational Toxicology Associates, 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 re- lease. The review of interim reports 15-21 was overseen by Robert Goyer (Uni- versity of Western Ontario [retired]). Appointed by the NRC, he was responsible for making certain that an independent examination of the interim reports was

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Preface xv carried out in accordance with institutional procedures and that all review com- ments were carefully considered. Responsibility for the final content of this re- port 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 acknowl- edges 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

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Contents NATIONAL RESEARCH COUNCIL COMMITTEE REVIEW OF ACUTE EXPOSURE GUIDELINE LEVELS OF SELECTED AIRBORNE CHEMICALS ................................. 3 APPENDIXES 1 AGENT BZ (3-QUINUCLIDINYL BENZILATE) ............................. 13 Acute Exposure Guideline Levels 2 ETHYL PHOSPHORODICHLORIDATE .......................................... 42 Acute Exposure Guideline Levels 3 n-HEXANE ............................................................................................. 66 Acute Exposure Guideline Levels 4 METHANESULFONYL CHLORIDE ............................................... 115 Acute Exposure Guideline Levels 5 NITRIC ACID ...................................................................................... 139 Acute Exposure Guideline Levels 6 PROPARGYL ALCOHOL ................................................................. 176 Acute Exposure Guideline Levels 7 VINYL ACETATE ............................................................................... 210 Acute Exposure Guideline Levels xvii

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