Acute Exposure Guideline Levels for Selected Airborne Chemicals

VOLUME 7

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 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. W81K04-06-D-0023 between the National Academy of Sciences and the U.S. Department of Defense. Any opinions, findings, conclu- sions, 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. International Standard Book Number-13: 978-0-309-12755-4 International Standard Book Number-10: 0-309-12755-6 Additional copies of this report are available from The National Academies Press 500 Fifth Street, NW Box 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.edu Copyright 2009 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 dis- tinguished scholars engaged in scientific and engineering research, dedicated to the further- ance 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 re- quires 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 Na- tional Academy of Sciences the responsibility for advising the federal government. The Na- tional Academy of Engineering also sponsors engineering programs aimed at meeting na- tional 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 responsibil- ity 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 pur- poses of furthering knowledge and advising the federal government. Functioning in accor- dance with general policies determined by the Academy, the Council has become the princi- pal 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. www.national-academies.org

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COMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS Members DONALD E. GARDNER (Chair), Inhalation Toxicology Associates, Raleigh, NC EDWARD C. BISHOP, HDR Engineering, Inc., Omaha, NE RAKESH DIXIT, MedImmune, Inc., Gaithersburg, MD JEFFREY W. FISHER, University of Georgia, Athens DAVID P. KELLY, Dupont Company, Newark, DE DAVID A. MACYS, Island County Health Department, Coupeville, WA FRANZ OESCH, University of Mainz, Mainz, Germany RICHARD B. SCHLESINGER, Pace University, New York, NY ROBERT SNYDER, Rutgers University, Piscataway, NJ JOHN A. THOMAS, Indiana University School of Medicine, Indianapolis FREDERIK A. DE WOLFF, Leiden University Medical Center, Leiden, The Netherlands Staff RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies KULBIR S. BAKSHI, Senior Program Officer RUTH E. CROSSGROVE, Senior Editor MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center RADIAH A. ROSE, Editorial Projects Manager PATRICK BAUR, Research Assistant KORIN THOMPSON, Project Assistant Sponsor U.S. DEPARTMENT OF DEFENSE v

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COMMITTEE ON TOXICOLOGY Members GARY P. CARLSON (Chair), Purdue University, West Lafayette, IN LAWRENCE S. BETTS, Eastern Virginia Medical School, Norfolk EDWARD C. BISHOP, HDR Engineering, Inc., Omaha, NE JAMES V. BRUCKNER, University of Georgia, Athens MARION F. EHRICH, Virginia Polytechnic Institute and State University, Blacksburg SIDNEY GREEN, Howard University, Washington, DC WILLIAM E. HALPERIN, UMDNJ–New Jersey Medical School, Newark MERYL H. KAROL, University of Pittsburgh, Pittsburgh, PA JAMES N. MCDOUGAL, Wright State University School of Medicine, Dayton, OH ROGER G. MCINTOSH, Science Applications International Corporation, Abingdon, MD GERALD N. WOGAN, Massachusetts Institute of Technology, Cambridge Staff SUSAN N. J. MARTEL, Senior Program Officer for Toxicology EILEEN N. ABT, Senior Program Officer for Risk Analysis ELLEN K. MANTUS, Senior Program Officer MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center TAMARA DAWSON, Program Associate RADIAH A. ROSE, Editorial Projects Manager vi

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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members JONATHAN M. SAMET (Chair), University of Southern California, Los Angeles RAMON ALVAREZ, Environmental Defense Fund, Austin, TX JOHN M. BALBUS, George Washington University, Washington, DC DALLAS BURTRAW, Resources for the Future, Washington, DC JAMES S. BUS, Dow Chemical Company, Midland, MI RUTH DEFRIES, Columbia University, New York, NY 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, Covanta Energy Corporation, Fairfield, NJ JUDITH A. GRAHAM (Retired), Pittsboro, NC WILLIAM M. LEWIS, JR., University of Colorado, Boulder JUDITH L. MEYER, University of Georgia, Athens DENNIS D. MURPHY, University of Nevada, Reno 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 KIMBERLY M. THOMPSON, Harvard School of Public Health, Boston, MA MARK J. UTELL, University of Rochester Medical Center, Rochester, NY Senior Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Scholar RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies EILEEN N. ABT, Senior Program Officer for Risk Analysis SUSAN N.J. MARTEL, Senior Program Officer for Toxicology KULBIR S. BAKSHI, Senior Program Officer ELLEN K. MANTUS, Senior Program Officer RUTH E. CROSSGROVE, Senior Editor 1 This study was planned, overseen, and supported by the Board on Environmental Stud- ies and Toxicology. vii

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OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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 (six volumes, 2000-2008) Toxicological Effects of Methylmercury (2000) Strengthening Science at the U.S. Environmental Protection Agency (2000) Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) viii

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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 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) 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), Vol- ume 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 re- sult of chemical spills, industrial explosions, fires, or accidents involving railroad cars and trucks transporting EHSs. Workers and residents in communities surround- ing industrial facilities where EHSs are manufactured, used, or stored and in com- munities along the nation’s railways and highways are potentially at risk of being exposed to airborne EHSs during accidental releases or intentional releases by ter- rorists. 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 estab- lishing 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 Expo- sure Guideline Levels for Hazardous Substances was published in 2001, providing updated procedures, methodologies, and other guidelines used by the National Ad- visory Committee (NAC) on Acute Exposure Guideline Levels for Hazardous Sub- stances and the Committee on Acute Exposure Guideline Levels (AEGLs) in devel- oping the AEGL values. Using the 1993 and 2001 NRC guidelines reports, the NAC—consisting of members from EPA, the U.S. Department of Defense (DOD), the U.S. Department of Energy (DOE), the U.S. 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 seventh volume in the series 2 As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986. xi

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xii Preface Acute Exposure Guideline Levels for Selected Airborne Chemicals. It reviews the AEGLs for acetone cyanohydrin, carbon disulfide, monochloroacetic acid, and phe- nol for scientific accuracy, completeness, and consistency with the NRC guideline reports. The committee’s review of the AEGL documents involved both oral and writ- ten presentations to the committee by the NAC authors of the documents. The committee examined the draft documents and provided comments and recommenda- tions 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 determina- tions have been made for an AEGL document, it is published as an appendix in a volume such as this one. Two interim reports of the committee that led to this report were reviewed in draft form by individuals selected for their diverse perspectives and technical exper- tise, in accordance with procedures approved by the NRC’s Report Review Com- mittee. 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 two of the com- mitttee’s interim reports, which summarize the committee’s conclusions and rec- ommendations for improving NAC’s AEGL documents for monochloroacetic acid and phenol (Thirteenth Interim Report of the Committee on Acute Exposure Guide- line Levels, 2005) and acetone cyanohydrin and carbon disulfide (Fourteenth In- terim Report of the Committee on Acute Exposure Guideline Levels, 2006): Deepak K. Bhalla (Wayne State University), David W. Gaylor (Gaylor and Associates, LLC), and Sam Kacew (University of Ottawa). Although the reviewers listed above have provided many constructive com- ments and suggestions, they were not asked to endorse the conclusions or recom- mendations, nor did they see the final draft of this volume before its release. The review of the interim report completed in 2005 was overseen by Sidney Green, Jr. (Howard University). The review of the interim report completed in 2006 was over- seen by Robert A. Goyer, professor emeritus, University of Western Ontario. Ap- pointed by the NRC, they were responsible for making certain that an independent examination of the interim reports were 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.). The committee acknowl-

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Preface xiii edges James J. Reisa, director of the Board on Environmental Studies and Toxicol- ogy, and Susan Martel, senior program officer for toxicology, for their helpful guid- ance. Kulbir Bakshi, project director for his work in this project, and Raymond Wassel for bringing the report to completion. Other staff members who contributed to this effort are Ruth Crossgrove (senior editor), Mirsada Karalic-Loncarevic (manager of the Technical Information Center), Radiah Rose (editorial projects manager), Aida Neel (program associate), and Korin Thompson (project assistant). 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

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Contents NATIONAL RESEARCH COUNCIL COMMITTEE REVIEW OF ACUTE EXPOSURE GUIDELINE LEVELS FOR SELECTED AIRBORNE CHEMICALS............................................................................... 3 ROSTER OF THE NATIONAL ADVISORY COMMITTEE FOR ACUTE EXPOSURE GUIDELINE LEVELS FOR HAZARDOUS SUBSTANCES ................................................................................................... 9 APPENDIXES 1 ACETONE CYANOHYDRIN............................................................... 13 Acute Exposure Guideline Levels 2 CARBON DISULFIDE .......................................................................... 50 Acute Exposure Guideline Levels 3 MONOCHLOROACETIC ACID ....................................................... 135 Acute Exposure Guideline Levels 4 PHENOL ............................................................................................... 178 Acute Exposure Guideline Levels xv

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