Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Initial Report

Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations

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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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Initial Report Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations 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, D.C. 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, 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. International Standard Book Number-13: 978-0-309-11366-3 International Standard Book Number-10: 0-309-11366-0 Additional copies of this report are available from The National Academies Press 500 Fifth Street, NW Box 285 Washington, DC 20001 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.edu Copyright 2008 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 responsibility 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 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 COMBINED EXPOSURES TO HYDROGEN CYANIDE AND CARBON MONOXIDE IN ARMY OPERATIONS Members WILLIAM E. HALPERIN (Chair), UMDNJ–New Jersey Medical School, Newark GARY P. CARLSON, Purdue University, West Lafayette, IN RONALD F. COBURN, University of Pennsylvania School of Medicine, Philadelphia JAMES E. DENNISON, Century Environmental Hygiene, LLC, Fort Collins, CO JEFFREY W. FISHER, University of Georgia, Athens CHIU-WING LAM, Wyle Laboratories JSC Toxicology Group, Houston, TX JAMES J. MCGRATH, Texas Tech Health University Sciences Center, Lubbock GEORGE C. RODGERS, University of Louisville, Louisville, KY SYLVIA S. TALMAGE, Oak Ridge National Laboratory, Oak Ridge, TN Staff KULBIR S. BAKSHI, Senior Program Officer AIDA NEEL, Program Associate RADIAH ROSE, Senior Editorial Assistant v

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COMMITTEE ON TOXICOLOGY Members WILLIAM E. HALPERIN (Chair), UMDNJ–New Jersey Medical School, Newark LAWRENCE S. BETTS, Eastern Virginia Medical School, Norfolk EDWARD C. BISHOP, HDR Engineering, Inc., Omaha, NE JAMES V. BRUCKNER, University of Georgia, Athens GARY P. CARLSON, Purdue University, West Lafayette, IN MARION F. EHRICH, Virginia Polytechnic Institute and State University, Blacksburg SIDNEY GREEN, Howard University, Washington, DC 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 EILEEN N. ABT, Senior Program Officer for Risk Analysis KULBIR S. BAKSHI, Senior Program Officer ELLEN K. MANTUS, Senior Program Officer SUSAN N. J. MARTEL, Senior Program Officer for Toxicology JENNIFER SAUNDERS, Associate Program Officer AIDA NEEL, Program Associate MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center TAMARA DAWSON, Senior Program Assistant RADIAH ROSE, Senior Editorial Assistant vi

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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members JONATHAN M. SAMET (Chair), Johns Hopkins University, Baltimore, MD RAMON ALVAREZ, Environmental Defense, Austin, TX JOHN M. BALBUS, Environmental Defense, Washington, DC DALLAS BURTRAW, Resources for the Future, Washington, DC JAMES S. BUS, Dow Chemical Company, Midland, MI RUTH DEFRIES, University of Maryland, College Park COSTEL D. DENSON, University of Delaware, Newark E. DONALD ELLIOTT, Willkie Farr & Gallagher LLP, Washington, DC MARY R. ENGLISH, University of Tennessee, Knoxville J. PAUL GILMAN, Oak Ridge Center for Advanced Studies, Oak Ridge, TN SHERRI W. GOODMAN, Center for Naval Analyses, Alexandria, VA JUDITH A. GRAHAM, American Chemistry Council, Arlington, VA WILLIAM P. HORN, Birch, Horton, Bittner and Cherot, Washington, DC WILLIAM M. LEWIS, JR., University of Colorado, Boulder JUDITH L. MEYER, University of Georgia, Athens DENNIS D. MURPHY, University of Nevada, Reno PATRICK Y. O’BRIEN, ChevronTexaco Energy Technology Company, Richmond, CA DOROTHY E. PATTON (retired), Chicago, IL DANNY D. REIBLE, University of Texas, Austin JOSEPH V. RODRICKS, ENVIRON International Corporation, Arlington, VA ARMISTEAD G. RUSSELL, Georgia Institute of Technology, Atlanta ROBERT F. SAWYER, University of California, Berkeley KIMBERLY M. THOMPSON, Massachusetts Institute of Technology, Cambridge MONICA G. TURNER, University of Wisconsin, Madison MARK J. UTELL, University of Rochester Medical Center, Rochester, NY CHRIS G. WHIPPLE, ENVIRON International Corporation, Emeryville, CA LAUREN ZEISE, California Environmental Protection Agency, Oakland Senior Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Scholar RAYMOND A. WASSEL, Senior Program Officer for Environmental Sciences and Engineering EILEEN N. ABT, Senior Program Officer for Risk Analysis SUSAN N.J. MARTEL, Senior Program Officer for Toxicology KULBIR 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 Studies and Toxicology. vii

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OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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 (five volumes, 2000-2007) 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) Review of EPA's Environmental Monitoring and Assessment Program (three volumes, 1994-1995) Science and Judgment in Risk Assessment (1994) Pesticides in the Diets of Infants and Children (1993) Dolphins and the Tuna Industry (1992) Science and the National Parks (1992) Human Exposure Assessment for Airborne Pollutants (1991) Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991) Decline of the Sea Turtles (1990) Copies of these reports may be ordered from the National Academies Press (800) 624-6242 or (202) 334-3313 www.nap.edu viii

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OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, Volume 1 (2007), Volume 2 (2007) 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) 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 (2007) Review of the US Navy’s Human Health Risk Assessment of the Naval Air Facility at Atsugi, Japan (2000) Methods for Developing Spacecraft Water Exposure Guidelines (2000) Review of the U.S. Navy Environmental Health Center’s Health-Hazard Assessment Process (2000) Review of the U.S. Navy’s Exposure Standard for Manufactured Vitreous Fibers (2000) Re-Evaluation of Drinking-Water Guidelines for Diisopropyl Methylphosphonate (2000) Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23, and HFC-404a (2000) Review of the U.S. Army’s Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) Toxicity of Military Smokes and Obscurants, Volume 1(1997), Volume 2 (1999), Volume 3 (1999) Assessment of Exposure-Response Functions for Rocket-Emission Toxicants (1998) Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (1996) Permissible Exposure Levels for Selected Military Fuel Vapors (1996) Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994), Volume 2 (1996), Volume 3 (1996), Volume 4 (2000) ix

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Preface In support of the Health Hazard Assessment (HHA) for armored vehicles, the U.S. Army’s Center for Health Promotion and Preventive Medicine (CHPPM) performed weapons-emissions testing for various firing scenarios. CHPPM evaluated emissions of carbon monoxide, hydrogen cyanide, oxides of nitrogen, sulfur dioxide, ammonia, and carbon dioxide. Generally, CHPPM evaluates the concentrations of these gases against the permissible exposure limits established by various agencies and organizations. Because military personnel in armored vehicles will be exposed to a mixture of gases, concerns were raised about potential additive or synergistic toxic effects, specifically the combined effects of simultaneous exposures to hydrogen cyanide and carbon monoxide, because both gases produce similar toxic effects. Because of these concerns, the Army prepared a report that provides guidance on assessing combined exposures to low levels of carbon monoxide and hydrogen cyanide. The Department of Defense (DOD) then requested that the National Research Council (NRC) independently evaluate the Army’s proposed guidance on assessing combined exposures to hydrogen cyanide and carbon monoxide and recommend exposure limit guidelines for combined exposures to these chemicals. The NRC was asked to prepare two reports. For the initial report, the task was to determine whether the hazard presented from simultaneous exposures to hydrogen cyanide and carbon monoxide warrants a combined exposure assessment, and if so, whether the use of the hazard quotient approach is a reasonable method of assessment. The committee’s second report, to be completed next year, will address the remainder of the task assigned to it (the complete statement of task is described in the summary of the report). In response to DOD’s request, the NRC convened the Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations. The members of the committee were selected by the NRC for their expertise in occupational health and medicine, physiology, pharmacokinetics, toxicology, inhalation toxicology, epidemiology, physiologically-based pharmacokinetic modeling, and risk assessment. Biographical information on the committee members is provided in the Appendix. A draft of this initial report was reviewed by individuals selected for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: Robert Goyer, University of Western Ontario; Sam Kacew, University of Ottawa; David Macys, Island County Health Department; and Deepak Bhalla, Wayne State University. Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Edward Bishop, HDR Engineering, Inc., appointed by the Division on Earth and Life Studies, who was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all xi

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xii Preface 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: Glenn Leach, Mathew Bazaar, Steve Kistner, and Col. John Rowe (all from the U.S. Army, Department of Defense). We are grateful to James J. Reisa, director of the Board on Environmental Studies and Toxicology (BEST), for his helpful comments. Other staff members who contributed to this effort are Ruth Crossgrove, senior editor; Aida Neel, program associate and Radiah Rose, senior editorial assistant. The committee particularly acknowledges Kulbir Bakshi, project director for the committee, for bringing the report to completion. Finally, we would like to thank all members of the committee for their expertise and dedicated effort throughout the development of this report. William E. Halperin, Chair Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations

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Contents Summary ....................................................................................................................................................... 1 1 Introduction .......................................................................................................................................... 4 2 Mechanisms of Carbon Monoxide and Hydrogen Cyanide Toxicity................................................... 7 3 A Brief Review of Hydrogen Cyanide and Carbon Monoxide Toxicity.............................................. 9 4 Summary of the Effects of Combined Exposure to Carbon Monoxide and Hydrogen Cyanide and Recommendation for Combined-Exposure Risk Assessment................................................................................................................................. 11 5 Pharmacokinetics and Mathematical Modeling for Assessing Toxicity of Mixtures of Chemicals................................................................................................................... 13 6 Appropriateness of Measurement of Blood or Air Levels of Cyanide............................................... 16 7 Conclusions and Recommendations................................................................................................... 18 References................................................................................................................................................... 20 Appendix Biographic Information on the Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations........................................................ 23 xiii

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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Initial Report

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