Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants

VOLUME 3

Committee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants

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 Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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 W81K04-06-D-0023 between the National Academy of Sciences and the U.S. Department of Defense. Any opinions, findings, conclusions, or recommenda- tions expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number 13: 978-0-309-14379-0 International Standard Book Number 10: 0-309-14379-9 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 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 Na- tional 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 further- ing 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 adminis- tered 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 EMERGENCY AND CONTINUOUS EXPOSURE GUIDANCE LEVELS FOR SELECTED SUBMARINE CONTAMINANTS Members DAVID DORMAN (Chair), North Carolina State University, Raleigh REBECCA BASCOM, Pennsylvania State University College of Medicine, Hershey DAROL DODD, The Hamner Institutes for Health Sciences, Research Triangle Park, NC WANDA HASCHEK-HOCK, University of Illinois at Urbana-Champaign, Urbana JAMES LOCKEY, University of Cincinnati College of Medicine, Cincinnati, OH JOHN MORRIS, University of Connecticut School of Pharmacy, Storrs JOHN O’DONOGHUE, University of Rochester School of Medicine and Dentistry, Rochester, NY ANDREW SALMON, California Environmental Protection Agency, Oakland KATHLEEN THIESSEN, SENES Oak Ridge, Inc., Oak Ridge, TN JOYCE TSUJI, Exponent Environmental Group, Inc., Bellevue, WA Staff ELLEN MANTUS, Project Director NORMAN GROSSBLATT, Senior Editor HEIDI MURRAY-SMITH, Associate Program Officer MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center KORIN THOMPSON, Program Assistant (up to November 2008) PANOLA GOLSON, Senior Program Assistant Sponsor U.S. DEPARTMENT OF DEFENSE 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 JOYCE TSUJI, Exponent, Inc., Bellevue, WA 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 ROSE, Editorial Projects Manager vi

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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY Members ROGENE F. HENDERSON (Chair), Lovelace Respiratory Research Institute, Albuquerque, NM RAMON ALVAREZ, Environmental Defense Fund, Austin, TX  TINA BAHADORI, American Chemistry Council, Arlington, VA JOHN M. BALBUS, George Washington University, Washington, DC MICHAEL J. BRADLEY, M.J. Bradley & Associates, Concord, MA DALLAS BURTRAW, Resources for the Future, Washington, DC JAMES S. BUS, Dow Chemical Company, Midland, MI JONATHAN Z. CANNON, University of Virginia, Charlottesville GAIL CHARNLEY, HealthRisk Strategies, Washington, DC RUTH DEFRIES, Columbia University, New York, NY RICHARD A. DENISON, Environmental Defense Fund, Washington, DC H. CHRISTOPHER FREY, North Carolina State University, Raleigh J. PAUL GILMAN, Covanta Energy Corporation, Fairfield, NJ RICHARD M. GOLD, Holland & Knight, LLP, Washington, DC LYNN R. GOLDMAN, Johns Hopkins University, Baltimore, MD JUDITH A. GRAHAM (retired), Pittsboro, NC HOWARD HU, University of Michigan, Ann Harbor ROGER E. KASPERSON, Clark University, Worcester, MA TERRY L. MEDLEY, E. I. du Pont de Nemours & Company, Wilmington, DE DANNY D. REIBLE, University of Texas, Austin JOSEPH V. RODRICKS, ENVIRON International Corporation, Arlington, VA 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 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 vii

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OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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 (seven volumes, 2000-2009) 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 the 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) 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), Volume 5 (2008) x

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Preface A submarine is an enclosed and isolated environment when submerged. Its crew works, eats, and sleeps in this environment and is exposed to air contami- nants 24 h/day, unlike workers in a typical occupational environment, who have a respite from workplace exposures at the end of the workday or workweek. To protect the health of submariners, the U.S. Navy has developed 1-h and 24-h emergency exposure guidance levels (EEGLs) and 90-day continuous exposure guidance levels (CEGLs) for a number of chemical contaminants. In 1995, the Navy began reviewing and updating submarine exposure guidance levels and asked the Committee on Toxicology (COT) of the National Research Council (NRC) to conduct an independent review of several chemi- cals. As a result of the Navy's initial request, NRC convened a committee that reviewed and published two reports on 21 chemicals. As a follow-on activity to that work, the Navy requested review of an additional five chemicals. Accord- ingly, this third volume provides the committee’s rationale and recommenda- tions for EEGLs and CEGLs for acetaldehyde, hydrogen chloride, hydrogen fluoride, hydrogen sulfide, and propylene glycol dinitrate. This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures ap- proved by 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 of 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 thank the following for their review of this report: John R. Balmes, University of California, San Francisco; Alan H. Hall, Toxicology Consulting and Medical Translating Services, Inc.; Wendy J. Heiger-Bernays, Boston University School of Public Health; Charles H. Hobbs, Lovelace Respiratory Research Institute; Nu-May Ruby Reed, California Envi- ronmental Protection Agency; Laura Van Winkle, University of California, Davis; and James G. Wagner, Michigan State University. xi

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xii Preface 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 the report was overseen by E. Eugene McConnell, ToxPath, Inc. Appointed by NRC, he was responsible for making certain that an independent examination of the report was carried out in accordance with institutional proce- dures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the committee and the insti- tution. The committee is grateful for the assistance of the NRC staff in preparing this report: Ellen Mantus, project director; James Reisa, director of the Board on Environmental Studies and Toxicology; Heidi Murray-Smith, associate program officer; Mirsada Karalic-Loncarevic, manager, Technical Information Center; Norman Grossblatt, senior editor; Korin Thompson, program assistant (up to November 2008); and Panola Golson, senior program assistant. Finally, I thank the members of the committee for their dedicated efforts throughout the devel- opment of this report. David Dorman, Chair Committee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants

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Contents SUMMARY ...................................................................................................................... 3 1 INTRODUCTION ........................................................................................... 8 The Committee’s Charge, 8 Population Characteristics, 9 The Submarine Environment, 10 The Committee’s Approach to Its Charge, 13 Organization of Report, 17 References, 17 2 ACETALDEHYDE ........................................................................................ 20 Physical and Chemical Properties, 20 Occurrence and Use, 20 Summary of Toxicity, 22 Toxicokinetic and Mechanistic Considerations, 31 Inhalation Exposure Levels from the National Research Council and Other Organizations, 33 Committee Recommendations, 33 Carcinogenicity Assessment, 38 Data Adequacy and Research Needs, 39 References, 40 3 HYDROGEN CHLORIDE ............................................................................ 46 Physical and Chemical Properties, 46 Occurrence and Use, 47 Summary of Toxicity, 47 Toxicokinetic and Mechanistic Considerations, 59 Inhalation Exposure Levels from the National Research Council and Other Organizations, 60 Committee Recommendations, 60 Data Adequacy and Research Needs, 65 References, 65 4 HYDROGEN FLUORIDE............................................................................. 70 Physical and Chemical Properties, 70 Occurrence and Use, 70 xiii

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xiv Contents Summary of Toxicity, 71 Toxicokinetic and Mechanistic Considerations, 93 Inhalation Exposure Levels from the National Research Council and Other Organizations, 95 Committee Recommendations, 95 Data Adequacy and Research Needs, 101 References, 102 5 HYDROGEN SULFIDE ............................................................................. 110 Physical and Chemical Properties, 110 Occurrence and Use, 110 Summary of Toxicity, 111 Toxicokinetic and Mechanistic Considerations, 124 Inhalation Exposure Levels from the National Research Council and other Organizations, 128 Committee Recommendations, 128 Data Adequacy and Research Needs, 132 References, 133 6 PROPYLENE GLYCOL DINITRATE ...................................................... 139 Physical and Chemical Properties, 139 Occurrence and Use, 139 Summary of Toxicity, 140 Toxicokinetic and Mechanistic Considerations, 151 Inhalation Exposure Levels from the National Research Council and Other Organizations, 154 Committee Recommendations, 154 Data Adequacy and Research Needs, 157 References, 157 APPENDIX A ............................................................................................................... 160 APPENDIX B ............................................................................................................... 164 GLOSSARY .................................................................................................................. 165 TABLES AND FIGURES TABLES S-1 Comparison of U.S. Navy’s Current Exposure Guidance Levels with Those Recommended by the Committee, 6 1-1 Characteristics of Crew and Patrols for U.S. Navy Nuclear-Powered Submarines, 11 2-1 Physical and Chemical Properties of Acetaldehyde, 21 2-2 Selected Inhalation Exposure Levels for Acetaldehyde from the National Research Council and Other Agencies, 34

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Contents xv 2-3 Emergency and Continuous Exposure Guidance Levels for Acetaldehyde, 34 3-1 Physical and Chemical Properties of Hydrogen Chloride, 47 3-2 Hydrogen Chloride: Human Exposure Studies, 52 3-3 Selected Inhalation Exposure Levels for Hydrogen Chloride from the National Research Council and Other Agencies, 61 3-4 Emergency and Continuous Exposure Guidance Levels for Hydrogen Chloride, 63 4-1 Physical and Chemical Properties of Hydrogen Fluoride, 71 4-2 Effects of Hydrogen Fluoride in Controlled Human Studies, 75 4-3 Summary of Selected Endocrine Effects Associated with Oral Fluoride Exposure in Humans, 81 4-4 Effects of Hydrogen Fluoride in 6-Hour or Longer Animal Studies, 86 4-5 Summary of Results of Positive Genotoxic Studies of Fluoride, 92 4-6 Selected Inhalation Exposure Levels for Hydrogen Fluoride from the National Research Council and Other Agencies, 96 4-7 Emergency and Continuous Exposure Guidance Levels for Hydrogen Fluoride, 96 4-8 Summary of Systemic Effects in Humans Associated with Chronic Intake of Fluoride from All Sources, 100 4-9 Estimated Fluoride Intakes (mg/kg-day) for Specified Exposure Situations, 101 5-1 Physical and Chemical Properties of Hydrogen Sulfide, 111 5-2 Hydrogen Sulfide-Induced Effects Observed in People, 119 5-3 Summary of Rat and Mouse LC50s, 120 5-4 Selected Inhalation Exposure Levels for Hydrogen Sulfide from the National Research Council and Other Agencies, 129 5-5 Emergency and Continuous Exposure Guidance Levels for Hydrogen Sulfide, 130 6-1 Physical and Chemical Properties of Propylene Glycol Dinitrate, 140 6-2 Selected Inhalation Exposure Levels for Propylene Glycol Dinitrate from the National Research Council and Other Agencies, 155 6-3 Emergency and Continuous Exposure Guidance Levels for Propylene Glycol Dinitrate, 155 FIGURES 1-1 Generalized schematic of a nuclear-powered attack submarine, 12 2-1 Calculation of the acetaldehyde reference concentration by Dorman et al. (2008), 37

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