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REVIEW OF SUBMARINE ESCAPE ACTION LEVELS FOR SELECTED CHEMICALS

Subcommittee on Submarine Escape Action Levels

Committee on Toxicology

Board on Environmental Studies and Toxicology

Division on Earth and Life Studies

National Research Council

NATIONAL ACADEMY PRESS
WASHINGTON, D.C.



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Review of Submarine Escape Action Levels for Selected Chemicals REVIEW OF SUBMARINE ESCAPE ACTION LEVELS FOR SELECTED CHEMICALS Subcommittee on Submarine Escape Action Levels Committee on Toxicology Board on Environmental Studies and Toxicology Division on Earth and Life Studies National Research Council NATIONAL ACADEMY PRESS WASHINGTON, D.C.

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Review of Submarine Escape Action Levels for Selected Chemicals NATIONAL ACADEMY PRESS 2101 Constitution Ave., N.W. Washington, D.C. 20418 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. DAMD17-99-C-9049 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 0-309-08294-3 Additional copies of this report are available from: National Academy Press 2101 Constitution Ave., NW Box 285 Washington, DC 20055 800–624–6242 202–334–3313 (in the Washington metropolitan area) http://www.nap.edu Copyright 2002 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Review of Submarine Escape Action Levels for Selected Chemicals THE NATIONAL ACADEMIES National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council 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. Bruce M.Alberts 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. Wm.A.Wulf 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. Kenneth I.Shine 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. Bruce M.Alberts and Dr. Wm.A.Wulf are chairman and vice chairman, respectively, of the National Research Council.

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Review of Submarine Escape Action Levels for Selected Chemicals SUBCOMMITTEE ON SUBMARINE ESCAPE ACTION LEVELS Members CHARLES HOBBS (Chair), Lovelace Respiratory Research Institute, Albuquerque, New Mexico MICHAEL ASCHNER, Wake Forest University School of Medicine, Winston-Salem, North Carolina DAVID BELLINGER, Harvard Medical School, Boston, Massachusetts GERMAINE BUCK, National Institute of Child Health and Human Development, Bethesda, Maryland ARTHUR B.DUBOIS, Yale University School of Medicine, New Haven, Connecticut ALAN H.HALL, Texas Tech University Health Science Center—El Paso, El Paso, Texas FREDERICK JOHANNSEN, Solutia, Inc., St. Louis, Missouri DAVID MOORE, Battelle Memorial Institute, Bel Air, Maryland JOYCE TSUJI, Exponent, Bellevue, Washington Staff ABIGAIL STACK, Project Director EILEEN ABT, Program Officer SUSAN MARTEL, Program Officer KATE KELLY, Editor MIRSADA KARALIC-LONCAREVIC, Information Specialist EMILY SMAIL, Senior Program Assistant JESSICA BROCK, Project Assistant KELLY CLARK, Senior Editorial Assistant Sponsor U.S. DEPARTMENT OF DEFENSE

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Review of Submarine Escape Action Levels for Selected Chemicals COMMITTEE ON TOXICOLOGY Members BAILUS WALKER, JR. (Chair), Howard University Medical Center and American Public Health Association, Washington, D.C MELVIN E.ANDERSEN, Colorado State University, Fort Collins, Colorado GERMAINE M.BUCK, National Institute of Health, Washington, D.C ROBERT E.FORSTER II, University of Pennsylvania, Philadelphia, Pennsylvania WILLIAM E.HALPERIN, New Jersey Medical School, Newark, New Jersey. CHARLES H.HOBBS, Lovelace Respiratory Research Institute and Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico SAMUEL KACEW, University of Ottawa, Ottawa, Ontario NANCY KERKVLIET, Oregon State University, Corvallis, Oregon MICHAEL J.KOSNETT, University of Colorado Health Sciences Center, Denver, Colorado MORTON LIPPMANN, New York University School of Medicine, Tuxedo, New York ERNEST E.MCCONNELL, ToxPath, Inc., Raleigh, North Carolina THOMAS E.MCKONE, Lawrence Berkeley National Laboratory and University of California, Berkeley, California HARIHARA MEHENDALE, University of Louisiana at Monroe, Monroe, Louisiana DAVID H.MOORE, Battelle Memorial Institute, Bel Air, Maryland LAUREN ZEISE, California Environmental Protection Agency, Oakland, California Staff KULBIR S.BAKSHI, Program Director SUSAN N.J.MARTEL, Program Officer ABIGAIL E.STACK, Program Officer AIDA NEEL, Administrative Assistant JESSICA BROCK, Project Assistant

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Review of Submarine Escape Action Levels for Selected Chemicals BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members GORDON ORIANS (Chair), University of Washington, Seattle, Washington JOHN DOULL (Vice Chair), University of Kansas Medical Center, Kansas City, Kansas DAVID ALLEN, University of Texas, Austin, Texas INGRID C.BURKE, Colorado State University, Fort Collins, Colorado THOMAS BURKE, Johns Hopkins University, Baltimore, Maryland WILLIAM L.CHAMEIDES, Georgia Institute of Technology, Atlanta, Georgia CHRISTOPHER B.FIELD, Carnegie Institute of Washington, Stanford, California J.PAUL GILMAN, Celera Genomics, Rockville, Maryland DANIEL S.GREENBAUM, Health Effects Institute, Cambridge, Massachusetts BRUCE D.HAMMOCK, University of California, Davis, California ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New Mexico CAROL HENRY, American Chemistry Council, Arlington, Virginia ROBERT HUGGETT, Michigan State University, East Lansing, Michigan JAMES H.JOHNSON, Howard University, Washington, D.C JAMES F.KITCHELL, University of Wisconsin, Madison, Wisconsin DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario JAMES A.MACMAHON, Utah State University, Logan, Utah WILLEM F.PASSCHIER, Health Council of the Netherlands, The Hague ANN POWERS, Pace University School of Law, White Plains, New York LOUISE M.RYAN, Harvard University, Boston, Massachusetts KIRK SMITH, University of California, Berkeley, California LISA SPEER, Natural Resources Defense Council, New York, New York Senior Staff JAMES J.REISA, Director DAVID J.POLICANSKY, Associate Director and Senior Program Director for Applied Ecology RAYMOND A.WASSEL, Senior Program Director for Environmental Sciences and Engineering KULBIR BAKSHI, Program Director for the Committee on Toxicology ROBERTA M.WEDGE, Program Director for Risk Analysis K.JOHN HOLMES, Senior Staff Officer RUTH E.CROSSGROVE, Managing Editor 1   This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.

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Review of Submarine Escape Action Levels for Selected Chemicals OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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) Toxicological Effects of Methylmercury (2000) Strengthening Science at the U.S. Environmental Protection Agency: Research-Management and Peer-Review Practices (2000) Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) Modeling Mobile-Source Emissions (2000) Toxicological Risks of Selected Flame-Retardant Chemicals (2000) Copper in Drinking Water (2000) Ecological Indicators for the Nation (2000) Waste Incineration and Public Health (1999) Hormonally Active Agents in the Environment (1999) Research Priorities for Airborne Paniculate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); II. Evaluating Research Progress and Updating the Portfolio (1999); III. Early Research Progress (2001) Ozone-Forming Potential of Reformulated Gasoline (1999) Risk-Based Waste Classification in California (1999) Arsenic in Drinking Water (1999) Brucellosis in the Greater Yellowstone Area (1998) 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 (5 reports, 1989–1995) Review of EPA’s Environmental Monitoring and Assessment Program (3 reports, 1994–1995) Science and Judgment in Risk Assessment (1994) Ranking Hazardous Waste Sites for Remedial Action (1994) Pesticides in the Diets of Infants and Children (1993) Setting Priorities for Land Conservation (1993) Protecting Visibility in National Parks and Wilderness Areas (1993) Dolphins and the Tuna Industry (1992) Science and the National Parks (1992) Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I–IV (1991–1993)

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Review of Submarine Escape Action Levels for Selected Chemicals 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 Academy Press (800) 624–6242 or (202) 334–3313 www.nap.edu

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Review of Submarine Escape Action Levels for Selected Chemicals OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY 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) 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) Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994), Volume 2 (1996), Volume 3 (1996), Volume 4 (2000)

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Review of Submarine Escape Action Levels for Selected Chemicals Preface The United States Navy seeks to protect crew members in disabled submarines from toxic effects caused by exposure to high concentrations of 8 gases: ammonia, carbon monoxide, hydrogen chloride, hydrogen cyanide, hydrogen sulfide, nitrogen dioxide, sulfur dioxide, and chlorine. The toxic effects resulting from exposure to the gases could impede crew members’ ability to escape after a serious accident. On-board fires would be anticipated as the principal sources of the first 7 gases; chlorine gas could be generated by the contact of seawater with a submarine’s batteries. The Navy Health Research Center’s Toxicology Detachment has proposed submarine escape action levels (SEALs)—concentrations above which crew members’ health and ability to escape could be jeopardized—for each gas. The Navy requested that the National Research Council (NRC) review independently the available toxicologic and epidemiologic data on the gases in question and evaluate the scientific validity of the Navy’s proposed SEALs. The NRC assigned the project to its Committee on Toxicology, and assembled the Subcommittee on Submarine Escape Action Levels to prepare this report. The subcommittee thanks Captain Kenneth Still (U.S. Navy), Commander Wayne Horn (U.S. Navy), and Lieutenant Cody Wilson (U.S. Naval Reserve) for their support of this project and for providing valuable background information. We also wish to express our gratitude to Dr. Paul Weathersby (U.S. Navy, Retired) and to Dr. Stephen Borron (International Toxicology Consultants) for providing information.

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Review of Submarine Escape Action Levels for Selected Chemicals The subcommittee visited the nuclear attack submarine, USS Dallas, docked at the Navy’s submarine base in Groton, Connecticut. Several members of the USS Dallas’s crew were helpful in giving a crew’s perspective on conditions aboard a submarine. The subcommittee members found the tour to be valuable to its work. This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC 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: Stephen Borron, International Toxicology Consultants, Washington, District of Columbia; Aaron Cohen, Health Effects Institute, Cambridge, Massachusetts; David Dorman, CIIT Centers for Health Research, Research Triangle Park, North Carolina; Robert Phalen, University of California, Irvine, California; and Nga Tran, Johns Hopkins School of Public Health, Baltimore, Maryland. Although the reviewers provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Joseph Borzelleca, Medical College of Virginia, Richmond, Virginia, who was appointed by NRC to ensure that an independent examination of this report was conducted 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. We are also grateful for the assistance of members of the NRC staff in the preparation of this report. The subcommittee acknowledges Abigail Stack, project director, and Kulbir Bakshi, program director of the Committee on Toxicology. Other staff members contributing to this report were James Reisa, director of the Board on Environmental Studies and Toxicology, Roberta Wedge, senior program officer; Eileen Abt, program officer; Susan Martel, program officer; Ruth Crossgrove, managing editor; Emily Smail, senior program assistant; and Jessica Brock, project assistant; and Kelly Clark, senior editorial assistant.

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Review of Submarine Escape Action Levels for Selected Chemicals Finally, we thank all members of the subcommittee for their expertise and dedicated effort throughout the study. Charles Hobbs, D.V.M Chair, Subcommittee on Submarine Escape Action Levels Bailus Walker Jr., Ph.D., M.P.H. Chair, Committee on Toxicology

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Review of Submarine Escape Action Levels for Selected Chemicals Contents     Summary   1 1   Introduction   7     Statement of Task,   10     Definitions of SEALs,   10     The On-board Population,   11     The Submarine Atmosphere,   12     The Navy’s Instructions for the Management of Toxic Gases,   13     The Subcommittee’s Approach to its Charge,   13     Comparison Between SEALs and Existing Exposure Guidance Levels,   19     Organization of the Report,   20     References,   20 2   Ammonia   22     Background Information,   22     Toxicokinetic Considerations,   24     Human Toxicity Data,   28     Experimental Animal Toxicity Data,   42     Navy’s Recommended SEALs,   58     Additional Recommendations from the NRC and Other Organizations,   58

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Review of Submarine Escape Action Levels for Selected Chemicals     Subcommittee Analysis and Recommendations,   58     Data Gaps and Research Needs,   61     References,   62 3   Carbon Monoxide   69     Background Information,   69     Toxicokinetic Considerations,   70     Human Toxicity Data,   71     Experimental Animal Toxicity Data,   82     Navy’s Recommended SEALs,   87     Additional Recommendations from the NRC and Other Organizations,   87     Subcommittee Analysis and Recommendations,   87     Data Gaps and Research Needs,   91     References,   91 4   Chlorine   97     Background Information,   97     Toxicokinetic Considerations,   98     Human Toxicity Data,   99     Experimental Animal Toxicity Data,   111     Mechanism of Action,   112     Navy’s Recommended SEALs,   113     Additional Recommendations from the NRC and Other Organizations,   123     Subcommittee Analysis and Recommendations,   123     Data Gaps and Research Needs,   125     References,   125 5   Hydrogen Chloride   132     Background Information,   132     Toxicokinetic Considerations,   133     Human Toxicity Data,   134     Experimental Animal Toxicity Data,   136     Navy’s Recommended SEALs,   147     Additional Recommendations from the NRC and Other Organizations,   147

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Review of Submarine Escape Action Levels for Selected Chemicals     Subcommittee Analysis and Recommendations,   147     Data Gaps and Research Needs,   149     References,   150 6   Hydrogen Cyanide   153     Background Information,   153     Toxicokinetic Considerations,   155     Human Toxicity Data,   158     Experimental Animal Toxicity Data,   163     Navy’s Recommended SEALs,   170     Additional Recommendations from the NRC and Other Organizations,   171     Subcommittee Analysis and Recommendations,   171     Data Gaps and Research Needs,   173     References,   173 7   Hydrogen Sulfide   178     Background Information,   178     Toxicokinetic Considerations,   180     Human Toxicity Data,   183     Experimental Animal Toxicity Data,   198     Other Considerations,   208     Navy’s Recommended SEALs,   209     Additional Recommendations from the NRC and Other Organizations,   209     Subcommittee Analysis and Recommendations,   212     Data Gaps and Research Needs,   213     References,   213 8   Nitrogen Dioxide   219     Background Information,   219     Toxicokinetic Considerations,   221     Human Toxicity Data,   222     Experimental Animal Toxicity Data,   229     Navy’s Recommended SEALs,   239     Additional Recommendations from Other Organizations,   239     Subcommittee Analysis and Recommendations,   239

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Review of Submarine Escape Action Levels for Selected Chemicals     Data Gaps and Research Needs,   241     References,   241 9   Sulfur Dioxide   248     Background Information,   248     Toxicokinetic Considerations,   249     Human Toxicity Data,   253     Experimental Animal Toxicity Data,   269     Mechanism of Action,   277     Navy’s Recommended SEALs,   278     Additional Recommendations from the NRC and Other Organizations,   278     Subcommittee Analysis and Recommendations,   278     Data Gaps and Research Needs,   281     References,   281 10   Conclusions and Recommendations   288

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Review of Submarine Escape Action Levels for Selected Chemicals Review of Submarine Escape Action Levels for Selected Chemicals

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