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i SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUORO- CARBONS HFC-236fa, HFC-23, and HFC-404a Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons Committee on Toxicology Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C.
ii 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 Nos. DAMD 17-89-C-9086 and DAMD 17-99-C-9049 between the National Academy of Sciences and the U.S. Department of Defense. Any opinions, find- ings, 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 0-309-07084-8 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 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America
iii 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. William 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. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council. www.national-academies.org
v SUBCOMMITTEE ON EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS GARY CARLSON (Chair), Purdue University, West Lafayette, Indiana MARION W. ANDERS, University of Rochester, Rochester, New York DAROL E. DODD, ManTech Environmental Technology, Inc., Dayton, Ohio HARIHARA M. MEHENDALE, Northeast Louisiana University, Monroe, Louisiana CHARLES REINHARDT, Chadds Ford, Pennsylvania ANNETTE SHIPP, The K.S. Crump Group, Inc., Ruston, Louisiana MARY VORE, University of Kentucky, Lexington, Kentucky ROBERT YOUNG, Oak Ridge National Laboratory, Oak Ridge, Tennessee Staff SUSAN N.J. PANG, Project Director RUTH E. CROSSGROVE, Editor MIRSADA KARALIC-LONCAREVIC, Information Specialist LEAH L. PROBST, Project Assistant EMILY L. SMAIL, Project Assistant Sponsor U.S. NAVY
vi COMMITTEE ON TOXICOLOGY BAILUS WALKER, JR. (Chair), Howard University Medical Center, Washington, D.C. MELVIN E. ANDERSEN, Colorado State University, Denver, Colorado GERMAINE M. BUCK, State University of New York at Buffalo GARY P. CARLSON, Purdue University, West Lafayette, Indiana JACK H. DEAN, Sanofi Pharmaceuticals, Inc., Malverne, Pennsylvania ROBERT E. FORSTER II, University of Pennsylvania, Philadelphia, Pennsylvania PAUL M.D. FOSTER, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina DAVID W. GAYLOR, U.S. Food and Drug Administration, Jefferson, Arkansas JUDITH A. GRAHAM, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina SIDNEY GREEN, Howard University, Washington, D.C. WILLIAM E. HALPERIN, National Institute for Occupational Safety and Health, Cincinnati, Ohio CHARLES H. HOBBS, Lovelace Respiratory Research Institute and Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico FLORENCE K. KINOSHITA, Hercules Incorporated, Wilmington, Delaware MICHAEL J. KOSNETT, University of Colorado Health Sciences Center, Denver, Colorado MORTON LIPPMANN, New York University School of Medicine, Tuxedo, New York THOMAS E. MCKONE, University of California, Berkeley, California ERNEST E. MCCONNELL, ToxPath, Inc., Raleigh, North Carolina DAVID H. MOORE, Battelle Memorial Institute, Bel Air, Maryland GÃNTER OBERDÃRSTER, University of Rochester, Rochester, New York JOHN L. O'DONOGHUE, Eastman Kodak Company, Rochester, New York GEORGE M. RUSCH, AlliedSignal, Inc., Morristown, New Jersey MARY E. VORE, University of Kentucky, Lexington, Kentucky ANNETTA P. WATSON, Oak Ridge National Laboratory, Oak Ridge, Tennessee Staff KULBIR S. BAKSHI, Program Director SUSAN N.J. PANG, Program Officer ABIGAIL STACK, Program Officer RUTH E. CROSSGROVE, Publications Manager KATHRINE J. IVERSON, Manager, Toxicology Information Center EMILY L. SMAIL, Project Assistant
vii BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY GORDON ORIANS (Chair), University of Washington, Seattle, Washington DONALD MATTISON (Vice Chair), March of Dimes, White Plains, New York DAVID ALLEN, University of Texas, Austin, Texas INGRID C. BURKE, Colorado State University, Fort Collins, Colorado WILLIAM L. CHAMEIDES, Georgia Institute of Technology, Atlanta, Georgia JOHN DOULL, University of Kansas Medical Center, Kansas City, Kansas CHRISTOPHER B. FIELD, Carnegie Institute of Washington, Stanford, California JOHN GERHART, University of California, Berkeley, California J. PAUL GILMAN, Celera Genomics, Rockville, Maryland BRUCE D. HAMMOCK, University of California, Davis, California MARK HARWELL, University of Miami, Miami, Florida ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New Mexico CAROL HENRY, Chemical Manufacturers Association, Arlington, Virginia BARBARA HULKA, University of North Carolina, Chapel Hill, North Carolina JAMES F. KITCHELL, University of Wisconsin, Madison, Wisconsin DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario JAMES A. MACMAHON, Utah State University, Logan, Utah MARIO J. MOLINA, Massachusetts Institute of Technology, Cambridge, Massachusetts CHARLES O'MELIA, Johns Hopkins University, Baltimore, Maryland WILLEM F. PASSCHIER, Health Council of the Netherlands KIRK SMITH, University of California, Berkeley, California MARGARET STRAND, Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C. TERRY F. YOSIE, Chemical Manufacturers Association, Arlington, Virginia JAMES J. REISA, Director DAVID J. POLICANSKY, Associate Director and Senior Program Director for Applied Ecology CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and Engineering KULBIR BAKSHI, Program Director for the Committee on Toxicology LEE R. PAULSON, Program Director for Resource Management ROBERTA M. WEDGE, Program Director for Risk Analysis
viii COMMISSION ON LIFE SCIENCES MICHAEL T. CLEGG (Chair), University of California, Riverside, California PAUL BERG (Vice Chair), Stanford University, Stanford, California FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOANNA BURGER, Rutgers University, Piscataway, New Jersey JAMES E. CLEAVER, University of California, San Francisco, California DAVID EISENBERG, University of California, Los Angeles, California JOHN EMMERSON, Fishers, Indiana NEAL FIRST, University of Wisconsin, Madison, Wisconsin DAVID J. GALAS, Keck Graduate Institute of Applied Life Science, Claremont, California DAVID V. GOEDDEL, Tularik, Inc., South San Francisco, California ARTURO GOMEZ-POMPA, University of California, Riverside, California COREY S. GOODMAN, University of California, Berkeley, California JON W. GORDON, Mount Sinai School of Medicine, New York, New York DAVID G. HOEL, Medical University of South Carolina, Charleston, South Carolina BARBARA S. HULKA, University of North Carolina, Chapel Hill, North Carolina CYNTHIA KENYON, University of California, San Francisco, California BRUCE R. LEVIN, Emory University, Atlanta, Georgia DAVID LIVINGSTON, Dana-Farber Cancer Institute, Boston, Massachusetts DONALD R. MATTISON, March of Dimes, White Plains, New York ELLIOT M. MEYEROWITZ, California Institute of Technology, Pasadena, California ROBERT T. PAINE, University of Washington, Seattle, Washington RONALD R. SEDEROFF, North Carolina State University, Raleigh, North Carolina ROBERT R. SOKAL, State University of New York, Stony Brook, New York CHARLES F. STEVENS, The Salk Institute, La Jolla, California SHIRLEY M. TILGHMAN, Princeton University, Princeton, New Jersey RAYMOND L. WHITE, University of Utah, Salt Lake City, Utah WARREN R. MUIR, Executive Director JACQUELINE K. PRINCE, Financial Officer BARBARA B. SMITH, Administrative Associate LAURA T. HOLLIDAY, Senior Program Assistant
ix OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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 Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); II. Evaluating Research Progress and Updating the Portfolio (1999) 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) Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (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) Issues in Risk Assessment (1993) Setting Priorities for Land Conservation (1993) Protecting Visibility in National Parks and Wilderness Areas (1993) Dolphins and the Tuna Industry (1992) Hazardous Materials on the Public Lands (1992) Science and the National Parks (1992) Animals as Sentinels of Environmental Health Hazards (1991) Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993) Human Exposure Assessment for Airborne Pollutants (1991) Monitoring Human Tissues for Toxic Substances (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
x OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Toxicological Risks of Selected Flame-Retardant Chemicals (2000) Arsenic in Drinking Water (1999) 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) Review of a Screening Level Risk Assessment for the Naval Air Facility at Atsugi, Japan (Letter Report) (1998) Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (1997) Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests: Answers to Commonly Asked Questions (1997) 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)
PREFACE xi Preface S PART of the effort to phase out the use of stratospheric ozone-depleting substances, such as chlorofluorocarbons (CFCs), the U.S. Navy is considering hydrofluorocarbons (HFCs) as replacements for the CFC refrigerants used aboard its submarines. Before using the HFCs, the Navy plans to set emergency exposure guidance levels (EEGLs) and continuous exposure guidance levels (CEGLs) to protect submariners from health effects that could occur as a result of accidental releases or slow leaks. In this report, the Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons of the National Research Council's (NRC's) Committee on Toxicology independently reviews the scientific validity of the Navy's proposed 1-hr and 24-hr EEGLs and 90-day CEGLs for two of the candidate refrigerantsâHFC-236fa and HFC-404a. In addition, the subcommittee reviews the the EEGLs and CEGL for HFC-23, one of the combustion products of HFC-236fa. This NRC report is intended to aid the Navy in using HFCs safely. This report has been reviewed in draft form by individuals chosen for their technical expertise and diverse perspectives in accordance with procedures approved by the NRC's Report Review Committee for reviewing NRC and Institute of Medicine reports. The purpose of that independent review was to provide candid and critical comments to assist the NRC in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness
PREFACE xii 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, who are neither officials nor employees of the NRC, for their participation in the review of this report: Melvin Andersen, Colorado State University; John Doull, The University of Kansas Medical Center; Ian Greaves, University of Minnesota; Robert Hamlin, Ohio State University; Joseph Rodricks, The Life Sciences Consultancy; and Richard Schlesinger, New York University School of Medicine. The individuals listed above have provided many constructive comments and suggestions. It must be emphasized, however, that responsibility for the final content of this report rests entirely with the authoring committee and the NRC. We gratefully acknowledge Dr. William Brock of DuPont's Haskell Laboratory and Dr. George Rusch of AlliedSignal, Inc., for providing background information on the HFCs and for making presentations to the subcommittee. We are grateful for the assistance of the NRC staff in preparing the report. Staff members who contributed to this effort are Carol A. Maczka, senior program director for the Toxicology and Risk Assessment Program; Kulbir S. Bakshi, senior program director of the Committee on Toxicology; Ruth E. Crossgrove, editor; Leah Probst and Emily Smail, project assistants; and Mirsada Karalic-Longcarevic, information specialist. We especially wish to recognize the contributions of project director, Susan N.J. Pang, who coordinated the project and contributed to the preparation of the subcommittee's report. Finally, we would like to thank all the members of the subcommittee for their dedicated efforts throughout the development of this report. Gary P. Carlson, Ph.D. Chair, Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons Bailus Walker, Jr., Ph.D., M.P.H. Chair, Committee on Toxicology
CONTENTS xiii Contents SUMMARY 1 1 INTRODUCTION 9 Statement of Task 10 Approach to the Study 10 Exposure Guidance Levels 10 Structure of the Report 13 References 13 2 HYDROFLUOROCARBON-236FA 14 Chemical and Physical Properties 14 Toxicokinetics 15 Toxicity Information 16 Summary 21 Exposure Guidance Levels 22 Recommendations 25 References 26 3 HYDROFLUOROCARBON-23 27 Chemical and Physical Properties 27 Toxicokinetics 28 Toxicity Information 29 Summary 34
CONTENTS xiv Exposure Guidance Levels 36 References 37 4 HYDROFLUOROCARBON-404A 40 HFC-143a 41 HFC-125 47 HFC-134a 54 Summary 71 Exposure Guidance Levels for HFC-404a 73 Calculations 74 References 76
xv Submarine Exposure Guidance Levels For Selected Hydrofluorocarbons:HFC-236fa, HFC-23, and HFC-404a