Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123

SUBCOMMITTEE TO REVIEW TOXICITY OF ALTERNATIVES TO CHLOROFLUOROCARBONS

COMMITTEE ON TOXICOLOGY

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

COMMISSION ON LIFE SCIENCES

NATIONAL RESEARCH COUNCIL

NATIONAL ACADEMYPRESS
WASHINGTON, D.C.,
1996



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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 SUBCOMMITTEE TO REVIEW TOXICITY OF ALTERNATIVES TO CHLOROFLUOROCARBONS COMMITTEE ON TOXICOLOGY BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY COMMISSION ON LIFE SCIENCES NATIONAL RESEARCH COUNCIL NATIONAL ACADEMYPRESS WASHINGTON, D.C., 1996

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 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 report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. 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 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. Harold Liebowitz 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 Alberts and Dr. Harold Liebowitz are chairman and vice chairman, respectively, of the National Research Council. The project was supported by the U.S. Department of Defense and the U.S. Environmental Protection Agency and administered by the U.S. Army under Contract No. DAMD 17-89-C-9086. Additional copies of this report are available from the Board on Environmental Studies and Toxicology, 2101 Constitution Avenue, N.W., Washington, D.C. 20418. Copyright 1996 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 SUBCOMMITTEETOREVIEWTOXICITYOFALTERNATIVESTOCHLOROFLUOROCARBONS BERNARDM. WAGNER(Chair), Wagner Associates, Millburn, N.J. W. KENTANGER, Oregon Health Sciences University, Portland, Oreg. CHARLESE. FEIGLEY, University of South Carolina, School of Public Health, Columbia, S.C. WALDERICOGENEROSO, Oak Ridge National Laboratory, Oak Ridge, Tenn. IANGRAVES, University of Minnesota, Minneapolis, Minn. ROBERTSNYDER, Environmental and Occupational Health Sciences Institute, Piscataway, N.J. GERALDN. WOGAN, Massachusetts Institute of Technology, Cambridge, Mass. GAROLDS. YOST, University of Utah, Salt Lake City, Utah Staff KULBIRS. BAKSHI, Project Director RUTHE. CROSSGROVE, Editor CATHERINEM. KUBIK, Senior Program Assistant LUCYFUSCO, Project Assistant Sponsors U.S. Navy, U.S. Air Force, U.S. Environmental Protection Agency

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 COMMITTEEONTOXICOLOGY ROGENEF. HENDERSON(Chair), Lovelace Biomedical and Environmental Research Institute, Albuquerque, N.Mex. DONALDE. GARDNER(Vice-Chair), Raleigh, N.C. DEBORAHA. CORY-SLECHTA, University of Rochester, Rochester, N.Y. ELAINEM. FAUSTMAN, University of Washington, Seattle, Wash. CHARLESE. FEIGLEY, University of South Carolina, Columbia, S.C. DAVIDW. GAYLOR, U.S. Food and Drug Administration, Jefferson, Ark. WALDERICOM. GENEROSO, Oak Ridge National Laboratory, Oak Ridge, Tenn. IANA. GREAVES, University of Minnesota, Minneapolis, Minn. SIDNEYGREEN, U.S. Food and Drug Administration, Laurel, Md. LOREND. KOLLER, Oregon State University, Corvallis, Oreg. MICHELEA. MEDINSKY, Chemical Industry Institute of Toxicology, Research Triangle Park, N.C. JOHNL. O'DONOGHUE, Eastman Kodak Company, Rochester, N.Y. ROBERTSNYDER, Environmental and Occupational Health Sciences Institute, Piscataway, N.J. BAILUSWALKER, JR., Howard University, Washington, D.C. ANNETTAP. WATSON, Oak Ridge National Laboratory, Oak Ridge, Tenn. HANSPETERR. WITSCHI, University of California, Davis, Calif. GERALDN. WOGAN, Massachusetts Institute of Technology, Cambridge, Mass. GAROLDS. YOST, University of Utah, Salt Lake City, Utah

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Staff, Committee on Toxicology KULBIRS. BAKSHI, Program Director MARVINA. SCHNEIDERMAN, Senior Staff Scientist MARGARETE. MCVEY, Program Officer RUTHE. CROSSGROVE, Editor CATHERINEM. KUBIK, Senior Program Assistant LUCYFUSCO, Project Assistant

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 BOARDONENVIRONMENTALSTUDIESANDTOXICOLOGY PAULG. RISSER(Chair), Miami University, Oxford, Ohio MICHAELJ. BEAN, Environmental Defense Fund, Washington, D.C. EULABINGHAM, University of Cincinnati, Cincinnati, Ohio PAULBUSCH, Malcolm Pirnie, Inc., White Plains, N.Y. EDWINH. CLARK, II, Clean Sites, Inc., Alexandria, Va. ALLANH. CONNEY, Rutgers University, Piscataway, N.J. ELLISCOWLING, North Carolina State University, Raleigh, N.C. GEORGEP. DASTON, Procter and Gamble Co., Cincinnati, Ohio DIANAFRECKMAN, Colorado State University, Fort Collins, Colo. ROBERTA. FROSCH, Harvard University, Cambridge, Mass. RAYMONDC. LOEHR, University of Texas, Austin, Tex. GORDONORIANS, University of Washington, Seattle, Wash. GEOFFREYPLACE, Hilton Head, S.C. DAVIDP. RALL, Washington, D.C. LESLIEA. REAL, Indiana University, Bloomington, Ind. KRISTINSHRADER-FRECHETTE, University of South Florida, Tampa, Fla. BURTONH. SINGER, Princeton University, Princeton, N.J. MARGARETSTRAND, Bayh, Connaughton and Malone, Washington, D.C. GERALD VANBELLE, University of Washington, Seattle, Wash. BAILUSWALKER, JR., Howard University, Washington, D.C. TERRYF. YOSIE, E. Bruce Harrison Co., Washington, D.C.

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Staff Program Directors, Board on Environmental Studies and Toxicology JAMESJ. REISA, Director DAVIDJ. POLICANSKY, Associate Director and Program Director for Natural Resources and Applied Ecology CAROLA. MACZKA, Program Director for Toxicology and Risk Assessment LEER. PAULSON, Program Director for Information Systems and Statistics RAYMONDA. WASSEL, Program Director for Environmental Sciences and Engineering

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 This page in the original is blank.

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 COMMISSIONONLIFESCIENCES THOMASD. POLLARD(Chair), The Johns Hopkins University, Baltimore, Md. FREDERICKR. ANDERSON, Cadwalader, Wickersham and Taft, Washington, D.C. JOHNC. BAILARIII, University of Chicago, Chicago, III. JOHNE. BURRIS, Marine Biological Laboratory, Woods Hole, Mass. MICHAELT. CLEGG, University of California, Riverside, Calif. GLENNA. CROSBY, Washington State University, Pullman, Wash. URSULAW. GOODENOUGH, Washington University, St. Louis, Mo. SUSANE. LEEMAN, Boston University, Boston, Mass. RICHARDE. LENSKI, Michigan State University, East Lansing, Mich. THOMASE. LOVEJOY, Smithsonian Institution, Washington, D.C. DONALDR. MATTISON, University of Pittsburgh, Pittsburgh, Pa. JOSEPHE. MURRAY, Wellesley Hills, Mass. EDWARDE. PENHOET, Chiron Corp., Emergyville, Calif. EMILA. PFITZER, Research Institute for Fragrance Materials, Hackensack, N.J. MALCOLMC. PIKE, University of Southern California, Los Angeles, Calif. HENRYC. PITOTIII, University of Wisconsin, Madison, Wisc. JONATHANM. SAMET, The Johns Hopkins University, Baltimore, Md. HAROLDM. SCHMECK, JR., North Chatham, Mass. CARLAJ. SHATZ, University of California, Berkeley, Calif. JOHNL. VANDEBERG, Southwestern Foundation for Biomedical Research, San Antonio, Tex. PAULGILMAN,Executive Director

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 OTHERRECENTREPORTS Board on Environmental Studies and Toxicology Upstream: Salmon and Society in the Pacific Northwest (1996) Science and the Endangered Species Act (1995) Wetlands: Characteristics and Boundaries (1995) Biologic Markers (Urinary Toxicology (1995), Immunotoxicology (1992), Environmental Neurotoxicology (1992), Pulmonary Toxicology (1989), Reproductive Toxicology (1989)) Review of EPA's Environmental Monitoring and Assessment Program (three reports, 1994-1995) Science and Judgment in Risk Assessment (1994) Ranking Hazardous Sites for Remedial Action (1994) Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations (1993) 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) Tracking Toxic Substances at Industrial Facilities (1990)

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Committee on Toxicology Permissible Exposure Levels for Selected Military Fuel Vapors (1996) Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994) and Volume 2 (1996) Nitrate and Nitrite in Drinking Water (1995) Guidelines for Chemical Warfare Agents in Military Field Drinking Water (1995) Review of the U.S. Naval Medical Research Institute's Toxicology Program (1994) Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms (1994) Health Effects of Ingested Fluoride (1993) Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances (1993) Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants (1992) Review of the U.S. Army Environmental Hygiene Agency Toxicology Division (1991) Permissible Exposure Levels and Emergency Exposure Guidance Levels for Selected Airborne Contaminants (1991) These reports may be ordered from the National Academy Press: (800) 624-6242 or (202) 334-3313

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 This page in the original is blank.

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Preface As part of the effort to phase out the use of stratospheric ozone-depleting substances, such as chlorofluorocarbons (CFCs) and Halon gases, the U.S. Navy is planning to substitute hydrofluorocarbon (HFC)-134a for the refrigerant CFC-12, and the Air Force is planning to substitute hydrochlorofluorocarbon (HCFC)-123 for the fire suppressant Halon 1211. The Navy asked the National Research Council (NRC) to review the toxicity data on HFC-134a and to recommend 1-hr and 24-hr emergency exposure guidance levels (EEGLs) and 90-day continuous exposure guidance levels (CEGLs). The Air Force requested the NRC to review the adequacy of the 1-min EEGL proposed by the Air Force for HCFC-123. In addition, the U.S. Environmental Protection Agency (EPA) requested the NRC to review the suitability of current methods for detecting and quantifying the risk of cardiac sensitization from exposure to CFCs and their substitutes. The NRC assigned these tasks to its Committee on Toxicology, which established the Subcommittee to Review Toxicity of Alternatives to

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Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 Chlorofluorocarbons. The subcommittee reviewed the toxicity data on the two CFC substitutes and the assessment protocol for cardiac sensitization. This report is intended to aid the Navy, the Air Force, and EPA in using CFC substitutes safely. Lieutenant Commander Kenneth Still, Commander Paul Gillooly, Captain David Macys, Dr. Robert Carpenter (all from the U.S. Navy), Dr. Jeffery Fisher (U.S. Air Force), Drs. Joseph Cotruvo and Rebecca Jones (both from EPA) are gratefully acknowledged for their interest and support of the project. Dr. James McDougal (formerly with the U.S. Air Force), Dr. George Rusch (Allied Signal Chemicals, Inc.), and Dr. Henry Trochimowicz (DuPont Chemical Company) are also thanked for providing valuable information. This report could not have been produced without the valuable efforts of the NRC staff, including Paul Gilman, executive director, Commission on Life Sciences; James J. Reisa, director, Board on Environmental Studies and Toxicology; Carol A. Maczka, director, Toxicology and Risk Assessment Program; Margaret McVey, program officer; Ruth E. Crossgrove, editor; Lucy Fusco, project assistant; and Catherine Kubik, senior program assistant. We especially acknowledge the subcommittee 's great debt to Kulbir Bakshi, who not only ably fulfilled the role of project director but also contributed substantially to the drafting and revision of the report. Without his skills and input, our task could not have been completed in such a timely manner. Finally, we would like to thank all the members of the subcommittee for their expertise, input, and support throughout our deliberations. Bernard M Wagner, M.D. Chair, Subcommittee to Review the Toxicity of Alternatives to Chlorofluorocarbons Rogene F. Henderson, Ph.D. Chair, Committee on Toxicology