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i Toxicological Risks of Selected Flame-Retardant Chemicals Subcommittee on Flame-Retardant Chemicals 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 mem- bers 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 between the National Academy of Sciences and U.S. Consumer Product Safety Commission (CPSC) was supported by Con- tract No. CPSC-C-99–1152. This report was prepared by the National Research Council as a result of a direction in the fiscal year 1999 appropriations for the United States CPSC. The views expressed in the report do not necessarily represent the views of CPSC. International Standard Book Number 0-309-07047-3 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 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 Acade my 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

iv

v SUBCOMMITTEE ON FLAME-RETARDANT CHEMICALS DONALD E.GARDNER (Chair), Inhalation Toxicology Associates, Inc., Raleigh, North Carolina JOSEPH F.BORZELLECA, Virginia Commonwealth University, Richmond, Virginia DAVID W.GAYLOR, National Center for Toxicological Research, Jefferson, Arkansas SIDNEY GREEN, Howard University, Washington, D.C. RICHARD HORROCKS, Bolton Institute, Bolton, U.K. MICHAEL A.JAYJOCK, Rohm and Haas Company, SpringHouse, Pennsylvania SAMUEL KACEW, University of Ottawa, Ottawa, Ontario, Canada JAMES N.MCDOUGAL, Geo-Centers, Inc., Wright-Patterson Air Force Base, Ohio RICHARD K.MILLER, University of Rochester, Rochester, New York ROBERT SNYDER, Rutgers University College of Pharmacy, Piscataway, New Jersey GARY C.STEVENS, University of Surrey, Guildford, Surrey, U.K. ROBERT G.TARDIFF, The Sapphire Group, Inc., Bethesda, Maryland MARY E.VORE, University of Kentucky, Lexington, Kentucky NRC Staff KULBIR BAKSHI, Project Director EILEEN ABT, Research Associate DARRYL ARFSTEN, Research Associate MICHELLE CATLIN, Post-Doctoral Research Associate KATHRINE IVERSON, Information Specialist EVELYN SIMEON, Senior Program Assistant

vi COMMITTEE ON TOXICOLOGY 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, University at Buffalo, State of New York ROBERT E.FORSTER II, University of Pennsylvania, Philadelphia, Pennsylvania PAUL M.D.FOSTER, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina WILLIAM E.HALPERIN, National Institute for Occupational Safety and Health, Cincinnati, Ohio CHARLES H.HOBBS, Lovelace Respiratory Research Institute, Albuquerque, New Mexico SAMUEL KACEW, University of Ottawa, Ottawa, Canada NANCY KERKVLIET, Oregon State University, Corvallis, Oregon 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 HARIHARA MEHENDALE, The University of Louisiana at Monroe 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 GÜNTER OBERDÖRSTER, 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 LAUREN ZEISE, California Environmental Protection Agency, Berkeley, California Staff KULBIR S.BAKSHI, Program Director SUSAN N.J.PANG, Program Officer ABIGAIL E.STACK, Program Officer RUTH E.CROSSGROVE, Publications Manager KATHRINE IVERSON, Manager, Toxicology Information Center EMILY SMAIL, Project Assistant EVELYN E.SIMEON, Senior Program 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 Senior Staff 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 S.EISENBERG, University of California, Los Angeles, California JOHN L.EMMERSON, Fishers, Indiana NEAL L.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 J.KENYON, University of California, San Francisco, California BRUCE R.LEVIN, Emory University, Atlanta, Georgia DAVID M.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 for Biological Studies, La Jolla, California SHIRLEY M.TILGHMAN, Princeton University, Princeton, New Jersey RAYMOND L.WHITE, University of Utah, Salt Lake City, Utah Staff 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 Strengthening Science at the U.S. Environmental Protection Agency: Research Management and Peer Review Practice (2000) Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) Modeling Mobile-Source Emissions (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 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 (202) 334–3313 www.nap.edu

OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY x OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers (2000) Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23, and HFC-404a (2000) Health Risk Assessment of Selected Flame-Retardant Chemicals (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) Review of a Screening Level Risk Assessment for the Naval Air Facility at Atsugi, Japan (Letter Report) (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)

PREFACE xi Preface THE U.S. Consumer Product Safety Commission (CPSC) is considering a possible flammability standard for upholstered furniture to reduce the incidence of death, injury, and properly loss from fires started by small open flames of matches, cigarette lighters, and other sources of ignition of upholstered furniture in U.S. residences. The most likely method of achieving this standard is to treat furniture upholstery with flame-retardant (FR) chemicals. However, concern has been expressed that potential health risks have been inadequately studied for many of the FR chemicals likely to be used. Some of them have been shown to cause a range of toxicity, including cancer, neurological, reproductive, and developmental effects. In its fiscal 1999 appropriations report, Congress directed CPSC to arrange for an independent study by the National Research Council (NRC) to conduct toxicological assessments for FR chemicals that are likely to be used as FRs for furniture upholstery. The NRC assigned the project to the Committee on Toxicology, which, in turn, established the Subcommittee on Flame-Retardant Chemicals. This report evaluates toxicological, epidemiological, and exposure data on the 16 specified FR chemicals, and characterizes risks to human health from exposure to furniture upholstery treated with such chemicals. It is hoped that the findings of the report will be useful to CPSC and Congress in making decisions regarding the safe use of FR chemicals in upholstered furniture fabric. The subcommittee was assisted by many people, including those who presented valuable information and documents during the subcommittee's public sessions at the National Academy of Sciences in Washington, DC, on July 30–31 and October 26–27, 1999, and in Irvine, CA, on September 22–24, 1990:

PREFACE xii Elizabeth Anderson (Sciences International, Inc.) Michael Babich (Consumer Product Safety Commission) Roger Berkley (American Textile Manufacturers Institute's Upholstery Fabric Committee) Patricia Bittner (Consumer Product Safety Commission) Joseph Carra (EPA's Office of Pollution Prevention and Toxics) Marcia Hardy (Albemarle Corporation) Judith MacGregor (Toxicology Consultant Services) Ronald Medford, (Consumer Product Safety Commission) George Miller (National Association of State Fire Marshalls) Vincent Piccirillo (NPC, Inc.) Cecilia Powell (Albright & Wilson) Richard Rose (Great Lakes Chemical Corporation) The Honorable Roger Wicker (U.S. Representative from Mississippi) Joseph Ziolkowski (Upholstered Action Furniture Council) This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise in accordance with procedures for reviewing NRC reports 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 NRC in making the 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, who are neither officials nor employees of the NRC, for their participation in the review of this report: Deepak Bhalla, Wayne State University; Jack Dean, Sanofi-Synthelabo, Inc.; John Doull, University of Kansas; Paul Foster, Chemical Industry Institute of Toxicology; Bruce Fowler, University of Maryland; Robert Goyer, University of Western Ontario; Rogene Henderson, Lovelace Respiratory Research Institute; Loren Koller, Oregon State University; Daniel Krewski, University of Ottawa; Thomas McKone, University of California, Berkeley; Günter Oberdörster, University of Rochester; and Vincent Piccirillo, NPC Incorporated. 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. The subcommittee gratefully acknowledges the assistance of its consultants, including the staff of Toxicology Excellence for Risk Assessment—Michael Dourson, Kenneth Poirier, Lynne Haber; Syracuse Research Corporation staff—Gary Diamond, Margaret Fransen, Patricia McGinnis, Marc Odin, and Randi Starmer; and Oak Ridge National Laboratory staff—Po-Yung Lu, Sylvia Milanez, Annetta Watson, and Robert Young, for drafting most of the initial

PREFACE xiii health risk assessments, which were reviewed and modified by the subcommittee. Appreciation is also extended to Edmund Crouch for his assistance with exposure assessments; Judith Fauls for her editorial assistance; and Charles Auer of EPA for providing information on FRs; and Marcia Hardy, Judith MacGregor, and Patricia Adair for providing the subcommittee with numerous current references. Appreciation is also extended to Alan Mann, University of Surrey, U.K.; Stewart Miller and Patricia Martin, Albright & Wilson; William Walt, DaimlerChrysler Corporation; Carl D'Ruiz and James Plautz, Ciba Specialty Chemicals Corporation; Robert J.Fensterheim, Chlorinated Paraffins Industry Association; and Philip Strong, U.S. Borax Incorporated for providing data on FR chemicals. The subcommittee also thanks the staff of the sponsor of this study, the U.S. Consumer Product Safety Commission, for their assistance and cooperation, including Ronald Medford, assistant executive director for hazard identification and reduction; Marry Ann Danello, associate executive director for health sciences; Lori Saltzman, director, Division of Health Sciences; Patricia Bittner, technical contract officer, Jacqueline Ferrante, Kristina Hatlelid, and Michael Babich, Division of Health Sciences; Dale Ray, Directorate for Economic Analysis (manager, Upholstered Furniture Project); Peter Nerret, contract officer, and Robert Frost, Division of Procurement Services. The subcommittee was ably assisted by the staff of the Subcommittee on Flame-Retardant Chemicals— especially Kulbir S.Bakshi, project director; Eileen Abt and Darryl Arfsten, research associates; Michelle Catlin, post-doctoral research associate; and Judy Estep, Pamela Friedman, Stephanie Parker, and Evelyn Simeon, administrative staff. These staff members merit special recognition for their thoughtful contributions and extraordinary efforts in producing the report, and for the many extra hours they worked to complete the report. The subcommittee is also thankful to the following NRC officials for their contributions to the project—Warren R.Muir (Executive Director, Commission on Life Sciences), James J.Reisa (Director, Board on Environmental Studies and Toxicology [BEST]), David Policansky (Associate Director, [BEST]), and Carol Maczka (Director, Toxicology and Risk Assessment Program [BEST]). Finally, we would like to express our thanks and admiration to the members of the subcommittee for their dedicated efforts throughout the development of this report. Donald E.Gardner Chair, Subcommittee on Flame-Retardant Chemicals Bailus Walker, Jr. Chair, Committee on Toxicology

PREFACE xiv

CONTENTS xv Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 15 The Charge to the Subcommittee 16 The Subcommittee's Approach to Its Charge 17 Flame Retardant Processes 18 California, United Kingdom, and European Experience 19 Organization of this Report 20 References 20 2 ASSESSMENT OF HEALTH RISKS FROM THE USE OF FLAME RETAR- 21 DANTS The Subcommittee's Risk Assessment Process 22 References 33 3 EXPOSURE ASSESSMENT METHODOLOGY 35 Dermal Exposure Scenario 37 Inhalation Exposure Scenario 42 Oral Exposure Scenario 49 References 51 4 HEXABROMOCYCLODODECANE 53 Physical and Chemical Properties 53

CONTENTS xvi Occurrence and Use 53 Toxicokinetics 54 Hazard Identification 55 Quantitative Toxicity Assessment 63 Exposure Assessment and Risk Characterization 65 Recommendations from Other Organizations 68 Data Gaps and Research Needs 69 References 69 5 DECABROMODIPHENYL OXIDE 72 Physical and Chemical Properties 72 Occurrence and Use 72 Toxicokinetics 74 Hazard Identification 75 Quantitative Toxicity Assessment 84 Exposure Assessment and Risk Characterization 88 Recommendations from Other Organizations 93 Data Gaps and Research Needs 94 References 94 6 ALUMINA TRIHYDRATE 99 Physical and Chemical Properties 99 Occurrence and Use 100 Toxicokinetics 100 Hazard Identification 105 Quantitative Toxicity Assessment 118 Exposure Assessment and Risk Characterization 120 Recommendations from Other Organizations 122 Data Gaps and Research Needs 122 References 123 7 MAGNESIUM HYDROXIDE 131 Physical and Chemical Properties 131 Occurrence and Use 131 Toxicokinetics 133 Hazard Identification 135 Quantitative Toxicity Assessment 142 Exposure Assessment and Risk Characterization 143 Recommendations from Other Organizations 145 Data Gaps and Research Needs 145 References 146

CONTENTS xvii 8 ZINC BORATE 149 Physical and Chemical Properties 149 Occurrence and Use 150 Toxicokinetics 151 Hazard Identification 155 Quantitative Toxicity Assessment 178 Exposure Assessment and Risk Characterization 181 Recommendations from Other Organizations 183 Data Gaps and Research Needs 183 References 184 9 CALCIUM AND ZINC MOLYBDATES 192 Physical and Chemical Properties 192 Occurrence and Use 192 Toxicokinetics 194 Hazard Identification 198 Quantitative Toxicity Assessment 214 Exposure Assessment and Risk Characterization 219 Recommendations from Other Organizations 222 Data Gaps and Research Needs 222 References 223 10 ANTIMONY TRIOXIDE 229 Physical and Chemical Properties 229 Occurrence and Use 229 Toxicokinetics 230 Hazard Identification 232 Quantitative Toxicity Assessment 250 Exposure Assessment and Risk Characterization 253 Recommendations from Other Organizations 256 Data Gaps and Research Needs 257 References 257 11 ANTIMONY PENTOXIDE AND SODIUM ANTIMONATE 262 Physical And Chemical Properties 262 Occurrence and Use 262 Toxicokinetics 263 Hazard Identification 265 Quantitative Toxicity Assessment 267 Exposure Assessment and Risk Characterization 268 Recommendations from Other Organizations 270

CONTENTS xviii Data Gaps and Research Needs 270 References 270 12 AMMONIUM POLYPHOSPHATES 273 Physical and Chemical Properties 273 Occurrence and Use 275 Toxicokinetics 275 Hazard Identification 277 Quantitative Toxicity Assessment 284 Exposure Assessment and Risk Characterization 285 Recommendations from Other Organizations 288 Data Gaps and Research Needs 288 References 288 13 PHOSPHONIC ACID, (3-{[HYDROXYMETHLY] AMINO}-3-OXOPROPYL)- 291 DIMETHYL ESTER Physical and Chemical Properties 291 Occurrence and Use 291 Toxicokinetics 294 Hazard Identification 294 Quantitative Toxicity Assessment 300 Exposure Assessment and Risk Characterization 301 Recommendations from Other Organizations 304 Data Gaps and Research Needs 304 References 304 14 ORGANIC PHOSPHONATES 307 Physical and Chemical Properties 307 Occurrence and Use 307 Toxicokinetics 309 Hazard Identification 310 Quantitative Toxicity Assessment 324 Exposure Assessment and Risk Characterization 327 Recommendations from Other Organizations 334 Data Gaps and Research Needs 334 References 335 15 TRIS MONOCHLOROPROPYL PHOSPHATE 338 Physical and Chemical Properties 338 Occurrence and Use 340

CONTENTS xix Toxicokinetics 341 Hazard Identification 342 Quantitative Toxicity Assessment 352 Exposure Assessment and Risk Characterization 353 Recommendations from Other Organizations 355 Data Gaps and Research Needs 355 References 355 16 TRIS(1,3-DICHLOROPROPYL-2) PHOSPHATE 358 Physical and Chemical Properties 358 Occurrence and Use 360 Toxicokinetics 360 Hazard Identification 363 Quantitative Toxicity Assessment 372 Exposure Assessment and Risk Characterization 378 Recommendations from Other Organizations 384 Data Gaps and Research Needs 384 References 384 17 AROMATIC PHOSPHATE PLASTICIZERS 387 Physical and Chemical Properties 387 Occurrence and Use 389 Toxicokinetics 389 Hazard Identification 393 Quantitative Toxicity Assessment 406 Exposure Assessment and Risk Characterization 409 Recommendations from Other Organizations 413 Data Gaps and Research Needs 413 References 413 18 TETRAKIS (HYDROXYMETHYL) PHOSPHONIUM SALTS 417 Physical and Chemical Properties 418 Occurrence and Use 419 Toxicokinetics 419 Hazard Identification 420 Quantitative Toxicity Assessment 430 Exposure Assessment and Risk Characterization 433 Recommendations from Other Organizations 436 Data Gaps and Research Needs 436 References 437

CONTENTS xx 19 CHLORINATED PARAFFINS 381 Physical and Chemical Properties 440 Occurrence and Use 442 Toxicokinetics 442 Hazard Identification 447 Quantitative Toxicity Assessment 479 Exposure Assessment and Risk Characterization 484 Recommendations from Other Organizations 488 Data Gaps and Research Needs 488 References 488 APPENDIX A: BIOGRAPHICAL SKETCHES 493 APPENDIX B: FLAME-RETARDANT COMPOSITION IN FABRICS: THEIR DURABILITY 499 AND PERMANENCE

xxi Toxicological Risks of Selected Flame-Retardant Chemicals

xxii

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Ignition of upholstered furniture by small open flames from matches, cigarette lighters, and candles is one of the leading causes of residential-fire deaths in the United States. These fires accounted for about 16% of civilian fire deaths in 1996. On average, each year since 1990, about 90 deaths (primarily of children), 440 injuries, and property losses amounting to 50 million dollars have resulted from fires caused by the ignition of upholstered furniture by small open flames. Certain commercial seating products (such as aircraft and bus seats) are subject to flammability standards and sometimes incorporate FR-treated upholstery cover materials, but there is no federal-government requirement for residential upholstered furniture, and it is generally not treated with FR chemicals.

It is estimated that less than 0.2% of all U.S. residential upholstery fabric is treated with flame-retardant (FR) chemicals. The Consumer Product Safety Act of 1972 created the U.S. Consumer Product Safety Commission (CPSC) as an independent federal regulatory agency whose mission is to protect the public from unreasonable risks of injury and death associated with consumer products. CPSC also administers the Flammable Fabrics Act, under which it regulates flammability hazards and the Federal Hazardous Substances Act (FHSA), which regulates hazardous substances including chemicals. In 1993, the National Association of State Fire Marshals petitioned CPSC to issue a performance-based flammability standard for upholstered furniture to reduce the risk of residential fires. The Commission granted that portion of the petition relating to small open flame ignition risks.

In response to concerns regarding the safety of FR chemicals, Congress, in the fiscal year 1999 appropriations report for CPSC, requested that the National Research Council conduct an independent study of the health risks to consumers posed by exposure to FR chemicals that are likely to be used in residential upholstered furniture to meet a CPSC standard. The National Research Council assigned the project to the Committee on Toxicology (COT) of the Commission on Life Sciences' Board on Environmental Studies and Toxicology. COT convened the Subcommittee on Flame-Retardant Chemicals, which prepared this report. Subcommittee members were chosen for their recognized expertise in toxicology, pharmacology, epidemiology, chemistry, exposure assessment, risk assessment, and biostatistics.

Toxicological Risks of Selected Flame-Retardant Chemicals is organized into 18 chapters and two appendices. Chapter 2 describes the risk assessment process used by the subcommittee in determining the risk associated with potential exposure to the various FR chemicals. Chapter 3 describes the method the subcommittee used to measure and estimate the intensity, frequency, extent, and duration of human exposure to FR chemicals. Chapters 4-19 provide the subcommittee's review and assessment of health risks posed by exposure to each of the 16 FR chemicals. Data gaps and research needs are provided at the end of these chapters.

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