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Asbestiform Fibers Nonoccupational Health Risks Committee on Nonoccupational Health Risks of Asbestiform Fibers Board on Toxicology and Environmental Health Hazards Commission on Life Sciences National Research Council NATIONAl ACADEMY pRESS Washington, D.C. 1984

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National Academy Press 2101 Constitution Avenue, NW Washlugton, DC 20418 NOTICE: The project that is the subject of this report was approved by the Gove ruing 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 Research Council was established 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 of advising the federal government. The Council operates in accordance with general policies determined by the Academy under the authority of its congresaion~1 charter of IS63, which establishes the Academy as a private, nonprofit, self-governing membership corporation. The Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Englneering in the conduct of their services to the government, the public, and the scientific and engineering communities. It is administered jointly by both Academies and the Institute of Medicine. The National Academy of Engineering and the Institute of Medicine were established in 1964 and 1970, respectively, under the charter of the National Academy of Sciences. The study reported here was supported by Contract EPA 68-01-4655 between the National Academy of Sciences and the Environmental Protection Agency. Library of Congress Catalog Card Number 84-60249 International Standard Book Number 0-309-03446-9 Printed in the United States of America .. 1 t t . l

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Commiltee on Nonoccupationa of Asbestiform Fibers Leater Brealow, Chairmsu . School of Public Health University of California Los Angeles, Calif. Richard Bates Health Effects Institute Cambridge, Mass. Henrik Bendixen Department of Anesthesiology Columbia University College of Physicians and Surgeons New York, N.Y. Strephen L. Brown Independent Consultant Portola Valley, Calif. Patricia A. Buffler University of Texas Health Science Center School of Public Health University of Texas at Houston Houston, Texas Arthur M. Langer Department of Com~,nity Medicine Environmental Sciences Laboratory Mt. Sinai School of Medicine New York, N.Y. Jeremiah Lynch Exxon Chemical Company East Millstone, N.J. t ~ Health Risks James A. Merchant Department of Preventive Medicine and Environmental Health and the Department of Internal Medicine College of Medicine University of Iowa Iowa City, Ia. Richard Monson Department of Epidemiology Harvard School of Public Health Boston, Mass. Brooke T. Mosaman Department of Pathology College of Medicine University of Vermont Burlington, Vt. Jamen E. Troako Department of Pediatrics and Human Development College of Human Medicine Michigan State University Eant Lansing, Mich. John Van Ryzin Division of Biostatistics School of Public Health Columbia University New York, N.Y. Tibor Zolta1 Department of Geology and Geophysics University of Minnesota Minneapolis, Minn. iii ..

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Consultant Warren Heir Department of Environmental Health Sciences School of }lygiene and Public Health The Johns Hopkins University Baltimore, Md. Hatior~al Research Council Staff Barbara Mandula, Study Director Frances M. Peter, Editor Pamela Smith, Research Assistant Waider~a Banks, A - inistrati~re Secretary Board on Toxicology and Environmental Health Hazards Gerald N. Wogan, Chairman Department of Nutrition and Food Science Massachusetts Institute of Technology Cambridge, Mass. Philip Landrigan, Co-Vice-Chairman National Institute for Occupational Safety and Health Robert Taft Iaboratories Cincinn~ ti, Ohio Donald Hornig, Co-llice-Chalrman S choo] of Public Health Ha rvard University Boston, Hass. Edwa rd Bresnick Eppley Institute for Cancer Research Dhi~reraity of Nebraska Medical Center Omaha, Nebraska Herman N. Eisen De pa rtment of Biology Ma ssachusett6 Institute of Technology Cambridge, Mass. Ronald Estabrook Department of Biochemistry University of Texas Medical School Della a, Ten ~ Emmanuel Farber Department of Pathology University of Toronto Toronto, Ontario Inlaid G. Hoel Biometry and Risk Assessment Program National Institute of Environmental Health Sciences Resea rch Triangle Park, N . C . Michael W. Lieberman Department of Pa thology Washington University School of Medicine St . Louis, Missouri Abraham }1. Lilienfeld School of Hygiene and Public health The Johns Hopkins University Baltimore, Maryland iv . ..

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BOARD ON TOXICOLOGY AND ENVIRONMENTAL HEALTH HAZARDS (Continued) Richard Merrill School of Law Unlversity of Virginia Charlottesville, Virginia 1 Vaun A. Newill Exxon Corporation Medicine and Environmental Health Department New York, New York John Peters Department of Family and Preventive Medicine University of Southern California School of Medicine Los Angele a, California Ex Of ficio Members Gary P. Carlson Purdue University School of Pharmacy and Pharmacal Science Department of Pharmacology and Toxicology Lafayette, Indiana Maureen Henderson School of Public Health and Community Medicine Department of Epidemiology University of Washington Seattle, Washington National Research Council Staff Robert G. Tardiff, Executive Director, until June 1983 Devra L. Davis, Executive Director, September 1983 to present Jacqueline K. Prince, Staff Assistant v Joseph V. Rodricks Environ Corporation Washington, D . C . Liane B. Russell Biology Division Oak Ridge National Laboratory Oak Ridge, Tennessee Ellen S ilbergeld Toxic s Program Environmental Defense Fund Washington, D . C. Roger O. McClellan Lovelace Inhalation Toxicology Research Institute Albuquerque, New Mexico Daniel B. Menzel Department of Pharmacology Duke University Medical Center Durham, North Carolina Norton Nelson Institute of Environmental Medicine New York University Medical Center New York, New York

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Preface Industrial progress during the twentieth century has contributed to our well-beirt8, but has also resulted in environmental changes that have increased risks to human health. Not only are greater quantities and varieties of hazardous materials being taken from the earth and used in many ways, but the use of synthetic materials with similar physical and chemical properties has also been growing. Adverse health effects from many of these new exposures have been receiving considerable attention. Radioactive substances, cigarette smoke, petrochemicals, and asbestos, for example, are well known for their potential to harm health. The health risks from exposure to these and other materials are provoking some alarm because of several characteristics that they have in common. Relatively small, sometimes minute, amounts may cause severe damage to health. People are often not aware of their exposure at the time it occurs. Cancer, a particularly feared disease, can result. Cancer and other adverse health effects typically occur many years after exposure began. Evidence linking the particular substance to subsequent disease may appear-ad be accepted--ouly decades after millions of people have been exposed. Asbestiform fibers, which for purposes of this report include both natural materials such as asbestos and synthetic materials such as fibrous glass, typify the problem. Although asbestos and some of its uses had been known for centuries, twentieth century industry brought a vast increase in mining and distribution of that material. Then, some years after hundreds of thousands of workers had been exposed, it became apparent that considerable damage to health, including cancer, Was occurring as a result. Ascertaining the harm precisely was complicated because other factors, especially cigarette smoking, often contributed to the same effects. As the hazard became more widely known in recent years, annual use of asbestos in the United States has dropped. However, asbestos had already been widely distributed in schools and other buildings, in the general outdoor air, and in some water supplies. Thus, tens of millions of people are still being esposed-`lthough usually to very small amounts. The usefulness of asbestos was so great that substitutes with some similar physical properties were developed for commercial purposes. Do these synthetic materials carry the same, or some, health risk because of the characteristics they share with the naturally occurring asbestos? Given the widespread occurrence of these materials, concerned federal agencies commissioned studies to examine the potential health risk from vii

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nonoccupational espo sure to asbestos. To one such study, the Safe Drinking Water Committee of the National Research Council sought to determine whether health damage was occurring because drinking water was contaminated with asbestos fibers. The committee found that the epidemioJogical studies of asbestos in drinking water had mayor limitations in design, but that the committee's risk estimates were compatible with the results of the epidemiological studies (National Research Council, 1983~. Generally, the amount of asbestos in the drinking waters studied would be likely to yield an increased risk too small to detect. The U.S. Consumer Product Safety Commission, in carrying out its responsibility for protecting consumers, sought guidance from a Chronic Hazard Advisory Panel on Asbestos. The latter body concluded that "asbestos at all levels of exposure ...~should be regarded] ... as a potential human carcinogen." Furthermore, the panel wrote, "It is prudent to behave as if asbestos fibers may be carcinogenic at low exposure levels and at small particle sizes" (U.S. Consumer Product Safety Commission, 1983~. There has also been concern about asbestos in schools, as evidenced by reports from the U.S. Environmental Protection Agency (1980) and the U.S. General Accounting Office (1982~. In a more general approach to the issue, broadening it beyond asbestos, the Environmental Protection Agency asked the National Academy of Sciences: to evaluate the human health risks associated with nonoccupational exposure to asbestiform fibers, with emphasis on inhalation of outdoor and indoor air, and to determine the extent to which the physical- chemical properties of the fibers may be associated with the development of various human diseases and the extent to which such information may be incorporated into assessing health risks resulting from exposure to the fibers. To conduct that study, the National Research Council established the Committee on Nonoccupational Health Risks of Asbestiform Fibers in August 1982. This is the report of that committee. I personally would like to thank the committee members, who worked extremely hard and persistently to bring the project to fruition. I could not imagine a more thoughtful, energetic, and cooperative group for approaching this comples problem. On behalf of the committee, I would also like to thank the many persons from various groups and agencies who viii !

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provided the committee with unpublished draft documents, or who took the time to answer questions and offer suggestions. Hey are too numerous to mention individually. However, Dr. Dennis Kotchmar, EPA project officer, deserves special mention, as do Mr. Colin Church, Dr. Robert Clifton, Dr. Jon Konzen, Dr. James Leineweber, Dr. Marvin Schneiderman, ant Mr. Paul White. The committee is also grateful to the capable and devoted NRC project staff, including Dr. Barbara Mandula, Ms. Pamela Smith, Ms. Dena Banks, Me. Frances Peter, and the many others who assisted them at various times, especially Me. Shirley Ash, Ms. LRslye Giese, Me. Jacqueline Prince, Ms. Mary Ellen Scheckenbach, and ~8. Bernidean Williams. Special thanks are also due Dr. Warren Muir, who was a consultant to the committee. Finally, I wish to thank Dr. Robert Tardiff, who was executive director of BOTEHH when the project began; Dr. Devra Davis, present executive director of BOTEHH, who energetically shepherded the project through its final stages; and Drs. Frederick Robbins and Alvin Lazen of the Commission on Life Sciences for their continued interest and support. Lester Breelow Chairman Committee on Nonoccupational Fibers 1X ..

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REFERENCES Nations l Research Counci l . 1983. Drinking Water and Health. Vol . 5 . A report of the Safe Drinking Water Committee, Commission on Life Sciences. National Academy Press, Washington, D.C. U.S. Consumer Product Safety Commission. 1983. Chronic Hazard Advisory Panel on Asbestos. Consumer Product Safety Co~ission, Washington, D.C. U.S. Environmental Protection Agency. 1980. Asbestos-Containing Materials in Schools. Health Effects and Magnitude of Exposure. Support document for proposed rule 6 on friable asbe~tos-containing materials in school buildings. Environmental Protection Agency, Washington, D.C. U.S. General Accounting Office. 1982. Asbestos in Schools: A Dilemma General Account ing Of f ice, Wash ington, D . C . . x .1 1

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Contents EXECUTIVE SUMMARY . . . . . . . . . . . Origin of the Study . . . . . . . . Major Findings and Recommendations 2 2 Evaluation al KINK ~ . . . . . . . . . . ~ ~ . . . . . . Physicochemical Properties and Health Effects . . . . . . Recommendations . . . . ~ . . . . . . . . . . . ~ . . . . Summary of the Study ~ . . . . . . . . . . . . . . . . . . ~ . Background . . . . ~ . . . . . . . . . ~ . . . . . . . ~ . Materials of Concern . . . . . . . . . . ~ ~ . . . . . ~ . Relationship of Fiber Characteristics to Health Effects ................... Measurement and Extent of Exposure . . . . . . . . . . . . 9 Health Effects Methodology . . . . . . . . . . . . . . . . 10 Health Effects of Asbestos 11 Health Effects of Nonasbestos Asbestiform Fibers ~ 12 Evidence Associating Fiber Properties with Adverse Health Effects 13 Risk Assessment 8 e ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ e 13 4 4 57 8 1 INTRODUCTION . . . . . . . . . . 16 Concurrent National Research Council and Government Activities Related to Asbestos . . . . . . . . . . 19 me Con mittee ' s Approach . . . . . . . . . 20 References . . . . . . . ~ . . . . . . . . 2 . . . . . . . . . . .^ ASBESTIFORM FIBERS: HISTORICAL BACKGROUND, TERMaNOLOGY, AND PHYSICOCHEMICAL PROPERTIES . . . . . . . . . . . . . . . 25 bestosin~story 25 MineralogicalTe~inology 26 ~ ~ ~ in__ ~ . . . 31 Physical~ropercles OI ~ Den ~llo~-m r ~ v=` D . ~ . . ~ . . , . . 31 Fiberlike Morphology . . . . . . . . . . . . . . . . . . . 32 Enhanced Strength and Flexibility 33 Diameter-Dependent Strength 33 Increased Physical and Chemical Durability 33 Defect-Free Surface Structure 34 Growth-Dependent Fiber Quality ......... 35 Sources on nluera' ram Lid . . . . . . . ~ . ~ _ _ ~ ~ _ ~ _ _ ~ ~ = _ _ ~ 4 ~ ~ _ ~ hi

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CONTENTS 2 (cont. 3 4 Biologically Relevant Physicochemical Properties . . . Re spirability . . . . . . . . Size and Aspect Ratio (Length:Diameter) ......... Durability . . . . . . . . . . . . . . . . . . ~ . . . . Flexibility and Tensile Strength ............ Chemical Composition e e - e Surface Area . . . . . ~ . . e ~ Surface Charge e ~ ~ ~ ~ ~ ~ ~ ~ 0 Standardized Asbestos Samples . - S''mm ~ ry Re commends tions . . . . References . . . . . . . . ASSESSING NONOCCUPATIONAL EXPOSURES TO ASBESTIFORM FIBERS .......... Definitions of Exposure ................... Asbestiform Fibers and Weir Sources.. ........... Exposure Potential for Asbestos ............... Types of Exposure e ~ - ~ ~ - Quantitative Exposure Estimates ............ Exposure to Other Natural Mineral Fibers . Attapulgite . . . . . . . . . . . . Erionite . . . . . . . . . . . Exposure to Man-Hade Fibers . . . . . . . . . . e e Man-Made Hineral Fibers . . . . . . . . . . e ~ ~ e e e e Esposure to Other Man-Made Fih~re e 36 36 36 37 38 t 38 39 39 39 40 42 43 48 i 48 52 55 55 61 68 69 70 71 71 75 76 e e e ~ e 77 e ~ ~ e ~ e e e a82 S''mmary and Recommendationse . References . . . . ~ MEASUREMENT OF EXPOSURE TO ASBESTIFORH FIBERS Measurement Techniques e ~ e e e e ~ - - Measuring Asbestos Dust in the Workolac The Impinger Techaique e ~ ~ e e The Membrane Pliter Techaique e e l Measuring Asbestos Dust in the Ambient Environment e e ~ e ~ e e86 Relationships Among Yarious Esposure Measurement Methods . e e e ~ e e e e ~ e e e e e e ~ e e ~ e ~ e ~ e e e87 Exposure to Chrysotile in the Ambient Environment e ~ e e e e .90 Complicatirtg Factors in Enviror~mental Assays 91 Puture Measurement of Esposure to Asbestiform Fibers 91 Recommendations . . . . . . . . . . . . e ~ ~ ~ ~ e ~ ~ ~ 0 ~ e93 References . e ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ e ~ ~ e e e ~ ~ e ~ ~ ~ .93 xii '

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r 1 CONTENTS 5 EFFECTS OF ASBESTIFORM FIBERS ON HUMAN HEALTH . ...... 97 Nature of Evidence eeeeeeeeeaeeee. Biodisposition of Fibers eeeeea~eeeee. Fiber Deposition eeeeeeeeeea~e. r:1 ~nrance and Transport eeee.e -~.e 97 ---100 eeeeee103 eeee.eeeeee106 C1inical Aepects of Asbestos-Associated Diseases . . . . . . . 107 Neceseary Assumptione Ueed in Determining Health Effects .................. 107 Sensitivity and Specificity of Clindcal Evidence . . ee.~108 General Diagnostic Measures 109 Disease Associated with Nonoccupational TnhAlation Exposures to Asbestiforn~ Fibers 114 Asbestos E~posure from Household Contacts 116 Neighborhood Exposure to Asbestos 116 Natural Sources of Asbestiform Fibers 117 Summary 119 Epidemiological Studies of Effects Resulting from the Ingestior' of Asbestos in Drinking Water 119 Occupational Epidemiological Studies-~Methodological Considerations .~123 Cancer Mortality in Occupational Cohorts Esposed to Asbestos .~125 Mining and Milling e.~128 - 128 ...... 131 .~131 MaDulaCl~uI:ll~5 ~ ~ e e ~ IDsulation e e e e e ~ ~ ~ ~ ~ ~ ~ ~ e Shipyard 8 e ~ ~ ~ ~ ~ e e e e e ~ Relative Carcinogenicity of Different Types of Asbestos ............ Effect 8 0 f Smoking . e e e e e e e ~ ~ e Summary . e ~e ~ ~ ~ e ~ e - ~ ~ e ~ ~ e e A`;bestosis and Asbestos-Associated Pleural Disease in Occupatio~1 Cohorts ....... Mortality Studie 8 ~ ~ ~ ~ ~ e e ~ ~ ~ ~ e e e Morbidity Studies . . e ~ ~ e e ~ ~ e Sllmmary . e e ~ e ~ e e ~ ~ ~ e ~ e ~ Hdalth Effects of Occupational Exposure to . . . . . 132 . . . . . . 133 . . . . . . 133 . . . . . . . . . 136 ....... 140 Man-Made Mine ra1 rlDer ~..... , . 141 ~--- . . . . . . . . . . . . . . . . . 141 e ~e 143 , e e ~145 e e ~e 146 ~e e e ~e 146 e ~e ~e ~146 e ~e ~e e e ~}48 e e e 149 MO r D~u1 1- ~ ~ ~ ~ e ~ , Mortality e e e ~ ~ e ~ ~ e ~ e e e e Summa ~ e e ~ ~ - - ~ ~ ~ ~ e e ~ ~ . = AdditiorA 1 Occupatio~A1 Epidemiological Studies Attapulgite e.~eee.~ee ~lceeeeeeeee.eee. Recommendations eeee..eeeee ~fere~ce8 eeeeee Xlil

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CONTENTS 6 IABORATORY STUDIES OF THE EFFECTS OF ASBESTIFORM FIBERS . . . 165 Studies in A~i~lal8 ~ ~ ~ ~ e ~ ~ e ~ e ~ e ~ ~ ~ e ~ ~ e e ~165 Lung Cancer . . e e e e e ~ e ~ e ~ ~ ~ ~ ~ e ~ ~ e ~ ~165 Mesothelioma . . e e e e e e e e ~ ~ ~ ~ ~ ~ e e e e e e 167 Fibrosis e e e e e e e e e e e e e e e e e ~ e e e ~ 0 e 168 Events in the Gastrointestinal Tract After Exposure to Asbestos e e e e e e e ~ ~ ~ e ~ ~ e e e e In Vitro Studies e e e e e e ~ e e e e e e e e ~ ~ e e e e e Hemolytic A`;says . . e e e ~ e e ~ e e e e e e ~ ~ ~ e e Cytotoxicity Studie8 e e ~ e e ~ e e ~ e ~ ~ e e ~ ~ e e Alterations in Cells of the Immune System After Exposure to Asbestiform Fibers . . . . . . O . . Effects on Fibroblasts in Vitro . . . . . . . . . . . . Initiation-Promotion Model of Carcinogenesis . . . O . . . . Interaction of Asbestiform Fibers with DNA . . . . . . . Tumor Promotion ~ . . . . . . . . . . . O . . . . . . . In Vitro Studies with Mesothelial Cells O . . . . . . . Toteractions Between Fibers and Polycyclic Aromatic Hydrocarbons (PAHs) . . . . . . . . . . . . . Conclusions . . . . . O . . . . . . O . . . . . e e ~ ~ ~ ~ e Asbestiform Fibers: Initiators and/or Promoters of Lung Tumors?. . . . . e ~ ~ ~ e e e e ~ e Asbestiform Fibers: Initiators and/or Promoters of Malignant Mesothelioma? . . . . e Asbestiform Fibers: Possible HechaDisme - of Fibrosis . . ~ . . ~ . . . . . . . e e ~ ~ ~ ~ e Su~lm~ ry ~ ~ ~ ~ ~ ~ e ~ ~ ~ ~ ~ ~ ~ ~ e Recommendations . . e ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ e e e References . . . ~ ~ O O . . . . . ~ . e ~ e 7 RISK AS SESSMENT . . . . . . . . . . . . e ~ e e ~ e e The Process of Risk Assessment . . e e e e e e e e e e e ~ ~ Quantitative Risk Assessment e e e e e e e e e e e e e e e e Mathematical Model for Carcinogenic Risk Estimate e e e e e e e e e e e e e e e e e e Published Risk A8sessments e e e ~ ~ ~ ~ e ~ ~ e e e e e ~ e Lung Cancer Risk From Nonoccupational Enviro~mental Exposures . . e e e ~ Mesothelioma Risk From Nonoccupational Environmental Exposures . . e e e e 169 170 170 171 ll - 172 173 173 175 176 177 177 177 177 179 180 180 183 184 200 200 205 206 208 208 209 Quantitative Risk Assesament for Nonoccupational Eavironmental E2posures ~ e e e e a e ~ e e e e e e e e e e Lifetime Risk Estimates for Lung Cancer and Mesothelioma e ~ e e e e e e e e e e e e e e e e ~ 211 Risk Assessments for Special Subpopulations e e e e e e 221 xiv 1 211

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CONTENTS 7 (cont.) Comparative Risk Assessment . . Methods e ~ e ~ ~ ~ ~ ~ ~ ~ e ~ General Methodological Considerations Scoring Considerations e ~ e ~ ~ ~ e Discussion of Comparative Risks. . e Summary and Recommendations References .222 .222 . .223 . .226 . .228 . .230 . .232 APPENDIX A: Asbestos Exposure and Human Disease. Hallmark Observations and Studies from 1898-1979 . . . . .237 APPENDIX B: APPENDIX C: Natural and Synthetic Fibrous Substances and Some of their Known Biological Effects O Fiber-Quality Parameters of Selected Asbestos, Whisker, and Glass Fibers . . - .244 APPENDIX D: Conceptual Model of Fiber Exposure . . . . . . . .261 APPENDIX E: Epidemiological Studies Among Cohorts Exposed to Asbestos . . . . . . . . . e ~ e ~ ~ ~ ~ 267 APPENDIX F: Effects of Administering Asbestiform Fibers to Animals. . . . . . . . . . e ~ ~ ~ ~ ~ ~ 300 APPENDIX G: Development of Some Equat ions Used for Quant itat ive Risk As se s sment . . . . . . . . . . . 311 APPENDIX H: Comparative Risk Assessment Score Sheet s . . . . . 314 APPENDIX I: Background Information on Members of the Committee on Nonoccupational Health Risks of Asbestiform Fibers . . . . . . . . . . . . . .332 xv

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