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Science and Judgment in Risk Assessment Committee on Risk Assessment of Hazardous Air Pollutants Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1994
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Page 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 competencies 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 project was supported by the U.S. Environmental Protection Agency under contract CR818293-01-0. Library of Congress Cataloging-in-Publication Data Science and judgment in risk assessment / Committee on Risk Assessment of Hazardous Air Pollutants, Board on Environmental Studies and Toxicology, Commission on Life Sciences., National Research Council. p. cm Includes bibliographal references and index. ISBN 0-309-04894-X 1. AirPollutionToxicologyUnited StatesStatistical methods. 2. Health risk assessmentStatistical methods. I. National Research Council (U.S.). Committee on Risk Assessment of Hazardous Air Pollutants. RA576.S365 1994 363.73'92'0973dc20 94-17475 CIP Copyright 1994 by the National Academy of Sciences. All rights reserved. Printed in the United States of America
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Page iii Committee On Risk Assessment Of Hazardous Air Pollutants KURT J. ISSELBACHER (Chairman), Massachusetts General Hospital, Charlestown, Mass. ARTHUR C. UPTON (Vice-Chairman), New York University Medical Center (retired), N.Y. JOHN C. BAILAR, McGill University School of Medicine, Montreal, Canada KENNETH B. BISCHOFF, University of Delaware, Newark, Del. KENNETH T. BOGEN, Lawrence Livermore National Laboratory, Livermore, Calif. JOHN I. BRAUMAN, Stanford University, Calif. DAVID D. DONIGER, Natural Resources Defense Council, Washington, D.C.* JOHN DOULL, University of Kansas Medical Center, Kansas City, Kan. ADAM M. FINKEL, Resources for the Future, Washington, D.C. CURTIS C. HARRIS, National Cancer Institute, Bethesda, Md. PHILIP K. HOPKE, Clarkson University, Potsdam, N.Y. SHEILA S. JASANOFF, Cornell University, Ithaca, N.Y. ROGER O. McCLELLAN, Chemical Industry Institute of Toxicology, Research Triangle Park, N.C. LINCOLN E. MOSES, Stanford University, Calif. D. WARNER NORTH, Decision Focus, Inc., Mountain View, Calif. CRAIG N. OREN, Rutgers University School of Law, Camden, N.J. REBECCA T. PARKIN, Beccam Services, Plainsboro, N.J. EDO D. PELLIZZARI, Research Triangle Institute, N.C. JOSEPH V. RODRICKS, Environ Corporation, Arlington, Va. ARMISTEAD G. RUSSELL, Carnegie-Mellon University, Pittsburgh, Penn. JAMES N. SEIBER, University of Nevada, Reno, Nev. STEVEN N. SPAW, Law Environmental Incorporated, Austin, Tex. JOHN D. SPENGLER, Harvard University, Boston, Mass. BAILUS WALKER, University of Oklahoma, Oklahoma City, Okla. HANSPETER WITSCHI, University of California, Davis, Calif. Staff RICHARD D. THOMAS, Program Director DEBORAH D. STINE, Study Director MARVIN A. SCHENIDERMAN, Senior Staff Scientist GAIL CHARNELY, Senior Staff Officer KATHLEEN STRATTON, Senior Staff Officer RUTH E. CROSSGROVE, Information Specialist ANNE M. SPRAGUE, Information Specialist RUTH P. DANOFF, Project Assistant SHELLEY A. NURSE, Senior Project Assistant CATHERINE M. KUBIK, Senior Project Assistant *Left committee in May 1993 upon becoming Deputy Director of the White House Office of Environmental Quality
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Page iv Board On Environmental Studies And Toxicology PAUL G. RISSER (Chair), University of Miami, Oxford, Ohio FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. MICHAEL J. BEAN, Environmental Defense Fund, Washington, D.C. EULA BINGHAM, University of Cincinnati, Cincinnati, Ohio EDWIN H. CLARK, Clean Sites, Inc., Alexandria, Va. ALLAN H. CONNEY, Rutgers University, N.J. JOHN L. EMMERSON, Eli Lilly & Company, Greenfield, Ind. ROBERT C. FORNEY, Unionville, Pa. ROBERT A. FROSCH, Harvard University, Cambridge, Mass. KAI LEE, Williams College, Williamstown, Mass. JANE LUBCHENCO, Oregon State University, Corvallis, Ore. HAROLD A. MOONEY, Stanford University, Stanford, Calif. GORDON ORIANS, University of Washington, Seattle, Wash. FRANK L. PARKER, Vanderbilt University, Nashville, Tenn., and Clemson University, Anderson, S. C. GEOFFREY PLACE, Hilton Head, S. C. DAVID P. RALL, Washington, D.C. LESLIE A. REAL, Indiana University, Bloomington, Ind. KRISTIN SHRADER-FRECHETTE, University of South Florida, Tampa, Fla. GERALD VAN BELLE, University of Washington, Seattle, Wash. BAILUS WALKER, JR., University of Oklahoma, Oklahoma City, Okla. Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Associate Director and Program Director for Natural Resources and Applied Ecology RICHARD D. THOMAS, Associate Director and Program Director for Human Toxicology and Risk Assessment LEE R. PAULSON, Program Director for Information Systems and Statistics RAYMOND A. WASSEL, Program Director for Environmental Sciences and Engineering
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Page v Commission On Life Sciences THOMAS D. POLLARD (Chair), Johns Hopkins Medical School, Baltimore, Md. BRUCE N. AMES, University of California, Berkeley, Calif. JOHN C. BAILAR, III, McGill University, Montreal, Canada J. MICHAEL BISHOP, Hooper Research Foundation, University of California Medical Center, San Francisco, Calif. JOHN E. BURRIS, Marine Biological Laboratory, Woods Hole, Mass. MICHAEL T. CLEGG, University of California, Riverside, Calif. GLENN A. CROSBY, Washington State University, Pullman, Wash. LEROY E. HOOD, University of Washington, Seattle, Wash. MARIAN E. KOSHLAND, University of California, Berkeley, Calif. RICHARD E. LENSKI, Michigan State University, East Lansing, Mich. EMIL A. PFITZER, Hoffmann-La Roche Inc., Nutley, N.J. MALCOLM C. PIKE, University of Southern California School of Medicine, Los Angeles, Calif. HENRY C. PITOT, III, University of Wisconsin, Madison, Wisc. PAUL G. RISSER, Miami University, Oxford, Ohio JOHNATHAN M. SAMET, University of New Mexico School of Medicine, Albuquerque, N.Mex. HAROLD M. SCHMECK, JR., Armonk, N.Y. CARLA J. SHATZ, University of California, Berkeley, Calif. SUSAN S. TAYLOR, University of California at San Diego, La Jolla, Calif. P. ROY VAGELOS, Merck & Company, Whitehouse Station, N.J. JOHN L. VANDEBERG, Southwestern Foundation for Biomedical Research, San Antonio, Tex. TORSTEN N. WIESEL, Rockefeller University, New York, N.Y. PAUL GILMAN, Executive Director
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Page vi The National Academy of Sciences is a private, non-profit, 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. Robert M. White 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. Robert M. White are chairman and vice chairman, respectively, of the National Research Council.
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Page vii Other Recent Reports Of The Board On Environmental Studies And Toxicology 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) Biologic Markers in Immunotoxicology (1992) Dolphins and the Tuna Industry (1992) Environmental Neurotoxicology (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) Biologic Markers in Pulmonary Toxicology (1989) Biologic Markers in Reproductive Toxicology (1989) Copies of these reports may be ordered from the National Academy Press (800) 624-6242 (202) 334-3313
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Page ix Preface In the Clean Air Act Amendments of 1990, Congress directed the administrator of the Environmental Protection Agency (EPA) to engage the National Academy of Sciences (NAS) in a review of the methods that EPA uses to estimates toxicological risk. The resulting charge to the National Research Council (NRC) can be summarized in a short set of questions: 1. Given that quantitative risk assessment is essential for EPA's implementation of the Clean Air Act, is EPA conducting risk assessments in the best possible manner? 2. Has EPA developed mechanisms for keeping its risk-assessment procedures current in the face of new developments in science? 3. Are adequate risk-related data being collected to permit EPA to carry out its mandates? 4. What, if anything, should be done to improve EPA's development and use of risk assessments? To meet the congressional mandate, and in response to the request from the administrator of EPA, the National Research Council established the Committee on Risk Assessment of Hazardous Air Pollutants under the the Board on Environmental Studies and Toxicology. The committee consisted of 25 members with expertise in medicine, epidemiology, chemistry, chemical engineering, environmental health, law, pharmacology and toxicology, risk assessment, risk management, occupational health, statistics, air monitoring, and public health. It included academics, industry scientists, public advocates, and state and local public-health officials.
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Page x The first meeting of the committee was held on October 31, 1991. In the first several meetings, presentations were made to the committee by committee members and by individuals or representatives of groups with special concerns in the development and use of risk assessment. Among the latter were presenters on behalf of the American Industrial Health Council, the Chemical Manufacturers Association, the American Petroleum Institute, the American Iron and Steel Institute, the American Chemical Society, such official public-health groups as the Texas Air Control Board and the State and Territorial Air Pollution Program Administrators, and such public-interest groups as the Natural Resources Defense Council and the Environmental Defense Fund. Presentations were also made by the representative of a paint manufacturer and by a senior member of an environmental consulting company. The committee also was greatly aided by the previous reports and workshops of the NRC's Committee on Risk Assessment Methodology. Early in the course of its deliberations the committee developed a set of issues for consideration and reply by EPA's Office of Air and Radiation and its Office of Research and Development. EPA's responses were presented to the committee during the committee's meetings in late March 1992. James Powell, of the U.S. Senate staff, described to the committee both the legislative history of the Clean Air Act Amendments and the concerns of senators in the evolution of EPA's development of regulations. Greg Wetstone, of the U.S. House of Representatives staff, spoke to the committee about the need for accurate risk assessments and exposure measures. Henry Habicht, Michael Shapiro, Robert Kellum, and William Farland of EPA discussed where EPA was in risk assessment and how it got there. Their briefings enabled the committee to get off to a quick start in its work. The committee was substantially helped in its activities by strong support from the NRC and BEST staff: Richard D. Thomas, the program director; Deborah D. Stine, the study director; Marvin A. Schneiderman, senior staff scientist; Norman Grossblatt, editor; Anne M. Sprague, information specialist; Ruth E. Crossgrove, information specialist; Ruth P. Danoff, project assistant; and Shelley A. Nurse and Catherine M. Kubik, senior project assistants. Finally, we must express our thanks and appreciation to the hard-working members of the committee, who struggled through long meetings, read mountains of documents, listened with interest and concern to many presentations, and then prepared what we consider to be a thoughtful, comprehensive, and balanced report. Kurt Isselbacher, M.D. Chairman Arthur Upton, M.D. Vice Chairman
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Page xi Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 16 Charge to the Committee 17 Conceptual Framework of the Report 21 PART I CURRENT APPROACHES TO RISK ASSESSMENT 23 2 RISK ASSESSMENT AND ITS SOCIAL AND REGULATORY CONTEXTS 25 General Concepts 25 Historical Roots 29 NRC Study of Risk Assessment in the Federal Government 33 Events After Release of the 1983 NRC Report 34 Uses of Risk Assessment in the Regulation of Hazardous Air Pollutants 36 Noncancer Risk Associated with Hazardous Air Pollutants 39 Public Criticism of Conduct and Uses of Risk Assessment 40 3 EXPOSURE ASSESSMENT 43 Introduction 43 Emission Characterization 47 Modeling Used in Exposure Assessment 50
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Page xii 4 ASSESSMENT OF TOXICITY 56 Introduction 56 Principles of Toxicity Assessment 56 New Trends in Toxicity Assessment 66 5 RISK CHARACTERIZATION 68 Introduction 68 Elements of Risk Characterization 69 PART II STRATEGIES FOR IMPROVING RISK ASSESSMENT 79 The Need for Risk-Assessment Principles 80 Reporting Risk Assessments 83 The Iterative Approach 84 6 DEFAULT OPTIONS 85 Adoption of Guidelines 85 Departures from Default Options 90 Current EPA Practice in Departing from Default Options 92 Findings and Recommendations 104 Process for Departures 105 7 MODELS, METHODS, AND DATA 106 Introduction 106 Emission Characterization 107 Exposure Assessment 112 Assessment of Toxicity 119 Findings and Recommendations 137 8 DATA NEEDS 144 Context of Data Needs 144 Implications for Priority-Setting 145 Data Needed for Risk Assessment 146 Data Management 156 Findings and Recommendations 157 9 UNCERTAINTY 160 Context of Uncertainty Analysis 160 Nature of Uncertainty 161 Problems with EPA's Current Approach to Uncertainty 166 Some Alternatives to EPA'S Approach 167 Specific Guidance on Uncertainty Analysis 175
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Page xiii Risk Management and Uncertainty Analysis 179 Comparison, Ranking, and Harmonization of Risk Assessments 183 Findings and Recommendations 184 10 VARIABILITY 188 Introduction and Background 188 Exposure Variability 196 Variability in Human Susceptibility 200 Conclusions 203 Findings and Recommendations 217 11 AGGREGATION 224 Introduction 224 Exposure Routes 225 Risk-Inducing Agents 226 Types of Nonthreshold Risk 229 Measures and Characteristics of Risk 234 Findings and Recommendations 240 PART III IMPLEMENTATION OF FINDINGS 243 12 IMPLEMENTATION 245 Priority-Setting and Section 112 245 Iterative Risk Assessment 246 EPA Practices: Points to Consider 252 Institutional Issues in Risk Assessment and Management 256 Summary 263 Findings and Recommendations 264 REFERENCES 269 APPENDIXES A Risk Assessment Methodologies: EPA's Responses to Questions from the National Academy of Sciences 289 B EPA Memorandum from Henry Habicht 351 C Calculation and Modeling of Exposure 375 D Working Paper for Considering Draft Revisions to the U.S. EPA Guidelines for Cancer Risk Assessment 383 E Use of Pharmacokinetics to Extrapolate from Animal Data to Humans 449 F Uncertainty Analysis of Health Risk Estimates 453
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Page xiv G Improvement in Human Health Risk Assessment Utilizing Site- and Chemical-Specific Information: A Case Study 479 H–1 Some Definitional Concerns About Variability 503 H–2 Individual Susceptibility Factors 505 I Aggregation 515 J A Tiered Modeling Approach for Assessing the Risks Due to Sources of Hazardous Air Pollutants 537 K Science Advisory Board Memorandum on the Integrated Risk Information System and EPA Response 583 L Development of Data Used in Risk Assessment 591 M Charge to the Committee 599 N–1 The Case for ''Plausible Conservatism" in Choosing and Altering Defaults 601 N–2 Making Full Use of Scientific Information in Risk Assessment 629 INDEX 641
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SCIENCE and DGMENT in Risk Assessment
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