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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (1997)
Commission on Life Sciences (CLS)

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests

TOXICOLOGIC ASSESSMENT OF THE ARMY'S ZINC CADMIUM SULFIDE DISPERSION TESTS

SUBCOMMITTEE ON ZINC CADMIUM SULFIDE

COMMITTEE ON TOXICOLOGY

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

COMMISSION ON LIFE SCIENCES

NATIONAL RESEARCH COUNCIL

NATIONAL ACADEMY PRESS
WASHINGTON, D.C.,
1997

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I

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests TOXICOLOGIC ASSESSMENT OF THE ARMY'S ZINC CADMIUM SULFIDE DISPERSION TESTS SUBCOMMITTEE ON ZINC CADMIUM SULFIDE COMMITTEE ON TOXICOLOGY BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY COMMISSION ON LIFE SCIENCES NATIONAL RESEARCH COUNCIL NATIONAL ACADEMY PRESS WASHINGTON, D.C., 1997

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests NATIONAL ACADEMY PRESS 2101 Constitution Avenue, NW Washington, DC 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 project was supported by contract DAMD 17-89-C-9086 between the National Academy of Sciences and the U.S. Army. Any opinions, findings, 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. Library of Congress Catalog Card Number 97-67216 International Standard Book Number 0-309-05783-3 Additional copies of this report are available from: National Academy Press 2101 Constitution Ave., NW Box 285 Washington, DC 20055 800-624-6242 or 202-334-3313 (in the Washington Metropolitan Area) http://www.nap.edu Copyright 1997 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests SUBCOMMITTEE ON ZINC CADMIUM SULFIDE ROGENE F. HENDERSON (Chair), Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico GERMAINE M. BUCK, State University of New York at Buffalo, New York JOHN E. CONNETT, University of Minnesota, Minneapolis, Minnesota ELAINE FAUSTMAN, University of Washington, Seattle, Washington CHARLES E. FEIGLEY, University of South Carolina, Columbia, South Carolina DONALD E. GARDNER, Inhalation Toxicology Associates, Raleigh, North Carolina DAVID W. GAYLOR, U.S. Food and Drug Administration, Jefferson, Arkansas ROBERT A. GOYER, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina LOREN D. KOLLER, Oregon State University, Corvallis, Oregon STEPHEN U. LESTER, Citizens Clearing House for Hazardous Waste, Falls Church, Virginia THOMAS E. MCKONE, University of California, Berkeley, California MICHAEL J. THUN, American Cancer Society, Atlanta, Georgia BAILUS WALKER, JR., Howard University, Washington, D.C. SUSAN D. WILTSHIRE, JK Research Associates, Inc., Hamilton, Massachusetts HANSPETER R. WITSCHI, University of California, Davis, California Sponsor: U.S. Army

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests Staff KULBIR S. BAKSHI, Project Director DIANE J. MUNDT, Senior Program Officer ERIN M. BELL, Research Associate SUSAN N. J. PANG, Research Associate RUTH E. CROSSGROVE, Staff Associate NORMAN GROSSBLATT, Editor LINDA LEONARD, Senior Project Assistant LUCY V. FUSCO, Project Assistant KATHRINE IVERSON, Information Specialist

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests COMMITTEE ON TOXICOLOGY ROGENE F. HENDERSON (Chair), Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico DONALD E. GARDNER (Vice-Chair), Inhalation Toxicology Associates, Raleigh, North Carolina GERMAINE M. BUCK, State University of New York at Buffalo, New York DEBORAH A. CORY-SLECHTA, University of Rochester, Rochester, New York KEVIN E. DRISCOLL, Procter & Gamble Company, Cincinnati, Ohio ELAINE M. FAUSTMAN, University of Washington, Seattle, Washington CHARLES E. FEIGLEY, University of South Carolina, Columbia, South Carolina DAVID W. GAYLOR, U.S. Food and Drug Administration, Jefferson, Arkansas IAN A. GREAVES, University of Minnesota, Minneapolis, Minnesota SIDNEY GREEN, Corning Hazleton, Inc., Vienna, Virginia WILLIAM E. HALPERIN, National Institute for Occupational Safety and Health, Atlanta, Georgia LOREN D. KOLLER, Oregon State University, Corvallis, Oregon GEORGE B. KOELLE, University of Pennsylvania, Philadelphia, Pennsylvania DANIEL KREWSKI, Health Canada, Ottawa, Ontario THOMAS E. MCKONE, University of California, Berkeley, California MICHELE A. MEDINSKY, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina JOHN L. O'DONOGHUE, Eastman Kodak Company, Rochester, New York ROBERT SNYDER, Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey BERNARD M. WAGNER, Wagner Associates, Inc., Millburn, New Jersey BAILUS WALKER JR., Howard University, Washington, D.C. ANNETTA P. WATSON, Oak Ridge National Laboratory, Oak Ridge, Tennesee HANSPETER R. WITSCHI, University of California, Davis, California GAROLD S. YOST, University of Utah, Salt Lake City, Utah

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests Staff KULBIR S. BAKSHI, Program Director MARGARET E. MCVEY, Program Officer SUSAN N. J. PANG, Research Associate ABIGAIL STACK, Research Associate RUTH E. CROSSGROVE, Editor CATHERINE M. KUBIK, Senior Program Assistant LINDA V. LEONARD, Senior Project Assistant LUCY V. FUSCO, Project Assistant

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY PAUL G. RISSER (Chair), Oregon State University, Corvallis, Oregon MAY R. BERENBAUM, University of Illinois, Urbana, Illinois EULA BINGHAM, University of Cincinnati, Cincinnati, Ohio PAUL BUSCH, Malcolm Pirnie, Inc., White Plains, New York EDWIN H. CLARK II, Clean Sites, Inc., Alexandria, Virginia ELLIS COWLING, North Carolina State University, Raleigh, North Carolina GEORGE P. DASTON, The Procter & Gamble Co., Cincinnati, Ohio PETER L. DEFUR, Virginia Commonwealth University, Richmond, Virginia DAVID L. EATON, University of Washington, Seattle, Washington DIANA FRECKMAN, Colorado State University, Ft. Collins, Colorado ROBERT A. FROSCH, Harvard University, Cambridge, Massachusetts DANIEL KREWSKI, Health & Welfare Canada, Ottawa, Ontario RAYMOND C. LOEHR, The University of Texas, Austin, Texas WARREN MUIR, Hampshire Research Institute, Alexandria, Virginia GORDON ORIANS, University of Washington, Seattle, Washington GEOFFREY PLACE, Hilton Head, South Carolina BURTON H. SINGER, Princeton University, Princeton, New Jersey MARGARET STRAND, Bayh, Connaughton and Malone, Washington, D.C. BAILUS WALKER, JR., Howard University, Washington, D.C. GERALD N. WOGAN, Massachusetts Institute of Technology, Cambridge, Massachusetts TERRY F. YOSIE, E. Bruce Harrison Co., Washington, D.C. Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Associate Director and Program Director for Natural Resources and Applied Ecology CAROL A. MACZKA, Program Director for 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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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests COMMISSION ON LIFE SCIENCES THOMAS D. POLLARD (Chair), The Salk Institute, La Jolla, California FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOHN C. BAILAR III, University of Chicago, Chicago, Illinois PAUL BERG, Stanford University School of Medicine, Stanford, California JOHN E. BURRIS, Marine Biological Laboratory, Woods Hole, Massachusetts SHARON L. DUNWOODY, University of Wisconsin, Madison, Wisconsin URSULA W. GOODENOUGH, Washington University, St. Louis, Missouri HENRY W. HEIKKINEN, University of Northern Colorado, Greeley, Colorado HANS J. KENDE, Michigan State University, East Lansing, Michigan SUSAN E. LEEMAN, Boston University School of Medicine, Boston, Massachusetts THOMAS E. LOVEJOY, Smithsonian Institution, Washington, D.C. DONALD R. MATTISON, University of Pittsburgh, Pittsburgh, Pennsylvania JOSEPH E. MURRAY, Wellesley Hills, Massachusetts EDWARD E. PENHOET, Chiron Corporation, Emeryville, California EMIL A. PFITZER, Research Institute for Fragrance Materials, Hackensack, New Jersey MALCOLM C. PIKE, University of Southern California, Los Angeles, California HENRY C. PITOT III, University of Wisconsin, Madison, Wisconsin JONATHAN M. SAMET, The Johns Hopkins University, Baltimore, Maryland CHARLES F. STEVENS, The Salk Institute, La Jolla, California JOHN L. VANDEBERG, Southwest Foundation for Biomedical Research, San Antonio, Texas PAUL GILMAN, Executive Director

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests OTHER RECENT REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY Carcinogens and Anticarcinogens in the Human Diet: A Comparison of Naturally Occurring and Synthetic Substances (1996) 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 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) Tracking Toxic Substances at Industrial Facilities (1990) Copies of these reports may be ordered from the National Academy Press (800) 624-6242 (202) 334-3313

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests OTHER RECENT REPORTS OF THE COMMITTEE ON TOXICOLOGY Toxicity of Military Smokes and Obscurants, Volume 1 (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), and Volume 3 (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)

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests 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. 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 Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests PREFACE DURING THE 1950s and 1960s, the U.S. Army conducted dispersion tests using particles of zinc cadmium sulfide (ZnCdS) as a nonbiologic simulant of biologic-warfare agents in a number of urban and rural locations in the United States and Canada. This report, by the Subcommittee on Zinc Cadmium Sulfide of the National Research Council's Committee on Toxicology, is intended to assist the Army and the U.S. Congress in their efforts to determine whether exposure to ZnCdS particles adversely affected the health of persons living in the areas where the dispersion tests were conducted. The report independently reviews the available toxicity data on ZnCdS and its components cadmium and zinc, assesses human exposures to ZnCdS, and characterizes the risk to people exposed to it through the Army's dispersion tests. The subcommittee was greatly assisted by several persons who provided information on the Army's ZnCdS dispersion tests and toxicity data on ZnCdS and its components. The subcommittee gratefully wishes to acknowledge William Barnett, Amy Birks, Leslie Burger, John Doesberg, Dennis Druck, Frederick Erdtman, Robert M. Gum, Bernard Ingold, Jeffrey Kirkpatrick, Francis O'Donnell, Forrest Oliverson, John Riggs, and Carmen J. Spencer—all of the U.S. Army—for their interest in and support of the project, as well as Amy S. Adair, Kenneth R. Boley, Monica Chavez, Cathy M. Collier, Marjorie A. Duske, Michael Erlandson, Christine Hawk, Thomas C. Keller, John L. Less, Derek D. Lick, Dobie O. McArthur, and Jennifer M. Tisdale—of the staff of the U.S. Congress. We are grateful to Edmund Crouch of Cambridge Environmental, Inc.,

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests for reviewing the Army's data on the ZnCdS dispersion tests and for estimating the doses and concentrations of ZnCdS particles. We are also grateful to Sheila Fabiano (USR Optronix), Terry Gordon (New York University Medical Center), Gunter Oberdörster (University of Rochester), and Bruce Parkinson (University of Colorado), for making presentations or providing material to the subcommittee. The subcommittee also wishes to thank the several hundred persons who took the time and made the effort to meet with or present material to the subcommittee at the public meetings. As chair of the subcommittee, I am grateful for the assistance of the National Research Council staff in the preparation of the report. Staff members who contributed to this effort are Paul Gilman, executive director of the Commission on Life Sciences; James J. Reisa, director of the Board on Environmental Studies and Toxicology; Carol A. Maczka, program director for toxicology and risk assessment; Diane J. Mundt and Erin M. Bell of the Medical Follow-up Agency, Institute of Medicine; Jamie E. Young, Board on Environmental Studies and Toxicology; Norman Grossblatt, editor; Susan N.J. Pang, research associate; Ruth E. Crossgrove, staff associate; and Lucy V. Fusco, project assistant. I especially wish to recognize the major contributions of the project director, Kulbir S. Bakshi, who exhaustively studied the literature and drafted several sections of the report. He worked tirelessly to obtain information, and he organized the study plan, the subcommittee and public meetings, the special presentations, and this final report. Finally, I would like to thank all the members of the subcommittee (who worked without compensation in public service) for their expertise and dedicated effort throughout the development of this report. The members of the subcommittee represented an unusually diverse set of disciplines, from laboratory scientists to epidemiologists to risk-communication experts. Despite this diversity, which was essential for consideration of the many issues involved in the problem we were addressing, the members worked together in a highly effective manner. Discussions were open, honest, and vigorous. For the untiring efforts of these dedicated people, I am sincerely grateful! Rogene F. Henderson, PhD Chair, Subcommittee on Zinc Cadmium Sulfide and Chair, Committee on Toxicology

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests CONTENTS SUMMARY   1 1 INTRODUCTION   17     ZnCdS Dispersion Tests   18     Public Concern in Response to ZnCdS Dispersion Tests   19     Tasks of the Subcommittee   20     Sources of Data   22     Structure of the Report   24 2 INPUT FROM THE PUBLIC   25     Nature of Comments   26     Specific Health Problems   29     Conclusions   30 3 TOXICITY AND RELATED DATA ON ZINC CADMIUM SULFIDE   32     Physical and Chemical Properties   32     Toxicokinetics and Bioavailability of ZnCdS: Availability of Cadmium from ZnCdS   35     Toxicity   35     Implications of Variable Composition   37     Conclusions and Recommendations   37 4 TOXICITY AND RELATED DATA ON SELECTED CADMIUM COMPOUNDS   39     Physical and Chemical Properties of Cadmium Compounds   40

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests     Toxicokinetics of Cadmium Compounds   42     Toxicity of Cadmium Compounds   43     Carcinogenicity of Cadmium Compounds   51     Conclusions   55 5 EXPOSURE ASSESSMENT   57     Zinc Cadmium Sulfide   57     Cadmium   60     Conclusions   65 6 RISK CHARACTERIZATION OF EXPOSURES TO ZINC CADMIUM SULFIDE   67     Risk Assessment for Noncancer Health Effects   68     Risk Assessment for Cancer   72     Conclusions   79 7 SCIENTIFIC FEASIBILITY OF EPIDEMIOLOGIC STUDY   82     Nature of Epidemiologic Investigations   83     Key Methodologic Issues   84     Types of Epidemiologic Studies   89     Conclusions   91 8 CONCLUSIONS AND RECOMMENDATIONS   94     Input from the Public   94     Toxicity and Related Data on Zinc Cadmium Sulfide   95     Toxicity and Related Data on Selected Cadmium Compounds   95     Exposure Assessment   96     Risk Assessment of ZnCdS Exposures   97     Feasibility of Epidemiologic Study   98     Recommendations   98 REFERENCES   100 APPENDIX A: Historical Background of the U.S. Biological Warfare Program   112 APPENDIX B: Summary of Doses and Concentrations of Zinc Cadmium Sulfide Particles from the Army's Dispersion Tests   122 APPENDIX C: Correspondence from the Army   296 APPENDIX D: Interaction of Zinc and Cadmium and Toxicity of Zinc Cadmium Sulfide Activators   299

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests APPENDIX E: Public Meetings Agendas   302 APPENDIX F: Sampling and Analytic Methods for Zinc Cadmium Sulfide   311 APPENDIX G: Review of AEHA Risk Assessment Reports on Zinc Cadmium Sulfide   316 APPENDIX H: Review of EPA, ATSDR, and CDC Comments on the Army's Risk Assessment Reports on Zinc Cadmium Sulfide   335 APPENDIX I: Cadmium Exposure Assessment, Transport, and Environmental Fate   338 GLOSSARY   361

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Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests TOXICOLOGIC ASSESSMENT OF THE ARMY'S ZINC CADMIUM SULFIDE DISPERSION TESTS

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