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Medical and Biologic Effects of Environmental Pollutants ARSENIC Committee on Medical and Biologic Effects of Environmental Pollutants DIVISION OF MEDICAL SCIENCES ASSEMBLY OF LIFE SCIENCES NATIONAL RESEARCH COUNCIL NATIONAL ACADEMY OF SC IENCE S WASHINGTON, D.C. 1977

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Other volumes in the Medical and Biologic Effects of Environmental Pollutants series (formerly named Biologic Effects of Atmospheric Pollutants): ASBESTOS (ISBN 0-309-01927-3) CHLORINE AND HYDROGEN CHLORIDE (ISBN 0-309-02519-2) CHROMIUM (ISBN 0-309-02217-7) COPPER (ISBN 0-309-02536-2) FLUORIDES (ISBN 0-309-01922-2) LEAD (ISBN 0-309-01941-9) MANGANESE (ISBN 0-309-02143-X) NICKEL (ISBN 0-309-02314-9) OZONE AND OTHER PHOTOCHEMICAL OXIDANTS (ISBN 0-309-02531-1) PARTICULATE POLYCYCLIC ORGANIC MATTER (ISBN 0-309-62027-1) SELENIUM (ISBN 0-309-02503-6) VANADIUM (ISBN 0-309-02218-5) VAPOR-PHASE ORGANIC POLLUTANTS (ISBN 0-309-02441-2) 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 work on which this publication is based was performed pursuant to Contract No. 68-02-1226 with the Environmental Protection Agency. International Standard Book Number 0-309-02604-0 Library of Congress Catalog Card No. 77-81690 Available from Printing and Publishing Office, National Academy of Sciences 2101 Constitution Avenue, N.W., Washington, D.C. 20418 Printed in the United States of America

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SUBCOMMITTEE ON ARSENIC ORVILLE A. LEVANDER, Agricultural Research Center, Beltsville, Maryland, Chairman ROY E. ALBERT, New York University Medical Center, New York R. K. BOUTWELL, University of Wisconsin, Madison, Wisconsin WILLIAM B. BUCK, Iowa State University, Ames, Iowa ANTHONY CAEABRESE, National Marine Fisheries Service, Milford, Connecticut CORLETTE C. CALVERT, Agricultural Research Center, Beltsville, Maryland ALDEN S. CRAFTS, University of California, Davis, California CYRUS FELDMAN, Oak Ridge National Laboratory, Oak Ridge, Tennessee MICHAEL FEElSCHER, U.S. Geological Survey, Washington, D.C. KURT I. IRGOLIC, Texas A&M University, College Station, Texas PHILIP C. KEARNEY, Agricultural Research Center, Beltsville, Maryland LYMAN MOORE, Bureau of Land Management, Salt Lake City, Utah S. A. PEOPLES, University of California, Davis, California JOSEPH H. SOARES, JR., University of Maryland, College Park, Maryland WARREN E. C. WACKER, Harvard University, Cambridge, Massachusetts DOROTHY B. WINDHORST, Hoffmann-La Roche, Inc., Nutley, New Jersey EDWIN A. WOOLSON, Agricultural Research Center, Beltsville, Maryland RALPH A. ZINGARO, Texas A&M University, College Station, Texas T. D. BOAZ, JR., Division of Medical Sciences, National Research Council, Washington, D.C., Staff Officer -- 111

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COMMITTEE ON MEDICAL AND BIOLOGIC EFFECTS OF ENVIRONMENTAL POLLUTANTS HERSCHEL E. GRIFFIN, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, Chairman RONALD F. COBURN, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania T. TIMOTHY CROCKER, University of California College of Medicine, Irvine, California CLEMENT A. FINCH, University of Washington School of Medicine, Seattle, Washington SHELDON K. FRIEDLANDER, California Institute of Technology, Pasadena, California ROBERT I. HENKIN, Georgetown University Hospital, Washington, D.C. IAN T. T. HIGGINS, School of Public Health, University of Michigan, Ann Arbor, Michigan JOE W. HIGHTOWER, Rice University, Houston, Texas HENRY KAMIN, Duke University Medical Center, Durham, North Carolina ORVILLE A. LEVANDER, Agricultural Research Center, Beltsville, Maryland DWIGHT F. METZLER, Kansas State Department of Health and Environment, Topeka, Kansas I. HERBERT SCHEINBERG, Albert Einstein College of Medicine, New York, New York RALPH G. SMITH, School of Public Health, University of Michigan, Ann Arbor, Michigan ROGER P. SMITH, Dartmouth Medical School, Hanover, New Hampshire T. D. BOAZ, JR., Division of Medical Sciences, National Research Council, Washington, D.C., Exec utive Direr tar iv

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Acknowledgments This document represents a coordinated effort on the part of the members of the Subcommittee on Arsenic, who reviewed and revised each other's work. Hence, it is more than a compilation of separate items written by separate authors. The contributions of individual authors are shown below. The summary, conclusions, and recom- mendations represent a consensus of the members of the Subcommit- tee. Chapter 1, the introduction, was written by Dr. Orville A. Levander, chairman of the Subcommittee. Chapter 2, on the chemistry of arsenic, was the work of Drs. Kurt J. Irgolic, Warren E. C. Wacker, and Ralph A. Zingaro. Chapter 3, on the distribution of arsenic in the environ- ment, contains the contributions of several authors, Dr. Edwin A. Woolson being responsible for its development. Mr. Lyman Moore and Drs. Michael Fleischer and Woolson prepared the section on natural sources. Drs. Philip C. Kearney and Woolson were responsible for the section on man-made sources, except the material on feed additives, which was prepared by Dr. William B. Buck; that on drugs and on war gases and riot-control agents, by Dr. S. A. Peoples; and that on dis- posal, by Dr. Corlette C. Calvert. The section on plants in Chapter 4, on the metabolism of arsenic, was the responsibility of Dr. Alden S. Crafts, but the remainder of the v

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Vl Acknowledgments chapter was prepared by Dr. Peoples. For Chapter 5, on the biologic effects of arsenic on plants and animals, Dr. Levander contributed the sections on microorganisms and laboratory animals, Dr. Crafts the section on plants, Dr. Buck that on domestic animals, Dr. Anthony Calabrese that on aquatic organisms, and Dr. Joseph H. Soares, Jr., that on wildlife. In Chapter 6, on the biologic effects of arsenic on man, the section on toxicity was written by Dr. Dorothy B. Windhorst, except for the part dealing with occupational episodes of toxicity, which was the work of Dr. Roy E. Albert; Dr. R. K. Boutwell contributed the sections on teratogenesis and on mutagenesis; and Drs. Albert and Boutwell were jointly responsible for the sections on car- cinogenesis and evaluation. Dr. Woolson compiled the material appearing in Appendix A, on the arsenic content of plants and plant products, and in Appendix B. on the arsenic content of animals. Mr. Cyrus Feldman was the author of Appendix C, on the determination of arsenic in natural materials. Ms. Joan Stokes checked all the bibliographic references for accu- racy and compiled the consolidated reference list. The manuscript was edited by Mr. Norman Grossblatt, who also compiled the glossary in coordination with Dr. Irgolic. Free use was made of the resources available at the National Library of Medicine, the National Agricultural Library, the Library of Con- gress, and the Air Pollution Technical Information Center of the Environmental Protection Agency. Also acknowledged is the assis- tance given to the Subcommittee by the National Research Council's Advisory Center on Toxicology, the National Academy of Sciences Library, the Environmental Studies Board, and various units of the National Research Council.

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Contents Introduction Chemistry of Arsenic Distribution of Arsenic in the Environment 4 Metabolism of Arsenic 5 Biologic Effects of Arsenic on Plants and Animals 6 Biologic Effects of Arsenic on Man 7 Summary and Conclusions 8 Recommendations Appendix A: Arsenic Content of Plants and Plant Products Appendix B: Arsenic Content of Animals Appendix C: Determining Traces of Arsenic in Natural Materials Glossary References Index e V11 4 16 80 117 173 216 227 233 243 255 263 277 323 /

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