Dioxins and Health Dioxins and Health Edited by Arnold Schecter State University ofN ew York Health Science Center at Syracuse Clinical Campus at Binghamton Binghamton, New York Springer Science +B usiness Media, LLC Library of Congress Cataloging-in-Publication Data Dioxins and health / edited by Arnold Schecter. p. era. Includes bibliographical references and index. ISBN 978-1-4899-1464-4 1. Dioxins—Toxicology. I. Schecter, Arnold. RA1242.D55D58 1994 615.9'512—dc20 94-40007 CIP This limited facsimile edition has been issued for the purpose of keeping this title available to the scientific community. 10 98765432 ISBN 978-1-4899-1464-4 ISBN 978-1-4899-1462-0 (eBook) DOI 10.1007/978-1-4899-1462-0 © 1994 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1994 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors Olav Axelson • Department of Occupational Medicine, University Hospital, S-581 85 Linkoping, Sweden Pier Alberto Bertazzi • Institute of Occupational Health, Epidemiology Section, University of Milan, 20122 Milan, Italy Linda S. Birnbaum • Environmental Toxicology Division, Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Yung-Cheng Joseph Chen • Department of Psychiatry, National Cheng Kung University Medical College, Tainan 70428, Taiwan, Republic of China George C. Clark • National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, North Carolina 27709 Barry Commoner • Center for the Biology of Natural Systems, Queens College CUNY, Flushing, New York 11367 Peter L. deFur • Environmental Defense Fund, Washington, D.C. 20009 Michael J. DeVito • Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 Alessandro di Domenico • Laboratory of Comparative Toxicology and Ecotoxicology, Italian National Institute of Health, 00161 Rome, Italy Mikael Eriksson • Department of Oncology, University Hospital, S-901 85 Umea, Sweden John P. Giesy • Department of Fisheries and Wildlife, Pesticide Research Center and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824 Yue-Liang Leon Guo • Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan 70428, Taiwan, Republic of China v vi Contributors Lennart Hardell • Department of Oncology, Orebro Medical Centre, S-701 85 Orebro, Sweden Chen-Chin Hsu • Department of Psychiatry, National Cheng Kung University Medical College, Tainan 70428, Taiwan, Republic of China James Huff • Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Nancy I. Kerkvliet • Department of Agricultural Chemistry and Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon 97331 Philip J. Landrigan • Department of Community Medicine, Mount Sinai School of Medicine, New York, New York 10029 George W. Lucier • National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, North Carolina 27709 James P. Ludwig • The SERE Group, Ltd., Victoria, British Columbia, Canada V8P 3C8 Yoshito Masuda • Daiichi College of Pharmaceutical Sciences, Fukuoka 815, Japan William 1. Nicholson • Department of Community Medicine, Mount Sinai School of Medicine, New York, New York 10029 James R. Olson • Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214 Richard E. Peterson • School of Pharmacy and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53706 Christoffer Rappe • Institute of Environmental Chemistry, University of Umea, S-901 87 Umea, Sweden Walter J. Rogan • Intramural Research Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Susan L. Schantz • Institute for Environmental Studies, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 Arnold Schecter • Department of Preventive Medicine, University of New York Health Science Center-Syracuse, Binghamton, New York 13903 Richard F. Seegal • New York State Department of Health, Wadsworth Center for Laboratories and Research, Albany, New York 12201, and School of Public Health, University at Albany, State University of New York, Albany, New York 12203 Ellen K. Silbergeld • Environmental Defense Fund, Washington, D.C., 20009, and Department of Epidemiology and Preventive Medicine, University of Maryland Medical School, Baltimore, Maryland 21201 Contributors vii James R. Startin • Ministry of Agriculture, Fisheries and Food, Food Science Laboratory, Norwich Research Park, Colney, Norwich NR4 7UQ, United Kingdom Anne Sweeney • School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77025 H. Michael Theobald • School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706 Donald E. Tillitt • National Fisheries Contaminant Research Center, U.S. Fish and Wildlife Service, Columbia, Missouri 65201 Angelika M. Tritscher • National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, North Carolina 27709 Mary K. Walker • School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706 Thomas Webster • Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts 02118 Mei-Lin M. Yu • Department of Public Health, National Cheng Kung University Medical College, Tainan 70428, Taiwan, Republic of China Sheila Hoar Zahm • Occupational Studies Section, Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, Rockville, Maryland 20892 Douglas R. Zook • Institute of Environmental Chemistry, University of Umea, S-901 87 Umea, Sweden. Present address: University of Groningen, Mass Spectrometry Center, 9713 AW Groningen, The Netherlands Preface This book originated in a series of cross-disciplinary conversations in the years 1984-1990 between the editor, who is a physician-researcher involved in clinical and laboratory research, and a dioxin toxicologist. During the years in which the conversations took place, an extraordinary amount of new scientific literature was published related to dioxins, defined for purposes of this text as the chlorinated dibenzo-p-dioxins, dibenzofurans, polychlorinated biphe nyls (PCB's) and other compounds that are structurally and toxicologically similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7 ,8-TCDD), the most extensively studied and most toxic of this group of chemicals. Dioxins also began to interest not only chemists and toxicologists, but also specialists from diverse disciplines such as wildlife and environmental science, immunology, neuroscience,public health, epidemiology, med icine, government, law, sociology, and journalism. Specialists from such varied disciplines, while familiar with their own literature, frequently did not have time to follow the dioxin literature outside their specialty area. In addition, each specialty had unique knowledge, methods, and perspectives. Cross disciplinary conversation was necessary, but all too frequently, specialists from the various disciplines did not speak the same language, resulting in misunderstanding. This text was written to help facilitate cross-disciplinary discourse in the dioxin field both by providing a one volume summary of the new and cutting edge dioxin research of the past few years and by offering a perspective as to how this data may relate to real issues of human and environmental health. Most major scientific areas involving dioxins have been included; however, the coverage has been somewhat condensed deliberately in order not to overwhelm the reader. The chapter authors are all scientists with international reputations in the dioxin scientific arena. They have been asked to address their chapters to an audience of well educated and intelligent professionals who may not be familiar with the authors' specialties, and have included highlights of their fields with a representative, but not necessarily encyclopedic, sampling of important references. Through this approach, the book should be accessible to the broadest range of health professionals and non-health professionals interested in dioxins, as well as to policy makers and the general public. Since the middle of this century, dioxins have been wide-spread and persistent environmental contaminants in the United States and other industrial countries. Be cause of their ubiquity, persistence, and known toxicity in animal laboratory studies, considerable concern arose regarding their presence in the food chain and in human tissue, and in the multiple types of potential health consequences in humans and ix x Preface animals, such as cancer, immune system compromise, reproductive and developmental disorders, neurological damage and endocrine system alterations. Although consider able controversy exists at the present time in many areas of dioxin research, with increasing human as well as laboratory studies, the extent of dioxin toxicity has become better characterized in many species, including humans. In their introductory overview of the dioxin debate, Thomas Webster and Barry Commoner provide a summary of some of the major current dioxin controversies. A review of the current understandings and controversies in dioxin risk assessment is presented in considerable depth by Ellen Silbergeld and Peter deFur. Douglas Zook and Christoffer Rappe, in reviewing chemical aspects of dioxins, examine the question of the environmental sources of dioxins, noting that the source of much (or most) dioxin production and discharge is unknown at this time. James Startin provides a review of what is currently known with respect to dioxins in the food chain, which is the imme diate source of over 90% of the dioxin body burden in the general population in in dustrial countries. He describes the challengesjnvolved in both analyzing the presence of dioxin in foods and in interpreting existing studies. In separate articles, Michael DeVito and Linda Birnbaum; James Olson; Nancy Kerkvliet; and Angelika Tritscher, George Clark, and George Lucier, many of whom were responsible for generating the original data presented in their chapters, discuss the toxicology, pharmacokinetics, immunotoxicology, and dose-response of dioxins and related chemicals at the cellular and molecular level, based on a variety of toxicologi cal and biochemical studies. The discussion regarding the threshold level of dioxins, below which there may be no serious health effects, is of particular importance in light of the present research and debate in this area. John P. Giesy, James Ludwig, and Donald Tillitt; and Mary Walker and Richard Peterson review the research on the effects of dioxin and related chemicals on wildlife health in general, and in biota in aquatic environments. The authors observe that many biological outcomes and mecha nisms are similar between species; however, correlation between the effects of dioxins on other animal species and humans is still not completely characterized. Specific laboratory and related findings on the developmental and reproductive toxicity of dioxins, dioxins and mammalian carcinogenesis, and the neurochemical and behavioral sequelae of exposure to dioxins and PCB's are discussed respectively in articles by H. Michael Theobald and Richard Peterson; James Huff; and Richard Seegal and Susan Schantz. The findings of Theobald and Peterson that low level maternal exposure of rats to dioxin at a sensitive time during pregnancy can lead to behavioral, reproductive, and. endocrine alterations in male offspring are especially significant when viewed in conjunction with the discussion of human epidemiological studies in later chapters. The final chapters in the text are devoted to more specific discussion of dioxins and related chemicals and human health. The difficulties in measuring dioxins and related chemicals in human tissue and the current "state of the art" are reviewed in a chapter by the editor, followed by a comprehensive overview of the literature on the human health effects of polychlorinated biphenyls provided by William J. Nicholson and Phillip 1. Landrigan. The epidemiological studies of dioxins and cancer and dioxin and reproduction are described in greater depth in respective articles by Lennart Har dell, Mikael Eriksson, Olav Axelson and Sheila Hoar Zahm; and Anne Sweeney. The Preface xi work concludes with reviews and analyses of three major incidents of dioxin exposure in humans by scientists who have been long involved in their study. Pier Bertazzi and Alessandro di Domenico discuss the dioxin industrial incident in Seveso, Italy in 1976. Yoshito Masuda describes the Japanese "Yusho" rice oil poisoning of 1968, and Chen Chin Hsu, Mei-Lin M. Yu, Yung-Cheng Joseph Chen, Yue-Liang Leon Guo, and Walter Rogan review and interpret the Taiwan Yu-cheng rice oil poisoning of 1979. While differences of opinion are reflected in the text, the authors generally agree that dioxins are highly dangerous and persistent synthetic chemicals which may cause a large number of different types of health consequences, and which can initiate harmful biological responses in a dose-dependent fashion. Dioxins appear to be causally linked to cancers, adverse reproductive and developmental outcomes, and immune system compromise. They have also been associated with endocrine, neurological, liver and skin damage, which may occur at relatively low doses in genetically sensitive individu als. The very long half lives of dioxins, especially 2,3,7,8-TCDD, the most toxic of the dioxins, in the environment and in humans are cause for concern. It is not known, however, whether all biological effects of dioxins are harmful, or whether some are attempts to adapt. Also, there are sex differences in cancer response and other dioxin toxic end points. It is now relatively well established that dioxins interact with the cytoplasmic aryl hydrocarbon, or aH receptor, to initiate a cascade of changes in signal transduction and gene expression. Because the aH receptor may have some normal functions, action via a transcription factor, and likely via altered cell differentiation and proliferation, may well provide significant information about disease states. Dioxin may be toxic due to the inappropriate movement of the dioxin receptor complex at an inappropriate time and/or for an inappropriate period. One exciting recent development in the field of dioxin research reviewed in these chapters is the research into the mechanisms for dioxin activity and the consideration of the meaning of this knowledge for human health and the possibilities of developing molecular biomarkers of susceptibility as well as biomarkers of exposure. The preparation of this book has taken several years. Each year has brought important new developments. Both the chapter authors and the editor realize that, although we have made every effort to make this text the most independent, compre hensive, and current available reference on dioxin and health, supplements and new editions will be necessary. Even as the text is delivered to the publisher, new discov eries are being made, and a bi-yearly update is being planned. By the next edition, new knowledge from laboratory and human research may have eliminated many of the current controversies surrounding dioxin and health. Until then, both the authors and editor hope that the reader derives as much enjoyment in reading this volume as we have derived from performing the research and preparing the text. Acknowledgments I wish to acknowledge and thank the chapter authors for their extraordinary effort and patience during editing. In addition, the chemists who helped generate the data of very high quality which I reviewed in my chapter on exposure assessment are gratefully