Job Name: 201299t Handbook on the Toxicology of Metals Job Name: 201299t Job Name: 201299t Handbook on the Toxicology of Metals Third Edition Editors: Gunnar F. Nordberg Bruce A. Fowler Monica Nordberg Lars T. Friberg Editorial Committee: Antero Aitio Ingvar Andersson Bruce A. Fowler Lars T. Friberg Gunnar F. Nordberg Monica Nordberg Peter Pärt Staffan Skerfving AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic press is an imprint of Elsevier Job Name: 201299t Academic Press is an imprint of Elsevier 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright © 2007, 1986, Elsevier B.V. All rights reserved. Except for Chapter 29 which is in the public domain. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Science &Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, E-mail: [email protected]. You may also complete your request online via the Elsevier homepage (http://elsevier.com), by selecting “Support & Contact” then “Copyright and Permission” and then “Obtaining Permissions.” Library of Congress Cataloging-in-Publication Data Handbook on the toxicology of metals / editors, Gunnar F. Nordberg … [et al.]. — 3rd ed. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-12-369413-3 (alk. paper) ISBN-10: 0-12-369413-2 (alk. paper) 1. Metals—Toxicology. I. Nordberg, Gunnar. [DNLM: 1. Metals—toxicity. 2. Environmental Expose—adverse effects. QV 275 H236 2007] RA1231.M52H36 2007 615.9’253—dc22 2007014098 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. ISBN: 978-0-12-369413-3 For information on all Academic Press publications visit our Web site at www.books.elsevier.com Printed in the United States of America 07 08 09 10 9 8 7 6 5 4 3 2 1 Job Name: 201299t Preface The Handbook on the Toxicology of Metals is a comprehensive in a larger format. For the interested reader who searches review dealing with the effects of metallic elements and more detailed information on specifi c topics, each chapter their compounds on biological systems. Special emphasis contains a large number of relevant references also to re- has been laid on the toxic effects in humans, although cent reviews whenever these are available. toxic effects in animals and biological systems in vitro are The development of modern devices in society de- also discussed whenever relevant. As a basis for a better mand new chapters which refl ect the present concerns understanding of the potential for adverse effects on of the use of new materials, such as semiconductors in human health, information is also given on sources, trans- electronic devices, metallic nanotechnology devices, and port, and transformation of metals in the environment platinum- and palladium-based catalytic converters. and on certain aspects of the ecological effects of metals. The increasing use of biomarkers in occupational The fi rst edition of the handbook appeared in 1979, and environmental health has made it necessary to add and was followed by a second edition in 1986. The work a new chapter on biological monitoring and biomar- rapidly fulfi lled the aims of the editors and became a kers. Immunotoxicology is an expanding fi eld, and standard reference work for physicians, toxicologists, and considerable achievements have been made in recent engineers in the fi elds of environmental and occupational years. A chapter on “immunotoxicology of metals” has health. There has been a long interval between the 2nd edi- therefore been included. Immunological and genetic tion and the present one, but the aims of this third edition fi ndings provide, in some cases, good explanations for are basically the same as those of the previous editions, the differences in susceptibility to development of dis- i. e., to provide easy access to basic toxicological data and ease from exposure to metals. Principles for prevention also give more in-depth treatment of some information, of the toxic effects of metals and risk assessment are including a general introduction to the toxicology and important chapters, somewhat expanded, and a new risk assessment of metals and their compounds. chapter on a related topic “Essential Metals: Assessing As with the previous editions, writing the 3rd edi- Risks from Defi ciency and Toxicity” brings up-to-date tion of this book has been a part of the activities within knowledge into this 3rd edition. the Scientifi c Committee on the Toxicology of Metals Before the manuscript of this 3rd edition could be under the International Commission on Occupational fi nalized, our co-editor and friend Professor Lars Health, and the editors are happy that the work to Friberg died. He was the main editor of the two fi rst make a third edition has been given a high priority editions of this handbook, and his ideas constituted the among members. In some cases, we have been honored basis for the present edition. His stringent analytical to include authors from outside of this committee. The views were invaluable, and his expertise and knowl- chapter authors have, as far as possible, been the same edge are greatly missed. We will also remember him as as those who wrote the second edition, but in many a loyal, generous, and warm friend, and hope that this cases, we were happy to introduce new colleagues. book will be a lasting tribute to his memory. Since the publication of the 2nd edition, a wealth of data The editors acknowledge each contributor to this has appeared, and several of the chapters dealing with book for their devotion and enthusiasm and for having specifi c metals have been completely rewritten; others prioritized the work to make the 3rd edition of Hand- have undergone a comprehensive updating. In order to book on Toxicology of Metals available to the reader. not expand the present book and make it much larger than the second edition, which was published in two volumes, Gunnar F. Nordberg some of the general chapters have been merged and short- Bruce A. Fowler ened, and the present book is published in one volume Monica Nordberg v Job Name: 201299t Job Name: 201299t Foreword: Outlook Metals – a new old environmental problem sources are environmental contaminants of special concern, because of increasing environmental expo- “Toxic metals” are one of the oldest environmental prob- sure and their established carcinogenicity. lems. Today, there are new dimensions of the problem, • Radon exposure is the best documented such as the production of metals in developing coun- environmentally related cause of cancer, but is tries, leading to occupational exposure and exposure localized in geographical areas where radon to the general public through the ambient air, drinking precursors (uranium) occur naturally in the water, food, and consumer products. High technology ground. Uranium can also contaminate drinking development has also resulted in new products that water, leading to kidney injuries. need more metals in, for example, electronics, fuel cells • Mercury at concentrations that are sometimes and car exhaust technology. E-waste, together with observed in the environment is well known to drug waste, are new waste problems. The use of metals have neurodevelopmental effects, for example, like gallium, indium, and germanium, which are used attention problems, reduced learning ability, and in semiconductors has increased steadily over the last slightly reduced IQ in children. Measures are now 25 years. The e-Waste problem is further augmented by being taken in Europe to reduce, inter alia, prenatal the export of electronic waste from developed to devel- mercury exposure in order to ensure that tolerable oping countries. Nanotechnology can also lead to un- daily intakes for pregnant women are not exceeded. foreseen problems caused by consumer products and • Lead is an established neurodevelopmental combustion of material based on nanoparticles. toxicant to humans. Mild mental retardation of Arsenic is a common toxic element which pro- children 0-4 years of age in the WHO-Europe duces clinical disease in India and Southeast Asia region resulting from lead exposure accounts for from drinking water. This region is also experiencing 4.4% of DALYs (disability adjusted life years). growing use in semiconductor production. High con- Recent studies on the effects of lead in humans centrations of arsenic in drinking water also occur in suggest that a “safe” exposure level currently South America and the U.S. Arsenic is a good example cannot be established. More data on lead showing how old knowledge is forgotten or ignored, exposure of European citizens are necessary and creating new problems. In a number of developing are currently being collected. A ban on leaded countries, this problem is further exacerbated by petrol has been very successful in lowering blood expanding human populations and the overexploita- lead levels in children, which clearly indicates a tion of ground water. reduced exposure. Environmental health problems—and successes • The global distribution of “new” metals used stories from the toxicology of metals—have been high- in automobile catalytic converters to reduce lighted in the EEA report on Environment and Health hydrocarbon pollution is clearly shown in the 2005. Some of the key conclusions concerning toxic Arctic. Concentrations of platinum, palladium, metals are: and rhodium in ice and snow in Greenland have • A number of chemicals are potentially carcinogenic. increased rapidly since the 1970; the same trend has Approximately 500 metals are classifi ed as carcino- been observed in Germany.