LEWIS PUBLISHERS Boca Raton London New York Washington, D.C. SECOND EDITION Toxicology and Environmental Hazards RICHARD B. PHILP HUMAN HEALTH Ecosystems and ©2001 CRC Press LLC This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. Visit the CRC Press Web site at www.crcpress.com © 2001 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 1-56670-568-1 Library of Congress Card Number 2001001149 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper Library of Congress Cataloging-in-Publication Data Philp, Richard B. Ecosystems and human health : toxicology and environmental hazards / Richard B. Philp – 2nd ed. p. cm. Includes bibliographical references and index. ISBN 1-56670-568-1 1. Environmental toxicology. 2. Environmental health. I. Title. RA1226 .P48 2001 615.9'02 dc21 2001001149 CIP ©2001 CRC Press LLC Dedication Elizabeth, Brendan, Douglas, Danielle, William, Nathan, Danny, Anders, Margaret, Matthew, Jemma, Lauren, and kids everywhere. Perhaps this book will help them to look after this place better than we did. Also for my wife Joan, who is my calm harbor in a stormy world. ©2001 CRC Press LLC Foreword There is a commonly held myth in our society that anything that is “natural” is good, wholesome, and healthful, whereas anything that is “synthetic” is bad, toxic, and harmful. The mere mention of the word chemical is enough to strike terror into the heart of any food faddist. This attitude is, at best, naïve and, at worst, dangerous. Toxic substances abound in nature, ranging from inorganic heavy metals such as arsenic and mercury, through organic substances such as hydrocyanic acid, to complex enzymes and other proteins of the neurotoxins and coagulant-anticoagulants present in venoms and toxins. One of the more serious environmental hazards may be natural radon gas, and cancer from solar radiation is a real concern. Increasingly, it is becoming necessary for students of environmental sci- ences to know something of toxicology and for students of toxicology to know something of the environment. This text is designed to bridge these fields by acquainting the student with the major environmental hazards — both man- made and natural — and with the risks to human health that they pose. It is designed such that topics are generally introduced in the early chapters and covered in greater detail in subsequent ones. This is neither an environmen- talist's handbook nor does it deal exclusively with toxicology; rather, it attempts to strike a balance between the extremes of opinion and to indicate where information is inconclusive. Examples of major accidental exposures of humans to chemical toxicants are used liberally and case studies taken from reported incidents are provided. Historical background of the develop- ment of a class of chemicals or a particular environmental problem is often provided in the belief that an educated student should know more than merely the technical aspects of the field. It is hoped that this text will assist students in acquiring the information and judgmental skills necessary to differentiate between real and perceived risks, as well as acquaint them with the toxicology of important chemicals in the environment. Because most people spend 8 hours daily, 5 days weekly in the workplace, it constitutes an important component of our environment and it will be considered as such. Richard B. Philp, D.V.M., Ph.D. ©2001 CRC Press LLC About the Author Richard B. Philp, D.V.M., Ph.D., is an emeritus professor and former Chair of the Department of Pharmacology and Toxicology at the University of Western Ontario. After graduating from the Ontario Veterinary College, he practiced veterinary medicine in Illinois and in Ontario and also served as a public health officer in a small Ontario town. He obtained his Ph.D. in pharmacology from the University of Western Ontario and did postdoctoral studies at the Royal College of Surgeons of England in London. He has served on advisory committees to Canadian federal and provincial govern- ments regarding the use of antibiotics in agriculture. He was Honorary Visiting Professor in the School of Pathology, University of New South Wales, and has authored or co-authored over 90 scientific papers, two books, and several book chapters. His current research involves the study of pollution along the Florida Gulf Coast and its effects on a species of marine sponge. ©2001 CRC Press LLC Contents Chapter 1 Principles of pharmacology and toxicology Introduction Pharmacokinetics Absorption Distribution Biotransformation Elimination Pharmacodynamics Ligand binding and receptors Biological variation and data manipulation Dose response Probit analysis Cumulative effects Factors influencing responses to xenobiotics Age Body composition Sex Genetic factors Presence of pathology Xenobiotic interactions Some toxicological considerations Acute vs. chronic toxicity Acute toxicity Peripheral neurotoxins Central neurotoxins Inhibitors of oxidative phosphorylation Uncoupling agents Inhibitors of intermediary metabolism Chronic toxicity Mutagenesis and carcinogenesis Sites of intracellular damage DNA repair Genetic predisposition to cancer Epigenetic mechanisms of carcinogenesis ©2001 CRC Press LLC The role of cell repair and regeneration in toxic reactions Response of tissues to chemical insult Fetal toxicology Teratogenesis Transplacental carcinogenesis Further reading Review questions Answers Chapter 2 Risk analysis and public perceptions of risk Introduction Assessment of toxicity vs. risk Predicting risk: workplace vs. the environment Acute exposures Chronic exposures Very low-level, long-term exposures Carcinogenesis Risk assessment and carcinogenesis Sources of error in predicting cancer risks Portal-of-entry effects Age effects Exposure to co-carcinogens and promoters Species differences Extrapolation of animal data to humans Hormesis Natural vs. anthropogenic carcinogens Reliability of tests of carcinogenesis Environmental monitoring Setting safe limits in the workplace Environmental risks: problems with assessment and public perceptions The psychological impact of potential environmental risks Voluntary risk acceptance vs. imposed risks Costs of risk avoidance Some examples of major industrial accidents and environmental chemical exposures with human health implications Radiation Formaldehyde Dioxin (TCDD) Some legal aspects of risk De minimis concept Delaney Amendment Statistical problems with risk assessment Risk management ©2001 CRC Press LLC The precautionary principle Further reading Review questions Answers Case study 1 Case study 2 Chapter 3 Water and soil pollution Introduction Factors affecting toxicants in water Exchange of toxicants in an ecosystem Factors (modifiers) affecting uptake of toxicants from the environment Abiotic modifiers Biotic modifiers Some important definitions Toxicity testing in marine and aquatic species Water quality Sources of pollution Some major water pollutants Chemical classification of pesticides Health hazards of pesticides and related chemicals Chlorinated hydrocarbons Chlorphenoxy acid herbicides Organophosphates (organophosphorus insecticides) Carbamates Acidity and toxic metals Chemical hazards from waste disposal The Love Canal story Problems with Love Canal studies Toxicants in the Great Lakes: implications for human health and wildlife Evidence of adverse effects on human health Evidence of adverse effects on wildlife Global warming and water levels in the Great Lakes The marine environment Aquatic toxicology Biological hazards in drinking water Anatomy of a small town disaster Further reading Review questions Answers Chapter 4 Airborne hazards Introduction ©2001 CRC Press LLC Types of air pollution Gaseous pollutants Particulates Smog Sources of air pollution Atmospheric distribution of pollutants Movement in the troposphere Movement in the stratosphere Water and soil transport of air pollutants Types of pollutants Gaseous pollutants Particulate pollutants Health effects of air pollution Acute effects Chronic effects Air pollution in the workplace Asbestos Silicosis Pyrolysis of plastics Dust CO and NO 2 Multiple chemical sensitivity Chemical impact of pollutants on the environment Sulfur dioxide and acid rain The chemistry of ozone Chlorine Global warming Water Carbon dioxide Methane Subtle greenhouse effects Global cooling: new Ice Age? Sulfur dioxide Motor vehicle exhaust Natural factors and climate change Remedies Further reading Review questions Answers Case study 3 Case study 4 Case study 5 Case study 6 Case study 7 Case study 8 ©2001 CRC Press LLC Chapter 5 Halogenated hydrocarbons and halogenated aromatic hydrocarbons Introduction Early examples of toxicity from halogenated hydrocarbons Physicochemical characteristics and classes of halogenated hydrocarbons Antibacterial disinfectants Herbicides Dioxin (TCDD) toxicity Hepatotoxicity Porphyria Chloracne Cardiovascular effects Carcinogenicity Neurotoxicity Reproductive toxicity Metabolic disturbances The role of the aryl hydrocarbon receptor (AhR) and enzyme induction Paraquat toxicity Insecticides Industrial and commercial chemicals Biphenyls Toxicity Pharmacokinetics and metabolism Biodegradation Accidental human exposures The problem of disposal Solvents Toxicity Mechanism of toxicity Trihalomethanes (THMs) Further reading Review questions Answers Case study 9 Case study 10 Chapter 6 Toxicity of metals Introduction Lead (Pb) Toxicokinetics of lead Cellular toxicity of lead Fetal toxicity Treatment [...]... production and the environment Meat vs grain Genetically modified plant foods The environment and cancer Further reading Chapter 15 Case study reviews Case study 1 Case study 2 Case study 3 Case study 4 Case study 5 Case study 6 Case study 7 Case study 8 Case study 9 Case study 10 Case study 11 Case study 12 Case study 13 Case study 14 Case studies 15 and 16 Case study 17 Case study 18 Case study 19 Case... pro-drug Figure 3 shows some examples of Phase I reactions and their consequences Phase I chemical reactions include oxidation, reduction, and hydrolysis and generally unmask or introduce a functional (reactive) group such as -NH2, -OH, -SH, or -COOH The oxidation reactions include N- and O-dealkylations, side-chain and aromatic hydroxylations, N-oxidation and hydroxylation, sulfoxide formation, and. .. risk of a toxic reaction Non-occupational exposures to solvents Further reading Review questions ©20 01 CRC Press LLC Answers Case study 14 Case studies 15 and 16 Case study 15 Case study 16 Chapter 8 Food additives, drug residues and other food toxicants Food additives Food and drug regulations Some types of food additives Artificial food colors Emulsifiers Preservatives and anti-oxidants Artificial sweeteners... through 11 illustrate arithmetic, semi-logarithmic, and probit plots for these data ©20 01 CRC Press LLC Table 2 Lethality Data in Fathead Minnows for Two Toxic Chemicals Lethality Fluorine (mg/L) Naphthalene (mg/L) 10 % 20% 60% 84 .1% 25.0 50.0 10 0.0 200.0 0.5 1. 0 2.0 4.0 Lethality of Naphthaline in Lethality of Fluorine in Fathead Fathead Minnows Minnows 10 0 75 75 50 50 25 Percent Mortality 10 0 25 0 0 1 2... excreted by the kidneys and are subjected to Phase II conjugation All chemicals need not be subjected first to Phase I transformations Many, if they possess the necessary functional groups (e.g., -OH, -NH2), are conjugated directly OH O HO ∗ OH HO DIETHYLSTILBESTROL CARCINOGENIC EPOXIDE ∗ O 1 12 2 10 C ∗ C HO 8 C EPOXIDE 3 9 4 7 6 OH 5 BENZO [A] PYRENE (BP) BP-7 , 8-DIOL-9 , 10 -EPOXIDE ( CARCINOGEN)... 20 Case study 21 Case study 22 Case study 23 Case study 24 Case study 25 ©20 01 CRC Press LLC chapter one Principles of pharmacology and toxicology The right dose differentiates a poison and a remedy — Paracelsus, 14 93 15 41 Introduction The past century has seen a tremendous expansion in the number of synthetic chemicals employed by humankind as materials, drugs, preservatives for foods and other products,... 0 1 2 3 4 5 0 0 Concentration (mg/L) 50 10 0 15 0 Concentration (mg/L water) Figure 9 Arithmetic plot of the data shown in Table 2 Semilogarithmic Plot of % Mortality vs Log of Concentration 10 0 Naphthaline Fluorine Percent Mortality 75 50 25 -0 .5 0.0 0.5 1. 0 1. 5 Log of Concentration 2.0 2.5 3.0 Figure 10 Semi-log plot of data shown in Table 2 and Figure 9 ©20 01 CRC Press LLC 200 Probability Units (probits)... Review questions Answers Case study 11 Case study 12 Case study 13 Chapter 7 Organic solvents and related chemicals Introduction Classes of solvents Aliphatic hydrocarbons Halogenated aliphatic hydrocarbons Aliphatic alcohols Glycols and glycol ethers Aromatic hydrocarbons Solvent-related cancer in the workplace Benzene Bis(chloromethyl) ether (BCME) Dimethylformamide (DMF) and glycol ethers Ethylene oxide... of +1 corresponds to 84 .1% responders NEDs are positive or negative relative to the mean; thus, a value of 5 is added to each to make them all positive The result is called a probit (for probability unit) Table 1 shows the equivalent probits and NEDs for given percent responses Table 1 Conversion of Percent Responders to Probit Units % Responding NED Probit 0 .1 2.3 15 .9 50.0 84 .1 97.7 99.9 –3 –2 1 0... 9 ©20 01 CRC Press LLC 200 Probability Units (probits) Probit Plot of Mortality for Naphthaline and Fluorine Probits vs Log of Concentration 6.0 Naphthaline Fluorine 5.5 5.0 4.5 4.0 3.5 -0 .5 0.0 0.5 1. 0 1. 5 2.0 Log of Concentration 2.5 3.0 Figure 11 Probit plot of the data shown in Table 2 and Figures 9 and 10 Cumulative effects It may be that the manifestation of toxicity does not occur until the individual . bibliographical references and index. ISBN 1- 5 667 0-5 6 8 -1 1. Environmental toxicology. 2. Environmental health. I. Title. RA1226 .P48 20 01 615 .9'02 dc 21 20 010 011 49 CIP ©20 01 CRC Press LLC Dedication . 8 Case study 9 Case study 10 Case study 11 Case study 12 Case study 13 Case study 14 Case studies 15 and 16 Case study 17 Case study 18 Case study 19 Case study 20 Case study 21 Case study 22 Case. www.crcpress.com © 20 01 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 1- 5 667 0-5 6 8 -1 Library of Congress Card Number 20 010 011 49 Printed in the United