SECOND EDITION Ecosystems and HUMAN HEALTH Toxicology and Environmental Hazards L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM SECOND EDITION Ecosystems and HUMAN HEALTH Toxicology and Environmental Hazards RICHARD B PHILP LEWIS PUBLISHERS Boca Raton London New York Washington, D.C L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM 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 Environmental toxicology Environmental health I Title RA1226 P48 2001 615.9'02 dc21 2001001149 CIP 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 Printed on acid-free paper L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM 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 L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM 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 sciences 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 manmade 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 environmentalist'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 development 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 hours daily, 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 L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM 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 governments 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 L1568_index_fm Page 317 Thursday, May 10, 2001 4:03 PM Index Carbamate insecticides, 83, 84, 212–213 Carbon dioxide, 117–118, 120–121 Carbon, dissolved organic, 76 Carbon monoxide, 107, 110, 120–121 Carbon tetrachloride, 129, 140–141, 168–169 Carcinogenesis, see also Cancer; Risk from chemicals; Toxicity age, 52 asbestos, 108–109 benzene, 171–173 bovine growth hormone (BGH), 196–197 cadmium, 156–157 case studies, 305 cost of risk avoidance, 61–62 diethylstilbestrol (DES), 194–196 dioxin, 133–135 environment, 302 environmental monitoring, 56–57 epigenetic mechanisms of, 33–34 exposure level, 47–49 exposure to co-carcinogens and promoters, 52 food additives, 179–201 hormesis, 54–55 hormone disruptions, 266–269 human vs animal anatomy, 52–54 industrial accidents, 62–64 of metals, 160 natural carcinogens in foods, 200–201 natural vs anthropogenic carcinogens, 55 no observable (adverse) effect level (NOAEL), 47–48 phorbol esters, 252, 253 portal of entry, 4, 50–52 public perceptions, 59–62 radiation, 278, 282–283 radon gas, 281–282 reliability of tests of, 55–56 response of tissues to chemical insult, 35 risk assessment of chemicals, 47–50, 59–62 role of cell repair and regeneration in toxic reactions, 34–35 saccharin, 185–186 sites of intracellular damage, 29–32 species differences, 52–54 317 transplacental, 37 voluntary risk acceptance vs imposed risk, 60–61 workplace exposure limits, 57–59 xenoestrogen interactions with E2 receptors, 264–265 Cardiac glycosides, 251 Carrageenin, 184 Carson, Rachel, 137, 209, 261 Case studies, 305–314 Ceiling exposure value (CEV), 58 Centers for Disease Control, U.S., 190 Central nervous system acute toxicity, 26–28 autonomic agents, 251–252 case studies, 308–310 insecticides, 211–212 lead poisoning, 148–149 metals, 147 organic solvents, 168 poisonous plants, 251–252 radiation, 278 Central neurotoxins, 27 Cesium, Chaos: From Theory to Applications, 293 Chaos theory, 293–294 Chelation arsenic, 158 cadmium, 157 lead, 151 mercury, 153–154 Chelators, food, 181 Chemicals, see also Hormones; Xenobiotics carcinogenic, 1–2, 29–32, 302 case studies, 305–314 disposal, 86–89 halogenated hydrocarbon, 129–142 law of mass action, multiple chemical sensitivity (MCS), 111–113 partition coefficient, pesticide, 82–86 from plants used in research and treatment, 254–255 Chernobyl, 279–280 Chlophenoxy compounds, 213 Chloracne, 132 Chlorinated hydrocarbons, 82, 83, 112; see also DDT L1568_index_fm Page 318 Thursday, May 10, 2001 4:03 PM 318 Ecosystems and human health: toxicology and environmental hazards Chlorine, 116 Chlorofluorocarbons (CFCs), 169, 306–307 Chloroform, 2, 140–141, 168–169 Chlorphenoxy acid herbicides, 83–84 Chlorphenyl acids, 82 Cholera, 95–96 Chromium, 158 Chronic fatigue syndrome (CFS), 111–112 Chronic toxicity, 28, 46–47 Ciguatoxin, 242–243 Clastogenesis, 29 Climate change global cooling, 119–121 global warming, 93, 116–119, 231, 294–296 natural factors, 121–122 Clostridium botulinum, 235–236, 287 Coating agents, 181 Coelenterate toxins, 246 Combustion engines, 120–121 Confined space problems, 305–307 Conjugation, 190 Conotoxins, 245 Convulsants, 254 Copper, 147 Corals, 246 Costs of risk avoidance, 61–62 Coumestrol, 266 Cumulative effects, 19–20 Cyanide, 27–28 detoxification of hydrogen, 253, 254 Cyanogenic glycosides, 253 Cyclamate, 186 D DDT, 2, 6, 82, 83, 90, 208–210, 261, 264, 270 Defoaming agents, 181 Delaney Amendment, 64–65 De minimis concept, 64 Deoxynivalenol, 231–232 Detergents, 81–82 Dibenz[a,h]anthracene Dicarboximides, 215 Dichloromethane, 140–141 Dieldrin, 90 Diet and drug interactions, 26 Diethylstilbestrol (DES), 37, 61, 193–196, 261–262 males, 265, 266–268 Dimethylformamide (DMF) and glycol ethers, 173–174 Dimethylsulfide (DMS), 292 Dinitrophenols, 213–214 Dinoflagellates, 244–245 Dioxin, 27, 50, 63–64 airborne, 105–106 carcinogenesis, 133–135 chloracne, 132 enzyme induction, 135–137 hepatotoxicity of, 132 herbicides, 213 metabolic disturbances, 135 neurotoxicity of, 135 porphyria, 132 reproductive toxicity of, 135 toxicity of, 131–135 water pollution, 90 Diquat, 214–215 Disinfectants, antibacterial, 130–131 Disposal of hazardous contaminants, 86 Dissociation constant (pKa), Dissolvers of microtubules, 252 Distribution of substances through the body, 5–6 Dithiocarbamates, 215 DNA (deoxyribonucleic acid) arsenic poisoning, 157 benzene, 172 carcinogenic chemicals, 29–32 repair, 32–33 Dodds, Charles, 193 Domoic acid, 244 Dose response, 14–16 carcinogenesis, 47–48 hormesis, 54–55 management of cancer risk, 66–67 Dough conditioners, 182 Drainage source of pollution, 80 Drugs, see also Chemicals; Xenobiotics resistance, 188–192 Dust, 110 L1568_index_fm Page 319 Thursday, May 10, 2001 4:03 PM Index E Echinoderm venoms, 246 Ecology chaos theory, 293–294 feedback loops, 297 Gaia hypothesis, 291–293 interconnected systems, 294–297 Economic toxicology definition of, Electromagnetic radiation, extra-lowfrequency (ELF), 285–286 Elimination, 10–12 age, 20–21 Emphysema silicosis, 109 Emulsifiers, 181, 184 Environmental monitoring, 56–57 Environmental Protection Agency (EPA), U.S., 2, 48–49 Environmental toxicology, carcinogenic hazards in the environment, 38 carcinogens encountered in industry, 38 chaos theory, 293–294 chemical impact of pollutants, 114–116 feedback loops, 297 food production, 297–302 Gaia hypothesis, 291–293 global warming, 294–296 interconnected systems, 294–297 pesticides, 218 psychological impact of potential risk, 60 risk assessment of chemicals, 59–62 Enzyme induction, 10, 12 aryl hydrocarbon receptor (AhR), 135–137 Epigenetic mechanisms of carcinogenesis, 33–34 Equinox, 93 Ergotism, 225–227 Estrogen, 263–266; see also Reproductive injury Ethanol, 169 Ethylene glycol, 170–171 Ethylene oxide, 174 319 Exchange of toxicants in ecosystems, 74 Exposure level and carcinogenic risk, 47–49 in the workplace, 57–59 Extenders, food, 181 Extrapolation and predicting cancer risk, 52–54 F Favism, 198 Feedback loops, 297, 298 Feingold, Benjamin, 183 Fetal toxicology diethylstilbestrol (DES), 194–195, 265 Great Lakes, 90–91 lead poisoning, 150 mothers’ milk, 11–12 placenta, 35–36 radiation, 278–279, 283 teratogenesis, 35–37 xenobiotics, 22 Fillers, food, 181 Fimreite, Norvald, 154–155 Firefighters, 108–110 Fixatives, 181 Flavor enhancers, 181, 187 Folic acid, 36 Folpet, 215 Food, see also Livestock additives case studies, 311, 311–312 food and drug regulations, 179–180 types, 180–182 case studies, 308, 313–314 colors, 181, 182–183 drug residues, 187–197 genetically modified, 300–302 irradiation, 286–287 meat vs grain debate, 297–300 natural carcinogens in, 200–201 natural toxicants in, 197–201 production and the environment, 297–302 Food and Drug Act Canada, 179–180 U.S., 64 Food and Drug Administration (FDA), U.S., 64 L1568_index_fm Page 320 Thursday, May 10, 2001 4:03 PM 320 Ecosystems and human health: toxicology and environmental hazards Forensic toxicology definition of, Formaldehyde air pollution, 105 industrial accidents, 62–63 Free radicals, 32 Freon, 107 Freshwater, see Water Fumigants, 182 Fumonisins, 228–229 Fungicides, 182, 215; see also Mycotoxins Furcelleran, 184 Fusarium, 231 G Gaia hypothesis, 123, 291–293 Gaseous pollutants in air, 103–104, 106–107, 114–119 radon gas, 281–282 in water, 103–104 Gasoline, 107 Gender and xenobiotics, 21–22 Genetic factors as biotic modifiers, 78 genetically modified foods, 300–302 genetic predisposition to cancer, 33 Genetic factors and xenobiotics, 22–24 Glazing agents, 181 Global cooling, 119–121 Global warming, 93 carbon dioxide, 117–118 domino effects, 294–296 methane, 118–119 water, 116 Glycols and glycol ethers, 170–171 Goldwin, Marvin, 279–280 Grains detoxification of, 234–235 production and the environment, 297–299 Gram-negative bacteria, 189 Grassy Narrows story, 154–155 Great Lakes, the, 90–93, 105–106 Greenhouse effect, see Global warming Greenland ice cap, 118, 119–120 Groundwater, see Water Guimond, R., 276 Gulf of Mexico, 93–94 H Halling, Hildegard, 131 Halogenated aliphatic hydrocarbons, 168–169 Halogenated hydrocarbons antibacterial disinfectants, 130–131 biphenyls, 138–140 dioxin, 131–135 herbicides, 131 paraquat toxicity, 137 physiochemical characteristics and classes, 130–142 polybrominated biphenyls (PBBs), 138–140 solvents, 140–141 structural formula of, 130 toxicity, 129–130 trihalomethanes (THMs), 141–142 Halogens, 129 Hanford release, 280–281 Hemlock, 254, 314 Herbal remedies, 199–200 Herbicides, 84, 131; see also Pesticides bipyridyl, 214–215 carbamate, 215 chlorphenoxy compound, 213 dinitrophenol, 213–214 triazine, 215 Hexachlorobenzene, 90, 215, 268 Hexachlorophene, 130–131 Hiroshima, 278–279 Hooker Chemical Company, 87–89 Hormesis, 54–55, 276 Hormones disruption mechanisms, 263–266 extrapolating test results to humans, 270–271 female human studies, 268–269 livestock, 270 male human studies, 266–268 modulation of hormone activity through effects on the Ah receptor, 265–266 physiology of estrogens and androgens, 262–263 phytoestrogens, 266 wildlife, 270 L1568_index_fm Page 321 Thursday, May 10, 2001 4:03 PM Index Human vs animal anatomy, 52–53, 270–271 Humectants, 182 Hydrogen sulfide, 107 Hydroscopic agents, 182 I Icthyotoxin, 244 Illnesses, see also Cancer; Hormones aflatoxin, 227–228 aleukia, 227 allergy, 193 biphenyls, 139–140 chronic fatigue syndrome (CFS), 111–112 emphysema, 109 ergotism, 225–227 favism, 198 herbal remedies, 199–200 immune function, 112 infectious diseases, 193 lead poisoning, 148–149 mercury poisoning, 152–153 multiple chemical sensitivity (MCS), 111–113 mycotoxins, 225–229 nitrates, 184–185 organic solvents, 168–172 snake venom, 246–249 toxic oil syndrome, 198–199 Industrial accidents, see also Radiation; Solvents, organic air pollution, 104 dioxin (TCDD), 63–64 formaldehyde, 62–63 Lake Apopka incident, 262 waste disposal, 86–87 Infectious drug resistance (IDR), 188–192 Inhibitors of intermediary metabolism, 28 Inhibitors of oxidative phosphorylation, 27–28 Insecticides, 83, 84, 137–138; see also DDT; Pesticides botanical, 213 carbamate, 212–213 insect resistance, 217 insect sterilization, 216 321 natural, 213 organochlorine (chlorinated hydrocarbon), 209–210 organophosphorus, 211–212 Interactions, drug, 25–26 Iodine, 3, 279–280 Irish moss, 184 Irradiation of foodstuffs, 286–287 Isopropyl alcohol, 170 J Jellyfish, 246 Jukes, Thomas, 188 K Kidneys arsenic poisoning, 157 cadmium poisoning, 156 chemical elimination, 10–12 chromium poisoning, 158 lead poisoning, 149–150 metals, 159 paraquat toxicity, 137 presence of pathology, 24–25 solvents, 140–141 L Lake Apopka incident, 262 Lanthanum, 160 Law of mass action, Lead, 2, 90, 147 case studies, 308–310 poisoning treatment, 151 sources of, 148–149 toxicity of, 149–150 fetal, 150 Leukemia benzene, 172–173 radiation injury, 283 Ligand binding and receptors, 12–13 Light stress, 77 Lindane, 210 Liver cadmium poisoning, 156 chemical elimination, 12 dioxin, 132 L1568_index_fm Page 322 Thursday, May 10, 2001 4:03 PM 322 Ecosystems and human health: toxicology and environmental hazards metals, 159 paraquat toxicity, 137 presence of pathology, 24–25 solvents, 140–141 Livestock, see also Food additives allergies, 193 bovine growth hormone (BGH), 196–197 diethylstilbestrol (DES), 193–196 drug resistance, 188–192 ergotism, 227 fumonisins, 229 hormone disruptions, 270 infectious diseases, 193 production and the environment, 297 trichothecenes, 231–233 Lorenz, Edward, 293 Love Canal, 87–89 Lovelock, James E., 291–292 M Maclean’s magazine, 94 Management of cancer risk, 66–67 Manganese, 159 Margulis, Lynn, 291–292 Marine and aquatic species, see also Aquatic environments corals, 246 DDT, 209–210 dinoflagellates, 244–245 jellyfish, 246 Lake Apopka incident, 262 mercury poisoning, 154–155 mollusk, 245 pesticides, 262 scalefish, 242–244 sea anemones, 246 sea urchins, 246 shellfish, 244–245 stinging, 245 toxic and venomous, 242–246, 313 toxicity testing in, 79 Maturing agents, 182 Mercury, 2, 90, 147 carcinogenesis, 160 case studies, 306 Grassy Narrows story, 154–155 mercuric chloride, 152 methyl, 37, 152–153 poisoning treatment, 153–154 sources of, 151–152 toxicity of, 152, 153 wildlife, 154–155 Metabolic disturbances from dioxin, 135 from ethylene glycol, 171 Metallothioneins, 160 Metals aluminum, 85–86 arsenic, 157–158 cadmium, 155–157 carcinogenesis, 160 chelation, 151, 153–154, 157, 158 chromium, 158 heavy, 2, 147 acidity, 84–86 unusual exposure sources, 161 intoxication, 147 lead, 2, 90, 147, 148–151 mercury, 151–155 metallothioneins, 160 toxicity of, 159 Methane, 107, 118–119 case studies, 306 Methanol, 169–170 Methoxychlor, 210 Methylene chloride, 140–141 Methylmercury, 37, 152–153; see also Mercury Microwaves, 283–284 Milk, mothers’, 11–12 Minimum lethal dose, 15, 18 Mirex, 90 Mismatch repair, 33 Modifiers affecting uptake of toxicants from environment, 74–78 Molds, see Mycotoxins Mollusk venoms, 245 Monoethyl ethylene glycol, 171 Monomethyl ethylene glycol, 171 Monosodium glutamate (MSG), 187, 311, 312–313 Monsanto, 134 Morgan, K Z., 276 Motor vehicle exhaust, 120–121 Mount St Helen’s, 104 Multiple chemical sensitivity (MCS), 111–113 L1568_index_fm Page 323 Thursday, May 10, 2001 4:03 PM Index Municipal sewage discharge as source of pollution, 80 Municipal storm drains as source of pollution, 80 Mushrooms, toxic, 250–254 Mutagenesis, 29–32; see also Carcinogenesis Ames test for, 55, 65 Mycotoxins aflatoxins, 227–228 aleukia, 227 definition of, 225 detoxification of grains, 234–235 economic impact of, 230–231 ergotism, 225–227 fumonisins, 228–229 fusarium, 231 trichothecenes, 231–233 N National Cancer Institute, U.S., 268 National Institute of Occupational Safety and Health (NIOSH), U.S., 56, 133 National Resources Defense Council (NRDC), U.S., 65 Nephrons, 10–12 Neurotoxins, 27–28 dioxin (TCDD), 135 venomous arthropods, 250 venomous snakes, 248 Nitrates, 184–185, 310 Nitric acid, 114 Nitrogen dioxide, 107, 110 Nitrogen monoxide, 107 Nitrous oxide, 114–115 No observable (adverse) effect level (NOAEL), 15, 47–48, 58 No observable effect level (NOEL), 58–59 Nuclear disasters Chernobyl, 279–280 Hanford release, 280–281 Hiroshima, 278–279 Three Mile Island, 280 Nutrition as a biotic modifier, 78 323 O Occupational Safety and Health Administration (OSHA), U.S., 64 Ochratoxin A, 230 Okadaic acid, 244 Organochlorine insecticides, 209–210, 269 Organophosphorus, 82, 84, 211–212 Overcrowding as a biotic modifier, 78 Oxygen water pollution, 77 Ozone air pollution, 107 chemistry of, 115 depletion in the stratosphere, 115 P Paraquat, 83, 214–215 Paraquat toxicity, 137 Particulates, 104, 107 Partition coefficient, Patulin, 230 Pentachlorophenol, 215 Peripheral neurotoxins, 27 Persistant organic poisons (POPs), 263 Pesticides biological method, 216 chemical classification, 82–83 environmental contamination, 218 fungicide, 215 government regulation of, 216–217 health hazards of, 83–86 herbicide, 213–215 history of, 207–209 insecticide, 209–213 insect resistance, 217 Lake Apopka incident, 262 multiple resistance, 217 nonspecificity, 218 risk assessment of chemicals, 218–219 source of pollution, 82 sources of, 207–208 pH, 76, 77 Pharmacodynamics biological variation and data manipulation, 13–14 L1568_index_fm Page 324 Thursday, May 10, 2001 4:03 PM 324 Ecosystems and human health: toxicology and environmental hazards cumulative effects of xenobiotics, 19–20 dose response, 14–16 ligand binding and receptors, 12–13 minimum lethal dose, 15, 18 no observable (adverse) effect level (NOAEL), 15 probit analysis, 17–18, 19 quantal response, 14–15 Pharmacokinetics absorption, 4–5 biotransformation, 6–10 of biphenyls, 139 distribution, 5–6 elimination, 10–12 law of mass action, Pharmacology, definition of, Phase I reactions, 6–9 Phase II reactions, 9–10 Phenylketonuria (PKU), 186, 187 Photochemical transformations, 77 Phrobol esters, 252, 253 Phytoestrogens, 266, 269 Pickering Nuclear Plant, 283 Pinocytosis, Placenta, 35–36, 37 Plants, toxic, 250–254, 314 Plasmids, 189–190 Plasticizers, food, 182 Polar ice cap, 118 Polishing agents, 181 Pollution air atmospheric distribution of pollutants, 105–106 case studies, 307 chemical impact, 114–116 gaseous, 73 gaseous pollutants, 103–104, 106–107 health hazards, 107–108 methane, 118–119 movement in the troposphere, 105–106 particulates, 104, 107 smog, 104 sources of, 104–105 stratosphere, 106 types of pollutants, 106–107 workplace, 108–113 water and soil, 73–98, 93–94 detergents, 81–82 disposal of hazardous contaminants, 86 heavy metals, 84–86 pesticides, 82–83 pollutants, 81–82 sources of, 80–81 waste disposal, 86–89 well water, 86–87 Polybrominated biphenyls (PBBs), 138–140 Polychlorinated biphenyls (PCBs), 2, 90, 138–140 Polycyclic aromatic hydrocarbons, see also Halogenated hydrocarbons paraquat toxicity, 137 Polycyclic aromatic hydrocarbons (PAHs), adverse effects on human health, 90–93 Porphyria, 132 Portal of entry, 4, 50–52, 308 P′P′-DDT, see DDT Precautionary principle, 67–68 Pregnancy diethylstilbestrol (DES), 194–195 Great Lakes, 90–91 radiation, 278–279, 283 xenobiotics, 22 Presence of pathology and xenobiotics, 24–25 Preservatives, food, 184–185 Probit analysis, 17–18, 19 Propylene glycol, 171 Proto-oncogenes, 30–32 Public perceptions psychological impact of potential risk, 60 voluntary risk acceptance vs imposed risk, 60–61 Pulmonary disease, 24–25 Pyrogallol tannins, 251 Pyrolysis of plastics, 109–110 Q Quantal response to chemicals, 14–15 L1568_index_fm Page 325 Thursday, May 10, 2001 4:03 PM Index R Radiation, see also Industrial accidents Chernobyl, 279–280 damage measurement, 278 definition of, 275–276 energy measurement, 277–278 extra-low-frequency (ELF) electromagnetic, 285–286 Hanford release, 280–281 Hiroshima, 278–279 industrial accidents, 62 major nuclear disasters, 278–279 microwaves, 283–284 radon gas, 281–282 sources of, 276 studies, 285–286 Three Mile Island, 280 tissue sensitivity to, 282–283 types of, 277 ultraviolet, 284 in the workplace, 285–286 Radon gas, 281–282 Rain acid, 84–85, 114–115 as source of pollution, 80 Rasmussen, C., 276 Reactions, chemical, 6–10 Receptors and ligand binding, 12–13 Reproductive injury diethylstilbestrol (DES), 261–262 from dioxin, 135 female human studies, 268–269 male human studies, 265, 266–268 physiology of estrogens and androgens, 262–263 Response of tissues to chemical insult, 35 Risk from chemicals, see also Carcinogenesis age, 52 assessing environmental, 59–62 avoidance, costs of, 61–62 carcinogenesis, 47–50 exposure to co-carcinogens and promoters, 52 extrapolation, 52–54 human vs animal anatomy, 52–54 legal aspects, 64–65 management, 66–67 325 pesticides, 218–219 portal of entry, 50–52 precautionary principle, 67–68 predicting, 46–47, 49, 50–56 sources of error in predicting, 50–56 species differences, 52–54 statistical problems with assessment, 65–66 voluntary acceptance vs imposed risk, 60–61 Role of cell repair and regeneration in toxic reactions, 34–35 Roosevelt, Theodore, 185 Rous, Peyton, 30 S Saccharin, 185–187 Salmonella typhimurium, 287 Saxitoxin, 244 Scalefish toxins, 242–244 Science, 118 Scombroid poisoning, 243 Sea anemones, 246 Sea urchins, 246 Selective breeding, 216 Sequestrants, food, 181 Severinghaus, Jeffrey, 117–118 Sewage discharge detergents, 81–82 source of pollution, 80 Sex and xenobiotics, 21–22 Shellfish toxins, 244–245 Short-term exposure value (STEV), 58 Sierra Legal Defense Fund (SLDF), 107 Silent Spring, 137, 209, 261 Silicosis, 109 Smog, 104 Smoking cadmium poisoning, 156 case studies, 305 Smoking Freedom Society, 61 Snakes, venomous, 246–249 Solubility, lipid, 5, Solvents, organic, 140–141; see also Industrial accidents aliphatic hydrocarbon, 168 aromatic hydrocarbon, 171–174 bis(chloromethyl) ether (BCME), 173 L1568_index_fm Page 326 Thursday, May 10, 2001 4:03 PM 326 Ecosystems and human health: toxicology and environmental hazards carbon tetrachloride, 129, 140–141, 168–169 case studies, 305–306 chlorofluorocarbons (CFCs), 169 chloroform, 2, 140–141, 168–169 classes of, 168–172 dimethylformamide (DMF) and glycol ethers, 173–174 ethanol, 169 ethylene oxide, 174 factors affecting toxicants, 175 halogenated aliphatic hydrocarbons, 168–169 methanol, 169–170 non-occupational exposure to, 175 trichloroethylene, 169 in the workplace, 167, 172–173 Species differences as a biotic modifier, 77–78 carcinogenesis, 52–54 Spiders, 250 Stabilizers, food, 182 Statistical problems with risk assessment, 65–66 Sterilization, insect, 216 Stinging fishes, 245 Storm drains, 80 Stratosphere, 106, 115 Sulfur dioxide, 106, 114–115, 120 Sulfur trioxide, 106 Surfactants, food, 181 Sweeteners, 182, 185–187 Synergistic interactions between drugs, 25–26 T T-2 toxin, 230 Temperature feedback loops, 297, 298 water pollution, 76 Teratogenesis, 35–37 Testosterone, 262–263 Tetrodotoxin, 243 Thalidomide, 36, 131, 215 Three Mile Island, 280 Threshold limit values (TLV), 59 Time-weighted average exposure value (TWAEV), 58 Tissue perfusion, Toxaphene, 90 Toxicants in aquatic environments, 94–95 exchange in ecosystems, 74 in foods, natural, 197–201 Great Lakes, 90–93 natural, 81, 197–201 uptake from the environment, 74–78 Toxicity, see also Carcinogenesis absorption, 4–5 acute, 26–28 age, 20–21, 52 of algae, 235 of arsenic, 158 biological variation and data manipulation, 13–14 biotransformation, 6–10 of biphenyls, 138 body composition, 21 of cadmium, 156–157 central neurotoxins, 27 chemical elimination, 10–12 cumulative effects of xenobiotics, 19–20 of dinoflagellates, 244–245 of dioxin, 131–135 distribution, 5–6 dose response, 14–16 factors influencing responses to xenobiotics, 20–26 of food and food additives, 180–201 of food colors, 182–183 gender, 21–22 genetic factors, 22–24 of grains, 234–235 of halogenated hydrocarbons, 129–142 inhibitors of intermediary metabolism, 28 inhibitors of oxidative phosphorylation, 27–28 of land animals, 246–250 ligand binding and receptors, 12–13 of marine animals, 241–246 of mercury, 152, 153 of metals, 2, 147–161 minimum lethal dose, 15, 18 of mycotoxins, 225–236 no observable (adverse) effect level (NOAEL), 15 L1568_index_fm Page 327 Thursday, May 10, 2001 4:03 PM Index of organic solvents, 167–175 peripheral neurotoxins, 27 of pesticides, 82–86, 207–220 of plants and mushrooms, 250–254 portal of entry, 4, 50–52 presence of pathology, 24–25 probit analysis, 17–18, 19 of radiation, 278 risk assessment of chemicals, 45–46 of scalefish, 242–244 of shellfish, 244–245 of stinging fishes, 245 studies, 92 testing in marine and aquatic species, 79 uncoupling agents, 28 water pollution, 74–79, 75 xenobiotic interactions, 25–26 Toxic oil syndrome, 198–199 Toxicology definition of, Transplacental carcinogenesis, 37 Triazines, 215 Trichloroethane, 308 Trichloroethylene, 169 Trichothecenes, 231–233 Trihalomethanes (THMs), 141–142 Troposphere, 105–106 Tyrosine, 186–187 U Ultraviolet radiation, 284 Uncoupling agents, 28 Uranium, 159 V Venomous arthropods, 249–250 Venomous snakes, 246–249 Vesicants, 251 Vinyl chloride, 2, 107 Vomitoxin, 231 W Walkerton, Ontario, Canada, 96–98 Waste disposal air pollution, 104 327 of biphenyls, 140 Love Canal, 87–89 studies, 89 water pollution, 86–87 Water cholera, 95–96 dissolved organic carbon in, 76, 93–94 distribution of toxicants, 75 drinking, 95–98 from drinking wells, 86–87, 97–98 factors affecting toxicants, 74–79 global warming, 93, 116 Great Lakes, 90–93, 105–106 Gulf of Mexico, 93–94 hardness, 76, 77 light stress, 77 modifiers affecting uptake of toxicants from the environment, 74–78 oxygen, 77 pH, 76, 77 pollutants, 81–82 quality, 79–80 sources of contaminants, 95–98 temperature, 76 toxicant exchange in ecosystems, 74 toxicity testing in marine and aquatic species, 79 transport of air pollutants, 106 Wells, water, see Water Wildlife, see also Livestock DDT, 138 hormone disruptions, 263–264, 270 mercury poisoning, 154–155 pesticides, 220 toxic and venomous land animals, 245–250 marine animals, 241–246 water pollution, 98 Workplace risks, 57–59 air pollution, 108–113 benzene, 172–173 bis(chloromethyl) ether (BCME), 173 case studies, 305–307 confined space problems, 305–307 dimethylformamide (DMF) and glycol ethers, 173–174 ethylene oxide, 174 organic solvents, 167 radiation, 285–286 L1568_index_fm Page 328 Thursday, May 10, 2001 4:03 PM 328 Ecosystems and human health: toxicology and environmental hazards X Xenobiotics, see also Chemicals absorption, 4–5, 310 biological variation and data manipulation, 13–14, 270–271 biotransformation of, 6–10 body composition, 21 in the body, fates of, 51 case studies, 305–314 cumulative effects, 19–20 definition of, distribution through the body, 5–6 dose response, 14–16 elimination from the body, 10–12 estrogens, 263 factors influencing responses, 20–26 gender, 21–22 genetic factors, 22–24 interactions between, 25–26 law of mass action, ligand binding and receptors, 12–13 minimum lethal dose, 15, 18 no observable (adverse) effect level (NOAEL), 15 partition coefficient, pharmacodynamics, 12–20 pharmacokinetics, 4–12 phase I reactions, 6–9 phase II reactions, 9–10 portal of entry, 308–310 presence of pathology, 24–25 probit analysis, 17–18, 19 water pollution, 73 xenoestrogen interactions with E2 receptors, 264–265 Xylitol, 186 Z Zearalonone, 231 .. .SECOND EDITION Ecosystems and HUMAN HEALTH Toxicology and Environmental Hazards L1568_ FM_fm Page Thursday, May 10, 2001 4:00 PM SECOND EDITION Ecosystems and HUMAN HEALTH Toxicology and Environmental. .. 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 Environmental toxicology Environmental. .. Page 10 Thursday, May 10, 2001 4:07 PM 10 Ecosystems and human health: toxicology and environmental hazards An important concept in understanding toxication and detoxication of xenobiotics is enzyme