Ebook Concepts and applications in veterinary toxicology - an interactive guide: Part 1

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Part 1 book "Concepts and applications in veterinary toxicology - an interactive guide" includes content: General principles of toxicology; disposition and fate of toxicants; mechanism of toxicity; toxic effects of pesticides and agrochemicals; toxic effects of metals and micronutrients; toxicologic hazards of solvents, gases, vapors, and other chemicals; toxicities from human drugs

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PK Gupta VetBooks.ir Concepts and Applications in Veterinary Toxicology An Interactive Guide
VetBooks.ir Concepts and Applications in Veterinary Toxicology
VetBooks.ir PK Gupta Concepts and Applications in Veterinary Toxicology An Interactive Guide
PK Gupta VetBooks.ir Toxicology Consulting Group Academy of Sciences for Animal Welfare Bareilly, Uttar Pradesh, India ISBN 978-3-030-22249-9 ISBN 978-3-030-22250-5 (eBook) https://doi.org/10.1007/978-3-030-22250-5 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
VetBooks.ir Preface The book entitled Concepts and Applications in Veterinary Toxicology: An Interactive Guide covers a broad spectrum of topics for the students specializing in veterinary toxicology and veterinary medical practitioners. The major emphasis of the book is to briefly highlight specialized topics essential for veterinary specialists. A great attention has been given to common toxicants to which several species, including pet animals, are exposed to a variety of toxicants. The subject of veteri- nary toxicology is complicated greatly by the wide variations in responses of domestic, companion, aquatic, wild, and zoo species to toxicants. Therefore, emphasis has also been given to species variation and diagnostic toxicology includ- ing clinical management that is more relevant to veterinary profession. The author’s own experience in different branches of veterinary toxicology has been abstracted in this book. In the last few decades, veterinary toxicologists have faced the enor- mous task of dealing with a flood of new farm chemicals and household products. Understanding the complete profile (especially mechanisms of toxicity) of each toxicant is the biggest challenge for today’s veterinary toxicologists. This book has 15 chapters that cover several topics, such as general principles of toxicology, current status, factors affecting toxicity, absorption, distribution, metab- olism, excretion, mechanism of toxicity, toxic effects of various xenobiotics, poi- sonings of poisonous and venomous organisms, toxicities from human drugs, bacteria and cyanobacteria (blue-green algae), mycotoxicosis, feed contaminant toxicity, and food hazards in pets and veterinary drug residue hazards. The last chapter is exclusively devoted to veterinary clinical toxicology which deals with the principles of diagnosis, followed by the general management of poisoning of the patients including methods of removal of poisons from the body and treatment of poisoning. Each chapter in this book starts with the introduction and key points relevant to the topic, then concept and applications, followed by questions and answers that include short questions and answers, multiple choice questions, true/false or cor- rect/incorrect statements, fill in the blanks, and match the statements. It is a unique book in veterinary toxicology that is prepared to offer a comprehensive concepts and application resource to veterinary toxicologists, students, teachers, clinicians, and animal health scientists. This book is more student-teacher-friendly, is targeted primarily for the classroom and practitioners, and is written in a manner to v
vi Preface stimulate interest on various facets of the subject and make it more exciting. The VetBooks.ir sample exercises of questions and answers will support active learning because these exercises will not only be a useful tool for the teachers of veterinary toxicol- ogy who need inspiration when composing questions for their students but will also help all teachers practicing in medical toxicology and toxicologists engaged in various disciplines. Therefore, the author believes that this book would serve the students, academic institutions, and industry as follows: • It is a good resourse for veterinary medical practitioners and will be an excellent contribution for the students who need a study aid for veterinary toxicology but want more than a textbook as they need a self-testing regime. • It will be a useful tool for the teachers of veterinary toxicology who need inspira- tion when composing questions for their students. • It will also help the established toxicologists to test their own knowledge of understanding the subject matter. • It will be useful at universities and colleges and in industry for in-house training courses in veterinary toxicology, which I know exist in some pharmaceutical and chemical companies. • It is required for all those who want to study for the veterinary toxicology boards and other examinations. Thus, the main strength of this book is that it reflects the breadth and multidisci- plinary nature of veterinary toxicology with the subject needed to improve the engagement and understanding of the subject having a very wide audience. Toxicology is a rapidly evolving field. Suggestions and comments are welcome to help the author improve the contents of the book. Please also suggest the deficien- cies need to be covered at drpkg_brly@yahoo.co.in or drpkg1943@gmail.com if you have any topics you feel should be better covered in any future editions. Bareilly, Uttar Pradesh, India PK Gupta
VetBooks.ir Disclaimer The information, including text, questions and answers, illustrations, etc., in the book is based on standard textbooks in the area of specialization. However, it is well known that with the advancement of science, the standard of care in the practice of veterinary medicine changes rapidly. Many drugs that were indicated for the treat- ment of a certain ailment in the beginning get superseded by others. With long-term use, their effects and effectiveness become apparent, or else, the use was advocated for some other problem. Though all the efforts have been made to ensure the accu- racy of the information, the possibility of human error still remains. Therefore, nei- ther the author nor the publisher guarantees that the information contained in the book is absolute. Anyone using the veterinary clinical information contained in this book has to be, therefore, duly cautious. It is particularly important to check drug dosages, indications, interactions, and contraindications with the manufacturer’s most recent product information. Neither the author nor the publisher should be responsible for any damage that results from the use of the information contained in any part of this book. vii
VetBooks.ir Contents 1 General Principles of Toxicology�� 1 1.1 Introduction�� 1 .2 1 Roots in Veterinary Medicine and Toxicology�� 2 .3 1 Toxicology and the Risk Paradigm �� 4 1.4 Scope of Toxicology �� 5 1.5 Current Status�� 6 .6 1 Definitions, Classification, and Toxicity Rating �� 7 1.7 Toxicity Rating�� 8 1.8 Sources of Poisoning�� 9 1.8.1 Malicious Poisoning �� 10 1.8.2 Accidental Poisoning�� 10 1.9 Factors Affecting the Activity of Toxicants�� 10 .9.1 1 Host Factors (Biologic Factors)�� 10 .9.2 1 Factors Related to Exposure �� 13 1.9.3 Chemical Factors�� 13 1.10 Natural Law Concerning Toxicity�� 14 1.10.1 Dose-Response Relationship�� 14 .10.2 ypes of Dose-Response Relationship�� 15 1 T .10.3 ariables of Dose-Response Curves �� 15 1 V 1.11 Interaction with Receptors�� 17 1.12 Questions and Answers �� 21 1.12.1 Short Questions and Answers �� 21 1.12.2 Multiple Choice Questions �� 22 .12.3 ill in the Blanks�� 24 1 F .12.4 rue or False Statements�� 25 1 T 1.12.5 Match the Statements�� 25 Further Reading �� 26 2 Disposition and Fate of Toxicants �� 27 2.1 Introduction�� 27 2.2 Absorption�� 29 .2.1 2 Translocation of Xenobiotics Across Membranes�� 29 2.2.2 Toxicant Absorption�� 31 2.2.3 Species Differences in Absorption�� 32 ix
x Contents 2.3 Distribution �� 33 VetBooks.ir .3.1 2 Species Differences in Distribution�� 34 2.4 Biotransformation �� 34 2.5 Excretion �� 34 .6 2 Induction or Inhibition of Metabolizing Enzymes�� 36 2.7 Bioactivation and Tissue Toxicity �� 36 2.8 Essentials of Toxicokinetic Principles�� 36 2.9 Question and Answers�� 37 2.9.1 Short Question and Answers�� 37 2.9.2 Multiple Choice Questions �� 40 2.9.3 in the Blanks�� 41 Fill 2.9.4 True or False Statements�� 42 2.9.5 Match the Statements�� 43 Further Reading �� 44 3 Mechanism of Toxicity�� 45 3.1 Introduction�� 45 3.2 Mechanism of Action�� 46 3.3 Mode of Action �� 46 3.3.1 Nonspecific �� 47 3.3.2 Specific Type�� 47 3.4 Mechanism of Toxicity �� 48 3.4.1 Steps Involved in the Process of Mechanisms of Toxicity�� 48 3.4.2 Factors Responsible for Cellular Dysfunction�� 48 .5 3 Forms of Cell Deaths�� 50 3.5.1 Necrosis�� 50 3.5.2 Apoptosis�� 51 3.6 Questions and Answers �� 52 3.6.1 Short Questions and Answers �� 52 3.6.2 Multiple-Choice Questions �� 54 3.6.3 in the Blanks�� 56 Fill 3.6.4 True or False Statements�� 57 3.6.5 Match the Statements�� 57 Further Reading �� 58 4 Toxic Effects of Pesticides and Agrochemicals�� 59 4.1 Introduction�� 59 4.2 Definitions and Classifications�� 61 4.2.1 Definitions�� 61 4.2.2 Classification�� 61 4.3 Toxicity of Insecticides �� 62 4.4 Herbicide Toxicity�� 62 4.4.1 Organophosphate and Carbamate Insecticides �� 63 4.4.2 Chlorinated Hydrocarbon Compounds (Toxicity)�� 68 4.4.3 Insecticides Derived from Plants (Toxicity) �� 68 4.4.4 Synthetic Pyrethroid Insecticides�� 70
Contents xi 4.5 Fungicides �� 70 VetBooks.ir 4.6 Rodenticide Poisoning�� 71 4.6.1 Anticoagulant Rodenticides (Warfarin and Congeners) �� 71 4.6.2 Nonanticoagulant Rodenticide (Bromethalin)�� 72 4.6.3 Cholecalciferol Toxicosis�� 72 4.6.4 Zinc Phosphide�� 73 4.7 Molluscicide Poisoning�� 74 4.8 Solvents and Emulsifier Toxicity�� 74 4.9 Sulfur and Lime-Sulfur �� 75 4.10 Questions and Answers �� 75 4.10.1 Short Questions and Answers �� 75 4.10.2 Multiple Choice Questions �� 77 4.10.3 ill in the Blanks�� 79 F 4.10.4 rue or False Statements�� 80 T 4.10.5 Match the Statements�� 81 Further Reading �� 82 5 Toxic Effects of Metals and Micronutrients�� 83 5.1 Introduction�� 83 5.2 Arsenic (Sankhyal, Somalkar)�� 85 5.2.1 Mechanism of Action�� 85 5.2.2 Toxicity �� 85 5.3 Cadmium Poisoning�� 87 5.3.1 Mechanism of Toxicity �� 87 5.3.2 Toxicity �� 87 .4 5 Cobalt Deficiency (Vitamin B12 Deficiency) �� 88 5.5 Chromium Toxicity �� 89 5.6 Iodine Toxicity/Deficiency�� 89 5.6.1 Toxicity �� 89 5.6.2 Iodine Deficiency (Goiter)�� 90 5.7 Phosphorus�� 91 5.8 Copper Poisoning/Deficiency �� 92 5.8.1 Toxicity �� 92 5.8.2 Copper Deficiency�� 93 5.9 Fluoride Toxicoses�� 94 5.9.1 Toxicity �� 95 5.10 Iron Toxicoses �� 96 5.11 Lead Poisoning�� 97 5.11.1 Mechanism of Action�� 97 5.11.2 Toxicity �� 98 5.11.3 Treatment�� 99 5.12 Manganese Toxicity�� 100 5.12.1 Mechanism of Action�� 100 5.12.2 Toxicity �� 100 5.12.3 Treatment�� 101
xii Contents 5.13 Mercury Poisoning�� 101 VetBooks.ir 5.13.1 Mechanism of Action�� 102 5.13.2 Toxicity �� 103 5.13.3 Treatment�� 103 5.14 Molybdenum Poisoning�� 104 5.14.1 Mechanism of Action�� 104 5.14.2 Toxicity �� 104 5.14.3 Treatment�� 106 5.15 Selenium Poisoning�� 106 5.15.1 Mechanism of Action�� 106 5.15.2 Toxicity �� 107 5.15.3 Treatment�� 108 5.16 Zinc Toxicosis �� 108 5.17 Salt Poisoning/Deficiency�� 109 5.17.1 Mechanism of Action�� 109 5.17.2 Toxicity �� 110 5.17.3 Treatment�� 110 .18 ulfur and Lime-Sulfur Poisoning/Deficiency�� 111 5 S 5.18.1 Mechanism of Action�� 111 5.18.2 Toxicity �� 112 5.18.3 Treatment�� 112 5.19 Questions and Answers �� 113 5.19.1 Short Questions and Answers �� 113 5.19.2 Multiple Choice Questions �� 115 5.19.3 ill in the Blanks�� 117 F 5.19.4 rue or False Statements�� 117 T 5.19.5 Match the Statements�� 118 Further Reading �� 119 6 Toxicologic Hazards of Solvents, Gases, Vapors, and Other Chemicals �� 121 6.1 Introduction�� 121 6.2 Solvent Toxicity�� 123 6.2.1 Alcohols and Glycols�� 123 6.2.2 Petroleum Toxicity�� 125 6.3 Toxic Gases and Vapors�� 126 6.3.1 Carbon Monoxide (CO)�� 126 6.3.2 Hydrogen Sulfide�� 127 6.3.3 Oxides of Nitrogen (Silo Filler’s Disease)�� 128 6.3.4 Gaseous Ammonia�� 129 6.3.5 Smoke Inhalation�� 129 6.3.6 Phosphine Gas Sources �� 130 6.4 Organic Compounds �� 131 .5 6 Brominated Flame Retardants (BFRs) and Perfluorinated Compounds (PFCs) �� 131 .6 6 Persistent Halogenated Aromatic (PHAs) Poisoning�� 132
Contents xiii 6.7 Coal-Tar Product Poisoning�� 133 VetBooks.ir 6.8 Pentachlorophenol (PCP) Poisoning�� 133 6.9 Smoke Inhalation�� 134 6.10 Household Hazards �� 134 6.10.1 Chlorine Bleaches �� 135 6.10.2 etergents, Soaps, and Shampoos�� 135 D 6.11 Questions and Answers �� 136 6.11.1 Short Questions and Answers �� 136 6.11.2 Multiple Choice Questions �� 138 6.11.3 Match the Statements�� 141 Further Reading �� 142 7 Toxicities from Human Drugs�� 143 7.1 Introduction�� 143 .2 7 Toxicities from Over-the-Counter Drugs�� 144 7.2.1 Decongestants �� 145 7.2.2 Antihistamines�� 145 7.2.3 Gastrointestinal Drugs�� 146 7.2.4 Antacids�� 147 7.2.5 Analgesics �� 147 7.2.6 Multivitamins and Iron �� 148 7.2.7 Topical Preparations�� 149 7.2.8 5-Hydroxytryptophan�� 149 7.2.9 Herbal Supplements (Toxicity) �� 149 .3 7 Toxicities from Prescription Drugs �� 150 7.3.1 Cardiovascular Medications�� 150 7.3.2 Phenothiazine Tranquilizers/Benzodiazepines�� 152 7.3.3 Antidepressants and Sleep Aids�� 153 7.3.4 Muscle Relaxants (Toxicity) �� 155 7.3.5 Topical Agents (Toxicity)�� 155 7.3.6 Toxicities from Nonsteroidal Prescription Drugs �� 155 7.3.7 Toxicities from Illicit and Abused Drugs�� 156 7.4 Questions and Answers �� 160 7.4.1 Short Questions and Answers �� 160 7.4.2 Multiple Choice Questions �� 161 7.4.3 in the Blanks�� 162 Fill Further Reading �� 163 8 Poisonous and Venomous Organisms �� 165 8.1 Introduction�� 165 8.2 Classification of Venomous Arthropods�� 166 .3 8 Arachnids (Spiders, Scorpions, Whip Scorpions, Solpugids, Mites, and Ticks)�� 167 8.3.1 Spiders�� 167 8.3.2 Scorpions�� 168 8.3.3 Ticks Paralysis�� 169
xiv Contents .4 8 Myriapoda: Centipedes and Millipedes�� 170 VetBooks.ir .5 8 Insects: Heteroptera (True Bugs) and Hymenoptera (Ants, Bees, Wasps, and Hornets),�� 171 8.5.1 Ants, Bees, Wasps, and Hornets�� 171 .6 8 Blister Beetle Poisoning (Cantharidin Poisoning)�� 173 8.7 Toad Poisoning�� 174 8.8 Snake Poisoning�� 175 8.8.1 Crotalids�� 175 8.8.2 Elapids�� 177 8.9 Lizards�� 178 8.10 Questions and Answers �� 179 8.10.1 Short Questions and Answers �� 179 8.10.2 Multiple Choice Questions �� 181 8.10.3 Fill in Blanks�� 184 8.10.4 rue or False Statements�� 184 T Further Reading �� 185 9 Bacterial and Cyanobacterial (Blue- reen Algae) �� 187 G 9.1 Introduction�� 187 9.2 Botulinum Toxins (Botulism) �� 188 9.3 Enterotoxemias (Clostridium perfringens Infections)�� 190 9.3.1 Type A Enterotoxemia (Necrotic Enteritis)�� 191 9.3.2 Type B and C Enterotoxemia (Lamb Dysentery)�� 191 9.3.3 Type D Enterotoxemia (Pulpy Kidney Disease, Overeating Disease)�� 192 9.4 Blue-Green Algae Poisoning (Cyanobacterial Toxins) �� 193 9.5 Questions and Answers �� 195 9.5.1 Short Questions and Answers �� 195 9.5.2 Multiple Choice Questions �� 197 9.5.3 in the Blanks�� 198 Fill 9.5.4 True or False Statements�� 199 9.5.5 Match the Statements�� 200 Further Reading �� 201 10 Mycotoxicoses�� 203 10.1 Introduction�� 203 10.2 Aflatoxicosis �� 204 10.3 Ochratoxin A Toxicity�� 206 10.4 Ergotism�� 207 10.5 Estrogenism and Vulvovaginitis (Fusarium Estrogenism)�� 209 10.6 Facial Eczema �� 211 0.7 1 Fescue Lameness (Fescue Foot) �� 212 10.8 Fumonisin Toxicosis �� 213 10.9 Mycotoxic Lupinosis�� 214 10.10 Trichothecene Toxicosis�� 215 10.11 Ryegrass Staggers �� 217
Contents xv 10.12 Paspalum Staggers�� 217 VetBooks.ir 10.13 Slaframine Toxicosis�� 218 10.14 Degnala Disease�� 218 10.15 Tremorgenic Mycotoxins�� 220 10.16 Questions and Answers �� 220 10.16.1 Short Questions and Answers �� 220 10.16.2 Multiple Choice Questions �� 221 10.16.3 in the Blanks�� 223 Fill 10.16.4 True or False Statements�� 224 10.16.5 Match the Statements�� 224 Further Reading �� 225 11 Poisonous Plants�� 227 11.1 Introduction�� 227 11.2 Astragalus and Oxytropis Species�� 228 11.2.1 Locoweeds�� 228 11.2.2 Nitro-Containing Astragalus (Milkvetches) �� 229 11.2.3 Seleniferous Astragalus�� 231 11.3 Larkspurs (Delphinium spp.)�� 232 11.4 Lupines (Lupinus spp.)�� 233 11.5 Poison Hemlock (Conium maculatum)�� 235 11.6 Water Hemlock (Cicuta spp.)�� 237 1.7 1 Ponderosa Pine Needles (Pinus spp.)�� 238 11.8 Rayless Goldenrod (Haplopappus heterophyllus)�� 239 11.9 Broom Snakeweed (Gutierrezia spp.)�� 240 11.10 Halogeton (Halogeton glomeratus)�� 241 11.11 Pyrrolizidine Alkaloid-Containing Plants �� 242 11.12 Photosensitizing Plants �� 244 11.12.1 Primary Photosensitization �� 244 11.12.2 Secondary Photosensitization �� 245 11.13 Bracken Fern (Pteridium and Aquilinum)�� 246 11.14 Cannabis sativa (Cannabaceae Family)�� 248 11.15 Colchicum autumnale L�� 249 11.16 Datura�� 251 1.17 leander Plants (Apocynaceae Family)�� 252 1 O 11.18 Aconitum napellus�� 253 11.19 Ricinus communis �� 254 11.20 Lantana Poisoning�� 256 11.21 Descurainia pinnata�� 258 1.22 lants Containing Cyanogenic Glycosides �� 259 1 P 1.23 itrate- and Nitrite-Accumulating Plants �� 263 1 N 11.24 Toxicity of Yew (Taxus spp.) Alkaloids�� 265 11.25 Senna occidentalis (Fabaceae Family)�� 266 11.26 Strychnine Poisoning�� 267 11.27 Mushroom Poisoning�� 268
xvi Contents 11.28 Questions and Answers �� 269 VetBooks.ir 11.28.1 Short Questions and Answers �� 269 11.28.2 Multiple Choice Questions �� 271 11.28.3 in the Blanks�� 274 Fill 11.28.4 True or False Statements�� 275 11.28.5 Match the Statements�� 276 Further Reading �� 277 12 Feed Contaminant Toxicity �� 279 12.1 Introduction�� 279 12.2 Melamine and Cyanuric Acid �� 280 12.3 Ionophore Toxicity�� 281 12.3.1 Toxic Myopathies in Ruminants and Pigs�� 281 12.3.2 Toxic Myopathy in Poultry �� 281 12.3.3 Nonprotein Nitrogen Poisoning�� 281 12.4 Questions and Answers �� 283 12.4.1 Short Questions and Answers �� 283 12.4.2 Multiple Choice Questions �� 284 12.4.3 in the Blanks�� 285 Fill 12.4.4 True or False Statements�� 286 Further Reading �� 287 13 Food Hazards�� 289 13.1 Introduction�� 289 13.2 Avocado Poisoning �� 290 13.3 Chocolate Poisoning �� 291 13.4 Beard Doughs�� 293 13.5 Macadamia Nuts �� 293 13.6 Xylitol �� 294 13.7 Raisins and Grapes�� 294 13.8 Questions and Answers �� 295 13.8.1 Short Questions�� 295 13.8.2 Multiple Choice Questions �� 297 13.8.3 in the Blanks�� 298 Fill 13.8.4 True or False Statements�� 299 Further Reading �� 300 1 Veterinary Drug Residue Hazards �� 301 4 14.1 Introduction�� 301 14.2 Background �� 302 14.3 Public Health Significances�� 303 14.4 Withdrawal Times �� 303 14.5 Questions and Answers �� 304 14.5.1 Short Questions�� 304 14.5.2 Multiple Choice Questions �� 306
Contents xvii 14.5.3 in the Blanks�� 307 Fill VetBooks.ir 14.5.4 True or False Statements�� 307 Further Reading �� 308 15 Veterinary Clinical Toxicology�� 309 15.1 Introduction�� 309 15.2 Diagnosis of Toxicosis�� 310 15.2.1 Collection of Samples �� 311 15.2.2 Procedure for Submission of Samples�� 312 15.2.3 Samples for Toxicology Examination�� 312 15.2.4 Analytical Methods in Toxicology�� 314 15.3 Principles of Therapy�� 315 15.3.1 Prevention of Further Poison Absorption�� 315 15.3.2 Enhancement of Poison Elimination�� 316 15.3.3 Supportive Treatment�� 316 15.3.4 Specific Antidotes �� 317 15.4 Questions and Answers �� 317 15.4.1 Short Questions and Answers �� 317 15.4.2 Multiple Choice Questions �� 322 15.4.3 in the Blanks�� 325 Fill 15.4.4 True or False Statements�� 326 15.4.5 Match the Statements�� 327 Further Reading �� 328 Index�� 329
1 VetBooks.ir General Principles of Toxicology Abstract This chapter deals with the general principles and emergence of science-based toxicology and the scope and current status of veterinary toxicology. The future of veterinary toxicologists is very bright because this science will further expand as people and animals will continue to be poisoned by more and different chemi- cals. Several factors such as age, strain, species variation, pregnancy, physical state, and chemical properties of the toxicant and environmental factors can greatly influence the toxicity of a specific compound. The dose-response rela- tionship, or exposure-response relationship, describes the change in the effect on an organism. Many toxicants/xenobiotics exert their effects by interacting with specific receptors in the body. Therefore, this chapter briefly summarizes a quali- tative description of the adverse effect arising from a particular chemical or phys- ical agent irrespective of dose or exposure. Keywords General toxicology · Principles of toxicology · Factors affecting toxicity · Dose- response relationship · Interactions · Receptors · Hazards · Risk assessment · Questions and answers bank · Multiple choice questions 1.1 Introduction This chapter deals with the general principles of toxicology, factors affecting toxic- ity, emergence of science-based toxicology, and the scope and current status of vet- erinary toxicology. In addition, this chapter also highlights the key points about the subject matter followed by sample questions and answers that are in the format of short questions, multiple choice questions, fill in the blanks, and true/false state- ments as relevant to general principles of toxicology and their toxic effects on ani- mal health. © Springer Nature Switzerland AG 2019 1 PK Gupta, Concepts and Applications in Veterinary Toxicology, https://doi.org/10.1007/978-3-030-22250-5_1
2 1 General Principles of Toxicology Key Points VetBooks.ir • Toxicology assimilates knowledge and techniques from biochemistry, biology, chemistry, genetics, mathematics, medicine, pharmacology, phys- iology, and physics. • The word “toxicology” is derived from the Greek word toxicon which means “poison” and logos which means to study. • The evolution of veterinary toxicology occurred concurrently with the evo- lution of its two roots: the profession of veterinary medicine and the sci- ence of toxicology. • Veterinary toxicology involves the evaluation of toxicosis and deficiencies, identification and characterization of toxins and determination of their fate in the body, and treatment of toxicosis. • Veterinary toxicology in its earliest years had a major focus on poisonous plants and then on antidotes for various toxins. • Modern toxicology assimilates knowledge and techniques from most branches of sciences such as biochemistry, biology, chemistry, genetics, mathematics, medicine, pharmacology, physiology, and physics. • After the World War II, the mid-1950s witnessed the strengthening of vari- ous laws in the United States and other developed countries in the world. • The future of veterinary toxicologists is very bright because this science will further expand as people and animals will continue to be poisoned by more and different chemicals. • Several factors such as age, strain, species variation, pregnancy, physical state, and chemical properties of the toxicant and environmental factors can greatly influence the toxicity of a specific compound. • The dose-response relationship, or exposure-response relationship, describes the change in the effect on an organism. • Many toxicants/xenobiotics exert their effects by interacting with specific receptors in the body. 1.2 R oots in Veterinary Medicine and Toxicology The adjective veterinary is derived from Latin: veterinary, beasts of burden. Obviously, the modern field of veterinary medicine extends beyond the “beasts of burden” to include all the domesticated animal species, both livestock and compan- ion animals, as well as non-domesticated species. Indeed, it has expanded to include nonmammalian species. Veterinary toxicology has now grown into a multifaceted discipline that utilizes many diverse sources of toxicologic information. Veterinary toxicologists can be involved in basic toxicology research, clinical toxicology, regu- latory toxicology, chemical risk assessment, and chemical food safety in private, academic, clinical, government, and commercial settings, among others. Like many areas of science, veterinary toxicology information is being generated at rates much
1.2 Roots in Veterinary Medicine and Toxicology 3 higher than most professionals can access it and incorporated its principles into VetBooks.ir practice. Veterinary toxicologists need access to a wide variety of information sources to remain abreast with current toxicologic information and to make sound clinical choices. The Internet has provided the veterinary toxicologist with a valu- able tool to access both historical and cutting-edge research information in a timely and cost-effective manner. The father of modern toxicology is generally acknowledged to be Philippus Aureolus Theophrastus Bombastus von Hohenheim (1493–1541), who referred to himself as Paracelsus, from his belief that his work was beyond the work of Celsus, a first-century Roman physician. Paracelsus is credited with the well-known statement: All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy. Paracelsus advanced many views that were revolutionary for his time that are now accepted as fundamental concepts for the field of toxicology. Since then, the evolution of veterinary toxicology occurred concurrently with the development of its two roots: the profession of veterinary medicine and the science of toxicology. The veterinary medicine profession was initially focused on domestic animals, particularly those used for food, fiber, and transportation and those used to provide power for agricultural endeavors and transportation. With the growth of more specialized agriculture and production practices, the profession, with its link- age to domestic livestock, stimulated growth of veterinary toxicology. Veterinary toxicology in its earliest years had a major focus on poisonous plants and then on antidotes for various toxins. By the mid-twentieth century, three movements trans- formed veterinary medicine: (i) The first was related to the traditional roots of the profession in animal agricul- ture and related to the increasing emphasis given to large-scale highly special- ized domestic livestock endeavors. This movement was a major factor in the growth of Colleges of Veterinary Medicine at land-grant universities in the United States, followed by some other countries. (ii) The second was related to the increased attention given to providing veterinary medical services to a growing population of companion animals—a population that included horses, dogs, and cats. ( iii) The third movement—the emergence of the comparative medicine character of veterinary medicine—became more apparent and was enhanced. During this period, veterinary toxicologists began to play an important role in veterinary medical diagnostics. The expansion of the various facets of toxicology has been the outcome of the need of an affluent society to protect itself from injuri- ous effects resulting from introduction of new chemicals, physical agents, and vari- ous industrial and consumer products. Therefore, application of the discipline of toxicology in the safety evaluation and risk assessment is of utmost importance in today’s modern life.
4 1 General Principles of Toxicology 1.3 T oxicology and the Risk Paradigm VetBooks.ir As indicated earlier, toxicology, like veterinary medicine, was also rapidly changing and evolving in the mid-twentieth century. These changes in the veterinary medical profession and the emergence of toxicology as a science emerged during a period when the general population was paying increased attention to the health risks and, its counterpoint, safety of new technologies and products. The mid-1950s witnessed the strengthening of the US Food and Drug Administration’s commitment to toxicology under the guidance of Arnold Lehman. Lehman, Fitzhugh, and their co-workers formalized the experimental program for the appraisal of food, toxicant, and cosmetic safety in 1955, updated by the US FDA in 1982. The Delaney clause (1958) of these amendments stated broadly that any chemical found to be carcinogenic in laboratory animals or humans could not be added to the US food supply. Regardless of one’s view of Delaney, it has served as an excellent starting point for understanding the complexity of the biological phe- nomenon of carcinogenicity and the development of risk assessment models. The end of the 1960s witnessed the “discovery” of TCDD as a contaminant in the herbicide Agent Orange (the original discovery of TCDD toxicity, as the “chick edema factor,” was reported in 1957). The expansion of legislation, journals, and new societies involved in toxicology was exponential during the 1970s and 1980s and shows no signs of slowing down. At present, there are several dozens of profes- sional, governmental, and other scientific organizations with thousands of members and over 120 journals dedicated to toxicology and related disciplines in the world. As an example of this diversification, one now finds toxicology graduate programs in medical schools, schools of public health, and schools of pharmacy as well as programs in environmental science and engineering. Now there are undergraduate programs in toxicology at several institutions. Surprisingly, courses in toxicology are now being offered in several liberal arts undergraduate schools as part of their biology and chemistry curricula. In the 1970s, several federal legislations passed by various countries focused on health impacts of environmental and occupational exposures and led to more for- malized approaches to evaluating the risks and safety of various exposures. The risk paradigm built on the long-standing pattern of linking sources of dose exposure to adverse health outcomes had guided toxicology from its earliest days. The original key elements of the risk paradigm were as follows: (i) Hazard identification (ii) Exposure-response assessment (iii) Exposure assessment (iv) Risk assessment The information developed in the risk assessment process is utilized in the risk management where decisions are made as to the need for, the degree of, and the steps to be taken to control exposures (the four major elements) of the chemical of concern (Fig 1.1).