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E-raamat: Fundamentals of Toxicology: Essential Concepts and Applications

(Indian Veterinary Research Institute, India)
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  • Ilmumisaeg: 26-Aug-2016
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128054031
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Fundamentals of Toxicology: Essential Concepts and ApplicationsSuurem pilt
  • Formaat: EPUB+DRM
  • Ilmumisaeg: 26-Aug-2016
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128054031
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Fundamentals of Toxicology: Essential Concepts and Applications provides a crisp, easy-to-understand overview of the most important concepts, applications, and ideas needed to learn the basics of toxicology. Written by a pre-eminent toxicologist with over five decades of teaching experience, this comprehensive resource offers the hands-on knowledge needed for a strong foundation in the wide field of toxicology.Fundamentals of Toxicology includes a clear structure divided into five units to assist learning and understanding.The first unit provides extensive coverage on the background of toxicology including commonly used definitions and historical perspective, while following units cover: basic concepts; regulatory requirements and good laboratory practices, including types of toxicology testing and evaluation; toxic agents and adverse effects on health; and analytical, forensic, and diagnostic toxicology. This is an essential book for advanced students in toxicology and across the biomedical sciences, life sciences, and environmental sciences who want to learn the concepts of toxicology, as well as early researchers needing to refresh outside of their specialty.Explains the essential concepts of toxicology in a clear fashionProvides in-depth coverage of testing protocols, common drugs, chemicals, and laboratory-based diagnostic and analytical toxicologyExplores the history, foundations, and most recent concepts of toxicologyServes as an essential reference for advanced students in toxicology and across the biomedical, life, and environmental sciences who want to learn the concepts of toxicology

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A concise, approachable overview of the basic concepts of toxicology, this foundational text covers commonly used definitions, historical perspectives, regulatory requirements, good laboratory practices, types of toxicology testing and evaluation, toxic agents and their adverse effects on health, and analytical, forensic, and diagnostic toxicology
About the Author xix
Foreword xxi
Preface xxiii
Unit I
Chapter 1 Introduction and historical background
3(6)
1.1 Introduction
3(1)
1.2 Historical Background
3(3)
1.2.1 Antiquity
3(1)
1.2.2 Middle Ages
4(1)
1.2.3 Age of Enlightenment
5(1)
1.3 Modem Toxicology
6(3)
1.3.1 After World War II
6(3)
Chapter 2 Definitions and scope of toxicology
9(10)
2.1 Definitions
9(1)
2.2 Sub-disciplines of Toxicology
10(1)
2.3 Toxicant and Types of Toxicants
11(1)
2.4 Toxicity and Toxic Effects
12(1)
2.4.1 Toxicity in Relation to Frequency and Duration of Exposure
12(1)
2.4.2 Toxicity in Relation to Time of Development and Duration of Induced Effects
13(1)
2.5 Dose and Related Terms
13(1)
2.6 Other Common Terms
14(1)
2.7 Sources of Poisoning
15(1)
2.7.1 Accidental Poisoning
16(1)
2.7.2 Malicious Poisoning
16(1)
2.7.3 Occupational Exposure
16(1)
2.8 Duration and Frequency of Exposure
16(3)
Chapter 3 Classification of poisons/toxicants
19(4)
3.1 Introduction
19(1)
3.2 Classification of Poisons
19(2)
3.3 Actions of Poisons
21(2)
Chapter 4 Factors affecting toxicity
23(8)
4.1 Introduction
23(1)
4.2 Factors Affecting Toxicity
23(8)
4.2.1 Host Factors
24(2)
4.2.2 Factors Related to the Toxicant or Associated With Xenobiotics
26(2)
4.2.3 Environmental Conditions
28(3)
Chapter 5 Natural laws concerning toxicology
31(14)
5.1 Introduction
31(1)
5.2 Tolerance
32(1)
5.3 Dose
32(3)
5.4 Time Action Curves
35(1)
5.5 Dose—Response Relationship
36(3)
5.5.1 Graded or Gradual Dose—Response Relationship
36(2)
5.5.2 Quantal or All-or-None Dose—Response Relationship
38(1)
5.6 Statistical Concept of Toxicity
39(1)
5.7 Variables of Dose—Response Curve
40(1)
5.8 Frequently Used Terms for Safety Evaluation of Drugs
41(1)
5.9 Interaction With Receptors
42(1)
5.10 Types of Xenobiotics
42(1)
5.11 Xenobiotic/Drug Interaction
42(1)
5.12 Nature and Extent of Toxicity Testing
43(2)
Chapter 6 Hazard and risk assessment
45(10)
6.1 Introduction
45(1)
6.2 Risk Assessment Approach
46(5)
6.2.1 Preliminary Evaluation
47(1)
6.2.2 Toxicity Assessment
47(2)
6.2.3 Exposure Assessment
49(2)
6.3 Conclusion
51(4)
Unit II
Chapter 7 Absorption, distribution, and excretion of toxicants
55(18)
7.1 Introduction
55(1)
7.2 Translocation of Xenobiotics Across Membranes
56(4)
7.2.1 Membrane Permeability
56(1)
7.2.2 Mechanism of Chemical Transfer
57(1)
7.2.3 Processes of Transport
57(3)
7.3 Absorption
60(4)
7.3.1 Gastrointestinal Absorption
60(2)
7.3.2 Skin Absorption
62(1)
7.3.3 Lungs Absorption
63(1)
7.3.4 Parenteral Administration
63(1)
7.4 Distribution
64(4)
7.4.1 Tissue Permeability Barriers
65(1)
7.4.2 Transfer Across Other Membranes
66(1)
7.4.3 Factors Affecting Distribution and Tissue Retention
66(2)
7.4.4 Binding to Biological Macromolecules and Toxic Effects
68(1)
7.4.5 Redistribution
68(1)
7.5 Excretion
68(5)
7.5.1 Renal Excretion
69(1)
7.5.2 Biliary Excretion
70(1)
7.5.3 Gastrointestinal Tract
71(1)
7.5.4 Expired Air
71(1)
7.5.5 Sweat
71(1)
7.5.6 Saliva
72(1)
7.5.7 Milk
72(1)
7.5.8 Vaginal Secretions
72(1)
7.5.9 Other Routes
72(1)
Chapter 8 Biotransformation
73(14)
8.1 Introduction
73(1)
8.2 Functions of Biotransformation
73(1)
8.3 Xenobiotic Metabolizing Enzymes
74(1)
8.4 Pathways of Biotransformation
75(7)
8.4.1 Phase I Reactions (Nonsynthetic or Nonconjugative Phase)
75(3)
8.4.2 Phase II Reactions or Conjugation/Synthetic Reactions
78(4)
8.5 Complex Nature of Biotransformation
82(1)
8.6 Induction and Inhibition of Metabolizing Enzymes
82(1)
8.6.1 Induction of Enzymes
82(1)
8.6.2 Inhibition of Enzymes
83(1)
8.7 Bioactivation and Tissue Toxicity
83(4)
8.7.1 Electrophiles
84(1)
8.7.2 Free Radicals
84(1)
8.7.3 Nucleophiles
85(1)
8.7.4 Other Pathways
85(2)
Chapter 9 Principles and basic concepts of toxicokinetics
87(24)
9.1 Introduction
87(1)
9.2 Essentials of Toxicokinetics/Pharmacokinetics Principles
88(1)
9.3 Plasma Drug Concentration Versus Time
88(2)
9.4 Orders of Rate Processes
90(1)
9.4.1 Zero-Order Process/Zero-Order Kinetics
90(1)
9.4.2 First-Order Process/First-Order Kinetics
90(1)
9.4.3 Mixed-Order Process/Mixed-Order Kinetics
90(1)
9.5 Toxicokinetics Models
91(15)
9.5.1 Classic Toxicokinetics
91(12)
9.5.2 Noncompartment Models/Noncompartment Analysis
103(1)
9.5.3 Physiological-Based Toxicokinetics
104(2)
9.6 Determination of Dose/Dosage Regimen
106(1)
9.7 Conclusion
107(4)
Unit III
Chapter 10 Toxicological testing: genesis
111(12)
10.1 Introduction
111(1)
10.2 Laws and Regulations
112(5)
10.2.1 Regulation in the United States
112(1)
10.2.2 Guidelines for Drugs
113(2)
10.2.3 Toxic Substances Control Act of the United States
115(1)
10.2.4 REACH Regulation of European Countries
116(1)
10.3 International Harmonization
117(1)
10.4 Role of Animal Testing
117(1)
10.5 Standard Information Requirements
118(1)
10.6 Recent Trends
119(2)
10.6.1 Avoid Unnecessary Testing
119(1)
10.6.2 Alternate Approaches
119(1)
10.6.3 Cheminformatics
120(1)
10.6.4 Nanomaterials
120(1)
10.7 Good Laboratory Practices
121(2)
10.7.1 Background
122(1)
10.7.2 Principles of Good Laboratory Practices
122(1)
Chapter 11 Toxicological testing: in vitro models
123(8)
11.1 Introduction
123(1)
11.2 Animal Welfare Legislation
123(1)
11.3 In Vitro Models
124(2)
11.3.1 Permanent Cell Lines
124(1)
11.3.2 Primary Cultures
125(1)
11.3.3 Organotypic or Whole Organ Cultures
126(1)
11.4 In Vitro Embryotoxicity Testing
126(4)
11.4.1 Principles of In Vitro Embryotoxicity Testing
127(1)
11.4.2 Use of In Vitro Models/Alternative Test Methods
128(1)
11.4.3 Rat/Mice Embryos as a Model
128(1)
11.4.4 Use of Cultured Embryos
129(1)
11.4.5 Endpoint Determination for In Vitro Testing Systems
130(1)
11.5 Conclusion
130(1)
Chapter 12 Toxicological testing: In vivo systems
131(20)
12.1 Introduction
132(1)
12.2 Administration of Toxicants
132(2)
12.2.1 Routes of Administration
132(1)
12.2.2 Chemical and Physical Properties
133(1)
12.2.3 Exposure and Environmental Fate
134(1)
12.3 In Vivo Tests
134(6)
12.3.1 Acute and Subchronic Toxicity Tests
134(1)
12.3.2 Acute Oral Toxicity Testing
135(1)
12.3.3 Eye Irritation
135(1)
12.3.4 Dermal Irritation and Sensitization
136(1)
12.3.5 Safety Pharmacology Studies
137(1)
12.3.6 Subchronic Tests
137(1)
12.3.7 Repeated-Dose Dermal Tests
138(1)
12.3.8 28-Day to 90-Day Inhalation Tests
138(1)
12.3.9 Chronic Tests
139(1)
12.3.10 Chronic Toxicity and Carcinogenicity
139(1)
12.4 Development and Reproductive Toxicity
140(7)
12.4.1 Testing Protocols
141(1)
12.4.2 Single- and Multiple-Generation Tests
142(2)
12.4.3 Teratology
144(2)
12.4.4 Perinatal and Postnatal Effects
146(1)
12.5 Special Tests
147(2)
12.5.1 Neurotoxicity
148(1)
12.5.2 Potentiation and Synergism
149(1)
12.5.3 Toxicokinetics and Metabolism
149(1)
12.5.4 Covalent Binding
149(1)
12.5.5 Immunotoxicity
149(1)
12.6 In Vitro and Other Short-Term Tests
149(1)
12.7 Ecological Effects
150(1)
12.8 Risk Analysis
150(1)
Chapter 13 Genotoxicity
151(14)
13.1 Introduction
151(1)
13.2 Historical Background
152(1)
13.3 Germ Cell Mutation
152(2)
13.4 DNA Mutations
154(1)
13.5 Mutagens Are Carcinogens
155(1)
13.6 Impact on Human Health
155(1)
13.7 DNA Damage and Mechanism
156(1)
13.8 Regulatory Requirements/Guidelines
157(1)
13.9 Assays for Detection of Genetic Alterations
157(7)
13.9.1 Prokaryote Mutagenicity
158(1)
13.9.2 Eukaryote Mutagenicity
159(2)
13.9.3 DNA Damage and Repair
161(1)
13.9.4 Chromosome Aberrations
161(2)
13.9.5 Mammalian Cell Transformation
163(1)
13.10 Conclusion
164(1)
Chapter 14 Preclinical toxicological investigations of pharmaceutical products
165(8)
14.1 Introduction
165(1)
14.2 Safety Evaluation of Pharmaceutical Products
166(5)
14.2.1 Discovery Phase
167(2)
14.2.2 Preclinical Toxicology Testing
169(1)
14.2.3 Preclinical Development Phase
169(1)
14.2.4 Studies of Environmental Safety
170(1)
14.2.5 Postmarketing Surveillance
170(1)
14.2.6 Estimation of the Dose
170(1)
14.3 Conclusion
171(2)
Chapter 15 Preclinical safety evaluation of biotechnology-derived products
173(4)
15.1 Introduction
173(1)
15.2 Background
173(1)
15.3 Regulatory Considerations
174(1)
15.4 General Principles
174(1)
15.5 General Toxicological Profile
174(2)
15.5.1 Absorption, Disposition, and Clearance in Relevant Animal Models
175(1)
15.5.2 Specific Toxicity Tests
175(1)
15.6 Conclusion
176(1)
Chapter 16 Preclinical regulatory toxicology for biomaterials and medical devices
177(8)
16.1 Introduction
177(1)
16.2 Regulations
178(1)
16.3 Objectives
178(1)
16.4 Extract Preparations
178(1)
16.5 Test Protocols
178(1)
16.6 Short-Term Tests
179(1)
16.6.1 Acute Toxicity
179(1)
16.6.2 Pyrogenicity
179(1)
16.6.3 Hemolytic Properties
179(1)
16.6.4 Intracutaneous/Intradermal Reactivity Test
179(1)
16.6.5 Skin Irritation
180(1)
16.7 Long-Term Tests
180(1)
16.7.1 Delayed Hypersensitivity/Sensitization Test
180(1)
16.7.2 Implantation
180(1)
16.7.3 Genotoxicity
181(1)
16.8 Supplementary Tests
181(1)
16.8.1 Subchronic Toxicity
181(1)
16.8.2 Chronic Toxicity
181(1)
16.8.3 Carcinogenicity
181(1)
16.8.4 Developmental and Reproductive Toxicity
182(1)
16.9 Conclusion
182(3)
Unit IV
Chapter 17 Toxic effects of pesticides (agrochemicals)
185(18)
17.1 Introduction
185(1)
17.2 Historical Background
186(1)
17.3 Definition and Classification
186(1)
17.4 Insecticides
187(11)
17.4.1 OC Insecticides
187(2)
17.4.2 OP and CM Compounds
189(3)
17.4.3 CMs Insecticides
192(3)
17.4.4 Botanical Insecticides
195(1)
17.4.5 Pyrethroid Insecticides
196(1)
17.4.6 New Insecticide Classes
196(2)
17.5 Herbicides
198(1)
17.6 Fungicides
199(1)
17.7 Rodenticides
200(1)
17.8 Fumigants
201(2)
17.8.1 Aluminum Phosphide
202(1)
17.8.2 Naphthalene (Mothballs)
202(1)
Chapter 18 Toxic effects of metals
203(12)
18.1 Introduction
203(1)
18.2 Arsenic (Sankhyal, Somalkar)
203(2)
18.3 Mercury (Quick Silver, Liquid Metal, Para, Padarasa)
205(3)
18.4 Lead (Shisha)
208(3)
18.5 Copper (Thambe, Blue Vitriol)
211(1)
18.6 Iron
212(3)
Chapter 19 Toxic effects of nonmetallics
215(6)
19.1 Introduction
215(1)
19.2 Toxicity of Nonmetallics
215(1)
19.3 Phosphorus
216(2)
19.4 Chlorine
218(1)
19.5 Bromine
218(1)
19.6 Iodine
219(1)
19.7 Formaldehyde (Formalin, Methyl Aldehyde, Methylene Oxide)
220(1)
Chapter 20 Neurotoxic agents
221(24)
20.1 Introduction
221(1)
20.2 Opium (Afim) Derivatives
222(3)
20.2.1 Opioid Poisoning
224(1)
20.3 Pethidine (Meperidine)
225(1)
20.3.1 Pethidine Addiction
225(1)
20.4 Alcohol
226(3)
20.5 Ethylene Glycol
229(1)
20.6 Chloroform
230(1)
20.7 Ether
230(1)
20.8 Chloral Hydrate (Trichloroacetaldehyde)
231(1)
20.9 Barbiturates
231(3)
20.9.1 Classification
232(2)
20.10 Benzodiazepines
234(1)
20.11 Hydrocarbons
235(1)
20.12 Insecticides
236(1)
20.13 Datura
236(1)
20.14 Cannabis
237(3)
20.14.1 Cannabis Addiction
239(1)
20.15 Cocaine
240(3)
20.15.1 Cocainism
242(1)
20.16 Strychnine
243(2)
Chapter 21 Toxic effects of cardiac poisons
245(8)
21.1 Introduction
245(1)
21.2 Oleanders
245(2)
21.3 Aconite
247(2)
21.4 Nicotine (Tobacco)
249(4)
Chapter 22 Toxic effects of asphyxiants
253(14)
22.1 Definition
253(1)
22.2 Classification
253(1)
22.2.1 Chemical Asphyxiants
254(1)
22.2.2 Simple Asphyxiants
254(1)
22.2.3 Respiratory/Pulmonary Irritant Asphyxiants
254(1)
22.2.4 Systemic Asphyxiants
254(1)
22.3 Carbon Monoxide
254(2)
22.4 Carbon Dioxide
256(1)
22.5 Cyanide (Prussic Acid, Cyanogen)
257(3)
22.6 Ammonia (NH3)
260(2)
22.7 War Gases
262(5)
22.7.1 Lachrymators (Tear Gases)
262(1)
22.7.2 Lung Irritants (Asphyxiants, Choking Gases)
262(1)
22.7.3 Nasal Irritants and Vomiting Gases (Sternutators)
263(1)
22.7.4 Nerve Gases
263(1)
22.7.5 Vesicants (Blister Gases)
263(1)
22.7.6 Paralysants (Nerve and Blood Poisons)
264(1)
22.7.7 Miscellaneous War Gases
264(3)
Chapter 23 Toxic effects of caustics (corrosives)
267(10)
23.1 Introduction
267(1)
23.2 Classification
267(1)
23.3 Acids
268(7)
23.3.1 Inorganic Acids/Mineral Acids
268(3)
23.3.2 Organic Acids
271(4)
23.4 Alkalis
275(2)
Chapter 24 Drug toxicity, dependence, and abuse
277(10)
24.1 Introduction
277(1)
24.2 Aspirin and Other Salicylates
278(1)
24.3 Paracetamol
278(1)
24.4 Drug Dependence and Abuse
279(6)
24.4.1 Definitions and Terminology
279(3)
24.4.2 Hallucinogens (Psychedelics)
282(1)
24.4.3 Lysergic Acid Diethylamide
282(2)
24.4.4 Peyote
284(1)
24.4.5 Amphetamines (Central Nervous System Stimulant, Hallucinogen)
284(1)
24.4.6 Carbon Tetrachloride
285(1)
24.5 Withdrawal Symptoms (Abstinence Syndrome)
285(2)
Chapter 25 Toxic effects of domestic chemicals
287(6)
25.1 Domestic/Household Poisons Classification
287(1)
25.2 Hydrocarbons
287(3)
25.2.1 Aliphatic Hydrocarbons
287(3)
25.2.2 Aromatic Hydrocarbons
290(1)
25.2.3 Halogenated Hydrocarbons
290(1)
25.3 Other Than Hydrocarbons
290(3)
Chapter 26 Toxic effects of poisonous plants
293(12)
26.1 Introduction
293(1)
26.2 Abrus precatorius
293(2)
26.3 Ricinus communis (Castor Oil Plant)
295(1)
26.4 Croton
296(1)
26.5 Calotropis
297(1)
26.6 Semecarpus anacardium
298(1)
26.7 Capsicum annuum
299(1)
26.8 Eucalyptus Globulus
300(1)
26.9 Colchicum (Colchicum autumnale)
301(1)
26.10 Ergot
302(3)
Chapter 27 Poisonous foods and food poisoning
305(6)
27.1 Introduction
305(1)
27.2 Microbial Toxins
305(1)
27.3 Food Poisoning
306(1)
27.4 Mycotoxins
307(1)
27.5 Algal Toxins
308(3)
Chapter 28 Poisons of animal origin
311(16)
28.1 Introduction
311(1)
28.2 Animal Poisons
312(1)
28.3 Arthropods
312(5)
28.3.1 Arachnids
313(2)
28.3.2 Myriapods (Centipedes, Chilopoda)
315(1)
28.3.3 Insects
316(1)
28.3.4 Cantharides (Spanish Fly Blister Beetle, Lytta)
317(1)
28.4 Mollusks
317(1)
28.4.1 Cone Snails
317(1)
28.5 Reptiles
318(9)
28.5.1 Lizards
318(1)
28.5.2 Venomous Snakes
319(5)
28.5.3 Nonvenomous Snakes
324(1)
28.5.4 Other Reptile Bites
325(1)
28.5.5 Alligators and Crocodile
325(1)
28.5.6 Iguana
325(2)
Chapter 29 Chemical food poisoning
327(6)
29.1 Introduction
327(1)
29.2 Mushrooms
327(1)
29.3 Poisonous Plant Toxins
328(1)
29.4 Poisonous Marine Bites and Stings
329(4)
29.4.1 Poisonous Fishes
329(1)
29.4.2 Shellfish
330(3)
Chapter 30 Health effects of radioactive materials
333(10)
30.1 Introduction
333(2)
30.1.1 Historical Background
333(1)
30.1.2 Regulatory Aspects of Radiation
334(1)
30.1.3 Standards for Radiation Exposure
334(1)
30.1.4 Units of Radiation
335(1)
30.2 Types of Radiation
335(8)
30.2.1 Nonionizing Radiation
336(1)
30.2.2 Ionizing Radiation
337(6)
Unit V
Chapter 31 Basic concepts of forensic toxicology
343(4)
31.1 Introduction
343(1)
31.2 History and Background
343(1)
31.3 Courtroom Testimony
344(1)
31.4 Investigation
344(3)
31.4.1 Collection of Information
344(1)
31.4.2 Collection of Specimens
345(1)
31.4.3 Toxicological Analysis
345(1)
31.4.4 Documentation and Data Interpretation
345(2)
Chapter 32 Applications in toxicology
347(8)
32.1 Introduction
347(1)
32.2 Objectives of Analytical Toxicology
347(1)
32.3 Analytical Schemes for Toxicant Detection
348(1)
32.4 Laboratory Analyses
348(2)
32.4.1 General Precautions
350(1)
32.5 Wet Chemistry
350(5)
32.5.1 Qualitative Analytical Tests
350(3)
32.5.2 Quantitative Analytical Methods
353(2)
Chapter 33 Clinical toxicology
355(10)
33.1 Introduction
355(1)
33.2 Historical Background
355(1)
33.3 Introduction of the Poison Control Center
356(1)
33.4 Acute Poisoning Deaths
357(1)
33.5 Causes of Poisoning
357(1)
33.6 Principles of Diagnosis
358(3)
33.6.1 Clinical History
358(1)
33.6.2 Physical Examination
358(2)
33.6.3 Analytical Evidence
360(1)
33.7 General Management of Poisoning
361(3)
33.7.1 Initial Stabilization
361(1)
33.7.2 Specific Measures
361(1)
33.7.3 Decontamination
362(2)
33.8 Dialysis
364(1)
33.9 Nursing and Psychiatric Care
364(1)
Chapter 34 Treatment of poisoning
365(4)
34.1 Introduction
365(1)
34.2 Specific Treatment (Administration of Antidotes)
365(4)
Further Reading 369(12)
Index 381
PK Gupta obtained his PhD in Toxicology and taught as Visiting Professor at both the University of Tennessee and West Virginia University in the United States before returning to India as Professor of Toxicology at the Indian Veterinary Research Institute. He is currently Director of the Toxicology Consulting Group and President of the Academy of Sciences for Animal Welfare. He has served as advisor to the World Health Organization, consultant to the United Nations Food and Agriculture Organization, and brings more than 50 years of expertise in animal toxicology to the project.
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