Temperature and Toxicology: An Integrative, Comparative, and Environmental Approach

Front cover......Page 1
Preface......Page 9
Acknowledgments......Page 11
Author......Page 13
Contents......Page 15
1.1 INTRODUCTION......Page 21
1.2 THE UNIQUE NATURE OF THERMOREGULATION......Page 23
1.3.1 Temperature Is a Benchmark of Acute Toxicity in Rodents......Page 26
1.3.2 Temperature Regulation as a Window to Autonomic Physiology......Page 27
1.4 THREE APPROACHES TO STUDYING TEMPERATURE AND TOXICOLOGY......Page 28
1.4.1 Integrative Approach......Page 29
1.4.3 Environmental Approach......Page 30
1.4.4 Presentation and Breadth of Coverage......Page 31
2.2 TERMINOLOGY......Page 33
2.3 HEAT BALANCE......Page 35
2.4 THE THERMOREGULATORY SYSTEM......Page 37
2.4.1 Interspecies Body Temperatures......Page 38
2.4.2 Thermal Homeostasis in the Unrestrained Rat......Page 40
2.5.1 Temperature Regulation as a Servo Control System......Page 42
2.5.2 Neurophysiological Mechanisms......Page 44
2.5.3 Neurochemical Mechanisms......Page 47
2.6 SET-POINT: REGULATED VERSUS FORCED CHANGES IN BODY TEMPERATURE......Page 49
2.7 THERMOEFFECTOR MECHANISMS AND THE THERMONEUTRAL ZONE......Page 52
2.7.1 Metabolic Thermogenesis......Page 55
2.7.1.2 Nonshivering Thermogenesis......Page 56
2.7.2 Peripheral Vasomotor Tone......Page 59
2.7.3 Evaporation......Page 62
2.7.3.2 Panting......Page 63
2.7.4 Behavioral Thermoregulatory Effectors......Page 64
2.7.5 Motor Activity: A Thermoeffector?......Page 68
2.8 POIKILOTHERMS......Page 69
3.1 INTRODUCTION......Page 71
3.2 GENERAL MECHANISMS......Page 72
3.4 HYPOTHERMIA: A COMMON RESPONSE IN RODENTS......Page 74
3.5 THERMOREGULATORY RESPONSE TO TOXICANTS......Page 76
3.5.1 Anticholinesterase Agents......Page 77
3.5.1.1 Correlation between Hypothermia and Cholinesterase Inhibition......Page 78
3.5.1.2 Integrated Thermoregulatory Responses......Page 82
3.5.1.3 CNS Mechanisms......Page 89
3.5.2 Chlordecone......Page 91
3.5.2.1 CNS Mechanisms......Page 92
3.5.3 Airborne Toxicants......Page 93
3.5.3.1 Ozone......Page 94
3.5.3.2 Carbon Monoxide......Page 96
3.5.4.1 Body Temperature and Metabolic Rate......Page 97
3.5.4.2 Brown Adipose Tissue......Page 99
3.5.4.3 Autonomic and Behavioral Effects......Page 101
3.5.4.4 Primate and Human Studies......Page 103
3.5.4.5 Neural Mechanisms......Page 104
3.5.4.6 Organotins......Page 106
3.5.5 Alcohols......Page 107
3.5.6.1 Human Responses......Page 108
3.5.7 Organic Solvents......Page 109
3.5.8 Formamidines......Page 110
3.6.1 DDT......Page 111
3.6.2.1 Thermogenesis......Page 113
3.6.2.2 Behavior......Page 114
3.7 PRE-NATAL AND POST-NATAL EFFECTS......Page 115
3.7.1 Dioxin and PCBs......Page 117
3.7.2 Anticholinesterase Agents......Page 118
3.7.3 Alcohol......Page 120
3.8 CHRONIC, SUBCHRONIC, AND REPEATED DOSING......Page 121
4.1 INTRODUCTION......Page 127
4.2.1 Temperature Coefficient and Q10......Page 128
4.2.2 Magnitude Versus Duration......Page 129
4.2.3 Lethality......Page 131
4.2.4 Patterns of Toxicity as a Function of Temperature......Page 133
4.2.6 Nervous System......Page 135
4.2.7 Cardiovascular System......Page 136
4.2.8 Liver and Kidney......Page 138
4.3.1 Temperature and Cell Death......Page 140
4.3.2 Chemotherapy......Page 142
4.3.3 Membrane Fluidity and Toxicity......Page 143
4.3.4 Toxic Mechanisms Attenuated by Hypothermia......Page 144
4.3.4.1 Reactive Oxygen Species......Page 146
4.3.5 Toxicant Mechanisms Exacerbated by Hypothermia......Page 147
4.4.1 Pulmonary Uptake......Page 150
4.4.2 Hepatic Metabolism......Page 152
4.5 TEMPERATURE ACCLIMATION......Page 153
4.5.2 Lethality......Page 154
4.5.3 Renal Toxicity and Temperature Acclimation......Page 155
4.5.4 Anticholinesterase Agents......Page 157
4.5.5 Lead Poisoning......Page 158
4.5.6 Ethanol and Cold Acclimation......Page 160
4.5.7 Chemical Carcinogens......Page 161
5.2 FEVER VERSUS HYPOTHERMIA AS ADAPTATIONS......Page 165
5.3 BEHAVIORAL THERMOREGULATION: A TOOL TO STUDY REGULATED VERSUS FORCED HYPOTHERMIA......Page 166
5.3.1 Defining the Limits of Normothermia in Toxicant- Exposed Subjects......Page 167
5.4 THERMOREGULATORY RESPONSE TO TOXICANTS: RELATIONSHIP TO OTHER PATHOLOGICAL INSULTS......Page 169
5.4.1 Hypoxia......Page 170
5.4.2 Endotoxemia......Page 172
5.5.1 Principles of Allometric Scaling......Page 175
5.5.2 Thermal Conductance and Toxicant-Induced Hypothermia......Page 178
5.6 HUMAN VERSUS RODENT......Page 179
5.7 RELEVANCE OF REGULATED HYPOTHERMIA IN TOXICOLOGY......Page 180
5.7.1 Assessment of Risk......Page 181
5.7.2 Hypothermia as Therapy in Poisonings?......Page 182
5.7.2.1 Changing the Set-Point to Treat Poisonings......Page 183
5.7.3 Evolution of Homeothermy and Resistance to Toxicants......Page 186
6.1 INTRODUCTION......Page 189
6.2 MECHANISM OF FEVER......Page 190
6.2.1 Rodents as a Model for Fever and Toxicology Studies......Page 191
6.3 FEVER AND CHOLINESTERASE-INHIBITING INSECTICIDES......Page 192
6.3.1 Fever Versus Hyperthermia......Page 194
6.3.2 Evidence That Anti-ChE Hyperthermia Is a Fever......Page 195
6.3.3 Manifestation of Fever: Day Versus Night......Page 199
6.4.1 Responses to Anti-ChEs......Page 200
6.4.2.2 Oxidative Phosphorylation Uncouplers......Page 204
6.4.2.3 Arsenic......Page 205
6.4.2.4 Turpentine......Page 206
6.5 ALCOHOL: REBOUND HYPERTHERMIA OR FEVER?......Page 207
6.6 CARBON MONOXIDE: TOXICANT AND ENDOGENOUS MEDIATOR OF FEVER......Page 209
6.7 METAL FUME FEVER......Page 210
6.8 INFLAMMATION, FEVER, AND THE P-450 PATHWAY......Page 212
6.9 IS TOXIC-INDUCED FEVER ADAPTIVE?......Page 214
7.1 INTRODUCTION......Page 215
7.3 THE PHYSICAL ENVIRONMENT......Page 216
7.3.1 Selecting an Appropriate Laboratory Test Environment......Page 219
7.4.1 Thermal Stress and Entry of Toxicants into the Body......Page 220
7.4.2 Sweating and Absorption of Toxicants......Page 222
7.4.3 Sweating and Toxicant Excretion......Page 225
7.5.1 Carbon Monoxide......Page 226
7.5.2.1 Animal Studies......Page 228
7.5.2.2 Human Studies......Page 229
7.6 AGRICULTURAL WORKERS AND PESTICIDE EXPOSURE......Page 230
7.7 TRAINED VERSUS SEDENTARY MODELS OF TOXICANT SUSCEPTIBILITY......Page 232
7.8.1 Psychological Stress......Page 235
7.8.2.1 Thermoregulation and Restraint......Page 238
7.8.2.2 Restraint and Response to Drugs and Toxicants......Page 239
7.8.3 Metallothionein Induction and Stress......Page 242
7.9 GULF WAR SYNDROME......Page 243
7.10 METEOROLOGICAL CONDITIONS AND ENVIRONMENTAL TOXICOLOGY......Page 244
7.11 ARSENIC, COLD STRESS, AND RAYNAUD’S DISEASE......Page 245
7.12 AMBIENT TEMPERATURE, POLLUTION, AND HUMAN MORTALITY......Page 246
7.12.1 Greenhouse Effect and Thermoregulation......Page 249
8.1 INTRODUCTION......Page 253
8.2 ECOTOXICOLOGY......Page 254
8.3 EFFECTS OF TEMPERATURE ON TOXICITY IN AQUATIC ORGANISMS......Page 255
8.3.1 Critical Thermal Maximum and Minimum......Page 258
8.4 FISH BEHAVIORAL THERMOREGULATION......Page 260
8.4.1 Endogenous Ethanol and Hypothermia......Page 266
8.4.2 Relationship between Behavior and Temperature- Dependent Lethality......Page 268
8.5 AMPHIBIANS......Page 272
8.6 INSECTS......Page 273
8.7 UNICELLULAR ORGANISMS......Page 276
8.8 RESPONSES TO WILDLIFE......Page 277
8.8.1 Birds......Page 278
8.8.2 Mammals......Page 281
9.2 GENETIC STRAIN VARIATION......Page 285
9.2.1 Intraspecies Variation......Page 286
9.2.2 Selective Breeding......Page 288
9.3 HEAT SHOCK PROTEINS......Page 290
9.3.1 Endotoxin and Heat Shock......Page 293
9.3.2 In Vivo Xenobiotic Studies......Page 294
10.1 INTRODUCTION......Page 299
10.2 FESCUE TOXICOSIS......Page 300
10.3 WILDLIFE AND TOXINS......Page 303
10.4 ALGAL TOXINS......Page 305
10.5 VENOMS......Page 309
REFERENCES......Page 315
A......Page 349
C......Page 350
E......Page 351
H......Page 352
I-J......Page 353
N......Page 354
R......Page 355
S......Page 356
T......Page 357
W......Page 358