Organophosphates Chemistry, Fate, and Effects (eBook)

Front Cover 1
Organophosphates Chemistry, Fate, and Effects 4
Copyright Page 5
Table of Contents 6
Contributors 14
Preface 18
Part I: Introduction 20
Chapter 1. Organophosphorus Compounds: 
22 
I. Introduction and Historical Development 22
II. 
24 
III. Inhibition of Acetylcholinesterase 29
IV. Toxic Effects Not Related to AChE Inhibition 33
V. Metabolism of Organophosphorus Compounds 34
References 36
Chapter 2. Preparation, Analysis, and Toxicity 
38 
I. Introduction 38
II. Preparation of Phosphorothiolates 42
III. Analysis of Phosphorothiolates 46
IV. Toxicity of Phosphorothiolates 53
V. Summary 61
Acknowledgments 62
References 62
Chapter 3. Degradation of OrganophosphorusInsecticides in Environmental Matrices 66
I. Introduction 66
II. Organophosphorus Insecticides in the Environment 68
III. Environmental Transport and 
72 
IV. Fate in Terrestrial and Aquatic Systems 83
V. Summary 91
References 92
Chapter 4. Species-Selective Toxicity of Organophosphorus Insecticides: 
98 
I. Introduction 98
II. Absorption and Elimination 99
III. Distribution 100
IV. Metabolism 101
V. Acetylcholinesterase Inhibition 106
VI. Conclusions 120
References 120
Chapter 5. Reactivation of Organophosphorus 
126 
I. Introduction 127
II. Cholinesterase Inhibition by 
129 
III. Chemical Reactivation 136
IV. Oxime Treatment after Organophosphorus Poisoning 139
V. Oximes and Carbamates 141
VI. Oxime Research 143
VII. 
150 
Acknowledgments 151
References 151
Part II: Metabolie Fate 158
Chapter 6. 
160 
I. Introduction 160
II. Catalytic Mechanism of Flavin-Containing Monooxygenases 162
HI. Flavin-Containing Monooxygenase as a Phosphorus Oxidase 163
IV. Sulfoxidation of Organophosphorus Compounds 165
V. Relative Contributions of Flavin-Containing and Cytochrome P450 
167 
VI. Species Differences 169
VII. Organ Differences 170
VIII. Cellular Distribution 171
References 171
CHapter 7. Role of Glutathione in the Mammalian Detoxication of Organophosphorus Insecticides 174
I. Introduction 174
II. Evidence Supporting a Role for Glutathione in 
175 
III. Evidence Against a Role for Glutathione in Metabolism 
178 
IV. Unanswered Questions 184
V. Summary 184
Acknowledgments 185
References 185
Chapter 8. Role of Phosphorotriester Hydrolases in 
188 
I. Introduction 188
II. Phosphohydrolases 189
III. Phosphorotriester Hydrolases 190
IV. Conclusions 198
Acknowledgments 198
References 198
Chapter 9. Detoxication of Organophosphorus Compounds by Carboxylesterase 202
I. Introduction 202
II. General Properties of Carboxylesterase 203
III. Problems of Nomenclature 204
IV. Potentiation of Organophosphorus Toxicity 205
V. Specificity of Carboxylesterase 206
VI. Recovery of Organophsophorus-Inhibited 
208 
VII. Variation in Organophosphorus Toxicity 209
VIII. Role of Carboxylesterase in Treatment of 
212 
IX. Conclusions 213
References 214
Chapter 10. Hepatic Disposition of Organophosphorus Insecticides: 
220 
I. Introduction 220
II. Biotransformation Enzymes 221
III. Hepatic Biotransformation in Vivo as a 
225 
IV. Disposition within the Hepatic Lobule 228
V· Unanswered Questions, Current Reasoning,and Future Issues 238
Acknowledgments 241
References 241
Chapter 11. The Role of Target Site Activation of Phosphorothionates in Acute Toxicity 248
I. Introduction 248
II. Anticholinesterase Potency 249
III. Hepatic Bioactivation Activity 249
IV. Protection by Aliesterases in the Liver and the Plasma 251
V. Target Site Phosphorothionate Bioactivation and Other 
252 
VI. Target Site Phosphorothionate Bioactivation in Vivo 255
VII. Summary 256
Acknowledgments 257
References 257
Chapter 12. Transdermal Penetration and Metabolism of Organophosphate Insecticides 260
I. Overview 260
II. 
262 
III. Assessing Environmental Effects 264
IV. Isolated Perfused Porcine Skin Flap 267
V. Conclusions 270
References 271
Part III: Toxic Effects—Noncholinergic 
274 
Chapter 13. Direct Actions of Organophosphorus Anticholinesterases 
276 
I. Introduction 277
II. Inhibition by Organophosphorus Compounds of 
281 
III. Action of Organophosphorus Compounds 
284 
IV. Toxicological and Therapeutic Implications 286
Acknowledgments 287
References 287
Chapter 14. Role of Second-Messenger Systems 
290 
I. Introduction 290
II. Acetylcholine Muscarinic Receptors 291
III. The Phosphoinositide-Protein Kinase C Pathway 292
IV. The Regulation of Cyclic AMP and 
294 
V. Organophosphorus Compounds and 
296 
VI. Summary and Conclusions 299
Acknowledgments 299
References 300
Chapter 15. Tolerance to Organophosphorus Cholinesterase Inhibitors 304
I. Introduction 304
II. Metabolic Dispositional Tolerance 306
III. Involvement of Changes in Cholinergic Functional States 308
IV. Other Mechanisms 311
Acknowledgments 313
References 313
Chapter 16. Interactions of Organophosphorus Compounds with Neurotoxic Esterase 318
I. Introduction 319
II. Inhibition of Esterases by Organophosphorus Compounds 321
III. Conventional View of the Role of NTE 
328 
IV. Predictors of Neuropathic Potential of 
331 
V. Challenges to the Conventional View of 
334 
VI. Conclusions 337
Acknowledgments 338
References 339
Part IV: Toxic Effects—Organismal 344
Chapter 17 Triphenyl Phosphite: A Type II 
346 
I. Introduction 346
II. Actions of Organophosphorus Esters 349
III. Triaryl Phosphites 354
IV. Summary 367
Acknowledgments 368
References 368
Chapter 18. Rodent Models of Organophosphorus-induced Delayed Neuropathy 372
I. Introduction 372
II. Neuropathic Distribution 373
III. Biochemical Index 375
IV. Pharmacological Manipulation 378
IV· Triphenyl Phosphite Neuropathy 379
VI. Mouse Model of OPIDN 381
VII. Interspecies Variations in OPIDN 381
VIII. Summary 382
References 382
Chapter 19 Immunotoxicity of Organophosphorus Compounds 386
I. Overview of the Immune System 386
II. Overview of Immunotoxicology 388
III. Immunotoxicity of Organophosphorus Compounds 390
IV. Cellular Targets and Mechanisms of Action 395
V. Summary and Conclusions 400
Acknowledgments 401
References 401
Chapter 20. Teratogenic Effects of Organophosphorus Compounds 406
I. Introduction 406
II. Teratogenic Organophosphorus Compounds 408
III. Mechanisms of Teratogenesis 422
V. Overview 429
Acknowledgments 429
References 430
Chapter 21 Neurobehavioral Effects of Organophosphorous Compounds 438
I. Introduction 438
II. Human Studies 439
III. Animal Studies 440
IV. Conclusions 448
References 448
Part V: Summary and Conclusions 452
Chapter 22. Summary and Conclusions 454
Index 460