Reproductive and Developmental Toxicology, Second Edition, is a comprehensive and authoritative resource that provides the latest literature on this complex subject with a primary focus on three core components—parent, placenta, and fetus—and the continuous changes that occur in each. Enriched with relevant references describing every aspect of reproductive toxicology, this revised and updated resource addresses the totality of the subject, discussing a broad range of topics, including nanoparticles and radiation, gases and solvents, smoking, alcohol and drug abuse, and metals, amongst others.
With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages, also including discussions on reproductive and developmental toxicity in domestic animals, fish, and wildlife.
Completely revised and updated to include the most recent developments in the field, the book is an essential resource for advanced students and researchers in toxicology, as well as biologists, pharmacologists, and teratologists from academia, industry, and regulatory agencies.
1. Chapter 1. Introduction - p. 3 2. Chapter 2. Reproductive Anatomy and Physiology - p. 7 3. Chapter 3. Pharmacokinetics in Pregnancy - p. 39 4. Chapter 4. Physiologically Based Pharmacokinetic Models in Reproductive and Developmental Toxicology - p. 51 5. Chapter 5. Drugs and Chemical Contaminants in Human Breast Milk - p. 67 6. Introduction - p. 68 7. Breast-Feeding - p. 69 8. Drug Excretion Into Breast Milk - p. 70 9. Drug Disposition in the Infant - p. 76 10. Drugs That Should Be Used With Caution - p. 78 11. Commonly Used Herbal Products - p. 82 12. Nonmedicinal Substances - p. 83 13. Environmental Pollutants - p. 86 14. Concluding Remarks and Future Directions - p. 94 15. Section II. Toxicity Testing Models and Safety Evaluation - p. 98 16. Chapter 6. Reproductive and Developmental Safety Evaluation of New Pharmaceutical Compounds - p. 101 17. Chapter 7. Juvenile Toxicology Testing - p. 129 18. Chapter 8. Postmarket Surveillance and Regulatory Considerations in Reproductive and Developmental Toxicology: A Food and Drug Administration Perspective - p. 145 19. Chapter 9. OECD Guidelines for In Vivo Testing of Reproductive Toxicity - p. 163 20. Chapter 10. Guidelines for Reproductive and Developmental Toxicity Testing and Risk Assessment of Chemicals - p. 179 21. Chapter 11. Validated and Nonvalidated Mechanism-Based Methods for Testing Developmental Toxicity - p. 193 22. Chapter 12. Relevance of Animal Testing and Sensitivity of End Points in Reproductive and Developmental Toxicity - p. 211 23. Chapter 13. Embryonic Toxic Lesions and Stem Cell Therapy - p. 225 24. Chapter 14. In Vitro and Alternative Approaches to Developmental Neurotoxicity - p. 241 25. Chapter 15. In Vitro Biomarkers of Developmental Neurotoxicity - p. 255 26. Introduction - p. 255 27. Cell Proliferation and Apoptosis - p. 256 28. Neurite Outgrowth - p. 265 29. Neurotransmission/Synaptogenesis - p. 270 30. Cytoskeleton - p. 272 31. Transcription Factors and Signaling Pathways - p. 275 32. Concluding Remarks and Future Directions - p. 277 33. Chapter 16. Using Zebrafish to Assess Developmental Neurotoxicity - p. 289 34. Chapter 17. Caenorhabditis elegans as a Model to Assess Reproductive and Developmental Toxicity - p. 303 35. Chapter 18. A Primate as an Animal Model for Reproductive and Developmental Toxicology Testing - p. 315 36. Section III. Nanoparticles and Radiation - p. 329 37. Chapter 19. Developmental Toxicity of Engineered Nanomaterials - p. 333 38. Chapter 20. Toxicity of Radiation: Biological Effects of Ionizing Radiation Exposure on Reproduction - p. 359 39. Section IV. Gases and Solvents - p. 375 40. Chapter 21. Reproductive and Developmental Toxicity of Solvents and Gases - p. 379 41. Section V. Drugs of Abuse and Addiction, Smoking and Alcohol - p. 396 42. Chapter 22. Caffeine - p. 399 43. Chapter 23. Developmental Neurotoxicity of Abused Drugs - p. 413 44. Chapter 24. Effects of Alcohol on Embryo/Fetal Development - p. 431 45. Chapter 25. Cigarette Smoking and Reproductive and Developmental Toxicity - p. 447 46. Section VI. Pharmaceuticals and Food Additives - p. 463 47. Chapter 26. Thalidomide - p. 467 48. Chapter 27. Retinoids - p. 481 49. Chapter 28. Melamine and Cyanuric Acid - p. 493 50. Chapter 29. Ionophores - p. 503 51. Section VII. Metals - p. 518 52. Chapter 30. Boron - p. 521 53. Chapter 31. Arsenic, Cadmium, and Lead - p. 537 54. Introduction - p. 537 55. Arsenic - p. 538 56. Cadmium - p. 545 57. Lead - p. 551 58. Therapeutic Strategies - p. 559 59. Concluding Remarks and Future Directions - p. 560 60. Chapter 32. Manganese - p. 567 61. Chapter 33. Mercury - p. 583 62. Chapter 34. Selenium - p. 595 63. Section VIII. Pesticides, Industrial and Other Environmental Contaminants - p. 605 64. Chapter 35. Organophosphates and Carbamates - p. 609 65. Introduction - p. 609 66. Historical Background - p. 610 67. Toxicokinetics - p. 611 68. Adverse Outcome Pathways in General Toxicity - p. 612 69. Adverse Outcome Pathways in Reproductive and Developmental Toxicity - p. 613 70. Toxicity - p. 619 71. Biomarkers - p. 624 72. Risk Assessment - p. 625 73. Treatment - p. 625 74. Concluding Remarks and Future Directions - p. 625 75. Chapter 36. Chlorinated Hydrocarbons and Pyrethrins/Pyrethroids - p. 633 76. Chapter 37. Herbicides and Fungicides - p. 657 77. Chapter 38. Brominated Flame Retardants - p. 681 78. Introduction - p. 681 79. Environmental Contamination and Human Exposure - p. 683 80. Effects on Human Health - p. 685 81. Health Effects in Animals and Wildlife - p. 686 82. Toxicokinetics and Metabolites - p. 699 83. Concluding Remarks and Future Directions - p. 703 84. Chapter 39. Polychlorinated Biphenyls, Polybrominated Biphenyls, Polychlorinated Dibenzo-p-dioxins, and Polychlorinated Dibenzofurans - p. 711 85. Introduction - p. 711 86. Historical Background - p. 712 87. Toxicokinetics - p. 716 88. Health Effects - p. 718 89. Mechanism of Action - p. 731 90. Concluding Remarks and Future Directions - p. 736 91. Chapter 40. Reproductive Toxicity of Polycyclic Aromatic Hydrocarbons - p. 745 92. Chapter 41. Toxicity and Risk Assessment of Bisphenol A - p. 765 93. Chapter 42. Ethylene Glycol - p. 797 94. Chapter 43. Perfluorooctane Sulfonate and Perfluorooctanoic Acid - p. 811 95. Chapter 44. Phthalates - p. 829 96. Introduction - p. 829 97. Toxicokinetics - p. 835 98. Mechanism of Action - p. 837 99. Toxicity - p. 840 100. Risk Assessment and Phthalate Action Plans - p. 847 101. Concluding Remarks and Future Directions - p. 848 102. Chapter 45. Personal Care Products and Cosmetics - p. 857 103. Introduction - p. 858 104. Phthalates - p. 858 105. Parabens - p. 879 106. Triclosan - p. 889 107. Other Chemicals in PCPs - p. 893 108. Concluding Remarks and Future Directions - p. 894 109. Section IX. Phytotoxicants, Mycotoxins and Zootoxins - p. 899 110. Chapter 46. Toxic plants - p. 903 111. Chapter 47. Fumonisins - p. 925 112. Chapter 48. Aflatoxins, Ochratoxins, and Citrinin - p. 945 113. Chapter 49. Zootoxins - p. 963 114. Section X. Special Topics - p. 972 115. Chapter 50. Systems Toxicology and Predictive Modeling of Male Developmental Toxicity - p. 975 116. Chapter 51. Stem Cells in Developmental Toxicity Testing - p. 987 117. Chapter 52. Epigenetics in Reproduction and Development - p. 1005 118. Chapter 53. Mitochondrial Dysfunction in Reproductive and Developmental Toxicity - p. 1023 119. Chapter 54. Cell Signaling Mechanisms in Developmental Neurotoxicity - p. 1037 120. Chapter 55. Neuroinflammation and Oxidative Injury in Developmental Neurotoxicity - p. 1051 121. Chapter 56. Effects of Stress on Reproductive and Developmental Biology - p. 1063 122. Chapter 57. Disruption of Cholesterol Homeostasis in Developmental Neurotoxicity - p. 1077 123. Section XI. Endocrine Disruption, Mutagenicity, Carcinogenicity, Infertility and Teratogenicity - p. 1088 124. Chapter 58. Endocrine Disruption - p. 1091 125. Chapter 59. Developmental and Reproductive Disorders—Role of Endocrine Disruptors in Testicular Toxicity - p. 1111 126. Chapter 60. Mutagenicity and Carcinogenicity: Human Reproductive Cancer and Risk Factors - p. 1123 127. Chapter 61. Environmental Pollutants and Neural Tube Defects - p. 1139 128. Chapter 62. Teratogenicity - p. 1167 129. Chapter 63. Micro–Computed Tomography and Volumetric Imaging in Developmental Toxicology - p. 1183 130. Section XII. Toxicologic Pathology - p. 1205 131. Chapter 64. Toxicologic Pathology of the Reproductive System - p. 1209 132. Introduction - p. 1210 133. Reproductive Toxicity Studies - p. 1211 134. Hormonal Regulation of Male and Female Reproduction - p. 1212 135. Potential Mechanisms Involved in Reproductive Toxicity - p. 1214 136. Evaluation of Reproductive Toxicity - p. 1222 137. Nonneoplastic Lesions of Male and Female Reproductive Systems - p. 1227 138. Role of Toxicokinetics in Male and Female Reproductive Toxicity - p. 1231 139. Molecular Mechanisms of Teratogenesis - p. 1233 140. Concluding Remarks and Future Directions - p. 1235 141. Section XIII. Placental Toxicity - p. 1241 142. Chapter 65. The Placental Role in Developmental Programming - p. 1245 143. Chapter 66. Strategies for Investigating Hemochorial Placentation - p. 1259 144. Chapter 67. The Significance of ABC Transporters in Human Placenta for the Exposure of Fetus to Xenobiotics - p. 1275 145. Introduction - p. 1275 146. Structure, Localization, Function, and Polymorphisms of Human Placental ABC Transporters - p. 1278 147. Models to Study Human Placental Transporters - p. 1281 148. Studies on Transplacental Transport and Placental Transporters - p. 1288 149. Significance of ABC Transporters in Fetal Health and Important Targets for Future Studies - p. 1292 150. Concluding Remarks and Future Directions - p. 1294 151. Chapter 68. Placental Toxicity - p. 1301 152. Introduction - p. 1301 153. Placental Structure, Function, and Species Differences - p. 1302 154. Placental Barrier - p. 1304 155. Placental Susceptibility to Chemical Toxicity - p. 1305 156. Placental-Toxicity-Modifying Factors - p. 1305 157. Toxicity - p. 1306 158. Concluding Remarks and Future Directions - p. 1319 159. Chapter 69. Placental Pathology - p. 1327 160. Introduction - p. 1327 161. Maternal “Effect” Pathologies of the Placenta - p. 1328 162. Maldevelopment of the Placental Implantation Site - p. 1329 163. Intraplacental Interference to Maternal Flow - p. 1332 164. Fetal Pathologies of the Placenta - p. 1337 165. Primary Placental Pathologies - p. 1342 166. Concluding Remarks and Future Directions - p. 1343 167. Section XIV. Domestic and Wildlife Species - p. 1350 168. Chapter 70. Reproductive and Developmental Toxicity in Avian Species - p. 1353 169. Chapter 71. Endocrine Disruption in Wildlife Species - p. 1373 170. Chapter 72. Teratogenesis in Livestock - p. 1391 171. Index - p. 1409
Reproductive and Developmental Toxicology, Second Edition, is a comprehensive and authoritative resource that provides the latest literature on this complex subject with a primary focus on three core components—parent, placenta, and fetus—and the continuous changes that occur in each. Enriched with relevant references describing every aspect of reproductive toxicology, this revised and updated resource addresses the totality of the subject, discussing a broad range of topics, including nanoparticles and radiation, gases and solvents, smoking, alcohol and drug abuse, and metals, amongst others.
With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages, also including discussions on reproductive and developmental toxicity in domestic animals, fish, and wildlife.
Completely revised and updated to include the most recent developments in the field, the book is an essential resource for advanced students and researchers in toxicology, as well as biologists, pharmacologists, and teratologists from academia, industry, and regulatory agencies.
1. Chapter 1. Introduction - p. 3 2. Chapter 2. Reproductive Anatomy and Physiology - p. 7 3. Chapter 3. Pharmacokinetics in Pregnancy - p. 39 4. Chapter 4. Physiologically Based Pharmacokinetic Models in Reproductive and Developmental Toxicology - p. 51 5. Chapter 5. Drugs and Chemical Contaminants in Human Breast Milk - p. 67 6. Introduction - p. 68 7. Breast-Feeding - p. 69 8. Drug Excretion Into Breast Milk - p. 70 9. Drug Disposition in the Infant - p. 76 10. Drugs That Should Be Used With Caution - p. 78 11. Commonly Used Herbal Products - p. 82 12. Nonmedicinal Substances - p. 83 13. Environmental Pollutants - p. 86 14. Concluding Remarks and Future Directions - p. 94 15. Section II. Toxicity Testing Models and Safety Evaluation - p. 98 16. Chapter 6. Reproductive and Developmental Safety Evaluation of New Pharmaceutical Compounds - p. 101 17. Chapter 7. Juvenile Toxicology Testing - p. 129 18. Chapter 8. Postmarket Surveillance and Regulatory Considerations in Reproductive and Developmental Toxicology: A Food and Drug Administration Perspective - p. 145 19. Chapter 9. OECD Guidelines for In Vivo Testing of Reproductive Toxicity - p. 163 20. Chapter 10. Guidelines for Reproductive and Developmental Toxicity Testing and Risk Assessment of Chemicals - p. 179 21. Chapter 11. Validated and Nonvalidated Mechanism-Based Methods for Testing Developmental Toxicity - p. 193 22. Chapter 12. Relevance of Animal Testing and Sensitivity of End Points in Reproductive and Developmental Toxicity - p. 211 23. Chapter 13. Embryonic Toxic Lesions and Stem Cell Therapy - p. 225 24. Chapter 14. In Vitro and Alternative Approaches to Developmental Neurotoxicity - p. 241 25. Chapter 15. In Vitro Biomarkers of Developmental Neurotoxicity - p. 255 26. Introduction - p. 255 27. Cell Proliferation and Apoptosis - p. 256 28. Neurite Outgrowth - p. 265 29. Neurotransmission/Synaptogenesis - p. 270 30. Cytoskeleton - p. 272 31. Transcription Factors and Signaling Pathways - p. 275 32. Concluding Remarks and Future Directions - p. 277 33. Chapter 16. Using Zebrafish to Assess Developmental Neurotoxicity - p. 289 34. Chapter 17. Caenorhabditis elegans as a Model to Assess Reproductive and Developmental Toxicity - p. 303 35. Chapter 18. A Primate as an Animal Model for Reproductive and Developmental Toxicology Testing - p. 315 36. Section III. Nanoparticles and Radiation - p. 329 37. Chapter 19. Developmental Toxicity of Engineered Nanomaterials - p. 333 38. Chapter 20. Toxicity of Radiation: Biological Effects of Ionizing Radiation Exposure on Reproduction - p. 359 39. Section IV. Gases and Solvents - p. 375 40. Chapter 21. Reproductive and Developmental Toxicity of Solvents and Gases - p. 379 41. Section V. Drugs of Abuse and Addiction, Smoking and Alcohol - p. 396 42. Chapter 22. Caffeine - p. 399 43. Chapter 23. Developmental Neurotoxicity of Abused Drugs - p. 413 44. Chapter 24. Effects of Alcohol on Embryo/Fetal Development - p. 431 45. Chapter 25. Cigarette Smoking and Reproductive and Developmental Toxicity - p. 447 46. Section VI. Pharmaceuticals and Food Additives - p. 463 47. Chapter 26. Thalidomide - p. 467 48. Chapter 27. Retinoids - p. 481 49. Chapter 28. Melamine and Cyanuric Acid - p. 493 50. Chapter 29. Ionophores - p. 503 51. Section VII. Metals - p. 518 52. Chapter 30. Boron - p. 521 53. Chapter 31. Arsenic, Cadmium, and Lead - p. 537 54. Introduction - p. 537 55. Arsenic - p. 538 56. Cadmium - p. 545 57. Lead - p. 551 58. Therapeutic Strategies - p. 559 59. Concluding Remarks and Future Directions - p. 560 60. Chapter 32. Manganese - p. 567 61. Chapter 33. Mercury - p. 583 62. Chapter 34. Selenium - p. 595 63. Section VIII. Pesticides, Industrial and Other Environmental Contaminants - p. 605 64. Chapter 35. Organophosphates and Carbamates - p. 609 65. Introduction - p. 609 66. Historical Background - p. 610 67. Toxicokinetics - p. 611 68. Adverse Outcome Pathways in General Toxicity - p. 612 69. Adverse Outcome Pathways in Reproductive and Developmental Toxicity - p. 613 70. Toxicity - p. 619 71. Biomarkers - p. 624 72. Risk Assessment - p. 625 73. Treatment - p. 625 74. Concluding Remarks and Future Directions - p. 625 75. Chapter 36. Chlorinated Hydrocarbons and Pyrethrins/Pyrethroids - p. 633 76. Chapter 37. Herbicides and Fungicides - p. 657 77. Chapter 38. Brominated Flame Retardants - p. 681 78. Introduction - p. 681 79. Environmental Contamination and Human Exposure - p. 683 80. Effects on Human Health - p. 685 81. Health Effects in Animals and Wildlife - p. 686 82. Toxicokinetics and Metabolites - p. 699 83. Concluding Remarks and Future Directions - p. 703 84. Chapter 39. Polychlorinated Biphenyls, Polybrominated Biphenyls, Polychlorinated Dibenzo-p-dioxins, and Polychlorinated Dibenzofurans - p. 711 85. Introduction - p. 711 86. Historical Background - p. 712 87. Toxicokinetics - p. 716 88. Health Effects - p. 718 89. Mechanism of Action - p. 731 90. Concluding Remarks and Future Directions - p. 736 91. Chapter 40. Reproductive Toxicity of Polycyclic Aromatic Hydrocarbons - p. 745 92. Chapter 41. Toxicity and Risk Assessment of Bisphenol A - p. 765 93. Chapter 42. Ethylene Glycol - p. 797 94. Chapter 43. Perfluorooctane Sulfonate and Perfluorooctanoic Acid - p. 811 95. Chapter 44. Phthalates - p. 829 96. Introduction - p. 829 97. Toxicokinetics - p. 835 98. Mechanism of Action - p. 837 99. Toxicity - p. 840 100. Risk Assessment and Phthalate Action Plans - p. 847 101. Concluding Remarks and Future Directions - p. 848 102. Chapter 45. Personal Care Products and Cosmetics - p. 857 103. Introduction - p. 858 104. Phthalates - p. 858 105. Parabens - p. 879 106. Triclosan - p. 889 107. Other Chemicals in PCPs - p. 893 108. Concluding Remarks and Future Directions - p. 894 109. Section IX. Phytotoxicants, Mycotoxins and Zootoxins - p. 899 110. Chapter 46. Toxic plants - p. 903 111. Chapter 47. Fumonisins - p. 925 112. Chapter 48. Aflatoxins, Ochratoxins, and Citrinin - p. 945 113. Chapter 49. Zootoxins - p. 963 114. Section X. Special Topics - p. 972 115. Chapter 50. Systems Toxicology and Predictive Modeling of Male Developmental Toxicity - p. 975 116. Chapter 51. Stem Cells in Developmental Toxicity Testing - p. 987 117. Chapter 52. Epigenetics in Reproduction and Development - p. 1005 118. Chapter 53. Mitochondrial Dysfunction in Reproductive and Developmental Toxicity - p. 1023 119. Chapter 54. Cell Signaling Mechanisms in Developmental Neurotoxicity - p. 1037 120. Chapter 55. Neuroinflammation and Oxidative Injury in Developmental Neurotoxicity - p. 1051 121. Chapter 56. Effects of Stress on Reproductive and Developmental Biology - p. 1063 122. Chapter 57. Disruption of Cholesterol Homeostasis in Developmental Neurotoxicity - p. 1077 123. Section XI. Endocrine Disruption, Mutagenicity, Carcinogenicity, Infertility and Teratogenicity - p. 1088 124. Chapter 58. Endocrine Disruption - p. 1091 125. Chapter 59. Developmental and Reproductive Disorders—Role of Endocrine Disruptors in Testicular Toxicity - p. 1111 126. Chapter 60. Mutagenicity and Carcinogenicity: Human Reproductive Cancer and Risk Factors - p. 1123 127. Chapter 61. Environmental Pollutants and Neural Tube Defects - p. 1139 128. Chapter 62. Teratogenicity - p. 1167 129. Chapter 63. Micro–Computed Tomography and Volumetric Imaging in Developmental Toxicology - p. 1183 130. Section XII. Toxicologic Pathology - p. 1205 131. Chapter 64. Toxicologic Pathology of the Reproductive System - p. 1209 132. Introduction - p. 1210 133. Reproductive Toxicity Studies - p. 1211 134. Hormonal Regulation of Male and Female Reproduction - p. 1212 135. Potential Mechanisms Involved in Reproductive Toxicity - p. 1214 136. Evaluation of Reproductive Toxicity - p. 1222 137. Nonneoplastic Lesions of Male and Female Reproductive Systems - p. 1227 138. Role of Toxicokinetics in Male and Female Reproductive Toxicity - p. 1231 139. Molecular Mechanisms of Teratogenesis - p. 1233 140. Concluding Remarks and Future Directions - p. 1235 141. Section XIII. Placental Toxicity - p. 1241 142. Chapter 65. The Placental Role in Developmental Programming - p. 1245 143. Chapter 66. Strategies for Investigating Hemochorial Placentation - p. 1259 144. Chapter 67. The Significance of ABC Transporters in Human Placenta for the Exposure of Fetus to Xenobiotics - p. 1275 145. Introduction - p. 1275 146. Structure, Localization, Function, and Polymorphisms of Human Placental ABC Transporters - p. 1278 147. Models to Study Human Placental Transporters - p. 1281 148. Studies on Transplacental Transport and Placental Transporters - p. 1288 149. Significance of ABC Transporters in Fetal Health and Important Targets for Future Studies - p. 1292 150. Concluding Remarks and Future Directions - p. 1294 151. Chapter 68. Placental Toxicity - p. 1301 152. Introduction - p. 1301 153. Placental Structure, Function, and Species Differences - p. 1302 154. Placental Barrier - p. 1304 155. Placental Susceptibility to Chemical Toxicity - p. 1305 156. Placental-Toxicity-Modifying Factors - p. 1305 157. Toxicity - p. 1306 158. Concluding Remarks and Future Directions - p. 1319 159. Chapter 69. Placental Pathology - p. 1327 160. Introduction - p. 1327 161. Maternal “Effect” Pathologies of the Placenta - p. 1328 162. Maldevelopment of the Placental Implantation Site - p. 1329 163. Intraplacental Interference to Maternal Flow - p. 1332 164. Fetal Pathologies of the Placenta - p. 1337 165. Primary Placental Pathologies - p. 1342 166. Concluding Remarks and Future Directions - p. 1343 167. Section XIV. Domestic and Wildlife Species - p. 1350 168. Chapter 70. Reproductive and Developmental Toxicity in Avian Species - p. 1353 169. Chapter 71. Endocrine Disruption in Wildlife Species - p. 1373 170. Chapter 72. Teratogenesis in Livestock - p. 1391 171. Index - p. 1409
