Reproductive and Developmental Toxicology

Reproductive and Developmental Toxicology

3rd Edition - June 6, 2022

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  • Editor: Ramesh Gupta
  • Hardcover ISBN: 9780323897730

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Description

Reproductive and Developmental Toxicology, Third Edition is a comprehensive and authoritative resource, providing the latest literature on this complex subject by focusing 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 drugs of abuse, and metals, among others. In addition, it is the only resource to include reproductive and developmental toxicity in domestic animals, fish and wildlife With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages. Completely revised and updated to include the most recent developments in the field, this 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.

Key Features

  • Provides a complete, up-to-date, integrated source of information on the key risk stages during reproduction and development
  • Offers diverse and unique in vitro and in vivo toxicity models for reproductive and developmental toxicity testing in a user-friendly format that assists in comparative analysis
  • Includes new chapters on developments in systems toxicology and predictive modeling of male developmental toxicity, adverse outcome pathways in reproductive and developmental toxicology, ovarian and endometrial toxicity, developmental neurotoxicity of air pollution, and more

Readership

Researchers and advanced students in toxicology; biologists, pharmacologists, and teratologists from academia, industry, and governmental agencies; environmental scientists; regulatory agencies

Table of Contents

  • Cover image
  • Title page
  • Table of Contents
  • Copyright
  • Dedication
  • Contributors
  • Introduction
  • Section I. General
  • Chapter 1. Reproductive anatomy and physiology
  • Introduction
  • Important definitions and concepts
  • Review of normal human reproduction
  • Concluding remarks and future directions
  • Chapter 2. Pharmacokinetics in pregnancy
  • Introduction
  • Factors affecting pharmacokinetics in pregnancy
  • The fetal compartment
  • Highlighting the value of PK information in pregnancy: tocolytic therapy
  • Maternal disease and obstetrical complications
  • Origins of the knowledge gap
  • Current initiatives and future directions
  • Physiologically based pharmacokinetic (PBPK) modeling
  • Concluding remarks and future directions
  • Chapter 3. Physiologically based pharmacokinetic models in reproductive and developmental toxicology
  • Introduction
  • PBPK modeling: basic concepts and tools
  • PBPK modeling in reproductive and developmental toxicology
  • PBPK model applications in reproductive and developmental toxicology
  • Concluding remarks and future directions
  • Chapter 4. Adverse Outcome Pathways in reproductive and developmental toxicology
  • Introduction
  • AOPs in reproductive toxicity
  • AOPs on developmental toxicity
  • Issues relevant to reproductive and developmental AOPs
  • Concluding remarks and future directions
  • Disclaimer
  • Section II. Toxicity testing models, safety evaluation, and regulatory aspect
  • Chapter 5. Juvenile toxicology testing
  • Introduction
  • Considerations regarding toxicology studies conducted for submission to regulatory agencies
  • Anatomical and functional assessments
  • Concluding remarks and future directions
  • Chapter 6. Relevance of animal testing and sensitivity of end points in reproductive and developmental toxicity
  • Introduction
  • Choice of animal test models
  • Nonmammalian animal models
  • End points of reproductive toxicity
  • Male end points for reproductive studies
  • Female end points for reproductive studies
  • Couple-mediated end points for reproductive studies
  • Tests and test guidelines
  • Other guidelines
  • Types of studies
  • Single-generation reproduction study
  • Extended one-generation reproductive toxicity study
  • Multigeneration reproduction study
  • Reproductive assessment by continuous breeding study
  • Dominant lethal study
  • Total reproductive capacity
  • Path to alternative tests and concluding remarks
  • Chapter 7. Alternative methods to animal experimentation for testing developmental toxicity
  • Introduction
  • Methods for testing embryotoxicity based on animal cells
  • Methods for testing embryotoxicity based on human cells
  • Three-dimensional cultures and organoids for testing developmental toxicity
  • Alternative models based on embryos for testing developmental toxicology
  • Batteries of assays and integrated approaches to testing and assessment for testing developmental toxicity
  • Concluding remarks and future directions
  • Chapter 8. Use of computational toxicology tools to predict in vivo endpoints
  • Introduction
  • Methods: data sources used
  • Results
  • Concordance between in vivo data and predictions from CompTox tools
  • Discussion
  • Chapter 9. Guidelines for reproductive and developmental toxicity testing and risk assessment of chemicals
  • Introduction
  • Regulation of chemicals and guidelines
  • Risk assessment and the use of data from testing
  • Paradigm shifts and future directions
  • Chapter 10. Reproductive toxicity: in vivo testing guidelines from OECD
  • Introduction
  • Prenatal developmental toxicity study (OECD 414)
  • Two-generation reproduction toxicity study (OECD 416)
  • Reproduction/developmental toxicity screening test (OECD 421)
  • Combined repeated-dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422)
  • Developmental neurotoxicity study (OECD 426)
  • Extended one-generation reproductive toxicity study (OECD 443)
  • Other methods not included in the OECD test guidelines
  • Concluding remarks and future directions
  • Chapter 11. In vitro biomarkers of developmental neurotoxicity
  • Introduction
  • Cell proliferation and apoptosis
  • Heavy metals
  • Organic solvents
  • Pesticides
  • Polychlorinated biphenyls
  • Polybrominated diphenyl ethers
  • Neurite outgrowth
  • Heavy metals
  • Organic solvents
  • Pesticides
  • PCBs/dioxins
  • Neurotransmission/synaptogenesis
  • Heavy metals
  • Cytoskeleton
  • Heavy metals
  • Organic solvents
  • Pesticides
  • Polychlorinated biphenyls
  • Transcription factors and signaling pathways
  • Heavy metals
  • Organic solvents
  • Pesticides
  • PCBs and PBDEs
  • Concluding remarks and future directions
  • Chapter 12. Reproductive and developmental safety evaluation of new pharmaceutical compounds
  • Introduction
  • Overview of human pharmaceutical development process
  • Developmental and reproductive toxicity studies needed for development of innovative human pharmaceuticals
  • Interpretation of human risk from the reproductive and developmental toxicity studies in animals
  • Reproductive risks communication and management
  • Concluding remarks and future directions
  • Chapter 13. Using zebrafish to assess developmental neurotoxicity
  • Introduction
  • Early development
  • Alternative animal models
  • Practical considerations in zebrafish neurotoxicological research
  • Zebrafish as a model organism for developmental neurotoxicity testing
  • The importance of screens
  • Screening approaches using larval zebrafish: some basic principles
  • Zebrafish developmental neurotoxicity testing
  • Potential confounders and methodological challenges
  • The zebrafish/human connection
  • The zebrafish/ecotoxicology connection
  • Emerging novel technologies
  • Concluding remarks and future directions
  • Chapter 14. Caenorhabditis elegans as a model to assess reproductive and developmental toxicity
  • Introduction
  • C. elegans as a model organism
  • Concluding remarks and future directions
  • Chapter 15. Postmarket surveillance and regulatory considerations in reproductive and developmental toxicology: a Food and Drug Administration perspective
  • Introduction
  • Drugs intended for use in humans
  • Vaccines intended for use in humans
  • Drugs intended for use in animals
  • Section III. Nanoparticles and radiation
  • Chapter 16. Developmental toxicity of engineered nanomaterials
  • Introduction
  • Characteristics, production, and applications of some engineered industrial nanomaterials
  • Special features of nanomaterials in relation to their developmental toxicity
  • Exposure to engineered nanomaterial
  • Crossing biological barriers
  • Developmental toxicity of NPs
  • Concluding remarks and future directions
  • Chapter 17. Effects of ionizing radiation on reproduction and development
  • Introduction
  • Conceptual framework
  • Nomenclature
  • Sources of radiation dose
  • Key early events (prior to World War II) in radiation science
  • Historical overview of radiation protection standards
  • Early development of radiation protection standards
  • Discovery of fission changed the world
  • The Manhattan Project
  • The tolerance dose
  • The first nuclear weapons
  • Post–World War II nuclear weapons development and testing
  • Contemporary nuclear activities
  • Post–World War II research, advisory, and regulatory organizations
  • Health effects of nuclear weapons
  • Exposures to radioactive materials and radiation dose
  • Radiation induced health effects: sources of information on radiation effects
  • Japanese bombing cohorts
  • Results from studies with laboratory animals
  • Potential health effects (other than cancer) of prenatal exposure
  • Linear nonthreshold models
  • Current radiation protection guidance
  • Concluding remarks and future directions
  • Dedication
  • Section IV. Gases and solvents
  • Chapter 18. Reproductive and developmental toxicity of solvents and gases
  • Introduction
  • Carbon tetrachloride (CASRN 56-23-5)
  • Tetrachloroethylene (CASRN 127-18-4)
  • Styrene (CASRN 100-42-5)
  • Toluene (CASRN 108-88-3)
  • Benzene (CASRN 608-93-5)
  • Gasoline (CASRN 8006-61-9)
  • Kerosene and jet fuels
  • Concluding remarks and future directions
  • Section V. Drugs of abuse and addiction, smoking, and alcohol
  • Chapter 19. Developmental neurotoxicity of drugs of abuse
  • Introduction
  • Animal models of developmental neurotoxicity
  • Psychostimulants
  • Concluding remarks and future directions
  • Chapter 20. Effects of alcohol on embryo/fetal development
  • Introduction
  • Historical background and terminology used to describe the effects of alcohol
  • Clinical features of FAS/FASD
  • Pharmacokinetics of alcohol
  • Mechanisms of ethanol-induced teratogenesis
  • Effects of ethanol on reproduction and embryogenesis
  • CNS dysfunctions caused by prenatal alcohol exposure
  • Biomarkers of fetal alcohol exposure
  • Therapeutics of FASD
  • Concluding remarks and future directions
  • Chapter 21. Cigarette and E-cigarettes smoking and reproductive and developmental toxicity
  • Introduction
  • Cigarette smoking and reproductive and developmental toxicity
  • Pharmacokinetics/toxicokinetics
  • Mechanism of action
  • Toxicity of tobacco components
  • Fertility effects
  • Teratogenic effects
  • Peri- and postnatal effects
  • In vitro testing tobacco products
  • E-cigarettes and reproductive and developmental toxicity
  • Toxicity of E-cigarettes components
  • Toxicity
  • Conclusion remarks and future directions
  • Section VI. Pharmaceuticals, nutraceuticals, and food additives
  • Chapter 22. Thalidomide
  • Introduction
  • Historical background
  • Thalidomide embryopathy (thalidomide syndrome)
  • Pharmacology
  • Mechanism of action—adult clinical conditions
  • Mechanism of action—thalidomide embryopathy
  • Phocomelia
  • Framework of thalidomide teratogenicity
  • Toxicity and risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 23. Retinoids
  • Introduction
  • Metabolism
  • Retinoids in reproduction
  • Toxicity in general
  • Veterinary medicine
  • Developmental toxicity
  • Patchy perspective for vitamin A support
  • Anticancer effects in the reproductive system
  • Concluding remarks and future directions
  • Chapter 24. Safety of cannabis- and hemp-derived constituents in reproduction and development
  • Introduction
  • Role of the endocannabinoid system on reproductive functions
  • Reproductive and developmental toxicity of constituents of hemp and cannabis
  • Concluding remarks and future directions
  • Chapter 25. Caffeine
  • Introduction
  • Toxicokinetics
  • Mechanism of action
  • Toxicity
  • Risk assessment
  • Concluding remarks and future directions
  • Chapter 26. Melamine and cyanuric acid
  • Introduction
  • Historical background
  • Pharmacokinetics/toxicokinetics
  • Mechanism of action
  • Toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 27. Ionophores
  • Introduction
  • Pharmacology/pharmacokinetics/mechanism of action
  • Ionophore toxic syndrome
  • Safety and toxicity studies in cattle
  • Safety and toxicity studies in chickens
  • Safety and toxicity studies in pigs
  • Single-dose and multidose toxicity in laboratory animals
  • Reproductive and developmental toxicity
  • Reproductive safety in cattle
  • Reproductive safety in nontarget animal species
  • Risk assessment
  • Concluding remarks and future directions
  • Section VII. Metals
  • Chapter 28. Boron
  • Introduction
  • Historical background and sources
  • Exposure
  • Toxicokinetics
  • Mechanism of action
  • Toxicity
  • Therapeutic strategies
  • Concluding remarks and future directions
  • Chapter 29. Arsenic, cadmium, and lead
  • Introduction
  • Arsenic
  • Cadmium
  • Lead
  • Therapeutic strategies
  • Concluding remarks and future directions
  • Chapter 30. Mercury
  • Introduction
  • Historical background
  • Toxicokinetics
  • Mechanisms of neurotoxicity
  • Toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 31. Manganese
  • Introduction
  • Historical background
  • Pharmacokinetics/pharmacodynamics
  • Mechanism of action
  • Toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 32. Selenium
  • Introduction
  • Historical background
  • Pharmacokinetics/toxicokinetics
  • Mechanism of action
  • General toxicity
  • Toxic effects of selenium on reproduction
  • Treatment
  • Concluding remarks and future directions
  • Section VIII. Pesticides, industrial, and other environmental contaminants
  • Chapter 33. Organophosphates and carbamates
  • Introduction
  • Historical background
  • Toxicokinetics
  • Adverse outcome pathways in general toxicity
  • Adverse outcome pathways in reproductive and developmental toxicity
  • Toxicity
  • Biomarkers
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 34. Chlorinated hydrocarbons and pyrethrins/pyrethroids
  • Introduction
  • Historical background
  • Toxicokinetics
  • Adverse outcome pathways in general toxicity
  • Adverse outcome pathways in reproductive and developmental toxicity
  • Toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 35. Herbicides and fungicides
  • Introduction
  • Herbicides
  • Fungicides
  • Endocrine disruption
  • Concluding remarks and future directions
  • Chapter 36. Brominated flame retardants
  • Introduction
  • Environmental contamination and human exposure
  • Effects on human health
  • Health effects in animals and wildlife
  • Metabolic effects
  • Toxicokinetics and metabolites
  • Concluding remarks and future directions
  • Chapter 37. Polychlorinated biphenyls, polybrominated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans
  • Introduction
  • Historical background
  • Toxicokinetics
  • Health effects
  • Concluding remarks and future directions
  • Chapter 38. Reproductive toxicity of polycyclic aromatic hydrocarbons
  • Introduction
  • Historical background
  • Pharmacokinetics/toxicokinetics
  • Mechanism of action
  • Toxicity
  • Concluding remarks and future directions
  • Chapter 39. Bisphenol A—toxicity and risk assessment update with academic and regulatory perspectives and physiologically based pharmacokinetic modeling
  • Introduction
  • New advances in BPA PBPK modeling
  • The Consortium Linking Academic and Regulatory Insights on BPA toxicity (CLARITY-BPA) program
  • National Toxicology Program (NTP) studies
  • The CLARITY-BPA core study
  • Academic studies
  • The CLARITY-BPA study, its findings, and discussions
  • Other analysis of the NTP core study
  • Other CLARITY-BPA studies not in the integrative analysis by Heindel et al. (2020)
  • Non-CLARITY BPA studies
  • Concluding remarks and future directions
  • Chapter 40. Ethylene glycol
  • Introduction
  • Chronic toxicity/carcinogenicity
  • Reproductive toxicity
  • Developmental toxicity
  • Toxicokinetics
  • Mechanism of action
  • Risk assessment
  • Concluding remarks and future directions
  • Chapter 41. Perfluorooctane sulfonate and perfluorooctanoic acid
  • Introduction
  • Exposure
  • Toxicokinetics
  • Mechanisms involved in toxicity
  • Reproductive toxic effects
  • Concluding remarks and future directions
  • Chapter 42. Traffic-related air pollution and the developing brain
  • Air pollution: a complex mixture adversely affecting health
  • The central nervous system is an important additional target for air pollution
  • The developing central nervous system is peculiarly sensitive to environmental insult
  • Effects of air pollution on the developing nervous system
  • Developmental exposure to air pollution as a risk factor for autism spectrum disorder?
  • Mechanisms underlying the developmental neurotoxicity of air pollution
  • Future perspectives and research needs
  • Chapter 43. Environmental pollutants and embryonic implantation and embryonic development
  • Introduction
  • The process of embryo implantation
  • Environmental pollutants affecting embryo implantation
  • Mechanism of action of environmental pollutants on embryo implantation
  • Concluding remarks and future directions
  • Chapter 44. Personal care products and cosmetics
  • Introduction
  • Phthalates
  • Parabens
  • Triclosan
  • Other chemicals in PCPs
  • Concluding remarks and future directions
  • Chapter 45. UV screening chemicals
  • Introduction
  • Oxybenzone
  • Benzotriazole UV stabilizers
  • Concluding remarks and future directions
  • Section IX. Phytotoxicants and mycotoxins
  • Chapter 46. Toxic plants
  • Introduction
  • Locoweeds (Astragalus and Oxytropis spp.)
  • Pine needle abortion, ponderosa pine, and related species
  • Broom snakeweed
  • Mechanism of action
  • Prevention and treatment
  • Veratrum spp. (skunk cabbage, false hellebore)
  • Other plant species with suspected teratogenic activity
  • Concluding remarks and future directions
  • Chapter 47. Fumonisins
  • Introduction
  • Fumonisin in human foods
  • Fumonisin and sphingolipid metabolism
  • Pharmacokinetics and biomarkers of FB1 exposure
  • Systemic toxicity in animals
  • Reproductive and developmental toxicity
  • Fumonisin and neural tube defects (NTDs)
  • Proposed mechanisms of action for FB1-induction of NTDs
  • Additional mechanistic considerations
  • Fumonisins and growth retardation
  • Concluding remarks and future directions
  • Chapter 48. Aflatoxins, ochratoxins, and citrinin
  • Introduction
  • Historical background
  • Toxicokinetics
  • Mechanism of action
  • Toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Chapter 49. Trichothecenes and zearalenone
  • Introduction
  • Toxicokinetics
  • General toxicity
  • Reproductive and developmental toxicity
  • Risk assessment
  • Treatment
  • Concluding remarks and future directions
  • Section X. Special topics
  • Chapter 50. Drugs and chemical contaminants in human breast milk
  • Introduction
  • Breastfeeding
  • Drug excretion into breast milk
  • Drug disposition in the infant
  • Drugs that should be used with caution
  • Commonly used herbal products
  • Nonmedicinal substances
  • Environmental pollutants
  • Concluding remarks and future directions
  • Chapter 51. Stem cells in developmental toxicity testing
  • Introduction
  • Use of stem cells in developmental toxicology
  • Assays for predicting developmental osteotoxicity
  • Assays for predicting developmental neurotoxicity
  • Transcriptomic-based assays
  • Non–stem cell human cell lines
  • Assays using human cells
  • Concluding remarks and future directions
  • Chapter 52. Embryonic and fetal toxic lesions and stem cell therapy
  • Introduction
  • Development and establishment of mammalian vasculogenesis and embryonic and fetal hematopoiesis
  • Experiments on the correction of impaired embryonic vasculogenesis and primary hematopoiesis
  • Concluding remarks and future directions
  • Chapter 53. Epigenetics in reproduction and development
  • Introduction
  • Major epigenetic reprogramming landmarks during development
  • Epigenetic modifications after birth
  • Concluding remarks and future directions
  • Chapter 54. Mitochondrial dysfunction in reproductive and developmental toxicity
  • Introduction
  • Mitochondrial structure
  • Mitochondria and energy production: oxidative phosphorylation
  • Mitochondria, ROS, and oxidative stress
  • Mitochondria and calcium homeostasis
  • The mitochondrial permeability transition
  • Regulation and significance of the MPT induction
  • Mitochondria in the germ line
  • Testis mitochondria and spermatogenesis
  • The particular characteristics of testicular bioenergetics
  • Mitochondria and toxicology studies in the reproductive system
  • Concluding remarks and future directions
  • Chapter 55. Cell signaling mechanisms in developmental neurotoxicity
  • Introduction
  • Developmental neurotoxic chemicals
  • Vulnerability of the developing brain
  • Cell signaling mechanisms in developmental neurotoxicity
  • Instability of cytoskeleton proteins
  • Mitochondrial dysfunction, free radicals generation, and oxidative stress
  • Impact on DNA synthesis
  • Gene expression deregulation
  • Protein modification
  • Epigenetic modifications
  • Cell signaling integration
  • Concluding remarks and future directions
  • Chapter 56. Neuroinflammation and oxidative injury in developmental neurotoxicity
  • Introduction
  • Neuroinflammation and oxidative damage
  • Suppression of innate immunity-mediated neuronal damage
  • Aging
  • Concluding remarks and future directions
  • Chapter 57. Effects of stress on reproductive function and fetal development
  • Introduction
  • Stress and its impact on biological systems
  • Neuroanatomy of stress response
  • Modulation of stress hormones during pregnancy
  • Stress and developmental biology
  • Animal studies on developmental biology
  • Stress and reproductive biology
  • Concluding remarks and future directions
  • Section XI. Endocrine disruption
  • Chapter 58. Endocrine disruption
  • Introduction
  • Definitions and important concepts
  • Mechanisms of endocrine disruption
  • Effects of endocrine-disrupting chemicals
  • Screening for endocrine disruptors
  • Remaining questions about endocrine disruption
  • Concluding remarks and future directions
  • Chapter 59. Role of endocrine disruptors in male infertility and impact of COVID-19 on male reproduction
  • Introduction
  • Development of male genital system
  • Male reproductive tract as target site
  • Hormonal control
  • Endocrine disruptors
  • Exposure and regulation of EDs
  • Association between EDs and testicular dysgenesis syndrome
  • Effect of various endocrine disruptors on male fertility
  • Molecular mechanism of endocrine-disrupting chemicals
  • COVID-19 impact on male reproductive hormones
  • Concluding remarks and future directions
  • Section XII. Infertility and teratogenicity
  • Chapter 60. Toxicology of reproduction process and problems of male infertility
  • Introduction
  • Early gametogenesis
  • Sperm chromatin organization and infertility
  • Antisperm antibodies. Effects of the immune system on reproductive processes
  • Y chromosome defects and male infertility
  • Environmental factors and induction of male infertility
  • Concluding remarks and future directions
  • Chapter 61. Environmental pollutants and neural tube defects
  • Introduction
  • Polycyclic aromatic hydrocarbons
  • Arsenic
  • Pesticides
  • Organic solvents
  • Ambient air pollution
  • Nitrate and nitrite
  • Disinfection byproducts
  • Concluding remarks and future directions
  • Chapter 62. Teratogenicity
  • Introduction
  • The principles of teratology
  • Birth defect prevalence
  • Teratogenesis and pregnancy
  • Workplace, occupation, and adverse reproductive effects
  • General testing methods for teratogenic effects in experimental animals
  • Neurodevelopmental toxicity
  • The role of epigenetics
  • Gene editing
  • Concluding remarks and future directions
  • Chapter 63. Micro-CT and volumetric imaging in developmental toxicology
  • Introduction
  • X-ray micro-imaging and micro-CT
  • Micro-CT imaging of unstained fetal skeletons
  • Micro-CT imaging of alizarin red-S stained fetuses
  • High-resolution micro-CT imaging of fetal bone microarchitecture
  • Noninvasive in vivo micro-CT imaging approach
  • Micro-CT imaging of contrast agent stained soft tissues and organs of fetuses
  • Other volumetric imaging modalities in developmental toxicology
  • Concluding remarks and future directions
  • Section XiiI. Toxicologic pathology
  • Chapter 64. Toxicologic pathology of the reproductive system
  • Introduction
  • Reproductive toxicity studies
  • Hormonal regulation of male and female reproduction
  • Morphology of female reproductive tract during the normal estrus cycle
  • Potential mechanisms involved in reproductive toxicity
  • Potential mechanisms and morphological pattern of female reproductive toxicity
  • Potential mechanisms and morphological pattern of male reproductive toxicity
  • Evaluation of reproductive toxicity
  • Endpoints used in the assessment of male and female reproductive toxicity
  • Nonneoplastic lesions of male and female reproductive systems
  • Role of toxicokinetics in male and female reproductive toxicity
  • Molecular mechanisms of teratogenesis
  • Concluding remarks and future directions
  • Section XIV. Placental toxicity
  • Chapter 65. The placental role in developmental programming
  • Introduction
  • Placental function and regulation
  • The placental barrier
  • Diffusion across the placenta
  • Placental transport
  • Regulation of placental transfer
  • The placenta as an endocrine organ
  • Fetal programming
  • Epidemiological evidence
  • Animal evidence
  • Pre- and periconceptional influences
  • Mechanisms of programming
  • Epigenetics and programming
  • Developmental alterations
  • Evolutionary perspectives
  • Programming summary
  • Other exposures
  • The “placental phenotype,” interventions, and treatments
  • Interventions
  • Concluding remarks and future directions
  • Chapter 66. Strategies for investigating hemochorial placentation
  • Introduction
  • Early development of the placenta
  • The definitive placenta in humans and rodents
  • Models of hemochorial placentation
  • Concluding remarks and future directions
  • Chapter 67. The significance of ABC transporters in human placenta for the exposure of fetus to xenobiotics
  • Introduction
  • Human placental ABC transporters
  • In vitro studies on transplacental transport and placental ABC transporters
  • Ex vivo and in vivo studies on placental transport and ABC transporters
  • Significance of ABC transporters in fetal health
  • Concluding remarks and future directions
  • Chapter 68. Placental toxicity
  • Introduction
  • Placental structure, function, and species differences
  • Placental barrier
  • Placental susceptibility to chemical toxicity
  • Placental-toxicity-modifying factors
  • Toxicity
  • Concluding remarks and future directions
  • Chapter 69. Placental pathology
  • Introduction
  • Vascular pathologies
  • Concluding remarks and future directions
  • Section XV. Domestic and wildlife species
  • Chapter 70. Endocrine disruption in wildlife species
  • Introduction
  • Pathways and exposure to endocrine disrupting chemicals
  • Endocrine disruption—life history
  • Adrenal cortex
  • Thyroid
  • Sex hormones and reproduction
  • Mechanisms of ECDs
  • Ecological effects
  • Anthropogenic noise
  • Concluding remarks and future directions
  • Chapter 71. Teratogenesis in livestock
  • Introduction
  • Embryology of domestic animals
  • Examples of terata
  • Teratogenic plants
  • Nutritional links with fetal development and teratology
  • Mycotoxins
  • Drugs
  • Prenatal and environmental influences—programing for life
  • Teratogenic viruses
  • Diagnosing causation
  • Concluding remarks and future directions
  • Chapter 72. Reproductive and developmental toxicity in avian species
  • Introduction
  • Background
  • Mating behavior and nest building
  • Ovipositing and reproductive outcomes
  • Endocrine disruption
  • Generation effects and teratology
  • Toxicology of specific agents
  • Concluding remarks and future directions
  • Index

Product details

  • No. of pages: 1556
  • Language: English
  • Copyright: © Academic Press 2022
  • Published: June 6, 2022
  • Imprint: Academic Press
  • Hardcover ISBN: 9780323897730

About the Editor

Ramesh Gupta

Ramesh Gupta
Dr. Ramesh C. Gupta, Professor & Head of Toxicology Department at Murray State university, is engaged in research on pesticide toxicity, neurodegenerative diseases, and nutraceuticals efficacy and safety. He has delivered lectures in UK, Australia, Italy, Japan, Germany, France, Switzerland, Spain, Czech Republic, China, South Korea, Sweden, and Turkey. He served the panels of NIH, CDC, NIOSH, and NAS. He has >450 publications to his credit, including seven major books with Elsevier: (1) Toxicology of Organophosphate and Carbamate Compounds, (2) Veterinary Toxicology: Basic and Clinical Principles, (3) Handbook of Toxicology of Chemical Warfare Agents, (4) Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology, (5) Reproductive and Developmental Toxicology, (6) Biomarkers in Toxicology and (7) Nutraceuticals: Efficacy, Safety and Toxicity. He is recipient of Murray State University's distinguished researcher award of the year-2006, and Outstanding research award of the year 2014. In 2019, he received a medal from The Royal Academy of Spanish Veterinary Sciences for his distinguished services to veterinary medicine. He is a diplomate of American Board of Toxicology, and fellow of American College of Toxicology, American College of Nutrition, and Academy of Toxicological Sciences. Dr. Gupta is a member of many professional societies, including SOT, Eurotox, ASPET, American College of Toxicology, and ISSX.

Affiliations and Expertise

Professor, Toxicology Department, Murray State University, Murray, Kentucky, United States of America Head, Toxicology Department, Murray State University, Murray, Kentucky, United States of America

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