Handbook of Developmental Neurotoxicology

Editor/Author Slikker, Jr., William, Paule, Merle G., and Wang, Cheng
Publication Year: 2018
Publisher: Elsevier Science & Technology

ISBN: 978-0-12-809394-8
Category: Psychology
Image Count: 98
Book Status: Pending
Predicted Release Month: Sept 2019
Table of Contents

Handbook of Developmental Neurotoxicology, Second Edition, provides a comprehensive view of the fundamental aspects of neurodevelopment, the pathways and agents that affect them, relevant clinical syndromes, and risk assessment procedures for developmental neurotoxicants.

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Table of Contents

  • List of Contributors
  • Preface and Acknowledgments
  • Part I Cellular and molecular morphogenesis of the nervous system
  • Introduction
  • Brain Morphogenesis and Developmental Neurotoxicology
  • I. Introduction
  • II. Marr Proposed Computational Models be Integrated Over Three Levels
  • III. Morphogenetic Features Emerge From Interactions Across Multiple Levels of Biological Organization
  • A. Sensory Pathways Encode Features of Sense Organs and the Environment
  • B. Neurovascular Coupling (NVC) is Essential to Brain Connectivity
  • C. Engrams Exist at Multiple Structural Levels
  • IV. Whole Brain Assessment of Larval Zebrafish Reveals Patterns of Connectivity
  • V. Conclusions: Morphology Informs Predictive Models of Developmental Neurotoxicity
  • Acknowledgments
  • Abbreviations
  • References
  • Neural Cell Adhesion Molecules in Normal and Abnormal Neural Development
  • I. Introduction
  • II. The Expression Levels of NCAM and PSA–NCAM During the Development
  • III. Regulating PSA–NCAM Expression and Cell Migration
  • IV. Requirement of PSA–NCAM for Activity-Induced Synaptic Plasticity
  • Acknowledgments
  • References
  • Neurite Development and Neurotoxicity
  • I. Introduction
  • A. Molecular Mechanisms Underlying Neurite Growth
  • 1. Applications in Neurotoxicology: Addressing Molecular Mechanisms
  • B. Genetic Modulation of Neurite Development
  • 1. Examples of Genetic Modulation by Neurotoxicants
  • C. Cell Death Mechanisms and Neurite Development
  • 1. Relevance to Neurotoxicology: Addressing Cell Death Mechanisms
  • D. Stem/Progenitor Cells and Neurite Development
  • 1. Applications of Stem Cell Technology for Neurotoxicology
  • E. Neurite Growth and State-of-the-Art Techniques
  • 1. Overview
  • 2. High-Content Imaging
  • 3. Applications Using HCI
  • 4. Three-Dimensional Approaches
  • 5. Nanotechnology and Neurite Development
  • 6. Bioengineering and Neurite Development
  • II. Conclusions
  • Acknowledgment
  • References
  • Myelin: Structure, Function, Pathology, and Targeted Therapeutics
  • I. Introduction
  • II. Myelin Architecture and Assembly: Old and New Perspectives
  • A. Traditional View of Myelin
  • B. Recent Findings: Myelin Structure and Functions
  • III. Neuron–Glia Communication and its Regulation
  • IV. Myelinating Glial Cell Lineages in Peripheral and Central Nervous Systems
  • A. Schwann Cells
  • B. Oligodendrocytes
  • V. Chemical Composition of Vertebrate Myelin
  • VI. Dysmyelination: Myelin Mutant Models for Dysmyelination
  • VII. Demyelination: Effect of Various Factors on Developmental Myelination
  • A. Malnutrition
  • B. Thyroid Deficiency
  • VIII. Remyelination and CNS Disorders: Myelin to Axonal Regeneration
  • IX. Newer Treatment Strategies for Myelin Disorders
  • X. Conclusions
  • Acknowledgment
  • References
  • Part II Developmental neurobiology/toxicology
  • Introduction
  • Neurotrophic Factors
  • I. Neurotrophic Factors
  • II. Expression Pattern and Regulation
  • III. Neurotrophin Receptors
  • IV. Neurotrophic Factors in Cell Survival and Cell Death
  • V. Neurotrophins and Synaptic Plasticity
  • VI. Neurotrophins and Behavior
  • VII. Other Neurotrophic Factors
  • VIII. Clinical Correlates to Neurodegenerative Disorders
  • IX. Clinical Correlates to Psychiatric Disorders
  • X. Genetic Polymorphisms
  • XI. Neurotrophins as Therapeutic Agents
  • References
  • Serotonin Signaling as a Target for Craniofacial Embryotoxicity
  • I. Introduction—Serotonin and Embryonic Development
  • II. Serotonin Signal Transduction
  • A. Serotonin Release and Selective Serotonin Reuptake Inhibitors
  • B. Serotonin Receptors and Receptor Antagonists
  • III. Role of Serotonin in Development
  • A. Placental Transfer of Serotonin
  • B. Serotonin and Craniofacial Development
  • C. Embryonic Precursors of the Facial Skeleton
  • D. Serotonin and Neural Crest Cells
  • E. Importance of Proper Orofacial Osteogenesis to Orofacial Development
  • F. Serotonin and Bone Development
  • IV. Conclusions
  • References
  • Neurotoxic and Neurotrophic Effects of GABAergic Agents on the Developing Brain
  • I. Introduction
  • II. The GABAergic System During Development
  • III. GABAergic Agents and Consequences of Perturbations of GABAergic System Development
  • IV. Animal Models of GABAergic System Perturbation
  • V. In Vitro and Cell-Based Models of GABAergic System Perturbation During Neurodevelopment
  • VI. Bioinformatic and Computational Approaches
  • VII. Protecting the Developing GABAergic System: Prospects for the Future
  • References
  • Neural Stem Cell Biology and Application to Developmental Neurotoxicity Assessment
  • I. Neural Stem Cells in the Developing Brain
  • II. Neural Stem Cells in the Adult Brain
  • III. NSCs-Derived from Embryonic Stem Cells and Induced Pluripotent Stem Cells
  • IV. Application of NSCs to Developmental Neurotoxicity Assessments
  • A. Status of Developmental Neurotoxicity Tests
  • B. Considerations on the Utilization of NSCs as an In Vitro Model for DNT Assessment
  • V. Conclusions
  • Acknowledgment
  • References
  • Apoptosis as a Mechanism of Developmental Neurotoxicity
  • I. Introduction
  • II. Molecular Mechanisms of Apoptosis in the Developing Nervous System
  • III. Physiological Roles of Apoptosis in Neurodevelopment
  • IV. Chemical-Induced Apoptosis
  • A. Anesthetics
  • B. Polychlorinated Biphenyls
  • C. Zinc
  • V. Conclusions
  • References
  • Periods of Susceptibility: Interspecies Comparison of Developmental Milestones During Ontogenesis of the Central Nervous System
  • I. Introduction
  • II. Overview of Central Nervous System Development
  • A. Neural Tube Formation
  • B. Cellular Components of the Neural Plate
  • C. Primary Neurulation
  • D. Formation of Cerebral Vesicles
  • E. Secondary Neurulation
  • F. Intramural Development and Nuclei
  • III. Developmental Milestones
  • A. Externally Observed Central Nervous System Developmental Milestones
  • B. Internally Observed Central Nervous System Developmental Milestones
  • C. Developmental Milestones Related to Myelination
  • D. Developmental Milestones of Cerebral Cortex
  • IV. Conclusions
  • References
  • Modeling the Neurovascular Unit In Vitro and In Silico
  • I. Introduction
  • II. Animal Models of BBB Development and Function
  • III. Cell-Based Models
  • IV. Static Three-Dimensional (3D) Models
  • V. Organotypic Culture Models (OCMs) and Microphysiological Systems (MPS)
  • VI. Implementing In Vitro BBB Models for DNT
  • VII. In Silico Models: BBB Permeability
  • VIII. In Silico Models: Virtual NVU
  • IX. Summary and Conclusions
  • Acknowledgments
  • References
  • Zebrafish as a Model for Developmental Biology and Toxicology
  • I. Introduction
  • II. Developmental Biology
  • A. Gastrulation
  • B. Organogenesis
  • C. Neurodevelopment
  • D. Neurulation
  • E. Neurogenesis
  • F. Eye
  • G. Brain
  • H. Behavior
  • III. Developmental Toxicology
  • A. Assessments and Chemicals Screened
  • B. Advancements
  • IV. Concordance With Mammalian Models
  • V. Conclusions
  • References
  • Using Caenorhabditis elegans to Study Neurotoxicity
  • I. Introduction
  • II. Studies of Specific Neurotoxins
  • A. Manganese
  • B. Selenium
  • C. Methylmercury
  • D. Other Toxins
  • III. Anesthetic-Induced Neurotoxicity
  • IV. Conclusions
  • References
  • Part III Synaptogenesis and neurotransmission
  • Introduction
  • Human 3D In Vitro Models for Developmental Neurotoxicity
  • I. Developmental Neurotoxicity Represents a Societal Testing Need
  • II. The Current Testing Approach for DNT In Vivo and In Vitro does not Satisfy our Needs
  • III. The Process of Developing In Vitro Strategies for DNT
  • IV. The Development of a Reproducible BMPS for Modeling Neurodevelopment and Testing its Perturbation
  • V. Ongoing Developments of the Mini-Brain
  • VI. Conclusions
  • Acknowledgment
  • References
  • Ontogeny of Monoamine Neurotransmitters
  • I. Introduction
  • II. Innervation of Terminal Fields
  • A. Ontogeny of Dopaminergic Innervation
  • B. Ontogeny of Noradrenergic Innervation
  • C. Ontogeny of Serotonergic Innervation
  • III. Neurochemical Synaptogenesis
  • A. Neurotransmitter Content
  • 1. Dopamine
  • 2. Norepinephrine
  • 3. Serotonin
  • B. Biosynthetic Enzymes
  • 1. Tyrosine Hydroxylase
  • 2. Dopamine β-Hydroxylase (DβH)
  • 3. Tryptophan Hydroxylase (TPH)
  • C. Reuptake Systems
  • 1. High-Affinity DA Uptake
  • 2. High-Affinity NE Uptake
  • 3. High-Affinity 5-HT Uptake
  • D. Monoaminergic Receptors
  • 1. Dopaminergic Receptors
  • 2. Noradrenergic Receptors
  • 3. Serotonergic Receptors
  • References
  • Developmental Toxicity Within the Central Cholinergic Nervous System
  • I. Introduction
  • II. The Cholinergic System in CNS Development
  • III. Vulnerable Time Periods of Developmental Neurotoxicity
  • IV. Functional Effects of Developmental Exposure to Anticholinesterases
  • V. Cholinergic Mechanisms of Developmental Neurotoxicity
  • VI. Other Cholinergic Developmental Neurotoxicants
  • A. Other Insecticides
  • B. Nicotine
  • C. Lead
  • D. Endocrine Disruptors
  • VII. Conclusions
  • References
  • Ontogeny of Second Messenger Systems
  • I. Introduction
  • II. Second Messenger Systems: General and Ontogenic Aspects
  • A. Cyclic Adenosine Monophosphate
  • B. Inositol Triphosphate and Diacylglycerol
  • C. Calcium
  • D. Nitric Oxide
  • III. Specific Roles of the Second Messenger System in Brain Development
  • A. Neurogenesis and Gliogenesis
  • B. Modulation of Apoptosis
  • IV. Developmental Neurotoxicants and Second Messenger Systems
  • A. Ethanol
  • B. Lead
  • V. Conclusions
  • References
  • The NMDA Receptors: Physiology and Neurotoxicity in the Developing Brain
  • I. Introduction
  • II. Molecular Structure of the NMDA Receptor
  • III. Functional Role of the NMDA Receptor
  • IV. Anatomical Distribution and Developmental Changes in NMDA Receptors in Brain
  • V. Role of the NMDA Receptor in Neurotoxicity During Brain Development
  • Acknowledgment
  • References
  • Part IV Nutrient and chemical disposition
  • Introduction
  • Physiologically Based Pharmacokinetic (PBPK) Models
  • I. Introduction
  • II. Selected PBPK Models for Developmental Neurotoxicology
  • A. Atrazine
  • B. Chlorpyrifos
  • C. Deltamethrin
  • D. Manganese
  • E. Perchlorate and Iodine
  • III. Future Directions for Modeling CNS Active Materials
  • Acknowledgment
  • References
  • Blood—“Brain Barrier: Physiological and Functional Considerations
  • I. Introduction
  • II. Development of the Blood–Brain Barrier
  • A. Role of Astrocytes in BBB Development
  • B. Role of Pericytes in BBB Development
  • C. Signaling Pathways Involved in BBB Development
  • III. Disruption of the Blood–Brain Barrier
  • A. Drugs of Abuse
  • B. Neurodegenerative Diseases
  • IV. Summary
  • References
  • Toxicological Mechanisms of Engineered Nanomaterials: Role of Material Properties in Inducing Different Biological Responses
  • I. Introduction
  • II. Manganese NP Toxicity
  • III. The Role of Charge in Gold Nanotoxicity
  • IV. Toxicity of Amorphous Silica Nanoparticles
  • V. Unique Cellular Interactions of Silver Nanoparticles
  • VI. Chronic Toxicity of Nanoparticles in Enhanced Models
  • VII. Impact of Nanoparticles on Cellular Mitochondria
  • VIII. Understanding Molecular Mechanisms of Nanoparticle Toxicity Through Gene-Editing Technology
  • References
  • Food and Nutrient Exposure Throughout the Life Span: How Does What We Eat Translate Into Exposure, Deficiencies, and Toxicities?
  • I. Introduction
  • II. Nutrient Assessment
  • III. Bioavailability and Beyond
  • IV. Current Nutrient Standards
  • V. Global Causes of Deficiency
  • VI. Global Causes of Toxicity
  • VII. Effects of Deficiency and Excessive Amounts of Selected Nutrients
  • A. Iron
  • B. Zinc
  • C. Folic Acid
  • D. Vitamin A
  • E. Vitamin D
  • VIII. Approaches to Addressing Micronutrient Deficiencies
  • A. Pill Supplementation Programs
  • B. Fortification
  • C. Multiple Micronutrient Fortified Beverages and Foods
  • D. Microencapsulation
  • E. Agricultural Enhancement of Micronutrient Content of Foods
  • IX. Further Directions in Research About Lifelong Effects of Nutrition
  • A. Dietary Intake to Prevent Disease
  • B. Neonatal Microbiome
  • X. Summary
  • References
  • The Microbiome Gut—“Brain Axis
  • I. Introduction
  • II. What is the Human Microbiome?
  • III. What is the Gut–Brain Axis?
  • IV. Current Knowledge on how the Intestinal Microbiota Influences the Gut–Brain Axis
  • V. Intestinal Microbiota-Derived Neuroactive Metabolites
  • VI. Neurological Disorders
  • VII. Conclusions and Research Data Gaps
  • Acknowledgments
  • Definitions for the Gut–Brain Axis
  • References
  • Drug and Chemical Contaminants in Breast Milk: Effects on Neurodevelopment of the Nursing Infant
  • I. Introduction
  • II. Effects of Breastfeeding on Infant Neurodevelopment
  • III. Exposure of Nursing Infants to Drugs in Breast Milk
  • A. Mammary Gland Structure
  • B. Mechanisms of Xenobiotics Secretion Into Milk
  • 1. Ionization Characteristics
  • 2. Lipid Solubility
  • 3. Plasma Protein Binding
  • C. Quantitative Estimation of Infant Drug Exposure Via Breast Milk
  • IV. Effects of Maternal Exposure to Environmental Contaminants on the Nursing Infant
  • A. Metals and Inorganic Compounds
  • 1. Lead
  • 2. Methlymercury
  • 3. Arsenic
  • B. Persistent Organic Pollutants (POP)
  • 1. Polychlorinated Dibenzodioxins (Dioxins) and Polychlorinated Dibenzofurans (Furans)
  • 2. Polychlorinated Biphenyls
  • V. Drugs and Nonmedicinal Substances
  • A. Marijuana (Cannabis)
  • B. Other Nonmedicinal and Medicinal Substances
  • VI. Information Resources
  • VII. Conclusions
  • References
  • Part V Behavioral assessment
  • Introduction
  • Behavioral Phenotyping in Developmental Neurotoxicology—Simple Approaches Using Unconditioned Behaviors in Rodents
  • I. Introduction
  • II. Basic Considerations
  • III. Simple Unlearned Behaviors and Other Measures for Assessing Developmental Neurotoxicity
  • A. Measures of Physical Growth
  • B. Appearance of Physical Developmental Landmarks
  • C. Sleep–Activity Cycle
  • 1. Activity and Circadian Rhythms
  • 2. Sleep Cycle
  • D. Sensory Function
  • 1. Olfactory Orientation
  • 2. Auditory Startle Reflex
  • 3. Psychophysical Methods
  • 4. Other Tests of Sensory Deficits
  • E. Motor Development
  • 1. Primitive Motor Behaviors
  • 2. Other Motor Functions
  • F. Activity and Exploratory Behavior
  • 1. Activity
  • 2. Exploratory Behavior
  • 3. Pharmacologically Induced Changes in Locomotor Activity
  • G. Species- and Sex-Specific Behaviors
  • 1. Grooming
  • 2. Reproductive and Parental Behaviors
  • 3. Aggressive Behaviors
  • 4. Unlearned Social and Play Behaviors
  • 5. Ultrasonic Vocalizations
  • H. Anxiety- and Depression-Like Behaviors
  • IV. Behavioral Test Batteries in Developmental Neurotoxicology
  • A. Test Batteries Designed for Rats
  • 1. Cincinnati Test Battery
  • 2. Collaborative Behavioral Teratology Study Test Battery
  • 3. European Collaborative Study
  • B. Test Batteries Designed for Mice
  • C. Newer Rodent Testing Batteries for Rodents and Design Considerations
  • V. Conclusions
  • References
  • Psychometric Tools to Study Cognition, Sensory Functioning, and Social Behavior in Infant and Adolescent Nonhuman Primates
  • I. Developmental Assessments for Young Macaque Infants (Birth to 3–4 Months of Age)
  • II. Assessing Cognition in Older Infants and Juveniles
  • III. Methodologies for Measuring Learning and Memory
  • IV. Tests of Cognition Suitable for Infant and Adolescent Monkeys
  • V. Raising the Bar on Difficulty: Measuring Complex Learning Abilities
  • VI. Tools to Measure Vision and Hearing
  • VII. Social Behavior in Play Groups and Mother–Infant Pairs
  • VIII. Concluding remarks
  • Acknowledgment
  • References
  • Automated Assessment of Cognitive Function in Nonhuman Primates
  • I. Introduction
  • II. Measuring Cognition Very Early in Life
  • III. Evaluation of Cognitive Abilities from Late Infancy into Adulthood
  • IV. Toxicological Testing Using Operant Methods During Development
  • Acknowledgment
  • References
  • Determining the Validity of Preclinical Behavioral Assessments for Extrapolation to a Clinical Setting
  • I. Introduction
  • II. Ecological Validity
  • III. Face Validity
  • IV. Convergent Validity
  • V. Construct Validity
  • VI. Predictive Validity
  • VII. Conclusions
  • Acknowledgment
  • References
  • Behavioral Outcome as a Primary Organizing Principle for Mechanistic Data in Developmental Neurotoxicity
  • I. Current Challenges in Risk Assessment
  • II. Organizing Principles for Mechanistic Data in Developmental Neurotoxicity are Needed Because the Brain is a “Complex Adaptive System”
  • III. Changes in Mechanistic Function During Neurodevelopment and Developmental Toxic Exposure May be Indistinguishable
  • IV. Behavior as an Organizing Principle for Mechanistic Data
  • A. Approaches for Using Behavior as an Organizing Principle for Mechanistic Data
  • B. Examples of Using Behavior as an Organizing Principle for Mechanistic Data
  • V. Using a Single Behavioral Outcome at a Single Developmental Stage to Develop a Hierarchy of Mechanistic Effects: Rearing in Preadolescent Lead-Exposed Mice
  • VI. Which Mechanisms Have Been Associated With Mouse and Rat Rearing Behavior?
  • VII. Is There Mechanistic Evidence That Lead Exposure Disrupts Cholinergic Transmission?
  • VIII. How do We Understand Other Mechanistic Effects From Lead Exposure Relative to the Cholinergic System Disruption Indicated by Rearing Behavior?
  • IX. Does Evidence Suggest That Disruptions in the Cholinergic System Impact Glutamate/GABA Function?
  • X. What was Gained by Using Rearing Behavior at Preadolescence as a Starting Point for Organizing Extant Mechanistic Data?
  • XI. Limitations
  • XII. Using a Single Behavioral Outcome Measured at Multiple Developmental Stages to Understand the Salience of a Given Mechanism Across a Developmental Trajectory: Elevated Plus Maze (EPM) Performance as a Behavioral Measure of Anxiety
  • XIII. Bisphenol A as a Developmental Neurotoxicant
  • XIV. Anxiety as a Domain of Concern in BPA Risk Assessment
  • XV. EPM Anxiety and BPA Effects at Multiple Developmental Stages
  • XVI. What Brain Mechanisms are Relevant to EPM-Assessed Anxiety?
  • XVII. What Mechanism Pathways are Plausible Candidates for Developmental BPA Effects on EPM Anxiety?
  • A. GABA and Glutamate at One Life Stage
  • B. ERβ, Glutamate, and Spine Synapse Density Pathway
  • XVIII. What is Gained by Using Behavior as an Organizing Principle?
  • XIX. Limitations
  • XX. Concluding Remarks
  • References
  • Part VI Clinical assessment and epidemiology
  • Introduction
  • Evaluation of the Human Newborn Infant
  • I. Introduction
  • II. A First Impression
  • A. Pregnancy Outcome
  • B. Apgar Score
  • C. Neonatal Screening Programs
  • III. Neurobehavioral Evaluations
  • A. Neurologic Examination of the Full-Term Newborn Infant
  • B. Neonatal Behavioral Assessment Scale
  • C. Bayley Scales of Infant and Toddler Development
  • D. Infants With Perinatal Risk Factors
  • 1. Neurobehavioral Examinations of the Preterm Infant
  • 2. General Movements
  • 3. NICU Network Neurobehavioral Scale
  • 4. The Assessment for Premature Infant Behavior
  • 5. Newborn Individualized Developmental Care and Assessment Program
  • 6. Infant Behavioral Assessment–Intervention Program
  • 7. Looking Behavior Assessment
  • 8. Pain Assessment
  • IV. Neuroimaging
  • A. Cranial Ultrasound
  • B. Magnetic Resonance Imaging
  • 1. Diffusion Tensor Imaging
  • 2. Functional MRI
  • C. Transcranial Doppler
  • D. Near-Infrared Spectroscopy
  • V. Neurophysiological Assessments
  • A. Electroencephalogram
  • B. Evoked Potentials
  • 1. Auditory Brainstem Responses
  • 2. Visual Evoked Potentials
  • 3. Somatosensory Evoked Potential
  • VI. Perinatal Risk Scores
  • A. Clinical Risk for Babies and Score for Acute Neonatal Physiology
  • B. Perinatal Risk Inventory and Nursery Neurobiological Risk Score
  • C. New Perinatal Risk Scores
  • VII. Discussion
  • Acknowledgments
  • References
  • Neuropsychological Assessment of Children in Studies of Developmental Neurotoxicity
  • I. Introduction
  • II. Selecting the Age at Which to Conduct a Neuropsychological Assessment
  • III. Considerations in Designing an Assessment Battery
  • IV. Interpretation
  • References
  • Neurodevelopmental Assessment of the Older Infant and Child
  • I. Epidemiology of Pediatric Neurodevelopmental and Behavioral Disorders
  • II. Toolkit for Evaluation
  • References
  • Longitudinal Studies of the Effects of Prenatal Cocaine Exposure on Development and Behavior
  • I. Methodological Issues in the Study of Prenatal Cocaine Exposure
  • A. Theoretical Model
  • B. Sample Selection and Assessment of Substance Use During Pregnancy
  • C. Selection of a Comparison Group and Measurement of Covariates
  • II. A Longitudinal Study of Prenatal Cocaine Exposure: The Maternal Health Practices and Child Development Project
  • A. Sample Selection and Study Design
  • B. Pattern of Cocaine Use and Sample Characteristics
  • C. Covariates of Cocaine Use
  • III. Results From the Maternal Health Practices and Child Development Project and Other Longitudinal Investigations of Prenatal Cocaine Exposure
  • A. Growth
  • B. Central Nervous System/Cognitive Development
  • C. Temperament/Mood
  • D. Behavior and Substance Use
  • IV. Conclusions
  • References
  • Assessment of Case Reports and Clinical Series
  • I. Introduction
  • II. Recognition of Patterns of Anomalies
  • III. Syndromes of Cognitive or Behavioral Abnormalities
  • IV. Limitations of Pattern Recognition
  • References
  • Part VII Specific neurotoxic syndromes
  • Introduction
  • Fetal Minamata Disease: A Human Episode of Congenital Methylmercury Poisoning
  • I. Introduction
  • II. Human Episodes
  • III. Neuropathology of Fetal Minamata Disease
  • A. Minamata Cases
  • B. Iraqi Cases
  • 1. Placental and Mammary Transfer
  • 2. Experimental Congenital Mercury Poisoning
  • 3. Biomolecular Basis of Neurotoxicity in FMD
  • IV. Concluding Remarks
  • References
  • The Developmental Neurotoxicity of Cadmium
  • I. Introduction
  • II. Prenatal and Postnatal Cadmium Exposure
  • III. Mechanisms of Developmental Neurotoxicity
  • IV. Neurobehavioral Outcomes in Animals
  • V. Neurodevelopmental Outcomes in Children and Adolescents
  • VI. Conclusions
  • References
  • Developmental Neurotoxicology of Lead: Neurobehavioral and Neurological Impacts
  • I. Lead Neurotoxicity in Children
  • A. Cognitive Function
  • B. Academic Achievement
  • C. Specific Mental Domains
  • D. Disturbances in Mood and Social Conduct
  • E. Summary
  • II. Neurological Effects of Lead Neurotoxicity in Animals: Cognition and Plasticity
  • A. Lead and Neurotransmitter Release
  • B. Lead and Glutamatergic NMDA Receptors
  • C. Lead Neurotoxicity and Synaptic Plasticity
  • D. Lead Exposure and the Susceptibility to Alzheimer's Disease
  • E. Lead and Retinal Function
  • F. Neurobehavioral Toxicity of Lead: Schedule-Controlled Behavior
  • G. Neurobehavioral Toxicity of Lead: Memory
  • H. Lead Neurotoxicity and Structural Synaptic Plasticity
  • I. Summary
  • References
  • Fetal Alcohol Spectrum Disorder
  • I. Introduction
  • II. Epidemiology of Alcohol Consumption in Pregnancy
  • III. Alcohol Mechanism of Action
  • A. Provocative Factors
  • B. Permissive Factors
  • IV. Epigenetics
  • V. Epidemiology of FASD and Economic Burden
  • VI. FASD Diagnosis
  • VII. FASD Disabilities
  • VIII. FASD and Mental Health
  • IX. FASD Challenges and Future Directions
  • X. FASD Prevention
  • XI. Conclusions
  • References
  • Developmental Neurotoxicity of Nicotine and Tobacco
  • I. Tobacco and Nicotine Exposure During Pregnancy
  • II. Epidemiological Studies Find Neurobehavioral Dysfunction Associated With Tobacco Exposure in Pregnancy
  • III. Animal Models Show that Nicotine Exposure During Development Causes Neurobehavioral Impairment
  • IV. Nicotine Disrupts Neuronal Development
  • V. Neurotoxicity of Other Compounds in Tobacco
  • VI. Second Hand Smoke
  • VII. Other Nicotinic Compounds
  • VIII. Conclusions
  • Acknowledgments
  • Abbreviations
  • References
  • Developmental Neurobehavioral Neurotoxicity of Insecticides
  • I. Introduction
  • II. Organochlorines
  • A. Insecticidal Versus Off-Target Acute Toxicity
  • B. Developmental Toxicity
  • III. Organophosphates
  • A. Insecticidal Versus Off-Target Acute Toxicity
  • B. Developmental Neurotoxicity
  • IV. Carbamates
  • A. Insecticidal Versus Off-Target Acute Toxicity
  • B. Developmental Neurotoxicity
  • V. Pyrethroids
  • A. Insecticidal Versus Off-Target Acute Toxicity
  • B. Developmental Neurotoxicity
  • VI. Neonicotinoids
  • A. Insecticidal Versus Off-Target Acute Toxicity
  • B. Developmental Neurotoxicity
  • VII. Concluding Remarks
  • Acknowledgments
  • References
  • Developmental Exposure to Polychlorinated Biphenyls Induces Deficits in Inhibitory Control and May Enhance Substance Abuse Risk
  • I. Introduction
  • A. What Are Polychlorinated Biphenyls (PCBs)?
  • B. Environmental Toxicology and Bioaccumulation
  • II. Developmental Neurobehavioral Neurotoxicity of PCBs
  • A. PCBs Cause Inhibitory Control Deficits
  • B. PCBs Alter Psychostimulant Behavioral Pharmacology
  • III. Developmental PCB Exposure Impairs Dopamine Function
  • A. Stimulated Peak Dopamine Release Changes After Developmental PCB Exposure
  • B. Developmental PCB Exposure Alters Dopamine Transporter Activity
  • C. Dopamine Autoreceptor Sensitivity Increases After Developmental PCB Exposure
  • IV. Perinatal PCB Exposure Changes the Developing Brain, But Males May Be More Sensitive
  • V. Where Do We Go From Here?
  • A. Do PCBs Increase Psychostimulant Addiction Risk?
  • B. Future Research
  • References
  • Developmental Neurotoxicity of General Anesthetics
  • I. Introduction
  • II. Classes of Anesthetics and Mechanisms of Action
  • III. Nonclinical Studies of Anesthetic-Induced Neurotoxicity
  • A. General Anesthesia-Induced Apoptotic Neurodegeneration
  • B. General Anesthesia-Induced Deficits in Cognitive Function
  • C. Dose-Dependent and Duration-Dependent Effects
  • D. Combined Exposures
  • E. Mechanisms Responsible for Neurocognitive Dysfunction
  • IV. Clinical Studies
  • V. Protective Compounds
  • VI. Conclusions
  • Acknowledgment
  • References
  • Maternal Drug Abuse and Adverse Effects on Neurobehavior of Offspring
  • I. Introduction
  • II. Opiates
  • A. Neonatal Abstinence Syndrome
  • B. Neurobehavioral Outcomes for Older Infants/Children
  • C. Polydrug
  • D. Summary
  • III. Cocaine
  • A. The Newborn Period
  • B. Childhood
  • C. Adolescence
  • D. Summary
  • IV. Cannabinoids/Marijuana
  • A. The Newborn Period
  • B. Childhood
  • C. Adolescence
  • D. Summary
  • V. Methamphetamine
  • A. The Newborn Period
  • B. Childhood
  • C. Summary
  • VI. MDMA
  • VII. Transgenerational and Paternal Exposures
  • VIII. Summary
  • References
  • Developmental Neurotoxicology of Antiepileptic Drugs
  • I. Introduction
  • II. Neurobehavioral Effects of Prenatal Exposure to Monotherapy Treatment
  • A. Phenobarbital
  • B. Phenytoin
  • C. Carbamazepine
  • D. Valproic Acid
  • E. Lamotrigine
  • F. Levetiracetam
  • III. Putative Underlying Causes of Neuroteratogenic Effects
  • A. Neurogenesis
  • B. Migration
  • C. Apoptosis
  • D. Synaptogenesis
  • IV. Conclusions
  • References
  • Part VIII Risk assessment
  • Introduction
  • Current Approaches to Risk Assessment for Developmental Neurotoxicity
  • I. Introduction
  • II. Risk Assessment Paradigm and General Concepts
  • III. Conduct and Considerations in Developmental Neurotoxicity Risk Assessment
  • A. Hazard Identification
  • B. Human Data
  • C. Animal Toxicology Data
  • 1. Other Study Types
  • D. Other Data
  • E. Evidence Integration
  • F. Dose–Response Analysis
  • G. Exposure Assessment
  • H. Risk Characterization
  • IV. Common Data Gaps for DNT Studies of Environmental Chemicals
  • V. Summary
  • References
  • Animal/Human Concordance
  • I. Introduction
  • II. Human Conditions
  • A. Thyroid Toxicants
  • B. Methylmercury
  • C. Inorganic Lead
  • D. Phenytoin
  • E. Fetal Alcohol Spectrum Disorder
  • F. Polychlorinated Biphenyls (PCBs)
  • III. Assessment of Neurobehavioral Development in Infants and Children
  • A. Attention-Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder
  • B. Test Batteries for Infants and Children
  • IV. Animal Models
  • A. General Concepts and Indications
  • B. Alternative (Nonmammalian) Species
  • 1. Zebrafish (Danio rerio)
  • C. Regulatory Guidelines
  • 1. Pharmaceuticals: US FDA and ICH Guidelines
  • 2. DNT Guidelines (US EPA OCSPP 870.6300 and OECD TG 426)
  • 3. Other Guidelines (OECD TG 443)
  • D. Apical Tests
  • 1. Motor Activity
  • 2. Acoustic Startle Response (ASR)
  • 3. Neuropathology and Morphometry
  • V. Targeted Testing
  • A. Neurochemical (AChE and Thyroid Hormone)
  • B. Neurologic/Motor Function
  • C. Sensory Function
  • D. Cognition
  • E. Neuropathology and Morphometry
  • F. Socio-Sexual and Anxiety-Related Behaviors
  • G. In Vitro Test Systems
  • VI. Newer Models and Approaches
  • A. Imaging as a Biomarker of Developmental Insult and Lasting Effects
  • B. The Use of Microphysiological Systems to Simulate the Dynamic Functions
  • C. Use of the “Omic” Technologies
  • D. Additional Considerations for Assessing DNT
  • Abbreviations
  • References
  • Physiologically Based Pharmacokinetic Models in the Risk Assessment of Developmental Neurotoxicants
  • I. Introduction
  • II. Construction and Evaluation of PBPK Models
  • A. Model Representation
  • B. Model Parameterization
  • C. Model Simulation
  • D. Model Validation and Evaluation
  • III. Brain Dosimetry in PBPK Models
  • IV. PBPK Modeling of Developmental Neurotoxicants
  • V. Application of PBPK Models in the Risk Assessment of Developmental Neurotoxicants
  • References
  • Application of Quantitative Dose—“Response Data in Risk Assessment and the Incorporation of High-Throughput Data
  • I. Introduction
  • II. Problem Formulation
  • A. Planning and Scoping
  • B. Problem Formulation
  • III. Risk Assessment Fundamentals in the Federal Government
  • A. Maternal Effects
  • IV. Defining Adversity
  • V. Data From High-Throughput Assays
  • VI. Risk Quantitation
  • A. Quantifying the Point of Departure
  • B. Developing Uncertainty Factor Values
  • Acknowledgment
  • References