Handbook of Developmental Neurotoxicology
Handbook of Developmental Neurotoxicology
Editor/Author
Slikker, Jr., William, Paule, Merle G., and Wang, Cheng
Publication Year: 2018
Publisher: Elsevier Science & Technology
Single-User Purchase Price:
$225.00

Unlimited-User Purchase Price:
$337.50
ISBN: 978-0-12-809394-8
Category: Psychology
Image Count:
98
Book Status: Available
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.
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