Title Page -- Copyright Page -- Contents -- Contributors -- Preface -- Chapter 1 General Principles of Toxicology -- 1.1 BASIC DEFINITIONS AND TERMINOLOGY -- 1.2 TOXICOLOGY: A DIVERSE SCIENCE WITH TWO BASIC GOALS -- 1.3 HAZARD IDENTIFICATION FUNCTION -- 1.4 DOSE-RESPONSE/RISK ASSESSMENT FUNCTION -- Defining Dose and Response -- Dose-Response Graphs -- 1.5 HOW DOSE-RESPONSE DATA CAN BE USED -- 1.6 AVOIDING INCORRECT CONCLUSIONS FROM DOSE-RESPONSE AND HAZARD IDENTIFICATION DATA -- Species-Related Differences in Hazard and Dose-Response Information: A Frequent Problem that Raises Uncertainty for Animal-to-Human Extrapolations -- 1.7 ADDITIONAL FACTORS INFLUENCING HAZARD IDENTIFICATION AND DOSE-RESPONSE DATA -- Route of Exposure -- Sex -- Age -- Effects of Chemical Interaction (Synergism, Potentiation, and Antagonism) -- Modes of Chemical Interaction -- Genetic Makeup -- Health Status -- Chemical-Specific Factors -- 1.8 DESCRIPTIVE TOXICOLOGY: TESTING ADVERSE EFFECTS OF CHEMICALS AND GENERATING DOSE-RESPONSE DATA -- 1.9 EVIDENCE-BASED TOXICOLOGY -- 1.10 SUMMARY -- SUGGESTED READING -- Chapter 2 Xenobiotic Absorption, Distribution, Metabolism, and Excretion -- 2.1 XENOBIOTIC INTERACTIONS WITH THE BIOLOGICAL (CELL) MEMBRANE -- Membrane Structure -- Ionization of Xenobiotics -- 2.2 ABSORPTION -- Gastrointestinal Tract -- Lungs -- Skin -- 2.3 DISTRIBUTION -- Overview -- Albumin Binding -- 2.4 Metabolism -- Overview -- Metabolism Enzymes and Reactions -- Xenobiotic-Metabolizing Enzyme Induction -- 2.5 EXCRETION (ELIMINATION) -- Renal -- Biliary Excretion -- Respiration -- Milk -- 2.6 SUMMARY -- SUGGESTED READING -- Chapter 3 Toxicokinetics -- 3.1 INTRODUCTION -- Absorption, Distribution, Metabolism, and Elimination -- Toxicokinetic Modeling -- 3.2 TOXICOKINETIC MODELING FUNDAMENTALS -- Kinetic Processes -- Compartmental Analysis -- Clearance Modeling.

PBPK Modeling -- 3.3 APPLICATIONS OF TOXICOKINETICS -- Risk Assessment -- Chemical-Specific Adjustment Factors -- Interindividual Variability -- 3.4 CASE STUDY: TOXICOKINETICS OF DIBUTYL PHTHALATE -- Design of Kinetic Studies -- Analysis of Kinetic Studies -- Development of a PBPK Model -- Model Parameterization -- Model Validation -- Application of PBPK Model -- 3.5 TOXICOKINETICS IN THE FUTURE -- Interpretation of Human Biomonitoring Data -- Quantitative In Vitro to In Vivo Extrapolation -- Modeling of Pharmacodynamics -- 3.6 SUMMARY -- REFERENCES AND SUGGESTED READING -- Chapter 4 Omics Technologies in Toxicology -- 4.1 INTRODUCTION TO OMICS -- How Omics Came to Be -- 4.2 GENOMICS -- Change in Semantics for Microarrays -- Printing of Microarrays -- Preparing Target Molecules -- Hybridization of Microarrays -- Data Analysis for Gene Expression Microarrays -- Microarray Platforms -- MicroRNA Expression Profiling -- 4.3 PROTEOMICS -- 4.4 METABOLOMICS -- 4.5 PHARMACOGENOMICS -- 4.6 SYSTEMS BIOLOGY -- Trends in Data Analysis -- 4.7 SUMMARY -- SUGGESTED READING -- Chapter 5 Toxicity of the Hematopoietic System -- 5.1 HEMATOPOIESIS: ORIGINS OF HEMATOPOIETIC CELLS -- Myelopoiesis -- Erythropoiesis -- Thrombopoiesis -- Granulopoiesis -- Monopoiesis -- Lymphopoiesis -- 5.2 HEMATOTOXICITY: ASSAYS USED FOR ANALYSIS -- Complete Blood Count -- Peripheral Blood Smear -- Bone Marrow Aspirate and Biopsy -- Flow Cytometry/Immunophenotyping -- Chromosome Analysis -- Colony-Forming Units Assay -- 5.3 DISEASES OF THE HEMATOPOIETIC SYSTEM -- Anemia -- Neutropenia and Agranulocytosis -- Thrombocytopenia -- Aplastic Anemia -- Myeloproliferative Neoplasms -- Myelodysplastic/Myeloproliferative Neoplasms -- Myelodysplastic Syndromes -- Acute Myeloid Leukemia -- 5.4 HEMATOTOXINS: KNOWN HEMATOTOXIC AGENTS -- REFERENCES AND SUGGESTED READING.

Chapter 6 Hepatotoxicity: Toxic Effects on the Liver -- 6.1 PHYSIOLOGICAL AND MORPHOLOGICAL BASES OF LIVER INJURY -- Physiological Considerations -- Morphological Consideration -- 6.2 TYPES OF LIVER INJURY -- Hepatocellular Degeneration and Death -- Fatty Liver -- Cholestasis -- Vascular Injury -- Cirrhosis -- Tumors -- 6.3 EVALUATION OF LIVER INJURY -- Symptoms of Liver Toxicity -- Morphological Evaluation -- Blood Tests -- 6.4 SUMMARY -- REFERENCES AND SUGGESTED READING -- Chapter 7 Nephrotoxicity: Toxic Responses of the Kidney -- 7.1 RENAL STRUCTURE AND PHYSIOLOGY -- Overview of Kidney Structure and Function -- Nephron Structure and Heterogeneity -- Countercurrent Flow and Urinary Concentration Mechanism -- Membrane Transport Processes -- Summary of Physiological Factors Contributing to the Kidneys as a Target Organ for Toxic Chemicals -- 7.2 CLASSIFICATIONS OF RENAL INJURY -- Acute Kidney Injury -- Chronic Kidney Injury -- Responses at the Cellular Level -- 7.3 ASSESSMENT OF RENAL FUNCTION AND INJURY IN THE CLINIC AND IN IN VIVO ANIMAL MODELS -- Measurement of GFR -- Basic Urinalysis -- Secretion of Enzymes and Other Proteins into Urine as Biomarkers of Renal Injury and Site and Mechanism of Action -- 7.4 IN VITRO MODELS TO STUDY RENAL FUNCTION AND INJURY -- Isolated Perfused Kidney -- Renal Slices -- Isolated Tubules and Tubular Fragments -- Suspensions of Isolated Renal Cells and Primary Cell Culture -- Immortalized Cell Lines -- 7.5 EXAMPLES OF ENVIRONMENTAL, INDUSTRIAL, AND THERAPEUTIC CHEMICALS THAT PRODUCE NEPHROTOXICITY -- Halogenated Solvents: Tri- and Perchloroethylene -- Heavy Metals: Mercury and Cadmium -- Analgesics: Acetaminophen -- Antibiotics: Cephalosporins -- Antineoplastics: Cisplatin -- 7.6 SUMMARY -- SUGGESTED READING -- Chapter 8 Neurotoxicity: Toxic Effects on the Nervous System -- 8.1 Nervous System.

Central Nervous System -- Peripheral Nervous System -- Neurons -- Glia -- Blood-Brain Barrier -- 8.2 Neurotoxicological Agents -- 8.3 Neurotoxicants that Induce Neuronopathy -- 8.4 Neurotoxicants that Induce Axonopathy -- 8.5 Neurotoxicants that Induce Myelinopathy -- 8.6 Neurotoxicants that Induce Alterations of Neurotransmission at the Synapse -- 8.7 Role for Glia in Neurotoxicity -- 8.8 Evaluation of Neurotoxic Injury -- 8.9 Summary -- Suggested Reading -- Chapter 9 Dermatotoxicity: Toxic Effects on the Skin -- 9.1 HISTOLOGY -- 9.2 FUNCTIONS -- 9.3 TYPES OF DERMAL TOXICITY -- Irritant Dermatitis -- Allergic Contact Dermatitis -- Systemic Contact Dermatitis -- Photosensitivity (Photoirritation and Photoallergic Contact Dermatitis) -- Contact Urticaria Syndrome (Nonimmunological [NICU] and Immunological [ICU]) -- Toxic Epidermal Necrolysis -- Acneiform Dermatoses -- Pigment Disturbances -- Skin Cancer -- 9.4 SUMMARY -- SUGGESTED READING -- Chapter 10 Pulmonotoxicity: Toxic Effects in the Lung -- 10.1 ANATOMY AND PHYSIOLOGY OF RESPIRATORY SYSTEM -- Respiratory Tract -- Lung -- 10.2 GENERAL PRINCIPLES OF INHALATION TOXICOLOGY -- Gases -- H2S -- Other Respiratory Irritants -- Particles -- Particle Size -- Particle Deposition -- Particle Clearance -- 10.3 ACUTE RESPONSES OF THE RESPIRATORY SYSTEM TO INJURY -- Burden of Oxidative Stress in Response to Respiratory Injury -- Immune Reactivity in Response to Respiratory Injury -- Alteration of Airway Function -- Acute Pulmonary Edema -- 10.4 CHRONIC RESPONSE OF THE RESPIRATORY SYSTEM TO INJURY -- Chronic Obstructive Pulmonary Disease -- Fibrosis -- Asthma -- Silicosis -- Lung Cancer -- Other Lung Diseases -- 10.5 EVALUATION OF TOXIC DAMAGE IN THE RESPIRATORY SYSTEM -- Studies in Humans -- Studies in Animals -- Animal Exposure -- Pulmonary Function Test -- Lung Lavage Assay -- Lung Perfusion.

Fixation Technique for Morphological Study -- In vitro Approaches for Both Human and Animal Study -- Morphologic Techniques -- Microdissection -- Cell Culture -- 10.6 SUMMARY -- REFERENCES AND SUGGESTED READING -- Chapter 11 Immunotoxicity: Toxic Effects on the Immune System -- 11.1 BIOLOGY OF THE IMMUNE RESPONSE -- 11.2 TYPES OF IMMUNE REACTIONS AND DISORDERS -- Allergic Reactions -- Immunosuppression and Immune Enhancement -- Autoimmunity -- 11.3 CLINICAL TESTS FOR DETECTING IMMUNOTOXICITY -- Immunoglobulin Concentrations -- T- and B-Cell Concentrations -- Cutaneous Anergy -- In Vitro Tests -- Fluorescent Antinuclear Antibody Assay -- 11.4 TESTS FOR DETECTING IMMUNOTOXICITY IN ANIMAL MODELS -- 11.5 SPECIFIC CHEMICALS THAT ADVERSELY AFFECT THE IMMUNE SYSTEM -- Metals -- Polychlorinated Dibenzo(p)dioxins -- Dust and Particulates -- Pesticides -- Solvents -- Miscellaneous Agents -- 11.6 SUMMARY -- SUGGESTED READING -- Chapter 12 Toxic Effects on Reproduction -- 12.1 GENERAL PHYSIOLOGY OF THE MALE AND FEMALE REPRODUCTIVE SYSTEM -- The Male Reproductive System -- The Female Reproductive System -- 12.2 GENERAL METHODS TO ANALYZE REPRODUCTIVE TOXICANTS -- The Mammary Gland -- New Technologies to Assess Reproductive Toxicants -- 12.3 REPRODUCTIVE TOXICANTS -- Male Reproductive Toxicants -- Female Reproductive Toxicants -- REFERENCES AND SUGGESTED READING -- Chapter 13 Developmental Toxicology -- 13.1 BIRTH AND DEVELOPMENTAL ANOMALIES: TERATOLOGY -- The Principles of Teratology -- Birth Defect Prevalence -- 13.2 PHYSIOLOGY OF PREGNANCY -- Maternal Cardiovascular System -- Metabolism in the Prospective Mother -- Metabolism in the Fetus -- Metabolism in the Placenta -- Maternal Respiration -- Maternal Renal Function -- Summary of Pregnancy Physiology -- 13.3 WORKPLACE, OCCUPATION, AND ADVERSE REPRODUCTIVE EFFECTS -- Nursing/Health Care Workers.

Maternal and Paternal Exposure to Organic Solvents.