
A Practical Guide to Toxicology and Human Health Risk Assessment
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Content
- Intro
- Title Page
- Copyright Page
- Contents
- Foreword
- Preface
- Acknowledgment
- Chapter 1 Welcome to the World of Toxicology
- 1.1 Chemicals - They Are All Around Us
- 1.2 Synthetic or Naturally Occurring Chemicals - Which Are "Safer"?
- 1.3 Chemical Control Regulations
- 1.4 Perception of Chemical Risk
- 1.5 Why Is Toxicology Important?
- 1.6 Summary
- References
- Chapter 2 Basic Toxicological Terminology
- Introduction
- 2.1 The Cell
- 2.1.1 Stem Cells, Somatic Cells, and Germ Cells
- 2.2 Homeostasis
- 2.3 Adaptation and Cell Injury
- 2.4 Cellular Responses to Injury
- 2.5 Mode of Action and Mechanism of Action
- 2.6 Adverse Effects
- 2.7 Biological and Statistical Significance
- 2.8 Local and Systemic Effects
- 2.9 How Chemicals Cause Harm
- 2.10 Acute and Chronic Exposures
- 2.10.1 Acute and Chronic Exposures to Irritants and Corrosives
- 2.10.2 Subacute and Subchronic Exposure
- 2.11 Chemical Interactions in Mixtures
- 2.12 Summary
- References
- Chapter 3 The Dose Makes the Poison
- Introduction
- 3.1 Dose-Response and Dose-Effect Relationships
- 3.2 Internal and External/Exposure Dose
- 3.3 The Dose Makes the Poison: Dose-Response/Effect Curves
- 3.3.1 Dose-Response/Effect Curves - Thresholded Effects
- 3.3.2 Shape of the Dose-Response/Effect Curve
- 3.3.3 Absence of a Dose-Response Relationship
- 3.4 No Observed Adverse Effect Level (NOAEL)
- 3.5 Lowest Observed Adverse Effect Level (LOAEL)
- 3.6 What Affects the NOAEL and LOAEL?
- 3.7 No Observed Effect Level (NOEL)
- 3.8 Summary
- References
- Chapter 4 Toxicokinetics
- Introduction
- 4.1 Why Is Toxicokinetics So Useful?
- 4.2 ADME: Absorption, Distribution, Metabolism, and Excretion
- 4.2.1 Absorption
- 4.2.1.1 Transport Across Cellular Membranes
- 4.2.2 Exposure Routes
- 4.2.3 Absorption by the Oral Route (via the Gastrointestinal Tract)
- 4.2.3.1 First-Pass Metabolism
- 4.2.4 Absorption by the Inhalation Route
- 4.2.5 Absorption by the Skin
- 4.2.6 Absorption by Other Routes - Intravenous and Intraperitoneal Routes
- 4.2.7 Distribution (and Storage)
- 4.2.8 Apparent Volume of Distribution (Vd)
- 4.3 Biotransformation(Metabolism)
- 4.3.1 The Liver - Our Main Metabolizing Organ
- 4.3.2 Phase 1 and Phase 2 Reactions
- 4.3.3 Excretion
- 4.3.4 EliminationHalf-Life
- 4.4 Bioavailability and Area Under the Curve (AUC)
- 4.5 Assessment Approaches
- 4.5.1 OECD TG 428 Skin Absorption: In Vitro Method
- 4.5.2 OECD TG 427 Skin Absorption: In Vivo Method
- 4.5.3 Physiologically Based Toxicokinetics (PBTK) Model
- 4.6 Summary
- References
- Chapter 5 Factors That Modify Toxicity
- Introduction
- 5.1 Lifestyle Factors - Alcohol and Tobacco
- 5.2 Influence of Age
- 5.3 Health Status
- 5.4 Nutritional Status - Diet
- 5.5 Sex
- 5.6 Adaptation
- 5.7 Genetic Variability
- 5.8 Summary
- References
- Chapter 6 Local Effects
- Introduction
- 6.1 Irritants and Corrosives
- 6.2 Skin Structure
- 6.3 Irritant Contact Dermatitis
- 6.3.1 Acute Irritant Contact Dermatitis and Chronic (Cumulative) Irritant Contact Dermatitis
- 6.3.1.1 Acute Irritant Contact Dermatitis
- 6.3.1.2 Chronic (Cumulative) Irritant Contact Dermatitis
- 6.4 Chemical Corrosives
- 6.5 The Skin as a Target Organ - Severity of Effect
- 6.6 Chemical Irritants and Other Exposure Routes
- 6.6.1 Respiratory Irritation
- 6.6.2 Eye Irritation and Corrosion
- 6.7 Summary
- References
- Chapter 7 Systemic Effects
- Chapter 7.1 Chemical Allergies
- Introduction
- 7.1.1 Hypersensitivity
- 7.1.2 Allergies
- 7.1.3 Autoimmunity
- 7.1.4 Allergens, Hapten, Antigens, and Atopy
- 7.1.5 How an Allergy Develops
- 7.1.5.1 Induction/Sensitization Stage
- 7.1.5.2 Elicitation Stage
- 7.1.5.3 Dose-Response Relationships
- 7.1.6 Allergic Contact Dermatitis
- 7.1.6.1 Mechanism in the Development of Allergic Contact Dermatitis
- 7.1.6.1.1 Sensitization (Induction Phase)
- 7.1.6.1.2 Elicitation Phase
- 7.1.6.2 Chemical Structure and Skin Sensitization
- 7.1.7 Respiratory Allergy
- 7.1.7.1 Asthma
- 7.1.7.2 Diversity of Terminology
- 7.1.7.2.1 Work-Related Asthma
- 7.1.8 Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)
- 7.1.9 Can Skin Sensitizers Cause Respiratory Allergy and Vice Versa?
- 7.1.10 Summary
- References
- Chapter 7.2 Genetic Toxicology
- Introduction
- 7.2.1 Genotoxicity and Mutagenicity
- 7.2.2 The Dose Makes the Poison?
- 7.2.3 How Mutations Occur
- 7.2.3.1 Cell Structure
- 7.2.4 Cellular Replication
- 7.2.4.1 The Cell Cycle - Mitosis
- 7.2.4.2 Meiosis
- 7.2.4.3 Cellular Signaling and Cellular Replication
- 7.2.4.4 Control of Cell Replication
- 7.2.5 How Chemicals Cause Harm - Mutations
- 7.2.5.1 Gene Mutations
- 7.2.5.2 Changes in the Chromosome
- 7.2.6 Other Types of DNA Damage
- 7.2.7 DNA-Repair Mechanisms
- 7.2.8 Carcinogens and Mutagens
- 7.2.9 Summary
- References
- Chapter 7.3 Carcinogenicity
- Introduction
- 7.3.1 What Is Cancer?
- 7.3.1.1 Regulation of Cell Division and Growth
- 7.3.2 Chemical Carcinogenesis
- 7.3.2.1 Genetic Drivers of Carcinogenicity
- 7.3.2.2 Proto-oncogenes and Tumor-Suppressor Genes
- 7.3.2.3 Hallmarks of Cancer
- 7.3.3 Categories of Carcinogens
- 7.3.3.1 Genotoxic Carcinogens
- 7.3.3.2 Nongenotoxic Carcinogens (Epigenetic Carcinogens)
- 7.3.4 Benign and Malignant Tumors
- 7.3.5 Dose-Response Relationships
- 7.3.5.1 Saccharin - a Troubled Artificial Sweetener?
- 7.3.6 Causes of Cancer
- 7.3.7 Summary
- References
- Chapter 7.4 Reproductive and Developmental Toxicology
- Introduction
- 7.4.1 The Female Reproductive System
- 7.4.2 The Menstrual Cycle
- 7.4.2.1 The Ovarian Cycle
- 7.4.2.2 The Uterine Cycle
- 7.4.3 The Male Reproductive System
- 7.4.4 Production of Sperm (Spermatogenesis)
- 7.4.4.1 Structure of Sperm
- 7.4.5 The Reproductive Process and Fertilization
- 7.4.6 Organogenesis
- 7.4.7 The Endocrine System and Its Involvement in the Reproductive Process
- 7.4.7.1 The Hypothalamus-Pituitary-Gonad (HPG) Axis
- 7.4.7.1.1 How the HPG Axis Works
- 7.4.8 Sexual Reproduction and the Implications of Chemical Exposure
- 7.4.8.1 Effects on Fertility
- 7.4.8.2 Effects on the Male Reproductive System
- 7.4.8.2.1 A Note of Caution - Sperm Production
- 7.4.8.2.2 Adverse Effects - Males
- 7.4.8.3 Effects on the Female Reproductive System
- 7.4.8.3.1 Consequences of Chemical Exposure (Females)
- 7.4.8.3.2 Adverse Effects - Females
- 7.4.9 Effects on the Developing Organism - Developmental Toxicology
- 7.4.9.1 Variations and Malformations
- 7.4.10 Maternal Mediated Toxicity
- 7.4.11 Summary
- References
- Chapter 8 Target Organ Toxicity
- Chapter 8.1 The Liver
- Introduction
- 8.1.1 Histology of the Liver
- 8.1.1.1 Not All Hepatocytes Are Identical
- 8.1.2 Functions of the Liver
- 8.1.2.1 Metabolism (Biotransformation) of Xenobiotics
- 8.1.2.2 Production of Bile Acids and Salts for Fat Emulsification
- 8.1.2.3 Iron and Vitamin Storage
- 8.1.2.4 Synthesis of Glycogen from Glucose
- 8.1.2.5 Production of Plasma Proteins and Protein Metabolism
- 8.1.2.6 Excretion of Bilirubin in the Bile
- 8.1.2.7 Lipid Metabolism
- 8.1.3 The Liver and the Thyroid Gland
- 8.1.4 The Liver as a Target Organ
- 8.1.4.1 Adaptive Responses of the Liver
- 8.1.4.2 How the Liver Responds to Chemical Injury
- 8.1.4.2.1 Fatty Liver (Steatosis)
- 8.1.4.2.2 Cholestasis
- 8.1.4.2.3 Liver Cirrhosis
- 8.1.4.2.4 Liver Necrosis/Cytotoxicity
- 8.1.4.2.5 Liver Cancer
- 8.1.5 Peroxisome Proliferation
- 8.1.6 Common Indicators of Liver Injury
- 8.1.7 Summary
- References
- Chapter 8.2 The Kidney
- 8.2.1 Structure and Function of the Kidney
- 8.2.2 The Nephron
- 8.2.3 Filtration
- 8.2.4 Reabsorption and Secretion
- 8.2.5 Metabolic Ability of the Kidneys
- 8.2.6 Kidneys and Hormones
- 8.2.7 Why Are the Kidneys A Target Organ for Toxicity?
- 8.2.8 How Chemicals Cause Harm
- 8.2.8.1 Damage to the Proximal Tubules
- 8.2.8.2 a2u-Globulin Nephropathy
- 8.2.8.3 All Is Not Lost - Renal Injury
- 8.2.9 Common Indicators of Renal Injury
- 8.2.10 Summary
- References
- Chapter 8.3 The Immune System
- Introduction
- 8.3.1 Innate and Adaptive Immunity
- 8.3.2 The Organs of the Immune System
- 8.3.3 Cells of the Immune System
- 8.3.3.1 Lymphocytes Play a Pivotal Role in the Acquired Immune Response
- 8.3.3.2 Antigen-Presenting Cells
- 8.3.3.3 Signaling Molecules Involved in the Immune Response
- 8.3.3.4 B Cells and Humoral Immunity
- 8.3.3.5 Antibodies
- 8.3.3.6 Functions of the Antibody
- 8.3.4 The Immune System as a Target Organ
- 8.3.4.1 Consequences of Immunotoxicity
- 8.3.4.2 Assessment of Reduced Immunocompetence/Immunosuppression
- 8.3.5 Testing Methodology
- 8.3.5.1 Assessment of Enhanced Immunocompetence
- 8.3.6 Developmental Immunotoxicity (DIT)
- 8.3.7 Summary
- References
- Chapter 8.4 Hematopoietic System and Blood
- 8.4.1 Blood
- 8.4.1.1 White Blood Cells (Leucocytes)
- 8.4.1.2 Red Blood Cells (Erythrocytes)
- 8.4.2 Blood Formation
- 8.4.3 How Chemicals Cause Harm
- 8.4.3.1 Effects on the Red Blood Cells
- 8.4.3.2 Hypoxia
- 8.4.3.3 Effects on the White Blood Cells
- 8.4.3.4 Effects on the Bone Marrow
- 8.4.4 How to Detect Effects on the Bone Marrow and Blood
- 8.4.5 Summary
- References
- Chapter 8.5 The Nervous System
- 8.5.1 Introduction to the Nervous System
- 8.5.2 The Central Nervous System
- 8.5.2.1 The Blood-Brain Barrier (BBB)
- 8.5.3 The Peripheral Nervous System
- 8.5.4 The Cells of the Nervous System
- 8.5.4.1 Neurons and Neuroglial Cells
- 8.5.4.2 Classification of Neurons
- 8.5.4.3 The Basic Structure of the Neuron
- 8.5.4.4 Regeneration of Nerve Cells
- 8.5.4.5 Neuroglial Cells
- 8.5.5 Transmission of Information
- 8.5.5.1 The Synapse
- 8.5.6 The Nervous System as a Target Organ
- 8.5.6.1 Effects within the Central Nervous System (CNS)
- 8.5.6.2 Neuronopathy
- 8.5.6.3 Axonopathy
- 8.5.6.4 Myelinopathy
- 8.5.6.5 Interference with Neurotransmission
- 8.5.6.5.1 Effects on the Neurotransmitters
- 8.5.6.5.2 Other Effects
- 8.5.7 Assessment of Neurotoxicity
- 8.5.7.1 Starting Point
- 8.5.7.2 Use of Standard Repeated Dose Toxicity Studies
- 8.5.8 Developmental Neurotoxicity
- 8.5.9 Summary
- Additional Resources
- Chapter 8.6 The Respiratory Tract
- Introduction
- 8.6.1 Function and Structure
- 8.6.2 Defense Mechanisms
- 8.6.3 What Can Be Inhaled?
- 8.6.3.1 Gases and Vapors
- 8.6.3.2 Airborne Particulates
- 8.6.4 Deposition within the Respiratory System
- 8.6.4.1 Inhalable and Respirable Fraction
- 8.6.5 Respiratory Tract as a Target Organ
- 8.6.5.1 Respiratory Irritation
- 8.6.5.2 Emphysema
- 8.6.5.3 Pneumoconiosis - "dust in the lungs"
- 8.6.5.4 Lung Cancer
- 8.6.5.5 Immunological Reactions
- 8.6.6 Chemical Pneumonitis and Aspiration Pneumonia
- 8.6.7 Toxicity to the Lungs - by Other Exposure Routes
- 8.6.7.1 Assessment of Effects
- 8.6.8 Local Effects (to the Respiratory Tract)
- 8.6.9 Systemic Effects
- 8.6.10 Summary
- References
- Chapter 8.7 The Endocrine System
- Introduction
- 8.7.1 Hormones - Our Chemical Messengers
- 8.7.1.1 Exocrine Function
- 8.7.1.2 Neuroendocrine Cells
- 8.7.2 The Hypothalamus
- 8.7.3 The Endocrine Axis
- 8.7.3.1 The Hypothalamic-Pituitary-Gonadal (HPG) Axis
- 8.7.3.2 How the Endocrine Axis Works (HPG)
- 8.7.4 What Can Go Wrong?
- 8.7.5 Timing Is Everything
- 8.7.5.1 Endocrine Disruptors
- 8.7.5.2 Important Considerations
- 8.7.5.3 Does the Dose Make the Poison?
- 8.7.6 Assessment for Endocrine Disruption
- 8.7.6.1 The EATs Modalities
- 8.7.6.2 What Are the Requirements If There Is an Indication of the Potential for Endocrine-Disrupting Effects?
- 8.7.6.3 The US Endocrine Disruptor Screening Program
- 8.7.6.4 The OECD Approach for the Assessment of Endocrine Disruptors
- 8.7.7 Summary
- References
- Chapter 9 Assessment Methods
- Chapter 9.1 Assessment of Irritation and Corrosive Effects
- Introduction
- 9.1.1 Assessment Approaches
- 9.1.2 Physicochemical Properties
- 9.1.3 Human Data
- 9.1.4 QSAR and Read Across
- 9.1.5 In Vitro Testing
- 9.1.5.1 Top-down and Bottom-up Approach
- 9.1.5.2 Assessment of Corrosive Properties to Skin
- 9.1.5.2.1 In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (OECD TG 430)
- 9.1.5.2.2 In Vitro Skin Corrosion: Human Skin Model Test (OECD TG 431)
- 9.1.5.2.3 In Vitro Membrane Barrier Test (OECD TG 435)
- 9.1.5.2.4 Evaluation of the Results
- 9.1.5.3 Assessment of Irritation Properties to the Skin
- 9.1.5.4 Assessment of Eye Irritation/Corrosion Potential
- 9.1.5.4.1 Bovine Corneal Opacity and Permeability Test Method (OECD TG 437)
- 9.1.5.4.2 Isolated Chicken Eye Test (OECD TG 438)
- 9.1.5.4.3 Epiocular Test (OECD TG 492)
- 9.1.5.4.4 Fluorescein Leakage Test Method (OECD TG 460)
- 9.1.5.4.5 Short Time Exposure Test Method (STE) (OECD TG 491)
- 9.1.6 In Vivo Testing
- 9.1.7 Respiratory Irritation
- 9.1.8 Summary
- References
- Chapter 9.2 Assessment of Acute Toxicity
- Introduction
- 9.2.1 Nontesting Approaches
- 9.2.1.1 QSAR Models and Read Across
- 9.2.1.2 Human Exposure
- 9.2.1.3 In Vitro Studies
- 9.2.1.4 In Vivo Testing
- 9.2.1.5 Acute Oral Toxicity
- 9.2.1.5.1 The Fixed Dose Procedure (OECD TG 420)
- 9.2.1.5.2 The Acute Toxic Class Method (OECD TG 423)
- 9.2.1.5.3 The Up and Down Procedure Test Method (OECD TG 425)
- 9.2.1.6 Acute Dermal Studies (OECD TG 402)
- 9.2.1.7 Limit Tests - Oral and Dermal Exposure Routes
- 9.2.1.8 Acute Toxicity by Inhalation
- 9.2.1.8.1 Acute Inhalation Toxicity Test Guidelines - TG 403 and TG 436
- 9.2.1.8.2 Limit Tests - Inhalation Studies
- 9.2.2 Summary
- References
- Additional Resources
- Chapter 9.3 Repeated Dose Toxicity Testing
- 9.3.1 The Objectives of Repeated Dose Toxicity Testing
- 9.3.1.1 Types of Repeated Dose Toxicity Tests
- 9.3.1.2 Choice of Species
- 9.3.1.3 Group Sizes
- 9.3.1.4 Recovery Group
- 9.3.1.5 Selection of Appropriate Doses
- 9.3.1.6 Limit Tests
- 9.3.1.7 Choice of Vehicle
- 9.3.1.8 Exposure Routes
- 9.3.1.9 General Observations
- 9.3.1.10 Clinical Pathology
- 9.3.1.11 Hematology
- 9.3.1.12 Clinical (Bio)chemistry
- 9.3.1.13 Urinalysis
- 9.3.1.14 Gross Pathology and Histopathology
- 9.3.2 Limitations of Repeated Dose Toxicity Studies
- 9.3.3 Summary
- References
- Chapter 9.4 Assessment of Carcinogenicity
- Introduction
- 9.4.1 How to Identify Potential Carcinogens
- 9.4.2 Alternative Methods - (Q)SAR and Read Across
- 9.4.2.1 Short-Term Genetic Toxicity Tests
- 9.4.2.2 In Vitro Carcinogenicity Tests
- 9.4.3 How Useful Are These Alternative Methods for the Assessment of Carcinogenicity?
- 9.4.4 In Vivo Testing - Repeated Dose Toxicity Studies
- 9.4.4.1 Combined Chronic Toxicity/Carcinogenicity Studies (OECD TG 453)
- 9.4.4.2 In Vivo Studies - Carcinogenicity Studies (OECD TG 451)
- 9.4.4.2.1 Dose Selection
- 9.4.4.3 Human Evidence/Epidemiological Studies
- 9.4.4.4 Interpretation of Results
- 9.4.5 Summary
- References
- Additional Resources
- Chapter 9.5 Assessment of Genetic Toxicity
- Introduction
- 9.5.1 Approach to Testing
- 9.5.2 In Vitro Studies
- 9.5.2.1 The Effects of Metabolic Activation
- 9.5.2.2 Cytotoxicity and Exposure Concentrations
- 9.5.2.3 Concurrent Negative and Positive Controls
- 9.5.3 Gene Mutation Effects
- 9.5.3.1 Bacterial Reverse Mutation Assays
- 9.5.3.2 Mammalian Cell Gene Mutation Assays
- 9.5.3.3 Structural Chromosomal Aberrations and Aneuploidy
- 9.5.3.4 In Vitro Mammalian Cell Micronucleus Test (OECD TG 487)
- 9.5.3.5 In Vitro Chromosomal Aberration Study (OECD TG 473)
- 9.5.3.6 Evaluation of the In Vitro Results
- 9.5.4 In Vivo Testing
- 9.5.4.1 In Vivo Mouse Micronucleus Assay (OECD TG 474)
- 9.5.4.2 Why Are Erythrocytes Used in This Assay?
- 9.5.4.3 In Vivo Mammalian Bone Marrow Chromosome Aberration Test (OECD TG 475)
- 9.5.4.4 DNA Damage
- 9.5.4.5 The COMET Assay (OECD TG 489)
- 9.5.4.6 Transgenic Rodents
- 9.5.4.7 Evaluation of In Vivo Results
- 9.5.5 Germ-Cell Tests
- 9.5.5.1 Mammalian Spermatogonial Chromosome Aberration Test (OECD TG 483)
- 9.5.5.2 The Dominant Lethal Assay in Rodents (OECD TG 478)
- 9.5.5.3 Mouse Heritable Translocation Test (OECD TG 485)
- 9.5.6 Summary
- References
- Chapter 9.6 Assessment of Reproductive and Developmental Effects
- Introduction
- 9.6.1 Sources of Data
- 9.6.1.1 Human Evidence
- 9.6.1.2 (Q)SAR and Read Across
- 9.6.1.3 In Vitro Testing
- 9.6.2 In Vivo Data
- 9.6.2.1 Specific Reproductive Toxicity Testing
- 9.6.2.1.1 The One-Generation Reproductive Toxicity Study (OECD TG 415)
- 9.6.2.1.2 The Two-generation Reproductive Toxicity Study
- 9.6.2.1.3 The Extended One-Generation Reproductive Toxicity Study (EOGRT)
- 9.6.2.1.4 Repeated Dose Toxicity Studies
- 9.6.2.1.5 Screening Tests and Combined Studies
- 9.6.2.2 Other In Vivo Studies
- 9.6.3 Developmental Toxicity
- 9.6.4 Endocrine Disruption
- 9.6.5 Summary
- References
- Chapter 9.7 Assessment of Skin and Respiratory Sensitization
- Introduction
- 9.7.1 (Q)SAR and Read Across
- 9.7.2 Human Evidence
- 9.7.3 In Vitro Studies
- 9.7.3.1 OECD Adverse Outcome Pathway for Skin Sensitization
- 9.7.3.2 Regulatory Changes to Assessment of Skin Sensitizers
- 9.7.4 In Vivo Studies
- 9.7.4.1 The Murine Local Lymph Node Assay (LLNA)
- 9.7.4.2 The Guinea Pig Maximisation Test (GPMT),OECD TG 406
- 9.7.4.3 The Buehler Test (OECD TG 406)
- 9.7.5 Assessment of Potency
- 9.7.6 Respiratory Sensitizers
- 9.7.7 Summary
- References
- Chapter 10 Alternative Methods to Animal Testing
- 10.1 The Drive for Alternative Methods
- 10.1.1 A Different Approach?
- 10.2 Alternative Methods and the 3Rs
- 10.2.1 The 3Rs - Refinement, Reduction, and Replacement
- 10.3 In Vitro and Ex Vivo Methods
- 10.4 Twenty-First Century Toxicity Testing
- 10.4.1 The Tox21 Program
- 10.4.2 Adverse-Outcome Pathway Concept
- 10.4.3 QSARs and SARs
- 10.4.3.1 Limitations
- 10.4.4 Expert Systems
- 10.4.5 Grouping and Read Across
- 10.5 Physicochemical Data and Their Use in Hazard Identification and Exposure Assessment
- 10.5.1 Vapor Pressure
- 10.5.2 Viscosity
- 10.5.3 Water Solubility
- 10.5.4 Octanol-Water Partition Coefficient (log Kow/log P)
- 10.5.5 pH
- 10.5.6 Physical Form and Particle Size
- 10.5.7 Hydrolysis
- 10.5.8 Use of Physicochemical Data for Prediction of Human Health Effects and Exposure
- 10.6 Summary
- References
- Additional Reading/Resources
- Chapter 11 Human Health Risk Assessment
- Introduction
- 11.1 Human Health Risk Assessments - Prospective and Retrospective
- 11.2 Risk, Hazard, and Exposure
- 11.3 Chemical Risk Assessments
- 11.3.1 Hazard Identification
- 11.3.1.1 Klimisch Rating
- 11.3.1.2 Absence of Data Is Not the Same as No Hazard
- 11.3.1.3 Where New Data Are Not Required - Data Waiving
- 11.3.2 Hazard Characterization/Dose-Response Assessment
- 11.3.2.1 Nonlinear and Linear Dose Response
- 11.3.2.2 Nonlinear Dose-Response Assessment - Thresholded Effects
- 11.3.3 NOAELs and LOAELs
- 11.3.4 The Benchmark Dose (BMD)
- 11.3.4.1 How It Is Calculated - Nonlinear Dose-Response Evaluation
- 11.3.5 Modification of the Dose Descriptor (POD)
- 11.3.5.1 Safety Factors, Uncertainty Factors, and Assessment Factors
- 11.3.5.2 DNELS
- 11.3.5.3 Acceptable Daily Intake (ADI)
- 11.4 Linear Dose Response - Nonthresholded Effects
- 11.4.1 Issues Surrounding the Use of the Benchmark Dose Approach
- 11.4.2 Threshold of Toxicological Concern (TTC)
- 11.5 Exposure Assessment
- 11.5.1 Exposure Routes
- 11.5.2 Who Could Be Exposed and How?
- 11.5.3 How Does Exposure Occur?
- 11.5.4 Measure or Model Exposure?
- 11.6 Risk Characterization - Do We Have a Problem?
- 11.6.1 Risk-Management Measures
- 11.7 Summary
- References
- Glossary
- Index
- EULA
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