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Toxicology, 1. Fundamentals
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AbstractThe article contains sections titled:1.Introduction1.1.Definition and Scope1.2.Fields1.3.History1.4.Information Resources1.5.Terminology of Toxic Effects1.6.Types of Toxic Effects1.7.Dose‐Response: a Fundamental Issue in Toxicology1.7.1.Graphics and Calculations1.8.Dose‐Response Relationships for Cumulative Effects1.9.Factors Influencing Dose‐Response1.9.1.Routes of Exposure1.9.2.Frequency of Exposure1.9.3.Species‐Specific Differences in Toxicokinetics1.9.4.Miscellaneous Factors Influencing the Magnitude of Toxic Responses1.10.Exposure to Mixtures2.Absorption, Distribution, Biotransformation and Elimination of Xenobiotics2.1.Disposition of Xenobiotics2.2.Absorption2.2.1.Membranes2.2.2.Penetration of Membranes by Chemicals2.2.3.Mechanisms of Transport of Xenobiotics through Membranes2.2.4.Absorption2.2.4.1.Dermal Absorption2.2.4.2.Gastrointestinal Absorption2.2.4.3.Absorption of Xenobiotics by the Respiratory System2.3.Distribution of Xenobiotics by Body Fluids2.4.Storage of Xenobiotics in Organs and Tissues2.5.Biotransformation2.5.1.Phase‐I and Phase‐II Reactions2.5.2.Localization of the Biotransformation Enzymes2.5.3.Role of Biotransformation in Detoxication and Bioactivation2.5.4.Phase‐I Enzymes and their Reactions2.5.4.1.Microsomal Monooxygenases: Cytochrome P4502.5.4.2.Microsomal Monooxygenases: Flavin‐Dependent Monooxygenases2.5.4.3.Peroxidative Biotransformation: Prostaglandin‐synthase2.5.4.4.Nonmicrosomal Oxidations2.5.4.5.Hydrolytic Enzymes in Phase‐I Biotransformation Reactions2.5.5.Phase‐II Biotransformation Enzymes and their Reactions2.5.5.1.UDP‐Glucuronyl Transferases2.5.5.2.Sulfate Conjugation2.5.5.3.Methyl Transferases2.5.5.4.N‐Acetyl Transferases2.5.5.5.Amino Acid Conjugation2.5.5.6.Glutathione Conjugation of Xenobiotics and Mercapturic Acid Excretion2.5.6.Bioactivation of Xenobiotics2.5.6.1.Formation of Stable but Toxic Metabolites2.5.6.2.Biotransformation to Reactive Electrophiles2.5.6.3.Biotransformation of Xenobiotics to Radicals2.5.6.4.Formation of Reactive Oxygen Metabolites by Xenobiotics2.5.6.5.Detoxication and Interactions of Reactive Metabolites with Cellular Macromolecules2.5.6.6.Interaction of Reactive Intermediates with Cellular Macromolecules2.5.7.Factors Modifying Biotransformation and Bioactivation2.5.7.1.Host Factors Affecting Biotransformation2.5.7.2.Chemical‐Related Factors that Influence Biotransformation2.5.8.Elimination of Xenobiotics and their Metabolites2.5.8.1.Renal Excretion2.5.8.2.Hepatic Excretion2.5.8.3.Xenobiotic Elimination by the Lungs2.6.Toxicokinetics2.6.1.Pharmacokinetic Models2.6.1.1.One‐Compartment Model2.6.1.2.Two‐Compartment Model2.6.2.Physiologically Based Pharmacokinetic Models3.Mechanisms of Acute and Chronic Toxicity and Mechanisms of Chemical Carcinogenesis3.1.Biochemical Basis of Toxicology3.2.Receptor‐Ligand Interactions3.2.1.Basic Interactions3.2.2.Interference with Excitable Membrane Functions3.2.3.Interference of Xenobiotics with Oxygen Transport, Cellular Oxygen Utilization, and Energy Production3.3.Binding of Xenobiotics to Biomolecules3.3.1.Binding of Xenobiotics or their Metabolites to Cellular Proteins3.3.2.Interaction of Xenobiotics or their Metabolites with Lipid Constituents3.3.3.Interactions of Xenobiotics or their Metabolites with nucleic Acids3.4.Perturbation of Calcium Homeostasis by Xenobiotics or their Metabolites3.5.Nonlethal Genetic Alterations in Somatic Cells and Carcinogenesis3.6.DNA Structure and Function3.6.1.DNA Structure3.6.2.Transcription3.6.3.Translation3.6.4.Regulation of Gene Expression3.6.5.DNA Repair3.7.Molecular Mechanisms of Malignant Transformation and Tumor Formation3.7.1.Mutations3.7.2.Causal Link between Mutation and Cancer3.7.3.Proto‐Oncogenes and Tumor‐Suppressor Genes as Genetic Targets3.7.4.Genotoxic versus Nongenotoxic Mechanisms of Carcinogenesis3.8.Mechanisms of Chemically Induced Reproductive and Developmental Toxicity3.8.1.Embryotoxicity, Teratogenesis, and Transplacental Carcinogenesis3.8.2.Patterns of Dose‐Response in Teratogenesis, Embryotoxicity, and Embryolethality
Title: Toxicology, 1. Fundamentals
Description:
AbstractThe article contains sections titled:1.
Introduction1.
1.
Definition and Scope1.
2.
Fields1.
3.
History1.
4.
Information Resources1.
5.
Terminology of Toxic Effects1.
6.
Types of Toxic Effects1.
7.
Dose‐Response: a Fundamental Issue in Toxicology1.
7.
1.
Graphics and Calculations1.
8.
Dose‐Response Relationships for Cumulative Effects1.
9.
Factors Influencing Dose‐Response1.
9.
1.
Routes of Exposure1.
9.
2.
Frequency of Exposure1.
9.
3.
Species‐Specific Differences in Toxicokinetics1.
9.
4.
Miscellaneous Factors Influencing the Magnitude of Toxic Responses1.
10.
Exposure to Mixtures2.
Absorption, Distribution, Biotransformation and Elimination of Xenobiotics2.
1.
Disposition of Xenobiotics2.
2.
Absorption2.
2.
1.
Membranes2.
2.
2.
Penetration of Membranes by Chemicals2.
2.
3.
Mechanisms of Transport of Xenobiotics through Membranes2.
2.
4.
Absorption2.
2.
4.
1.
Dermal Absorption2.
2.
4.
2.
Gastrointestinal Absorption2.
2.
4.
3.
Absorption of Xenobiotics by the Respiratory System2.
3.
Distribution of Xenobiotics by Body Fluids2.
4.
Storage of Xenobiotics in Organs and Tissues2.
5.
Biotransformation2.
5.
1.
Phase‐I and Phase‐II Reactions2.
5.
2.
Localization of the Biotransformation Enzymes2.
5.
3.
Role of Biotransformation in Detoxication and Bioactivation2.
5.
4.
Phase‐I Enzymes and their Reactions2.
5.
4.
1.
Microsomal Monooxygenases: Cytochrome P4502.
5.
4.
2.
Microsomal Monooxygenases: Flavin‐Dependent Monooxygenases2.
5.
4.
3.
Peroxidative Biotransformation: Prostaglandin‐synthase2.
5.
4.
4.
Nonmicrosomal Oxidations2.
5.
4.
5.
Hydrolytic Enzymes in Phase‐I Biotransformation Reactions2.
5.
5.
Phase‐II Biotransformation Enzymes and their Reactions2.
5.
5.
1.
UDP‐Glucuronyl Transferases2.
5.
5.
2.
Sulfate Conjugation2.
5.
5.
3.
Methyl Transferases2.
5.
5.
4.
N‐Acetyl Transferases2.
5.
5.
5.
Amino Acid Conjugation2.
5.
5.
6.
Glutathione Conjugation of Xenobiotics and Mercapturic Acid Excretion2.
5.
6.
Bioactivation of Xenobiotics2.
5.
6.
1.
Formation of Stable but Toxic Metabolites2.
5.
6.
2.
Biotransformation to Reactive Electrophiles2.
5.
6.
3.
Biotransformation of Xenobiotics to Radicals2.
5.
6.
4.
Formation of Reactive Oxygen Metabolites by Xenobiotics2.
5.
6.
5.
Detoxication and Interactions of Reactive Metabolites with Cellular Macromolecules2.
5.
6.
6.
Interaction of Reactive Intermediates with Cellular Macromolecules2.
5.
7.
Factors Modifying Biotransformation and Bioactivation2.
5.
7.
1.
Host Factors Affecting Biotransformation2.
5.
7.
2.
Chemical‐Related Factors that Influence Biotransformation2.
5.
8.
Elimination of Xenobiotics and their Metabolites2.
5.
8.
1.
Renal Excretion2.
5.
8.
2.
Hepatic Excretion2.
5.
8.
3.
Xenobiotic Elimination by the Lungs2.
6.
Toxicokinetics2.
6.
1.
Pharmacokinetic Models2.
6.
1.
1.
One‐Compartment Model2.
6.
1.
2.
Two‐Compartment Model2.
6.
2.
Physiologically Based Pharmacokinetic Models3.
Mechanisms of Acute and Chronic Toxicity and Mechanisms of Chemical Carcinogenesis3.
1.
Biochemical Basis of Toxicology3.
2.
Receptor‐Ligand Interactions3.
2.
1.
Basic Interactions3.
2.
2.
Interference with Excitable Membrane Functions3.
2.
3.
Interference of Xenobiotics with Oxygen Transport, Cellular Oxygen Utilization, and Energy Production3.
3.
Binding of Xenobiotics to Biomolecules3.
3.
1.
Binding of Xenobiotics or their Metabolites to Cellular Proteins3.
3.
2.
Interaction of Xenobiotics or their Metabolites with Lipid Constituents3.
3.
3.
Interactions of Xenobiotics or their Metabolites with nucleic Acids3.
4.
Perturbation of Calcium Homeostasis by Xenobiotics or their Metabolites3.
5.
Nonlethal Genetic Alterations in Somatic Cells and Carcinogenesis3.
6.
DNA Structure and Function3.
6.
1.
DNA Structure3.
6.
2.
Transcription3.
6.
3.
Translation3.
6.
4.
Regulation of Gene Expression3.
6.
5.
DNA Repair3.
7.
Molecular Mechanisms of Malignant Transformation and Tumor Formation3.
7.
1.
Mutations3.
7.
2.
Causal Link between Mutation and Cancer3.
7.
3.
Proto‐Oncogenes and Tumor‐Suppressor Genes as Genetic Targets3.
7.
4.
Genotoxic versus Nongenotoxic Mechanisms of Carcinogenesis3.
8.
Mechanisms of Chemically Induced Reproductive and Developmental Toxicity3.
8.
1.
Embryotoxicity, Teratogenesis, and Transplacental Carcinogenesis3.
8.
2.
Patterns of Dose‐Response in Teratogenesis, Embryotoxicity, and Embryolethality.
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