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Public health and toxicology issues in drug research. Volume 2, Toxicity and Toxicodynamics /

This volume, part of the Advances in Product Development and Research Series, explores public health and toxicology issues in drug research. Edited by Rakesh Kumar Tekade, the book delves into various aspects of toxicity, including biomarkers, idiosyncratic drug reactions, dose selection, and toxico...

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Bibliographic Details
Corporate Author: ScienceDirect (Online service)
Format: eBook
Language:English
Published: [S.l.] : Academic Press, 2024.
Series:Advances in Pharmaceutical Product Development and Research Series
Subjects:
Drugs > Research.
Médicaments > Recherche.
Electronic books.
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Front Cover
  • PUBLIC HEALTH AND TOXICOLOGY ISSUES IN DRUG RESEARCH, VOLUME 2
  • PUBLIC HEALTH AND TOXICOLOGY ISSUES IN DRUG RESEARCH, VOLUME 2
  • Copyright
  • Contents
  • Contributors
  • 1
  • Biomarkers: Revolutionizing disease monitoring and therapeutic strategies
  • 1.1 Introduction to biomarkers
  • 1.2 Biomarker types
  • 1.2.1 Biomarkers of exposure
  • 1.2.1.1 Environmental exposure
  • 1.2.1.2 Genetic susceptibility
  • 1.2.1.3 Intermediate biomarkers
  • 1.2.2 Biomarkers of diseases
  • 1.2.2.1 Cardiac disorders
  • 1.2.2.2 Respiratory disorders
  • 1.2.2.3 Brain disorders
  • 1.2.2.4 Kidney malfunction
  • 1.2.2.5 Cancer
  • 1.3 Positive and negative influences of biomarkers
  • 1.4 Role of biomarkers in disease prevention, diagnosis and treatment
  • 1.5 Future perspective and challenges of biomarkers
  • 1.6 Conclusion
  • Acknowledgments
  • References
  • Further reading
  • 2
  • Connecting biotransformation with toxicity
  • 2.1 Introduction
  • 2.2 Role of hepatic enzymes in phase I of biotransformation
  • 2.2.1 Cytochrome P-450
  • 2.2.2 NADPH-cytochrome P-450 reductase
  • 2.2.3 Flavin-containing monooxygenase
  • 2.2.4 Nonmicrosomal enzymes
  • 2.3 Role of hepatic enzymes in phase II of biotransformation
  • 2.3.1 UDP-glucuronosyl transferase
  • 2.3.2 Sulfotransferase
  • 2.3.3 Glutathione-S-transferase
  • 2.4 Significance of CYP 450 in biotransformation of xenobiotics other than hepatic cells
  • 2.4.1 Respiratory tract
  • 2.4.2 Gastrointestinal tract
  • 2.4.3 Interaction of toxic metabolites with cellular components
  • 2.4.4 Free radical production
  • 2.4.5 DNA damage
  • 2.5 Case studies highlighting biotransformation-induced toxicity
  • 2.5.1 Pharmaceuticals
  • 2.5.1.1 Acetaminophen
  • 2.5.1.2 Diclofenac
  • 2.5.1.3 Troglitazone
  • 2.5.1.4 Valproic acid
  • 2.5.1.5 Tienilic acid
  • 2.5.2 Other environmental compounds
  • 2.5.2.1 Benzo(a)pyrene (B[a]P).
  • 2.5.2.2 Bisphenol-A
  • 2.6 Role of nanoparticles in biotransformation-induced toxicity
  • 2.7 Conclusion
  • Acknowledgments
  • References
  • 3
  • Idiosyncratic drug reactions and toxicities
  • 3.1 Introduction
  • 3.2 Clinical characteristics of idiosyncratic drug reactions
  • 3.2.1 Low incidence
  • 3.2.2 Latency period (time to IDR onset)
  • 3.2.3 Lack of dose dependency
  • 3.2.4 Adaptation (tolerance)
  • 3.2.5 Cross-reactivity and variability
  • 3.2.6 Genetic association
  • 3.2.7 Other factors
  • 3.3 Mechanistic hypotheses on IDRs
  • 3.3.1 Hapten hypothesis
  • 3.3.2 Danger hypothesis
  • 3.3.3 Inflammagen hypothesis
  • 3.3.4 Pharmacological interaction hypothesis
  • 3.3.5 Nonimmune hypothesis
  • 3.4 Role of drug metabolism in toxicity
  • 3.5 Drug-induced idiosyncratic reaction
  • 3.5.1 Skin rash
  • 3.5.1.1 Maculopapular rash
  • 3.5.1.2 Urticaria
  • 3.5.1.3 Stevens-Johnson syndrome and toxic epidermal necrolysis
  • 3.5.2 Liver injury
  • 3.5.2.1 Hepatocellular liver injury
  • 3.5.2.2 Cholestatic injury
  • 3.5.3 Hematologic adverse reactions
  • 3.5.3.1 Thrombocytopenia
  • 3.5.3.2 Aplastic anemia
  • 3.5.3.3 Agranulocytosis
  • 3.6 Genetic basis of idiosyncratic toxicity
  • 3.7 Screening tools for idiosyncratic toxicity
  • 3.7.1 Characteristics of an ideal animal model
  • 3.7.2 Screening methods for potential idiosyncratic drug reactions
  • 3.7.2.1 Avoiding suspect functional groups
  • 3.7.2.2 Screening for glutathione conjugates
  • 3.7.2.3 Covalent bonding
  • 3.7.2.4 Using combinations of methods
  • 3.8 Prevention of IDRs in IDILI
  • 3.9 Conclusions
  • Abbreviations
  • Acknowledgments
  • References
  • 4
  • Importance of dose selection in toxicity studies
  • 4.1 Introduction
  • 4.2 Toxicity testing: An overview
  • 4.2.1 Genetic toxicity testing
  • 4.2.1.1 Comet assay/single gel electrophoresis
  • 4.2.1.2 Chromosomal aberration assay
  • 4.2.1.3 Ames test.
  • 4.2.1.4 Micronuclei test
  • 4.2.1.5 Sister chromatid exchange test
  • 4.2.2 Carcinogenicity testing
  • 4.2.2.1 BALB/c 3T3 cell transformation assay
  • 4.2.2.2 Bhas 42-cell transformation assay
  • 4.2.2.3 Syrian hamster embryo assay
  • 4.2.3 Neurotoxicity testing
  • 4.2.3.1 In vivo studies
  • 4.2.3.2 In vitro models
  • 4.2.4 Skin sensitization testing
  • 4.2.4.1 Guinea pig sensitization test
  • 4.2.4.2 Buehler test
  • 4.2.4.3 Local lymph node assay
  • 4.2.4.4 In vitro and in chemico studies
  • 4.3 Factors essential for dose selection
  • 4.3.1 Achievability
  • 4.3.2 Fit for purpose
  • 4.3.3 Practicality
  • 4.4 Selection of dose level
  • 4.4.1 Labeling and classification
  • 4.4.2 Read across and group approaches
  • 4.4.3 Evaluation of endocrine disruptive properties
  • 4.4.4 Higher-tier studies triggering
  • 4.4.5 Health impact assessment
  • 4.5 Dose selection method for toxicity studies
  • 4.5.1 Dose-response curve evaluation
  • 4.5.2 Toxicokinetics
  • 4.6 Case studies
  • 4.6.1 7-Methylxanthine
  • 4.6.2 17-Allylamino, 17-demethoxy geldanamycin
  • 4.6.3 Naphthalen-2-yl 3,5-dinitrobenzoate (SF1)
  • 4.6.4 Chitosan-solid lipid nanoparticle
  • 4.6.5 Curcumin nanoparticles
  • 4.6.6 Silver nanoparticles
  • 4.6.7 Zinc oxide nanoparticles
  • 4.6.8 Graphene oxide nanoparticles
  • 4.7 Conclusion
  • Abbreviations
  • Acknowledgments
  • References
  • 5
  • Implication of sex differences in toxicology
  • 5.1 Introduction
  • 5.2 Gender-based medicine and its importance
  • 5.3 Gender differences influencing toxicology
  • 5.3.1 Hormonal differences
  • 5.3.2 Enzyme differences
  • 5.3.3 Dose
  • 5.3.4 Diet intake
  • 5.3.5 Exposure
  • 5.3.6 Body weight variation
  • 5.3.7 Differences in organ response
  • 5.3.8 Occupational
  • 5.3.9 Behavioral lifestyle
  • 5.4 Sex differences influencing variations in toxicological parameters
  • 5.4.1 Absorption
  • 5.4.1.1 Level of transporters.
  • 5.4.2 Distribution
  • 5.4.2.1 Tissue drug binding
  • 5.4.2.2 Protein drug binding
  • 5.4.3 Metabolism
  • 5.4.3.1 Enzyme expression variation
  • 5.4.3.1.1 Phase I enzymes
  • 5.4.3.1.2 Phase II enzymes
  • 5.4.4 Elimination
  • 5.5 Conclusion
  • Abbreviations
  • Acknowledgments
  • References
  • 6
  • Toxicological risk assessment and risk management
  • 6.1 Introduction
  • 6.2 Importance of toxicological risk assessment and risk management
  • 6.3 Basic steps involved in toxicological risk assessment
  • 6.3.1 Hazard identification
  • 6.3.1.1 SAR
  • 6.3.1.2 In vitro or in vivo studies
  • 6.3.1.3 Epidemiological studies
  • 6.3.2 Hazard evaluation or dose-response assessment
  • 6.3.2.1 No-observed- adverse- effect level (NOAEL)
  • 6.3.2.2 BMD or benchmark dose lower confidence limit (BMDL)
  • 6.3.3 Exposure assessment
  • 6.3.3.1 Applied dose
  • 6.3.3.2 Absorbed/internal dose
  • 6.3.3.3 Potential dose
  • 6.3.4 Exposure assessment approaches
  • 6.3.4.1 Direct method
  • 6.3.4.1.1 Area monitoring
  • 6.3.4.1.2 Personal monitoring
  • 6.3.4.1.3 Dermal monitoring
  • 6.3.4.1.4 Biological monitoring
  • 6.3.4.2 Retrospective method
  • 6.3.4.2.1 Simulation studies
  • 6.3.4.2.2 Dose-reconstruction studies
  • 6.3.5 Characterization of risk assessment
  • 6.3.5.1 Transparency
  • 6.3.5.2 Clarity
  • 6.3.5.3 Consistency
  • 6.3.5.4 Reasonableness
  • 6.4 Uncertainty factors in toxicological risk assessment
  • 6.4.1 Uncertainties in dose-response assessment
  • 6.4.2 Uncertainties in exposure assessment
  • 6.5 Various strategies and techniques for risk assessment
  • 6.6 Epidemiological methods usage in risk assessment
  • 6.7 Emerging problems and challenges in risk assessment
  • 6.8 Conclusion
  • Abbreviations
  • Acknowledgments
  • References
  • 7
  • Adverse outcome pathway: A paradigm shift in chemical toxicological analysis
  • 7.1 Introduction
  • 7.2 Adverse outcome pathway.
  • 7.2.1 Molecular initiating events
  • 7.2.2 Key events
  • 7.2.3 Key event relationships
  • 7.2.4 Adverse outcomes
  • 7.2.4.1 Case study of US EPA's endocrine disruptor screening program
  • 7.3 Applications of AOP
  • 7.3.1 Establishing chemical categories
  • 7.3.2 Establishing quantitative structure-activity relationships
  • 7.3.3 Establishing the strategies for prioritization
  • 7.3.4 In vitro test development
  • 7.3.5 Integrated approaches to testing and assessment
  • 7.3.6 Used as multiscale data integration tools
  • 7.3.7 Quantitative AOP and AOP networks act as tools for real-life application
  • 7.3.8 Application of AOP in epigenetics
  • 7.3.9 Provide credibility for statistical relations
  • 7.4 Strategies for AOP development
  • 7.4.1 Bottom-up development of AOP
  • 7.4.2 Top-down development of AOP
  • 7.4.3 Middle-out development of AOP
  • 7.4.4 Development of AOP through case study
  • 7.4.5 Development of AOP by analogy
  • 7.4.6 Development of AOP through data mining
  • 7.5 Review and assessment process for AOP
  • 7.6 AOP Knowledge Base
  • 7.7 AOPs for nanomaterials
  • 7.8 AOPs for drug-induced diseases
  • 7.8.1 Narcosis
  • 7.8.2 Photoactivated toxicity
  • 7.8.3 Liver steatosis
  • 7.8.4 Liver fibrosis
  • 7.8.5 Cholestasis
  • 7.8.6 Skin sensitization
  • 7.8.7 Aneuploidy in offspring
  • 7.8.8 Emphysema
  • 7.8.9 Plaque formation
  • 7.8.10 Lung cancer
  • 7.8.11 Acute inhalation toxicity
  • 7.9 Epigenetic modification and AOP
  • 7.10 Advantages and limitations of AOP
  • 7.11 In vitro data and in silico models for predictive toxicology
  • 7.12 Conclusion and future perspective
  • Abbreviations
  • Acknowledgments
  • References
  • 8
  • Design of toxicokinetic studies
  • 8.1 Introduction
  • 8.2 Biopharmaceutical assessment before toxicology
  • 8.3 Dose-response relationship with toxicokinetics
  • 8.4 Sampling schedules in toxicokinetics.