
Thresholds of Genotoxic Carcinogens
From Mechanisms to Regulation
Description
Key Features
- Unites an international team of experts to provide a balanced overview of the current opinion on thresholds of genotoxic carcinogens
- Provides all the information readers need to determine a safe threshold for potential genotoxic carcinogens
- Includes information on the mechanisms of genotoxic carcinogens and how these can inform regulation
- Serves as an essential reference for any professional researchers in genetic toxicology and those involved in toxicological regulation
Readership
Table of Contents
Chapter 1. Qualitative and Quantitative Assessments on Low-Dose Carcinogenicity of Genotoxic Hepatocarcinogens: Dose–Response for Key Events in Rat Hepatocarcinogenesis
- Abstract
- Introduction
- Qualitative and Quantitative Analyses on Low-Dose Carcinogenicity of 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the Rat Liver
- Qualitative and Quantitative Analyses on Low-Dose Hepatocarcinogenicity of 2-Amino-3-methylimidazo[4,5-f]quinoline in the Rat Liver
- Qualitative and Quantitative Analysis on Low-Dose Hepatocarcinogenicity of N-nitrosodiethylamine in the Rat Liver
- Discussion
- References
Chapter 2. Thresholds for Hepatocarcinogenicity of DNA-Reactive Compounds
- Abstract
- Introduction
- Dose–Effect Studies of Initiation of Liver Carcinogenesis
- Conclusions
- Relevance to Humans
- References
Chapter 3. Interaction of Low-Dose Radiation and Chemicals in Cancer Risk
- Abstract
- Epidemiological Analysis of Cancer Risk
- Interaction of Radiation and Other Carcinogens
- Data From Animal Experiments
- Conclusion
- Acknowledgments
- References
Chapter 4. Possible Mechanisms Underlying Genotoxic Thresholds: DNA Repair and Translesion DNA Synthesis
- Abstract
- Introduction
- Challenges in Identification of Genotoxicity of Chemicals
- Possible Mechanisms Underlying Genotoxic Thresholds
- Significance of DNA Repair Mechanisms in the Suppression of Mutagenesis and Tumorigenesis in Mammals
- TLS as a Critical Factor for Mutagenesis
- Future Perspectives
- Acknowledgments
- References
Chapter 5. DNA Repair and Its Influence on Points of Departure for Alkylating Agent Genotoxicity
- Abstract
- Introduction
- The Paradigm Shift in Response to Low Doses of Alkylating Agents
- Alkylating Agent Mechanism of Action
- DNA Repair of Alkyl Adducts: Potential Influences on PoDs
- Mechanistic Evidence Supporting a PoD for EMS
- Mechanistic Evidence Supporting a PoD for ENU
- Mechanistic Evidence Supporting a PoD for MMS
- Mechanistic Evidence Supporting a PoD for MNU
- Concluding Remarks
- References
Chapter 6. The Role of Endogenous Versus Exogenous DNA Damage in Risk Assessment
- Abstract
- Introduction
- Aldehydes
- Alkylating Agents
- Oxidative Stress
- Ionizing Radiation
- Quantifying Complex Dose–Response Relationships to Support Risk Assessments
- Conclusion
- References
Chapter 7. Thresholds of Toxicological Concern for Genotoxic Impurities in Pharmaceuticals
- Abstract
- Introduction
- Genotoxic and Nongenotoxic Carcinogens
- Thresholds of Chemical Genotoxicity
- Risk Management for Genotoxic Carcinogens
- Risk Assessment and Control of Genotoxic Impurities in Pharmaceuticals
- Conclusion
- References
Chapter 8. Practical Thresholds in the Derivation of Occupational Exposure Limits (OELs) for Carcinogens
- Abstract
- Introduction
- Derivation of Occupational Exposure Limits for Carcinogenic Substances
- Concept of the German DFG (MAK (Maximale Arbeitsstoffkonzentration) Commission)
- Discourse and Further Development in Europe
- The Concept of SCOEL
- Recent Examples of Carcinogens With a Practical Threshold Assigned by SCOEL
- Conclusions
- Abbreviations
- References
Chapter 9. Experimental Design and Statistical Analysis of Threshold Studies
- Abstract
- Introduction
- No-Observed Genotoxic Effect Level
- Dose–Response Modeling
- Interpolation and Extrapolations
- Goodness of Fit Issues: Acceptance and Rejection of Models
- BMD Approach
- Mathematical Modeling for the BMD
- Software
- Conclusions
- Acronyms
- References
Chapter 10. Nrf2 as a Possible Determinant of the Threshold for Carcinogenesis
- Abstract
- Introduction
- The Regulation of Gene Expression by Nrf2
- The Susceptibility of Nrf2 Knockout Mice to Xenobiotics
- The Carcinogenicity and Mutagenicity of Xenobiotics in Nrf2 Knockout Mice
- Human Carcinogenesis in Regard to Nrf2 Activity
- Do Nrf2 and Nrf2-Regulating Genes Contribute to the Creation of a Threshold to Carcinogenesis?
- Conclusion
- Abbreviations
- References
Chapter 11. Assessment of Nongenotoxic Mechanisms in Carcinogenicity Test of Chemicals; Quinone, Quinone Imine, and Quinone Methide as Examples
- Abstract
- Quercetin
- Eugenol and Methyleugenol
- Phenacetin and Acetaminophen
- Menadione
- Ethoxyquin
- General Discussion for All the Chemicals Shown
- References
Chapter 12. Mode of Action and Assessment of Human Relevance for Chemical-Induced Animal Tumors
- Abstract
- Introduction
- Importance of Mode of Action (MOA) Analyses for Chemical-Induced Animal Tumors and Assessment of Human Relevance Based on MOA
- Human Relevance of the Constitutive Androstane Receptor (CAR) Activator-Induced Liver Tumors in Rodents Based on MOA
- Human Relevance of the Mutagen-Induced Tumors in Rodents Based on Threshold
- Future Prospects of the Mechanistic Research in Genotoxic and Nongenotoxic Tumor Inducers
- References
Product details
- No. of pages: 224
- Language: English
- Copyright: © Academic Press 2016
- Published: May 20, 2016
- Imprint: Academic Press
- eBook ISBN: 9780128018033
- Hardcover ISBN: 9780128016633
About the Editors
Takehiko Nohmi
Affiliations and Expertise
Shoji Fukushima
Affiliations and Expertise
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