Thresholds of Genotoxic Carcinogens

From Mechanisms to Regulation

Takehiko Nohmi, Shoji Fukushima

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128018033
• Topic: Medicine
• Subtopic: Toxicology

Thresholds of Genotoxic Carcinogens: From Mechanisms to Regulation brings together current opinion and research activities from Japan, the US, and Europe on the subject of genotoxic thresholds. In regulation, it is an adage that genotoxic carcinogens have no thresholds for action, and that they impose cancer risk on humans even at very low levels. This policy is frequently called into question as humans possess a number of defense mechanisms including detoxication, DNA repair, and apoptosis, meaning there is a threshold at which these genotoxic carcinogens take action.

The book examines these potential thresholds, describing the potential cancer risks of daily low-level exposure, the mechanisms involved (such as DNA repair, detoxication, translesion DNA synthesis), chemical and statistical methods of analysis, and the ways in which these may be utilized to inform policy. Thresholds of Genotoxic Carcinogens: From Mechanisms to Regulation is an essential reference for any professional researchers in genetic toxicology and those involved in toxicological regulation.

• 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

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Chapter 1. Qualitative and Quantitative Assessments on Low-Dose Carcinogenicity of Genotoxic Hepatocarcinogens: Dose–Response for Key Events in Rat Hepatocarcinogenesis
• Chapter 2. Thresholds for Hepatocarcinogenicity of DNA-Reactive Compounds
• Chapter 3. Interaction of Low-Dose Radiation and Chemicals in Cancer Risk
• Chapter 4. Possible Mechanisms Underlying Genotoxic Thresholds: DNA Repair and Translesion DNA Synthesis
• Chapter 5. DNA Repair and Its Influence on Points of Departure for Alkylating Agent Genotoxicity
• Chapter 6. The Role of Endogenous Versus Exogenous DNA Damage in Risk Assessment
• Chapter 7. Thresholds of Toxicological Concern for Genotoxic Impurities in Pharmaceuticals
• Chapter 8. Practical Thresholds in the Derivation of Occupational Exposure Limits (OELs) for Carcinogens
• Chapter 9. Experimental Design and Statistical Analysis of Threshold Studies
• Chapter 10. Nrf2 as a Possible Determinant of the Threshold for Carcinogenesis
• Chapter 11. Assessment of Nongenotoxic Mechanisms in Carcinogenicity Test of Chemicals; Quinone, Quinone Imine, and Quinone Methide as Examples
• Chapter 12. Mode of Action and Assessment of Human Relevance for Chemical-Induced Animal Tumors
• Index