Thresholds of Genotoxic Carcinogens: From Mechanisms to Regulation

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 carcinogensProvides all the information readers need to determine a safe threshold for potential genotoxic carcinogensIncludes information on the mechanisms of genotoxic carcinogens and how these can inform regulationServes as an essential reference for any professional researchers in genetic toxicology and those involved in toxicological regulation

Section 1: Thresholds of Genotoxic Carcinogens 1. Qualitative and quantitative approach on thresholds of genotoxic carcinogens 2. Thresholds for DNA-reactive Hepatocarcinogens 3. Interaction of N-ethyl-N-nitrosourea and Low Dose Radiation on T-cell Lymphamagenesis

Section 2: Mechanisms of Genotoxic Thresholds 4. Mechanisms Underlying Genotoxic Thresholds: DNA Repair and Translesion DNA Synthesis 5. Roles of DNA Repair in Points of Departure for Genotoxicity 6. The Role of Endogenous Versus Exogenous DNA Damage in Risk Assessment

Section 3: Regulation of Low Dose Genotoxic Carcinogens 7. Threshold of Toxicological Concern (TTC) to Control Mutagenic Impurities in Pharmaceuticals 8. Practical Thresholds in Occupational Exposure Limits for Carcinogens 9. Experiment Design and Statistical Analysis of Threshold Studies

Section 4: Mode of Action of Genotoxic Carcinogens at Low Doses 10. Nrf2 as a possible determinant of the threshold for carcinogenesis 11. Biochemical and Pathological Insights on the Safety Evaluations of Chemicals with Genotoxic Capabilities 12. Mode of Action and Human Relevance Analysis for Chemical-induced Animal Tumors