Genotoxicity risk assessment: a proposed classification strategy

Introduction:
This text outlines a proposed strategy for harmonizing genotoxicity risk assessment across the world. The authors, all from the US Environmental Protection agency (EPa), propose a classification system for agents based on their inherent genotoxicity, dose-response observed in the data, and an exposure analysis. This system leads to an initial level of concern for genotoxic risk to humans, which is then used to generate a final level of concern for genotoxic risk to humans after a total risk characterization is performed. The text emphasizes the importance of integrating newer thinking in testing battery design with the risk assessment process.

Key points:

* The EPa first published Guidelines for Mutagenicity Risk assessment in 1986, focusing mainly on transmissible germ cell genetic risk.
* Somatic cell genetic risk has also been considered, usually in support of carcinogenicity assessments.
* The proposed classification strategy involves three levels: initial level of concern, total risk characterization, and final level of concern.
* The classification is based on inherent genotoxicity, dose-response observed in the data, and an exposure analysis.
* The text suggests reexamining the existing EPa mutagenicity testing battery and integrating newer thinking in testing battery design with the risk assessment process.
* The proposed classification system aims to provide a harmonized approach to genotoxicity risk assessment across the world.
* The final level of concern and characterized genotoxicity risk assessment are communicated to decision-makers for possible regulatory actions and to the public.

Main message:
The main message of this text is the proposal of a harmonized approach to genotoxicity risk assessment that integrates newer thinking in testing battery design with the risk assessment process. The authors emphasize the importance of considering both germ cell and somatic cell genetic risk and propose a classification system that leads to an initial level of concern for genotoxic risk to humans, followed by a total risk characterization, and finally, a final level of concern. This system aims to provide a standardized approach to genotoxicity risk assessment that can be applied across different regulatory contexts and countries.

Dearfield, Kerry L, Michael C Cimino, Nancy E McCarroll, Irving Mauer, and Lawrence R Valcovic. “Genotoxicity Risk assessment: a Proposed Classification Strategy.” Mutation Research/Genetic Toxicology and Environmental Mutagenesis 521, no. 1–2 (November 2002): 121–35. https://doi.org/10.1016/S1383-5718(02)00236-X.