Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances

Abstract

One of the key outcomes of testing the potential genotoxicity or mutagenicity of a substance is the conclusion on whether the substance should be classified as a germ cell mutagen and the significance of this for other endpoints such as carcinogenicity. The basis for this conclusion are the criteria presented in classification and labelling systems such as the Globally Harmonized System for classification and labeling (GHS). This article reviews the classification criteria for germ cell mutagenicity and carcinogenicity and how they are applied to substances with evidence of mutagenicity. The implications and suitability of such a classification for hazard communication, risk assessment, and risk management are discussed. It is proposed that genotoxicity assessments should not focus on specifically identifying germ cell mutagens, particularly given the challenges associated with communicating this information in a meaningful way. Rather the focus should be on deriving data to characterize the mode of action and for use in the risk assessment of mutagens, which could then feed into a more robust, risk based management of mutagenic substances versus the current more hazard based approaches. Environ. Mol. Mutagen. 58:354-360, 2017. © 2017 Wiley Periodicals, Inc.

Applied genetic toxicology: From principles to practice

“…This includes stronger planning and scoping efforts to be incorporated early and regularly in the assessment process, and moving applied genotoxicity testing away from the yes/no testing paradigm and toward a risk assessment approach, including the quantitation of risk of adverse health outcomes, both cancer and noncancer, that can result from genetic damage. The commentary by Ball and Hollnagel briefly reviews the development of and revisions to the Globally Harmonized System (GHS) for Classification and Labeling of chemicals with a focus on the applicability of the GHS assessments, particularly the relevance to genotoxicity to an apical change (i.e., adverse effect) [Ball and Hollnagel, ]. The authors suggest some alternative means of hazard communication and characterization in an effort to provide an inclusive, risk‐based evaluation.…”