Mutat Res Genet Toxicol Environ Mutagen. 2023 May-Jun;888:503627. doi: 10.1016/j.mrgentox.2023.503627. Epub 2023 Mar 31.
ABSTRACT
Toxicity assays, including genotoxicity assays, are important components of human safety assessments. The interpretation of the results of such assays depends on several factors, including validation of test performance, statistical analysis of the results, and, most importantly, scientific judgment concerning the relevance of the findings to human health risk under anticipated exposure conditions. Ideally, decisions should be made on the basis of studies that allow consideration of the exposure-response relationship of any observed genotoxic outcome and an estimate of the risks associated with expected human exposures. However, in practice, the available data are often limited; it may be necessary to make judgements on the basis of assays that provide only hazard information that is not related to human exposure levels; also, sometimes, decisions are based on studies with non-human (or even non-mammalian) cells that may respond differently than human systems. Too often, in such situations, decisions are based only on whether “statistical significance” has been achieved in a particular assay, rather than on an overall judgement about the weight of scientific evidence with regard to human risk. Among regulators and toxicologists, the concept of “statistical significance” has played an important role in decision-making. Toxicologists often rely on statistical evaluations based on nominal fixed thresholds (P-value = 0.05 or 0.01), but these are arbitrary values. Such “statistical significance” is merely one of many factors that should be taken into account before drawing final conclusions for risk assessment. Other factors are also very important, including adherence to test guidelines and Good Laboratory Practices (GLPs).
PMID:37188432 | DOI:10.1016/j.mrgentox.2023.503627
