A proposal for a novel rationale for critical effect size in dose-response analysis based on a multi-endpoint in vivo study with methyl methanesulfonate.

摘要: Methyl methanesulfonate, a well-known direct-acting genotoxicant, was assessed in multi-endpoint study rats using six closely spaced dose levels. The main goal of the to investigate genotoxic response at very low doses and analyse this with dedicated statistical tools order find Point Departure (PoD) related metrics. Software packages like PROAST or EPA-BMDS require toxicologist define so-called critical effect size (CES) benchmark (BMR) choice has large impact on result PoD calculation. Currently, increases 5%, 10% 1 standard deviation over concurrent vehicle controls have been proposed for CES/BMR, values that may not be suited all genotoxicity endpoints. Based data obtained study, we propose an endpoint specific CES approach reflects typical evaluation process regulatory acceptable genotoxicology study. However, are aware ratio-based strategy will need more fully developed additional experimentation should mainly seen as starting point scientific discussion.