Evaluation of the mode of action and human relevance of liver tumors in male mice treated with epyrifenacil

This article evaluates the weight of evidence for this MOA based on the modified Bradford Hill criteria. The MOA data were aligned with the dose and temporal concordance, biological plausibility, coherence, strength, consistency, and specificity for a porphyria-mediated cytotoxicity MOA while excluding other alternative MOAs. Although the postulated MOA could qualitatively potentially occur in humans, we demonstrate that it is unlikely to occur in humans because of quantitative toxicodynamic and toxicokinetic differences between mice and humans. Therefore, this MOA is considered not relevant to humans, utilizing the IPCS Human Relevance Framework; consequently, a nonlinear, threshold dose response would be appropriate for human risk assessment.PMID:36210011 | DOI:10.1016/j.yrtph.2022.105268

Source: Regulatory Toxicology and Pharmacology : RTP - October 9, 2022 Category: Toxicology Authors: Satoki Fukunaga Keiko Ogata Ayumi Eguchi Kohei Matsunaga Kengo Sakurai Jun Abe Samuel M Cohen Hiroyuki Asano Source Type: research