Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.

ABSTRACT: To fulfil the promise of reducing reliance on mammalian in vivo laboratory animal studies, new approach methods (NAMs) need to provide a confident basis for regulatory decision-making. However, previous attempts to develop in vitro NAMs-based points of departure (PODs) have yielded mixed results, with PODs from U.S. EPA's ToxCast, for instance, appearing more conservative (protective) but poorly correlated with traditional in vivo studies. Here, we aimed to address this discordance by reducing the heterogeneity of in vivo PODs, accounting for species differences, and enhancing the biological relevance of in vitro PODs. However, we only found improved in vitro-to-in vivo concordance when combining the use of Bayesian model averaging-based benchmark dose modeling for in vivo PODs, allometric

SUBMITTER: Lu EH 

PROVIDER: S-EPMC11193089 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature