Predicting the developmental toxicity of 8-methyl-benzo[a]pyrene (BaP) by physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry and read-across from BaP.

ABSTRACT: The present study predicts an in vivo dose-response curve for developmental toxicity of 8-methyl-benzo[a]pyrene (8-MBaP) in rats using PBK model-facilitated reverse dosimetry and read-across from a previously developed model for BaP. As for BaP, in vitro developmental toxicity of 8-MBaP in the mouse embryonic stem cell test (mEST) was shown to require bioactivation to its 3-hydroxy metabolite (3-OH-8-MBaP). To facilitate extrapolation of the in vitro observed developmental toxicity of 3-OH-8-MBaP to an in vivo dose-response curve for 8-MBaP, a PBK model for 8-MBaP was built based on the previously developed PBK model for BaP. The PBK models for BaP and 8-MBaP were validated based on (i) comparison of predicted blood concentrations of BaP or 8-MaP to blood concentrations in rats dosed with

SUBMITTER: Wang D 

PROVIDER: S-EPMC12454603 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature