Use of physiologically based kinetic modeling to predict neurotoxicity and genotoxicity of methylglyoxal in humans.

ABSTRACT: This study aimed to evaluate human neurotoxicity and genotoxicity risks from dietary and endogenous methylglyoxal (MGO), utilizing physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry as a new approach methodology (NAM) to extrapolate in vitro toxicity data to in vivo dose-response predictions. A human PBK model was defined based on a newly developed and evaluated mouse model enabling the translation of in vitro toxicity data for MGO from human stem cell-derived neurons and WM-266-4 melanoma cells into quantitative human in vivo toxicity data and subsequent risk assessment by the margin of exposure (MOE) approach. The results show that the MOEs resulting from daily dietary intake did not raise a concern for endpoints for neurotoxicity including mitochondrial function,

SUBMITTER: Zheng L 

PROVIDER: S-EPMC11455947 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature