Predicting Mixture Effects over Time with Toxicokinetic-Toxicodynamic Models (GUTS): Assumptions, Experimental Testing, and Predictive Power.

ABSTRACT: Current methods to assess the impact of chemical mixtures on organisms ignore the temporal dimension. The General Unified Threshold model for Survival (GUTS) provides a framework for deriving toxicokinetic-toxicodynamic (TKTD) models, which account for effects of toxicant exposure on survival in time. Starting from the classic assumptions of independent action and concentration addition, we derive equations for the GUTS reduced (GUTS-RED) model corresponding to these mixture toxicity concepts and go on to demonstrate their application. Using experimental binary mixture studies with Enchytraeus crypticus and previously published data for Daphnia magna and Apis mellifera, we assessed the predictive power of the extended GUTS-RED framework for mixture assessment. The exte

SUBMITTER: Bart S 

PROVIDER: S-EPMC7893709 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature