Dynamic Modeling of Sublethal Mixture Toxicity in the Nematode Caenorhabditis elegans

Dynamic models for toxic effects [toxicokinetic-toxicodynamic (TKTD) models] are increasingly used in the analysis of toxicity data for single-chemical exposure. However, these models also offer a natural extension to the effects of chemical mixtures. Here, we demonstrate how a simple model for the energy budget (DEBkiss) can be used to interpret the effects of cadmium and fluoranthene, in both single and mixed exposure, on the nematode Caenorhabditis elegans. The data for all time points and all end points (growth and reproduction) are combined into a single coherent framework. These modeling results are compared to a more traditional independent-action approach based on the dose response curves for a single end point at a single time point. The analysis with DEBkiss does not lead to a radically different interpretation of the mixture effects, both indicating an antagonistic interaction in the mixture. The DEBkiss analysis does, however, provide much more insight into the relevant dynamic processes underlying the toxic effect on the organism and allows for the generation of mechanistic hypotheses that can be used to guide further research.