Toxicokinetic-Toxicodynamic models are an integrating concept for the quantification of toxic effects. As such they find application in the environmental risk assessment of chemicals, in-vitro to in-vivo toxicity extrapolation and quantification of adverse outcome pathways. For survival data we helped develop the General Unified Threshold model of Survival (GUTS). Bioaccumulation and biotransformation are key determinants of the internal dose and the variability of biotransformation across biological species and the large number of man-made chemicals in the environment is poorly understood.