Figure 2: Exploration of which toxicokinetic metric is toxicodynamically relevant. Severity grade of liver toxicity (points) in relation to (a) the peak concentration in the liver (g/g liver tissue) for coumarin in rat. (b) AUC in the liver (g/g × h) for coumarin in rat. A toxicokinetic model has been constructed for the rat, and and AUC were simulated with doses and duration of exposure taken from published studies (). The toxicological endpoint in the studies was liver toxicity the degree of which differed, and we graded the toxicity in a scale from 0 to 4. in the liver (liver peak concentration) was better correlated to liver toxicity than AUC in the liver indicating that it in the liver is the toxicologically relevant toxicokinetic metric.