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 (μg/g liver tissue) for coumarin in rat. (b) AUC in the liver (μg/g × h) for coumarin in rat. A toxicokinetic model has been constructed for the rat, and C _max⁡ and AUC were simulated with doses and duration of exposure taken from published studies (n = 11). 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. C _max⁡ in the liver (liver peak concentration) was better correlated to liver toxicity than AUC in the liver indicating that it C _max⁡ in the liver is the toxicologically relevant toxicokinetic metric.