Physiologically Based Modelling of Dioxins. I. Validation of a rodent toxicokinetic model

In this report a rodent Physiologically Based PharmacoKinetic (PBPK) model for 2,3,7,8-tetrachlorodibenzodioxin is described. Validation studies, in which model simulations of TCDD disposition were compared with in vivo TCDD disposition in rodents exposed to TCDD, showed that the model adequately predicted the in vivo toxicokinetics of TCDD across species (mouse, rat), dose-schedule (acute <=> semi-chronic <=> chronic) and route of administration (oral <=> subcutaneous). It was concluded that PBPK models are suited to establish quantitative relationships between the external dose of TCDD (amount of TCDD administered per kg body weight) and the internal dose (concentration of TCDD at the organ level). The relationship between internal dose and the resulting organ toxicity will be elaborated in subsequent reports. The results will be used in a quantitative risk assessment of the human exposure situation, in particular the exposure of suckling infants to dioxins from mother's milk.<br&gt