Combined global sensitivity analysis and population PBPK modeling for assessing consistency of TCDD toxicokinetics data in mice

Abstract : The study of TCDD biodistribution in mice has generated a large number of data since the 1970's. The complex mechanisms involved underscores the need for a synthesis of these data. We grouped data from thirteen studies (1983-2009). A PBPK model for TCDD in mice can be calibrated based on these studies. A population PBPK approach coupled with global sensitivity analyses permitted to assess the relative contribution of each study considered as an "individual". We could also identify the key parameters that contribute at most to explain the distribution of TCDD in mice body. This identification is clearly dependent on the dose but not on the exposure route.