A09_Basic of toxicokinetics

Presentation for HBM4EU Training School in Nijmegen (19-23 November 2018). The aim of this course is to help the trainees to understand basic of internal dose modelling, materialized by the physiology based toxicokinetic (PBTK) models. In recent years PBTK–based models keep gaining ground in regulatory exposure and risk assessment, describing in quantitative terms the absorption, metabolism, distribution and elimination (ADME) processes in the human body, with a focus on the effective dose at the expected target site. PBTK models aims at providing a comprehensive methodology for internal exposure assessment, by (a) translating external exposure into internal dosimetry and (b) allowing the identification of external and internal exposure through the assimilation of biomonitoring data. This provides very significant opportunities for advancing risk assessment towards exposure based assessments. PBTK models translate external exposures from multiple routes into internal exposure metrics, addressing the effects of exposure route in the overall bioavailability or the dependence on critical developmental windows of susceptibility, such as pregnancy, lactation and infancy. With regard to cumulative exposure, PBTK models offer the advantage of calculating the effect of the interactions among the mixture compounds at the level of metabolism. In this course, the main principles of toxicokinetic, QSARs for PBTK models parameterization and mixture chemical interactions will be provided.