Physiologically Based Kinetic (PBK) models predict the internal concentration of chemicals in diﬀerent organs after exposure. They are developed and applied to reduce animal studies for risk assessment. Goats are commonly kept for both recreation and consumption, making it a relevant species for assessing the risk of chemical exposures, e.g. due to medicine treatment or environmental pollution. In this study, an existing generic PBK model, previously developed by Radboud University, was adjusted to accurately ﬁt the goat physiology. It was then implemented and validated. The necessary model parameters were obtained by systematic literature review. The adjusted model was implemented into the software program R. In the early exposure phases, the new goat model accurately predicts internal tissue concentrations. This is not the case for all biological processes or in later exposure phases. The main reason for this is the lack of available physiological data for goats, such as body weight of organs and blood ﬂow fractions. For the missing parameters, values for sheep were used. In addition, insuﬃcient suitable studies were available for the validation of the goat-adjusted model. Here, values for toxicokinetic parameters, such as the absorption rate constant and clearance rates, were unavailable. Allometric scaling was used to extrapolate values for these parameters, using data from sheep and cattle. More in vitro and in vivo studies are necessary to reduce the knowledge gaps to allow the reliable application of the generic PBK model for goats.
|Date of Award||29 Jun 2020|
|Supervisor||Ad Ragas (Examiner), Lily Fredrix (Co-assessor) & Leonie Lautz MSc (External assessor)|