The importance of phenology in studies of plant-herbivore-parasitoid interactions

Promotie

Replacing animal experiments in developmental toxicity testing of phenols by combining in vitro assays with physiologically based kinetic (PBK) modelling

Promovendus ms. M (Marije) Strikwold
Promotor prof.dr.ir. IMCM (Ivonne) Rietjens
Copromotor prof. dr. RA Woutersen
dr. ir. A Punt
Organisatie Wageningen University, Sub-department of Toxicology
Datum

vr 29 april 2016 16:00 tot 17:30

Locatie Auditorium, building number 362
Generaal Foulkesweg 1
362
6703 BG Wageningen
0317-483592
Traditionally animal experiments are used to assess the toxicological safety of chemicals. An alternative to this is the use of in vitro toxicity tests, but these assays do not always reflect in vivo toxicity values. Translation of in vitro data to the in vivo situation is therefore an important, but still limiting step for the use of in vitro toxicity outcomes in the regulatory safety assessment of chemicals. In the present thesis we demonstrate how we can translate in vitro embryotoxicity data to in vivo developmental toxicity values for rat and human using physiologically based kinetic (PBK) models, which mathematically describe the absorption, distribution, metabolism and excretion (ADME) of a compound in an organism. Additionally, we demonstrate a modelling approach that integrates in vitro toxicity data, PBK modelling and Monte Carlo simulations to predict the effects of human interindividual variation in kinetics for phenol induced development toxicity. Altogether, this thesis may contribute to the replacement of animal studies for the safety testing of chemicals, and may lead towards an approach that is cheaper, non-animal based and more directly relevant for humans.