June 2025, Paris
5th International Congress on PFAS

Oral communication

Abstract: Mice are commonly used in neurodevelopmental studies, but the observed effects are rarely linked to internal concentrations of substances in the pup’s brain. PFOA has been found widespread in serum, breastmilk and placental cord blood, suggesting fetal and lactational exposures and a neurodevelopment disruption (Loccisano et al., 2012). It is therefore relevant to account for pre-gestational and maternal chemical exposures to better characterize the fetal and lactational exposure, particularly during the critical window of early brain development. This can be done using Physiologically Based Pharmacokinetic (PBPK) models which are useful tools to predict the pharmacokinetic behavior of xenobiotics in an organism. We have developed a generic PBPK model for mouse to determine the concentration in the offspring brain resulting from maternal oral exposure to PFOA. This model considers six compartments for the mother and five for the offspring including a brain compartment. Growth of the mother, since birth, and the pup, since the beginning of gestation, as well as the changes in organ volumes and blood flows are also described. The model has been parametrized for PFOA using parameter values from existing literature and adapted to mouse by calibrating the urinary parameter value. The estimated kinetics are in good accordance with the observed concentrations in different organs for the mother and offspring with different dose exposures. The model predicts the internal PFOA kinetics in the offspring brain throughout the neurodevelopmental window. In combination with the data obtained from in vitro studies on human neuronal cells, the in vitro to in vivo extrapolation with this PBPK model could be used to investigate developmental neurotoxicology.  

References 

Loccisano, A. E., et al., 2012. Evaluation of placental and lactational pharmacokinetics of PFOA and PFOS in the pregnant, lactating, fetal and neonatal rat using a  physiologically based pharmacokinetic model. Reprod Toxicol. 33, 468-490.