Human placental transfer of xenobiotics in health and disease: New approach methodologies for developmental and reproductive toxicology testing and mathematical modelling.

This review addresses an important and timely topic at the intersection of placental biology with respect to barrier transfer kinetics, toxicology and mathematical modelling in the context of emerging regulatory drivers to reduce and replace animal use in developmental and reproductive toxicology (DART) testing. The scope of this review is to provide a comprehensive overview of (i) placental structure and function across gestation, (ii) human-specific transfer mechanisms for nutrients and xenobiotics, (iii) ex vivo and in vitro human placental models, (iv) mathematical and computational modelling frameworks for placental transfer and (v) pathological influences on transfer kinetics. It aims to serve as a reference for physiologists, toxicologists and placental modelling specialists within the rapidly evolving field of non-animal technologies for DART testing.