Placental Passage of Benzoic acid, Caffeine, and Glyphosate in an Ex Vivo Human Perfusion System

Abstract

Ex vivo perfusion of the human term placenta is a method to study placental transfer without extrapolation from animal to human and with no ethical concerns for mother and child. However, ex vivo placenta perfusion has a limited potential within chemical screening and testing as the method is time-consuming. This study was an attempt to construct data needed to develop quantitative structure–activity relationship (QSAR) models that are able to predict placental transfer of new compounds. Placental transfer is a biological activity that statistically may be related to the physiochemical properties of a given group of compounds. Benzoic acid, caffeine, and glyphosate were chosen as model compounds because they are small molecules with large differences in physiochemical properties. Caffeine crossed the placenta by passive diffusion. The initial transfer rate of benzoic acid was more limited in the first part of the perfusion compared to caffeine, but reached the same steady-state level by the end of perfusion. The transfer of glyphosate was restricted throughout perfusion, with a lower permeation rate, and only around 15% glyphosate in maternal circulation crossed to the fetal circulation during the study period.

Acknowledgements

The work is a part of a larger study funded by the Danish Environmental Protection Agency (the pesticide research programme, MST J.nr 729-0014). The PhD stipendium for Tina Mose is funded by ReProTect (LSHB-CT-2004–503257) and the Danish National Graduate School of Public Health (GRASPH). The authors gratefully acknowledge the collaboration with the Maternity Unit at the National Hospital, Rigshospitalet.