Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system.

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.

Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure.

BACKGROUND: An increasing number of currently used pesticides are reported to possess oestrogen-like properties or to disturb the endocrine system in other ways. OBJECTIVES: To investigate if xeno-oestrogenic activity in serum can be used as a biomarker of the combined exposure to pesticides with oestrogen-like properties in an occupational setting. METHODS: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity. A fraction containing major xeno-oestrogens but without pharmaceutical and endogenously produced oestrogens was isolated from each serum sample by solid-phase extraction and tested for oestrogenic response in a MCF-7 cell proliferation assay. The pesticide exposure for each woman was categorised as low, medium or high based on information collected by detailed interviews of the women and the employers. RESULTS: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. CONCLUSIONS: The study illustrates the usefulness of this biomarker for qualitative assessment of the combined exposure to mixtures of oestrogen-like pesticides. Although the individual pesticides responsible for the xeno-oestrogenic response were not identified, the study demonstrates that, even within highly-controlled greenhouse operations, occupational exposure to oestrogen-like pesticides can result in detectable impacts on hormonal activity in the blood.