A review of the transplacental transfer of persistent halogenated organic pollutants: Transfer characteristics, influential factors, and mechanisms.

Persistent halogenated organic pollutants (HOPs) are a class of toxic chemicals, which may have adverse effects on fetuses via transplacental transfer from their mothers. Here, we review reported internal exposure levels of various HOPs (organochlorinated pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, short- and medium-chain chlorinated paraffins, and per- and poly-fluoroalkyl substances) in placenta, and both maternal and umbilical cord sera. We also present analyses of the transplacental transfer and placental distribution characteristics of each class of compounds, and discuss effects of several factors on the transfer and accumulation efficiencies of HOPs, as well as the main mechanisms of HOPs' transfer across the placental barrier. Reported compound-specific transplacental transfer efficiencies and distribution efficiencies, expressed as umbilical cord:maternal serum and placental:maternal serum concentration ratios (R and R, respectively), are summarized. Average published R values of the HOPs range from 0.24 to 3.08 (lipid-adjusted) and from 0.04 to 3.1 (based on wet weights), and are highest for perfluoroalkylcarboxylates (PFCAs) and tetrabromobisphenol A. Average published R values range from 0.14 to 1.02 (lipid-adjusted) and from 0.30 to 1.4 (based on wet weights). The broad R and R ranges may reflect effects of various factors, inter alia physicochemical properties of HOPs, metabolic capacities of mothers and fetuses, placental maturity, and differential expression of influx/efflux transporters in the placenta. Generally, HOPs' R values decline linearly with molecular size, and are curvilinearly related to solubility. Plasma protein binding affinity and the difference between maternal and fetal metabolic capacities may also affect some HOPs' transfer efficiencies. HOPs' molecular size may be influential. Transplacental transport of HOPs likely occurs mostly through passive diffusion, although influx/efflux transporters expressed on maternal and/or fetal sides of the placenta may also facilitate or hinder their transport. Overall, the review highlights clear gaps in our understanding of mechanisms involved in HOPs' transplacental transport.