Gestation Exposure to Organophosphate Esters: Structure-Dependent Transplacental Transfer Patterns, Mechanisms, and Toxicity

Organophosphate esters (OPEs), characterized by diverse chemical substituents, exhibit varying environmental exposure and toxicity profiles. Therefore, OPEs may have potential for placental transfer and could impact neonatal development. However, the structural-specific transplacental mechanisms and toxicity effects of the OPEs remain poorly understood. Herein, we develop an integrated evaluation system with human biomonitoring, uterine perfusion in pregnant rats, and placental cells. OPEs were frequently observed in maternal and cord whole blood, urine, and amniotic fluid samples (n = 41 sample sets) with median concentrations of 9.47, 9.31, 9.90, and 5.98 ng/mL, respectively. Rat uterine perfusion experiment suggested that chlor-OPEs exhibited relatively higher transplacental efficiency compared to alkyl- and aryl-OPEs. Passive diffusion dominated by lipophilicity (log K_ow) and transporters dominated active transport may be involved in the transplacental transportation mechanisms. The results from exposure experiments to placenta BeWo cells indicated that organophosphate triesters (tri-OPEs) (IC₅₀ values of 145 to 1464 μM) exhibited higher toxicity to the corresponding organophosphate diesters (di-OPEs) (IC₅₀ values of 752 to 1794 μM). In addition, chlor-OPEs represented significantly greater cytotoxic potential to placenta cells in comparison to alkyl and aryl-OPEs. More attention should be paid for chlor-OPEs as its higher transplacental and toxicity potential compared to alkyl- and aryl-OPEs.