Trans-Placental\nTransfer Mechanisms of Aromatic Amine\nAntioxidants (AAs) and <i>p</i>‑Phenylenediamine\nQuinones (PPD-Qs): Evidence from Human Gestation Exposure and the\nRat Uterine Perfusion Model

Aromatic amine antioxidants (AAs), as rubber additives,\nand their\nozone photochemical oxidation products of <i>p</i>-phenylenediamine\nquinone (PPD-Qs) have attracted great attention recently due to their\nwide environmental occurrences and toxicity. However, there is currently\nno research on the exposure risks during pregnancy and their trans-placental\ntransfer mechanisms. Herein, 20 AAs and six PPD-Qs were analyzed in\n60 maternal urine and fifty-six amniotic fluid samples (<i>n</i> = 53 pairs). ΣAAs (median: 8.57 and 15.4 ng/mL) and ΣPPD-Qs\n(0.236 and 2.29 ng/mL) were both observed, where the median concentration\nof PPD-Qs was significantly (<i>p</i> < 0.05) higher\nthan that of the parent PPDs (0.130 and 0.092 ng/mL) in the maternal\nurine and amniotic fluid samples, respectively. The result of the\nself-established rat uterine perfusion model and molecular docking\nanalysis suggested that passive diffusion and active transport patterns\nwere involved in the trans-placental transfer. This study will raise\nconcerns regarding intrauterine exposure and the trans-placental transfer\nmechanisms to AAs/PPD-Qs during pregnancy.