Trans-Placental Transfer Mechanisms of Aromatic Amine Antioxidants (AAs) and <i>p</i>-Phenylenediamine Quinones (PPD-Qs): Evidence from Human Gestation Exposure and the Rat Uterine Perfusion Model

Aromatic amine antioxidants (AAs), as rubber additives, and their ozone photochemical oxidation products of <i>p</i>-phenylenediamine quinone (PPD-Qs) have attracted great attention recently due to their wide environmental occurrences and toxicity. However, there is currently no research on the exposure risks during pregnancy and their trans-placental transfer mechanisms. Herein, 20 AAs and six PPD-Qs were analyzed in 60 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 (0.236 and 2.29 ng/mL) were both observed, where the median concentration of PPD-Qs was significantly (<i>p</i> < 0.05) higher than that of the parent PPDs (0.130 and 0.092 ng/mL) in the maternal urine and amniotic fluid samples, respectively. The result of the self-established rat uterine perfusion model and molecular docking analysis suggested that passive diffusion and active transport patterns were involved in the trans-placental transfer. This study will raise concerns regarding intrauterine exposure and the trans-placental transfer mechanisms to AAs/PPD-Qs during pregnancy.