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
Shaohan Zhang, Zhipeng Cheng, Xiaoying Li, Yumeng Shi, Hongkai Zhu, Tao Zhang, Lei Wang, Hongwen Sun
Abstract
Aromatic amine antioxidants (AAs), as rubber additives, and their ozone photochemical oxidation products of p -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 ( n = 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 ( p < 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.