Transplacental transfer of p-phenylenediamine antioxidants: Insights from human gestational exposure and an optimized BeWo cell monolayer model

Junxu Li; Fangfang Ren; Linping Cao; Hangbiao Jin; Yang Li

doi:10.1016/j.jhazmat.2025.139004

Transplacental transfer of p-phenylenediamine antioxidants: Insights from human gestational exposure and an optimized BeWo cell monolayer model

J Hazard Mater. 2025 Jun 24:495:139004. doi: 10.1016/j.jhazmat.2025.139004. Online ahead of print.

Authors

Junxu Li¹, Fangfang Ren², Linping Cao³, Hangbiao Jin⁴, Yang Li⁵

Affiliations

¹ Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China.
² Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
³ Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China.
⁴ Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China. Electronic address: hangbiao@zjut.edu.cn.
⁵ Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China. Electronic address: liyang2014@zju.edu.cn.

PMID: 40578198
DOI: 10.1016/j.jhazmat.2025.139004

Abstract

p-Phenylenediamine antioxidants (PPDs) have recently garnered significant attention due to their potential human toxicity. There is still a lack of research investigating their fetal exposure patterns and transplacental transfer behaviors during pregnancy. This study analyzed nine PPDs in 148 paired samples of maternal plasma, cord plasma, and placenta from China, and investigated the transcellular transfer dynamics of six PPDs using an optimized BeWo cell monolayer model. N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), N, N'-bis(1,4-dimethylpentyl)-p-phenylenediamine (77PD), and N-isopropyl-N'-phenyl-1,4-phenylenediamine (IPPD) were always the most abundant PPDs in maternal (detection frequencies 63-76 %, mean 0.055-0.26 ng/mL) and cord plasma (58-80 %, mean 0.029-0.15 ng/mL), as well as the placental tissue (66-81 %, mean 0.072-0.34 ng/g ww). Mean transplacental transfer efficiency (TTE) values of PPDs followed the decreasing order of N, N'-di-sec-butyl-1,4-phenylenediamine (44PD; 0.89 ± 0.21) > IPPD (0.79 ± 0.20) > N, N'-diphenyl-p-phenylenediamine (DPPD; 0.74 ± 0.17) > N-phenyl-N'-cyclohexyl-p-phenylenediamine (CPPD; 0.65 ± 0.16). The highest mean placental retention extent value was observed for CPPD (3.1 ± 0.44), followed by 44PD (2.3 ± 0.15) and 77PD (1.8 ± 0.40). Results from the TTE analysis and the optimized BeWo model suggest that passive diffusion and active transport mechanisms, influenced by physicochemical properties such as lipophilicity, govern the transplacental transfer of PPDs. These findings contribute to a deeper understanding of intrauterine exposure to PPDs and the mechanisms of maternal-fetal chemical exchange.

Keywords: 6PPD; 77PD; Optimized BeWo model; PPDs; Transplacental transfer.