2. Academic Validation
  3. Prenatal Exposure to Primary Aromatic Amines: Structure-Dependent Transplacental Transfer Mechanism and Toxicity

Prenatal Exposure to Primary Aromatic Amines: Structure-Dependent Transplacental Transfer Mechanism and Toxicity

  • Environ Sci Technol. 2026 Mar 3;60(8):6057-6069. doi: 10.1021/acs.est.5c15645.
Tao Zhang 1,  Jiye Zhang 2,  Kurunthachalam Kannan 3,  Ya-Nan Yao 4,  Zhipeng Cheng 5,  Hongwen Sun 5
Affiliations

Affiliations

  • 1 School of Agriculture and Biotechnology, Sun Yat-sen University, Shenzhen 518107, China.
  • 2 School of Environmental Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China.
  • 3 Wadsworth Center, New York State Department of Health, Albany, New York 12237, United States.
  • 4 Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen 518106, China.
  • 5 MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.
PMID: 41706595 DOI: 10.1021/acs.est.5c15645
Abstract

Primary aromatic amines (PAAs) are carcinogenic chemicals that are ubiquitous in indoor environments. However, little is known about their placental transfer and associated toxicity. Herein, we developed an approach integrating human biomonitoring, uterine perfusion experiments in pregnant rats, computational modeling, and in vitro placental cell bioassays. Nine of 30 PAAs including 8 PAAs with a monobenzene ring (e.g., aniline, ANI; ortho-toluidine, o-TD; para-toluidine, p-TD; ortho-anisidine, o-ANSD; 4-ethylaniline, 4-EA; 4-chloroaniline, 4-CA; and 3-chloroaniline, 3-CA) and 1 PAA with bis-benzene ring (2-naphthylamine, 2-NA), were widely detected (detection rate >50%) in 47 paired maternal and cord serum samples with median Σ9PAAs concentrations of 11.2 and 11.7 ng/mL, respectively. Transplacental transfer efficiencies (TTEs) of PAAs were notably high, with median values ranging from 0.91 (p-CD) to 1.60 (2-NA), indicating efficient placental transfer. Excluding 2-NA, both biomonitoring data and rat uterine perfusion experiments revealed a significant negative correlation between log Kow and TTEs (or PAA concentrations in fetal rat), supporting passive diffusion as a mechanism involved in placental transfer of monoaromatic PAAs. Crucially, molecular docking and molecular dynamics simulations indicated that 2-NA forms dynamically stable complexes with specific solute carrier (SLC) and ATP-binding cassette (ABC) transporters, suggesting a transporter-mediated active transport process. Cytotoxicity assays further indicated that 2-NA exhibited the highest toxicity among all PAAs. Moreover, in syncytialized BeWo cells, 2-NA exposure significantly compromised placental barrier integrity and function. The widespread presence of PAAs in maternal and fetal serum underscores the need for regulatory measures to reduce exposure, particularly among pregnant women and fetuses.

Keywords

human biomonitoring; placental barrier; primary aromatic amines; transplacental transfer; uterine perfusion.

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