Dermal absorption and percutaneous penetration of p-phenylenediamines (PPDs) and p-phenylenediamine quinones (PPD-Qs): Mechanisms and implications for human dermal exposure risks.

Dermal absorption constitutes a major exposure route for p-phenylenediamine antioxidants (PPDs) and their quinone derivatives (PPD-Qs), however, limited understanding of their penetration patterns and mechanisms constrains accurate risk assessment. This study employs human biomonitoring, an in vivo rat skin exposure model, and molecular docking simulations to investigate the dermal exposure risks and percutaneous penetration mechanisms of five PPDs and their corresponding PPD-Qs. These compounds were frequently detected in hand (n = 80) and forehead wipe samples (n = 74) from automobile dismantling workers, with median total concentration of 948 and 85.9 ng/m2, respectively. PPD-Qs exhibited substantially higher contamination levels than PPDs, suggesting a greater potential exposure risk for PPD-Qs. In vivo experiments confirmed dermal absorption of PPDs and PPD-Qs, followed by percutaneous penetration and tissue distribution, with distinct compound-specific patterns. 4-Phenylaminodiphenylamine quinone (DPPD-Q) displayed the largest permeable potential (17.3% and 23.0% in low- and high-dose group, respectively), warranting particular concern. Fecal excretion was identified as primary elimination pathway for dermally absorbed PPDs and PPD-Qs. Molecular docking further suggested protein-mediated active transport indicates a potential for interaction. Overall, these findings underscore the importance of accounting for bioavailability in dermal exposure assessment of organic contaminants.