Associations of Serum Substituted p-Phenylenediamine-Derived Quinone Levels with Oxidative Stress and Immune Function Biomarkers in a General Adult Population

Substituted p-phenylenediamine-quinones (PPD-Qs) are commonly employed as antioxidants in varying rubbers with potential biotoxicological implications in humans. Associations between human PPD-Q exposure and oxidative stress and immune system modulation remain insufficiently characterized. This study investigated the human exposure profile of six PPD-Q homologues and their associations with malondialdehyde (MDA) and immune function biomarkers in a general adult population from Quzhou, China. The six target PPD-Qs were detected in most human serum samples (n = 205), with 2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione (6PPD-Q) emerging as the dominant compound (mean 1.67 ng/mL; range < LOD–5.46 ng/mL). Serum MDA levels showed significant positive correlations with several PPD-Qs, such as 6PPD-Q, 2,5-bis(o-tolylamino)cyclohexa-2,5-diene-1,4-dione (DTPD-Q), and 2,5-bis(phenylamino)cyclohexa-2,5-diene-1,4-dione (DPPD-Q), suggesting enhanced oxidative stress in humans. Moreover, the serum C-reactive protein level was positively associated with DTPD-Q, 77PD-Q (2,5-bis((5-methylhexan-2-yl)amino)cyclohexa-2,5-diene-1,4-dione), and DPPD-Q; IgA was negatively associated with CPPD-Q (2-(cyclohexylamino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione) and 6PPD-Q; IgM was negatively associated with DPPD-Q and 6PPD-Q. These findings provide the first human correlational evidence suggesting associations between PPD-Q exposure and oxidative stress- and immune-related biomarkers, highlighting the need for further research and regulatory attention regarding these tire-derived pollutants.