Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999-2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (b_interaction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.