Individual and mixture effects of BTEX occupational exposure with hematologic and hepatic profiles in petrochemical workers and the metabolic mechanism.

Evidence on the association of occupational exposure to benzene, toluene, ethylbenzene, and xylene (BTEX) with hematologic and hepatic profiles were equivocal, and few studies have investigated overall effect of BTEX mixtures. Herein, significant higher concentrations (p < 0.05) of hippuric acid, 1,2-dihydroxybenzene, mandelic acid, trans, trans-muconic acid and phenylglyoxylic acid were found in petrochemical workers than the controls, in accordance with higher levels of hematologic and hepatic profiles found in petrochemical workers (p < 0.05). Occupational exposure to individual BTEX was associated with elevated levels of white blood cell (WBC), lymphocyte (LYMPH), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Further, the Weighted Quantile Sum Regression model and Bayesian Kernel Machine Regression model consistently identified a positive association between BTEX mixture exposure and WBC, LYMPH, and GGT. Xylene was the primary contributor to increased WBC, LYMPH, and GGT levels. Furthermore, BTEX exposure resulting in the increased inflammation indices were mainly related to perturbations of sphingolipid metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis. Whereas metabolites mediated the correlation between BTEX exposure and liver function indices were related to the perturbations of biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, sphingolipid metabolism, primary bile acid biosynthesis, etc. Our findings revealed potential health risk of occupational exposure to BTEX and might help one to understand the link between BTEX exposure and hematologic and hepatic profiles.