Combined effects of benzene, toluene, xylene, ethylbenzene, and styrene exposure on hearing loss mediated by oxidative stress at realistic low levels.

The link between benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) exposure and hearing loss (HL) is not well-established. This study investigated 1694 petrochemical workers in southern China to examine the effects of BTEXS urinary metabolites on auditory function, considering oxidative stress (OS) as a potential cause. Using generalized linear models, elastic net regression, and quantile g-computation, we evaluated the single and combined effects of BTEXS, OS indicators, and HL. Subgroup analysis explored interactions between BTEXS and cumulative noise exposure (CNE), while mediation analysis assessed OS's role in BTEXS-related HL. Positive associations were found between hippuric acid (HA) and HL (OR = 1.20, P < 0.05) and high-frequency hearing loss (HFHL) (OR = 1.22, P < 0.05). The ENET model linked 3&4-methylhippuric acid (3&4-MHA) with increased HFHL risk. The qgcomp model showed a 23% increased HL risk and a 20% increased HFHL risk per quartile increase in BTEXS exposure. Toluene metabolites (SBMA and HA) were significant contributors to HL, HFHL, and speech-frequency hearing loss (SFHL). Higher BTEXS SBMA, MA and HA levels exacerbated HL risk in workers exposed to CNE. Interaction analysis revealed synergistic effects between tt-MA and other metabolites on HFHL risk. Total SOD (TSOD) significantly mediated the BTEXS-HL relationship. These findings highlight a dose-effect association between BTEXS exposure and HL due to oxidative damage, with toluene metabolites being critical pollutants. BTEXS exposure also synergistically increased HL risk with noise.