Association between exposure to a mixture of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) and small airways function: A cross-sectional study.

BACKGROUND: Lung is one of the primary target organs of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). Small airways dysfunction (SAD) might be a sensitive indicator of early chronic respiratory disease. Here, we explored the relationships between exposure to BTEXS and small airways function, and identified the priority control pollutants in BTEXS mixtures. METHODS: 635 petrochemical workers were recruited. Standard spirometry testing was conducted by physicians. The cumulative exposure dose (CED) of BTEXS for each worker was estimated. The peak expiratory flow (PEF), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25∼75%), and the expiratory flow rate found at 25%, 50%, and 75% of the remaining exhaled vital capacity (MEF25%, MEF50%, and MEF75%) were measured. SAD was also evaluated based on measured parameters. The associations between exposure to BTEXS individuals or mixtures and small airways function were evaluated using generalized linear regression models (GLMs) and quantile g-computation models (qgcomp). Meanwhile, the weights of each homolog in the association were estimated. RESULTS: The median CED of BTEXS are 9.624, 19.306, 24.479, 28.210, and 46.781 mg/m3·years, respectively. A unit increase in ln-transformed styrene CED was associated with a decrease in FEF25∼75% and MEF50% based on GLMs. One quartile increased in BTEXS mixtures (ln-transformed) was significantly associated with a 0.325-standard deviation (SD) [95% confidence interval (CI): -0.464, -0.185] decline in FEF25∼75%, a 0.529-SD (95%CI: -0.691, -0.366) decline in MEF25%, a 0.176-SD (95%CI: -0.335, -0.017) decline in MEF75%, and increase in the risk of abnormal of SAD [risk ratios (95%CI): 1.520 (95%CI: 1.143, 2.020)]. Benzene and styrene were the major chemicals in BTEXS for predicting the overall risk of SAD. CONCLUSION: Our novel findings demonstrate the significant association between exposure to BTEXS mixture and small airways function decline and the potential roles of key homologs (benzene and styrene) in SAD.

Influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters in petrochemical workers: a cross-sectional study.

BACKGROUND: Ubiquitously distributed benzene is a known hematotoxin. Increasing evidence has suggested that erythroid-related hematologic parameters may be sensitive to benzene exposure. Fat content, which is also closely associated with erythroid-related hematologic parameters, may affect the distribution and/or metabolism of benzene, and eventually benzene-induced toxicity. METHODS: To explore the influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters, we recruited 1669 petrochemical workers and measured their urinary S-phenylmercapturic acid (SPMA) concentration and erythroid-related hematological parameters. Indices for fat content included body fat percentage (BF%), plasma total cholesterol (TC) and triglycerides (TG), and occurrence of fatty liver. RESULTS: The dose-response curve revealed U-shaped nonlinear relationships of SPMA with hematocrit (HCT) and mean corpuscular hemoglobin concentration (MCHC) (P-overall < 0.001, and P-nonlinear < 0.015), as well as positive linear associations and r-shaped nonlinear relationships of continuous fat content indices with erythroid-related hematological parameters (P-overall ≤0.005). We also observed modification effects of fat content on the associations between benzene exposure and erythroid-related hematological parameters, with workers of lower or higher BF% and TG more sensitive to benzene-induced elevation of MCHC (Pinteraction = 0.021) and benzene-induced decrease of HCT (Pinteraction = 0.050), respectively. We also found that some erythroid-related hematologic parameters differed between subgroups of workers with different SPMA levels and fat content combination. CONCLUSIONS: Our study suggested that benzene exposure, fat content, and their interactions may affect erythroid-related hematological parameters in petrochemical workers in a complex manner that are worthy of further investigation.

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.

Risk assessment and dose-effect of co-exposure to benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) on pulmonary function: A cross-sectional study.

Inhalation is the most frequent route and the lung is the primary damaged organ for human exposure to benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). However, there is limited information on the risk and dose-effect of the BTEXS mixture on pulmonary function, particularly the overall effect. We conducted a cross-sectional study in a petrochemical plant in southern China. Spirometry and cumulative exposure dose (CED) of BTEXS were used to measure lung function and exposure levels for 635 workers in 2020, respectively. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were tested and interpreted as percentages to predicted values [FVC or FEV1% predicted], and FEV1 to FVC ratio [FEV1/FVC (%)]. We found the reduction in FVC% predicted and the risk of lung ventilation dysfunction (LVD) and its two subtypes (mixed and restrictive ventilation dysfunction, MVD, and MVD) were significantly associated with BTEXS individuals. In addition, pulmonary function damage associated with BTEXS was modified by the smoking status and age. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-effect on lung function damage induced by the BTEXS mixture. Our results show wqs, an index of weighted quartiles for BTEXS, was potentially associated with the reduction in FVC and FEV1% predicted with the coefficients [95% confidence intervals (CI)] between -1.136 (-2.202, -0.070) and -1.230 (-2.265, -0.195). Odds ratios (ORs) and 95% CIs for the wqs index of LVD, MVD, and RVD were 1.362 (1.129, 1.594), 1.323 (1.084, 1.562), and 1.394 (1.096, 1.692), respectively. Furthermore, xylene, benzene, and toluene in the BTEXS mixture potentially contribute to the development of lung function impairment. Our novel findings demonstrated the dose-response relationships between pulmonary function impairment and the BTEXS mixture and disclosed the potential key pollutants in the BTEXS mixture.

Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes in a Follow-Up Study on Petrochemical Workers.

Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted a follow-up study in BTX-exposed petrochemical workers. Long-term exposure levels were quantified by measuring cumulative exposure (CE). Generalized weighted quantile sum (WQS) regression models and Benchmark Dose (BMD) Software were used to evaluate their combined effects and calculate their BMDs, respectively. Many hematologic parameters were significantly decreased at the four-year follow-up (p < 0.05). We found positive associations of CE levels of benzene, toluene, and xylene with the decline in monocyte counts, lymphocyte counts, and hematocrit, respectively (ß > 0.010, Ptrend < 0.05). These associations were stronger in subjects with higher baseline parameters, males, drinkers, or overweight subjects (Pinteraction < 0.05). BTX had positive combined effects on the decline in monocyte counts, red-blood-cell counts, and hemoglobin concentrations (Ptrend for WQS indices < 0.05). The estimated BMDs for CE levels of benzene, toluene, and xylene were 2.138, 1.449, and 2.937 mg/m3 × year, respectively. Our study demonstrated the hematological effects of long-term BTX co-exposure and developed 8h-RELs of about 0.01 ppm based on their hematological effects.