Metabolomics of Benzene Exposure and Development of Biomarkers for Exposure Hazard Assessment

Benzene, a common industrial solvent, poses significant health risks including poisoning and hematopoietic diseases. However, its precise toxicity mechanisms remain unclear. To assess the health impact of prolonged benzene exposure through metabolomic analyses of exposed workers and benzene-poisoned mice, aiming to identify biomarkers and minimize occupational hazards. This study compared 18 benzene-exposed workers with 18 non-exposed workers, matching for age, lifestyle, and BMI. The metabolites in the workers' samples were analyzed using ultra-high-performance liquid chromatography and mass spectrometry. A larger study included 118 exposed and 158 non-exposed workers, incorporating surveys and routine blood and urine tests with differential metabolites targeted via an enzyme-linked immunosorbent assay. The animal studies consisted of two 15- and 60-day benzene staining and control experiments on 28 C57BL/6J mice, followed by sample collection and organ analysis. The data analysis employed eXtensible Computational Mass Spectrometry (XCMS), Python, MetaboAnalyst 6.0, and SPSS24.0. The exposed workers exhibited altered metabolites indicating external benzene exposure, lower glucose levels, and changes in white blood cell counts and urinary ketone bodies. The plasma metabolomics revealed disturbances in energy and lipid metabolism. The benzene-exposed mice displayed reduced weight gain, behavioral changes, and organ damage. Oxidative stress and abnormal purine and lipid metabolism were observed in both the long-term benzene-exposed workers and benzene-exposed mice. Metabolic markers for the early detection of benzene exposure hazards were identified, underscoring the need to mitigate occupational risks.