Oxidative stress mechanisms and potential biomarkers of methyl acetate poisoning: a urinary metabolomics study in rat model and human occupational cohort

Background: Methyl acetate (MA) is a common industrial solvent that causes rapid blindness in large exposures. Its toxicologic mechanism is not fully elucidated currently. The currently used clinical marker for MA poisoning, formic acid, is unable to differentiate between MA exposure and methanol exposure, which hinders accurate diagnosis and exposure source tracing, and impairs the development and implementation of front-end preventive and control measures. Objective: This study utilized a cross-species, untargeted metabolomics approach, combining data from animal models and human cohorts, aiming to identify potential biomarkers for MA poisoning and provide new insights into its toxicological mechanisms. Methods: Subacute poisoning rat models of MA and methanol were established via gavage administration (n = 6 per group) and urine samples were collected. Meanwhile, 8 occupationally exposed MA-intoxicated patients and 10 healthy controls were enrolled, with their urine samples also being collected. All samples underwent untargeted metabolomic analysis using UPLC-QTOF/MS for comparative profiling among MA-exposed rats versus control rats, MA-exposed rats versus methanol-exposed rats, and MA-exposed patients versus healthy controls. Results: ) and S-adenosylhomocysteine (SAH) were significantly elevated in the MA exposure group in both rat and human samples, but were not detected in the methanol exposure group, showing high specificity and cross-species conservation. Conclusion: and SAH as potential and sensitive biomarkers for MA intoxication, offering a tool for differentiating MA from methanol exposure clinically.