ORIGINAL ABSTRACT

Glyphosate is one of the most widely used herbicide with high efficiency, low toxicity and broad-spectrum. In recent decades, increasing evidence suggests that glyphosate may cause adverse health effects on human beings. However, until now, there is little data on the human metabolic changes. Since occupational workers are under greater health risks than ordinary people, the understanding regarding the health effects of glyphosate on occupational workers is very important for the early warning of potential damage. In this study, serum metabolic alterations in workers from three chemical factories were analyzed by gas chromatography-mass spectrometry (GC-MS) to assess the potential health risks caused by glyphosate at the molecular level. It was found that the levels of 27 metabolites changed significantly in the exposed group compared to the controls. The altered metabolic pathways, including amino acid metabolism, energy metabolism (glycolysis and TCA cycle) and glutathione metabolism (oxidative stress), etc., indicated a series of changes occur in health profile of the human body after glyphosate exposure, and the suboptimal health status of human may further evolve into various diseases, such as Parkinson's disease, renal and liver dysfunction, hepatocellular carcinoma, and colorectal cancer. Subsequently, 4 biomarkers (i.e., benzoic acid, 2-ketoisocaproic acid, alpha-ketoglutarate, and monoolein) were identified as potential biomarkers related to glyphosate exposure based on the partial correlation analyses, linear regression analyses, and FDR correction. Receiver-operating curve (ROC) analyses manifested that these potential biomarkers and their combinational pattern had good performance and potential clinical value to assess the potential health risk associated with glyphosate exposure while retaining high accuracy. Our findings provided new insights on mechanisms of health effects probably induced by glyphosate, and may be valuable for the health risk assessment of glyphosate exposure.