First Human Biomonitoring Evidence of Strobilurin Fungicide Exposure in South China: Impact on Oxidative Stress and Liver Damage

<b>Background:</b> Strobilurin fungicides (SFs) are widely detected in the environment, but data on their occurrence in humans and potential health effects are scarce. <b>Objective:</b> This study aimed to characterize the exposure to SFs in a human population from South China and to investigate their potential association with biomarkers of oxidative stress and liver damage. <b>Methods:</b> In a cross-sectional study, we analyzed serum samples from healthy participants and secondary nonalcoholic fatty liver disease (S-NAFLD) patients. Concentrations of SFs and oxidative stress biomarkers including 8-iso-prostaglandin-F2α (8-PGF_2α), 11β-prostaglandin F2α (11-PGF_2α), 15(R)-prostaglandin F2α (15-PGF_2α), and 8-oxo-7,8-dihydro-20-deoxyguanosine (8-OHdG) were measured. Associations between SF exposure, liver function biomarkers, and S-NAFLD prevalence were assessed using multivariate regression models. A mediation analysis was conducted to explore the role of oxidative stress. <b>Results:</b> Azoxystrobin (AZ), fluoxastrobin (FLUO), and fenamidone (FE) were the predominant compounds, with median concentrations ranging from 0.016 to 0.042 ng/mL. Significant positive correlations were observed between all frequently detected SFs and oxidative stress biomarkers (<i>p</i> < 0.05). FE was associated with a modest, albeit statistically significant, prevalence of S-NAFLD. AZ and FE were also found to be statistically significantly associated with altered levels of direct bilirubin (DBIL, FDR-q < 0.05). The exploratory mediation analysis indicated a statistically significant indirect effect (17.1% to 31.2%), suggesting that lipid peroxidation biomarkers could serve as potential mediators between AZ exposure and DBIL levels. <b>Conclusions:</b> This study provides the first evidence of widespread SF exposure in a South Chinese population and reveals significant associations with oxidative stress and AZ exposure with liver function biomarkers (i.e., DBIL), with exploratory analyses suggesting a potential mediating role of oxidative stress in this relationship. However, the cross-sectional design precludes causal inference, and the modest effect sizes warrant cautious interpretation. These findings highlight the need for further longitudinal research to confirm the hepatotoxicity of SFs in humans.