Effects of DCBA exposure on liver fibrosis and NAFLD: a comprehensive investigation integrating NHANES data analysis, network toxicology, and molecular docking.

PURPOSE: This study examined associations between urinary 3-diethyl-carbamoyl benzoic acid (DCBA), the principal metabolite of the insect repellent DEET, and liver fibrosis (LF) as well as non-alcoholic fatty liver disease (NAFLD) using a nationally representative sample. Network toxicology approaches were employed to explore underlying molecular mechanisms.

METHODS

We analyzed 5,960 adults from NHANES with DCBA measurements obtained through liquid chromatography-tandem mass spectrometry. LF severity was determined using NAFLD Fibrosis Score (NFS ≥ 0.676), whereas NAFLD was identified via sex-specific alanine aminotransferase criteria. Weighted logistic regression models incorporated progressive adjustment for demographic, anthropometric, and clinical factors. Network toxicology identified molecular targets, with molecular docking and dynamics simulations validating mechanistic pathways.

RESULTS

DCBA exposure showed significant positive correlations with LF risk after full adjustment (OR = 1.254, 95% CI: 1.097-1.432, P < 0.001), demonstrating clear dose-response patterns (P-trend = 0.019). However, DCBA exhibited no meaningful relationship with NAFLD prevalence (OR = 1.002, 95% CI: 0.935-1.074, P = 0.954). Alcohol intake substantially modified the DCBA-LF relationship (interaction P = 0.002), showing stronger effects in drinkers (OR = 1.45, 95% CI: 1.23-1.69). Epidermal growth factor receptor emerged as the key molecular target with strongest binding capacity ( -6.9 kcal/mol).

CONCLUSION

DCBA displays selective correlations with hepatic fibrosis independent of steatotic processes, with alcohol potentiating fibrogenic effects. These results establish new exposure-response relationships for common environmental chemicals and advance mechanistic understanding for risk assessment applications.