Insights from Epidemiology and Network Toxicology into the Effect of Volatile Organic Compounds Exposure on Thyroid Function and the Underlying Mechanism.
Abstract
Volatile organic compounds (VOCs) are prevalent environmental pollutants posing significant risks to human health. However, their impact on thyroid function and the latent mechanism remain largely uncharted. This study utilized data of 1201 participants aged ≥20 years from National Health and Nutrition Examination Survey 2011-2012. Weighted generalized linear model (for single-analyte analysis) and quantile g-computation (QgComp) and Bayesian kernel machine regression (BKMR) (for mixture analysis) were employed to capture the individual and mixed effects of 16 VOCs metabolites (derived from 13 VOCs) on 10 thyroid function indicators. Network toxicology was employed to probe the underlying mechanism. In single-analyte effect analysis, we found several VOCs metabolites (e.g., N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine [AMCC] and N-Acetyl-S-(2-cyanoethyl)-L-cysteine [CYMA]) were positively associated with thyroglobulin (hTg), negatively associated with free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyrotrophic thyroxine resistance index (TT4RI), TSH index, and thyroid peroxidase antibodies (TPO-Ab), while nae associated with total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), or thyroglobulin antibodies (anti-hTg). Both mixture models (BKMR and QgComp) discovered that the mixture of 16 VOCs metabolites was positively related to TT3 (β=0.0161; 95% CI: 0.0056∼0.0265) and FT3 (0.0077; 0.0020∼0.0134) while negatively related to FT4 (-0.0158; -0.0248∼-0.0067), TSH (-0.0395; -0.0726∼-0.0065), TT4RI (-0.0552; -0.0883∼-0.0221), TSH index (-0.0336; -0.0556∼-0.0117), and TPO-Ab (-0.1001; -0.2066∼-0.0056). Hypothesis-generating network toxicology showed a significant enrichment in interleukin-17 (IL-17) signaling pathway linking VOCs exposure and thyroid dysfunction. Conclusively, exposure of general adults to single VOC and particularly multiple VOCs mixture was associated with thyroid function alteration, and the possible (hypothesis-generating) mechanism may involve IL-17 signaling pathway.