Urinary metabolites of volatile organic compounds as biomarkers of indoor exposure: evidence of sex differences in a cross-sectional study using the Korea National Health and Nutrition Examination Survey

Objectives: This study examined associations between indoor total volatile organic compound (TVOC) concentrations and urinary volatile organic compound (VOC) metabolites in Korean adults, focusing on potential sex-specific differences. We hypothesized that higher indoor TVOC exposure would be associated with higher urinary VOC metabolite concentrations and that these associations would differ by sex. Methods: We conducted a cross-sectional analysis of the 2020-2021 Korea National Health and Nutrition Examination Survey, which included the Republic of Korea's first population-based indoor air quality survey. The analysis included 1,859 adults aged ≥19 years who participated in the indoor air quality survey from July 2020 to August 2021. Indoor TVOC concentrations (µg/m³) were measured using standardized protocols. Nine urinary VOC metabolites were quantified, creatinine-adjusted, and log-transformed. Multivariable linear regression, sex-stratified analyses, and subgroup analyses among unemployed adults were performed to reduce potential confounding from occupational exposure. Results: Indoor TVOC concentrations were positively associated with urinary 2-methylhippuric acid (2-MHA; β=0.041; 95% confidence interval [CI], 0.029-0.052) and 3,4-MHA (β=0.040; 95% CI, 0.027-0.052), with no evident sex difference in the overall sample. However, among unemployed adults, sex-by-TVOC interaction terms were statistically significant for both metabolites, and associations were stronger in males for both 2-MHA (β=0.110 vs. 0.024) and 3,4-MHA (β=0.130 vs. 0.031) than in females. Conclusion: Indoor TVOC concentrations were associated with urinary VOC metabolites, particularly 2-MHA and 3,4-MHA. These findings support considering sex-specific patterns in VOC-related risk assessment and indoor air quality surveillance, interventions, and management.