Urinary PAH carboxylic acids as exposure biomarkers for methylated PAHs linked to urinary mutagenicity

Emerging evidence suggests that methylated polycyclic aromatic hydrocarbons (methyl-PAHs) exhibit greater carcinogenic potential than their unsubstituted parent PAHs. Previous studies in Xuanwei, China, reported elevated lung cancer risk among non-smoking women exposed to smoky coal and high ambient levels of methyl-PAHs, including 5-methylchrysene (5-MC). We conducted biomonitoring to evaluate internal dose markers of methylated PAHs including five PAH carboxylic acids (PAH-CAs) and dose markers of unsubstituted PAHs including five hydroxylated PAHs (OH-PAHs) in 48 women using four household fuel types (smoky coal without chimney, smoky coal with chimney, smokeless coal, and electricity). Urinary OH-PAHs and PAH-CAs showed a decreasing gradient from smoky coal without chimney to electric cooking. When contrasting smoky coal with chimney and smokeless coal, only PAH-CAs, particularly phenanthrene-2-carboxylic acid (2-PHECA) and dibenzofuran-4-carboxylic acid (4-DFCA), mirrored differences in airborne 5-MC and benzo[a]pyrene (BaP). Airborne 5-MC explained 50% of the variance in urinary 2-PHECA (R² = 0.50), compared with 30% explained by BaP (R² = 0.30). In 18 samples analyzed for mutagenicity, urinary 2-PHECA was strongly correlated with mutagenic potency (Spearman ρ = 0.74, p < 0.001), whereas 1-hydroxypyrene showed a weaker association (ρ = 0.49, p = 0.04). These findings suggest that PAH-CAs, particularly 2-PHECA, may serve as internal dose markers reflecting biologically relevant exposure to methylated PAHs associated with mutagenic potency.