Plasma DR-CALUX Bioactivity and Concurrent Clinical Biochemistry: A Secondary Cross-Sectional Analysis of SPES

Plasma bioassays provide functional measures of environmental mixtures whose relationship with clinical biochemistry warrants investigation. We examined dioxin-responsive chemically activated luciferase gene expression (DR-CALUX) bioactivity in the 600-participant intensive-biomonitoring subgroup of SPES in Campania, Italy. Quantifiable bioactivity was available for 594 participants, of whom 592 entered the principal analyses. Mixed models assessed the lipid-standardised DR-CALUX index in relation to two primary thyroid outcomes, nine secondary outcomes, and an exploratory panel of 54 clinical markers. Per index doubling, thyroid-stimulating hormone differed by −7.23% (95% CI −14.96 to 1.21; Holm-adjusted p = 0.182), and free thyroxine differed by −0.0047 ng/dL (−0.0233 to 0.0139; adjusted p = 0.621). Alanine and aspartate aminotransferase activities were lower by 9.33% (−14.22 to −4.17) and 8.01% (−12.31 to −3.50), respectively; both met the hepatic-family Benjamini–Hochberg criterion. Inverse estimates persisted with separate lipid adjustment and attenuated but remained inverse after restriction using common laboratory-report upper thresholds for both aminotransferases. All 54 global Benjamini–Yekutieli-adjusted p values exceeded 0.05; only the aminotransferases met the Benjamini–Hochberg comparison. These secondary aminotransferase associations merit further investigation of their biological basis and clinical significance. The primary thyroid findings remain inconclusive.