Exposure to a mixture of four metals and associations with urinary oxidative stress biomarkers in Uruguayan adolescents

The effects of low-level exposure to metal mixtures on oxidative stress (OS) in adolescents are poorly understood. We examined the associations of blood concentrations of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) with urinary levels of F2-isoprostane (F2-IsoP) and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Data for this cross-sectional study were drawn from the Salud Ambiental Montevideo cohort, which originally enrolled children at ages 6-8 years. In 2021-2023, participants - now aged 12.1 2.1 years - provided venous blood and spot urine samples. Metals were quantified in blood via Inductively Coupled Plasma-Tandem Mass Spectrometry (ICP-MS/MS), while urinary OS markers were measured using competitive enzyme immunoassay (F2-IsoP) and LC-MS (8-OHdG). Associations between metals, considered individually and as a mixture, and each OS marker were evaluated using multivariable linear regression and Bayesian Kernel Machine Regression, respectively. Of the 430 adolescents (49.3% male) who attended a study visit, 361 were included in the complete-case sample. Median blood concentrations were As 0.30 µg/L, Cd 0.06 µg/L, Hg 0.22 µg/L, and Pb 1.17 µg/dL. Correlations among metals were generally low. We observed no associations between individual metals and OS biomarkers, and no evidence of interactions among metals when modeled as a mixture. F2-IsoP concentrations decreased slightly with increasing quantiles of the metal mixture, but the effect size was minimal. The metal mixture was unrelated to 8-OHdG concentrations. In this cross-sectional study, we found little evidence that blood metals, either individually or as a mixture, were associated with OS in adolescents.