| Sumario: | Hexavalent chromium (Cr(VI)) can induce oxidative stress, genomic instability, and epigenetic modifications. In occupational settings, Cr(VI)-exposed workers may also be exposed to other toxicants, such as elements besides Cr, and per- and polyfluoroalkyl substances (PFAS). However, research on the extent of these co-exposures and their combined effects remains limited. The objective of this study was to characterize the exposure levels of ten elements and eight PFAS in Cr(VI)-exposed workers and to assess the combined effects of these exposure mixtures on biomarkers of oxidative stress and genomic instability. This study included 138 Cr(VI)-exposed workers and 96 controls from Swedish SafeChrom and Danish SAM-Krom studies. Concentrations of elements were measured by inductively coupled plasma mass spectrometry (ICP-MS), and PFAS were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Effect biomarkers, including 8-hydroxy-2′-deoxyguanosine (8-OHdG), mitochondrial DNA copy number (mtDNA-cn), telomere length (TL) and O6-methylguanine-DNA methyltransferase promoter (MGMT) methylation, were analyzed in blood. Bayesian Kernel Machine Regression and quantile-based g-computation models were used to evaluate the mixture effects. Exposed workers had higher concentrations of Cr, manganese, copper, zinc, lead, and perfluoroheptanoic acid (PFHpA), lower mtDNA-cn and longer TL compared to controls. In the SAM-Krom study, perfluorooctane sulfonic acid (PFOS) levels were significantly elevated among exposed workers, with the P95 reaching 2044 ng/mL. The exposure mixtures were associated with increased 8-OHdG and MGMT hypermethylation. Together, these findings highlight the complexity of multiple occupational exposures in Cr(VI)-related work environments and suggest that combined exposure may contribute to early biological alterations related to oxidative stress and DNA methylation.
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