Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability

By Zheshun Jiang, Yishan Liu, Christian Lindh, Daniela Pineda, Tanja K Carøe, Julia Catalán, Niels E Ebbehøj, Lucas Givelet, Anja J Huusom, Pete Kines, Annette M Krais, Kukka Aimonen, Thomas Lundh, Katrin Loeschner, Hamideh Rastkhani, Martin Tondel, Anne T Saber, Ulla Vogel, and Karin Broberg
Environ Pollut
October 12, 2025
DOI: 10.1016/j.envpol.2025.127255

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.

View on PubMed

Topics: