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

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; Karin Broberg; SafeChrom project team and SAM-Krom project team

doi:10.1016/j.envpol.2025.127255

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

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, Karin Broberg^*, SafeChrom project team and SAM-Krom project team

^*Corresponding author for this work

Department of Occupational and Environmental Medicine

Abstract

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.

Original language	English
Article number	127255
Journal	Environmental Pollution
Volume	387
ISSN	0269-7491
DOIs	https://doi.org/10.1016/j.envpol.2025.127255
Publication status	Published - 15 Dec 2025

Keywords

Effect biomarkers
Hexavalent chromium
Multiple exposure
Occupational exposure
PFAS

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Jiang, Z., Liu, Y., Lindh, C., Pineda, D., Carøe, T. K., Catalán, J., Ebbehøj, N. E., Givelet, L., Huusom, A. J., Kines, P., Krais, A. M., Aimonen, K., Lundh, T., Loeschner, K., Rastkhani, H., Tondel, M., Saber, A. T., Vogel, U., Broberg, K., & SafeChrom project team and SAM-Krom project team (2025). Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability. Environmental Pollution, 387, Article 127255. https://doi.org/10.1016/j.envpol.2025.127255

Jiang, Z, Liu, Y, Lindh, C, Pineda, D, Carøe, TK, Catalán, J, Ebbehøj, NE, Givelet, L, Huusom, AJ, Kines, P, Krais, AM, Aimonen, K, Lundh, T, Loeschner, K, Rastkhani, H, Tondel, M, Saber, AT, Vogel, U, Broberg, K & SafeChrom project team and SAM-Krom project team 2025, 'Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability', Environmental Pollution, vol. 387, 127255. https://doi.org/10.1016/j.envpol.2025.127255

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

abstract = "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.",

keywords = "Effect biomarkers, Hexavalent chromium, Multiple exposure, Occupational exposure, PFAS",

author = "Zheshun Jiang and Yishan Liu and Christian Lindh and Daniela Pineda and Car{\o}e, \{Tanja K.\} and Julia Catal{\'a}n and Ebbeh{\o}j, \{Niels E.\} and Lucas Givelet and Huusom, \{Anja J.\} and Pete Kines and Krais, \{Annette M.\} and Kukka Aimonen and Thomas Lundh and Katrin Loeschner and Hamideh Rastkhani and Martin Tondel and Saber, \{Anne T.\} and Ulla Vogel and Karin Broberg and \{SafeChrom project team and SAM-Krom project team\}",

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year = "2025",

month = dec,

day = "15",

doi = "10.1016/j.envpol.2025.127255",

language = "English",

volume = "387",

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T1 - Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability

AU - Jiang, Zheshun

AU - Liu, Yishan

AU - Lindh, Christian

AU - Pineda, Daniela

AU - Carøe, Tanja K.

AU - Catalán, Julia

AU - Ebbehøj, Niels E.

AU - Givelet, Lucas

AU - Huusom, Anja J.

AU - Kines, Pete

AU - Krais, Annette M.

AU - Aimonen, Kukka

AU - Lundh, Thomas

AU - Loeschner, Katrin

AU - Rastkhani, Hamideh

AU - Tondel, Martin

AU - Saber, Anne T.

AU - Vogel, Ulla

AU - Broberg, Karin

AU - SafeChrom project team and SAM-Krom project team

PY - 2025/12/15

Y1 - 2025/12/15

N2 - 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.

AB - 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.

KW - Effect biomarkers

KW - Hexavalent chromium

KW - Multiple exposure

KW - Occupational exposure

KW - PFAS

UR - https://www.scopus.com/pages/publications/105020834820

U2 - 10.1016/j.envpol.2025.127255

DO - 10.1016/j.envpol.2025.127255

M3 - Journal article

C2 - 41086906

AN - SCOPUS:105020834820

SN - 0269-7491

VL - 387

JO - Environmental Pollution

JF - Environmental Pollution

M1 - 127255

ER -

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

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Keywords

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