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J Expo Sci Environ Epidemiol. 2019 Mar;29(2):196-205. doi: 10.1038/s41370-018-0060-y. Epub 2018 Sep 5.

Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances.

Author information

1
Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden. samira.salihovic@medsci.uu.se.
2
MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden. samira.salihovic@medsci.uu.se.
3
Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
4
Massachusetts General Hospital, Harvard Medical School and Broad Institute, Boston, MA, USA.
5
Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
6
MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
7
Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
8
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
9
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.

Abstract

Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.

KEYWORDS:

Epidemiology; Metabolomics; PFOA; PFOS; Perfluoroalkyl substances; XCMS

PMID:
30185940
DOI:
10.1038/s41370-018-0060-y

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