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Environ Res. 2019 Feb 13;172:182-193. doi: 10.1016/j.envres.2019.02.018. [Epub ahead of print]

Multigenerational metabolic profiling in the Michigan PBB registry.

Author information

1
Department of Civil and Environmental Engineering, Tufts University, 200 College Ave, Medford MA 02155, United States; Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, 615 Michael St, Atlanta GA 30322, United States. Electronic address: douglas.walker@mssm.edu.
2
Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta GA 30322, United States. Electronic address: elizabeth.marder@oehha.ca.gov.
3
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, 50 University Ave Hall #7360, Berkeley CA 94720, United States. Electronic address: yyano@berkeley.edu.
4
Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta GA 30322, United States. Electronic address: mterrel@emory.edu.
5
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, 615 Michael St, Atlanta GA 30322, United States. Electronic address: yliang3@emory.edu.
6
Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta GA 30322, United States. Electronic address: dbbarr@emory.edu.
7
Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta GA 30322, United States. Electronic address: gm2815@cumc.columbia.edu.
8
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, 615 Michael St, Atlanta GA 30322, United States. Electronic address: dpjones@emory.edu.
9
Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta GA 30322, United States. Electronic address: mmarcus@emory.edu.
10
Department of Civil and Environmental Engineering, Tufts University, 200 College Ave, Medford MA 02155, United States. Electronic address: kurt_pennell@brown.edu.

Abstract

Although polychlorinated biphenyls and polybrominated biphenyls are no longer manufactured the United States, biomonitoring in human populations show that exposure to these pollutants persist in human tissues. The objective of this study was to identify metabolic variations associated with exposure to 2,2'4,4',5,5'-hexabromobiphenyl (PBB-153) and 2,2'4,4',5,5'-hexachlorobiphenyl (PCB-153) in two generations of participants enrolled in the Michigan PBB Registry (http://pbbregistry.emory.edu/). Untargeted, high-resolution metabolomic profiling of plasma collected from 156 individuals was completed using liquid chromatography with high-resolution mass spectrometry. PBB-153 and PCB-153 levels were measured in the same individuals using targeted gas chromatography-tandem mass spectrometry and tested for dose-dependent correlation with the metabolome. Biological response to these exposures were evaluated using identified endogenous metabolites and pathway enrichment. When compared to lipid-adjusted concentrations for adults in the National Health and Nutrition Examination Survey (NHANES) for years 2003-2004, PCB-153 levels were consistent with similarly aged individuals, whereas PBB-153 concentrations were elevated (p<0.0001) in participants enrolled in the Michigan PBB Registry. Metabolic alterations were correlated with PBB-153 and PCB-153 in both generations of participants, and included changes in pathways related to catecholamine metabolism, cellular respiration, essential fatty acids, lipids and polyamine metabolism. These pathways were consistent with pathophysiological changes observed in neurodegenerative disease and included previously identified metabolomic markers of Parkinson's disease. To determine if the metabolic alterations detected in this study are replicated other cohorts, we evaluated correlation of PBB-153 and PCB-153 with plasma fatty acids measured in NHANES. Both pollutants showed similar associations with fatty acids previously linked to PCB exposure. Thus, the results from this study show metabolic alterations correlated with PBB-153 and PCB-153 exposure can be detected in human populations and are consistent with health outcomes previously reported in epidemiological and mechanistic studies.

KEYWORDS:

Bioffect; Biomonitoring; High-resolution metabolomics; Polybrominated flame retardants; Polychlorinated biphenyls

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