Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry

• Type of Material: Article
• Authors: Susan Hoffman, Emory University; Donghai Liang, Emory University; Robert B. Hood, Emory University; Youran Tan, Emory University; Metrecia Terrell, Emory University; M. Elizabeth Marder, University of California, Davis; Hillary Barton, Emory University; Melanie A Pearson, Emory University; Douglas Walker, Emory University; Dana Boyd Barr, Emory University; Dean P. Jones, Emory University; Michele Marcus, Emory University
• Language: English
• Date: 2023-10-10
• Publisher: EHP Publishing
• Publication Version: Final Published Version
• Copyright Statement: EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
• Final Published Version (URL): https://doi.org/10.1289/EHP12657
• Title of Journal or Parent Work: Environmental Health Perspectives
• Volume: 131
• Issue: 10
• Start Page: 107005
• Grant/Funding Information: Funding was received from the National Institute for Environmental Health Science (NIEHS) grants: R24 ES028528, R01 ES025775, P30 ES019776 S1 and S2, T32 ES012870, and R21 ES032117.
• Keywords: Polybrominated biphenyls; organic pollutants; high-resolution metabolomics; polychlorinated biphenyls; endocrine-disrupting effects
• Research Categories: Health Sciences, Toxicology; Environmental Sciences; Health Sciences, Epidemiology

Abstract

Background: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. Objectives: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. Methods: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and Σ⁢PCB (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Results: Mean levels were 1.75 ng/mL [standard deviation (SD): 13.9] for PBB-153 and 1.04 ng/mL (SD: 0.788) for Σ⁢PCB. Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) 𝑝<0.2], respectively. There were 2,861 features associated with Σ⁢PCB (FDR 𝑝<0.2). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with Σ⁢PCB in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with Σ⁢PCB levels (level 1 evidence). Conclusions: Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that Σ⁢PCB was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657