Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences

Abstract

Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution of PCBs and OH-PCBs in the human brain has not been characterized. This study investigated the age-, sex-, and brain region-specific distribution of all 209 PCBs using gaschromatography–tandem mass spectrometry (GC–MS/MS) in neonatal ( N = 7) and adult ( N = 7) postmortem brain samples. OH-PCB analyses were performed by GC–MS/MS (as methylated derivatives) and, in a subset of samples, by nontarget liquid chromatography high-resolution mass spectrometry (Nt-LCMS). Fourteen higher chlorinated PCB congeners were observed with a detection frequency >50%. Six lower chlorinated PCBs were detected with a detection frequency >10%. Higher chlorinated PCBs were observed with higher levels in samples from adult versus younger donors. PCB congener profiles from adult donors showed more similarities across brain regions and donors than younger donors. We also assess the potential neurotoxicity of the PCB residues in the human brain with neurotoxic equivalency (NEQ) approaches. The median ΣNEQs, calculated for the PCB homologues, were 40-fold higher in older versus younger donors. Importantly, lower chlorinated PCBs made considerable contributions to the neurotoxic potential of PCB residues in some donors. OH-PCBs were identified for the first time in a small number of human brain samples by GC–MS/MS and Nt-LCMS analyses, and all contained four or fewer chlorine.

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

“…Eighty-one single or co-eluting PCB congeners were detected in zero samples; 76 in 1-10% of samples; 5 in 11-20% of samples; 7 in 21-50% of samples; and 4 in ≥50% of samples (Supplemental Table S1). These detection frequencies are lower than those in postmortem human brain using similar methods (Li, Hefti, et al, 2022). In both studies, highly chlorinated PCBs were more likely to be detected than lower chlorinated PCBs, despite the decreased response of the instrument as the degree of chlorination increases.…”

“…The four PCB congeners/congener pairs that were detected in ≥50% (n=52) of samples were selected for further analysis due to the increased robustness of statistical methods when censored data points represent less than half the data: PCBs 153s + 168, 170, 180 + 193, and 187. These PCB congeners were also detected in ≥50% of postmortem brain samples (Li, Hefti, et al, 2022) and found at high concentrations in maternal blood plasma, cord blood plasma, breast milk (Guvenius et al, 2003), and placenta (Naqvi et al, 2018). No PCB congeners were detected in fewer than 50% of all samples but in greater than 50% of one of the ASD diagnostic groups (ASD/non-TD/TD), indicating that we did not miss a congener that may discriminate between diagnostic groups.…”

“…PCBs 153 + 168 and 180 + 193 had higher median and mean concentrations than PCBs 170 or 187. PCB 153 and PCB 180 have previously been detected as among the 12 most abundant PCB congeners in maternal serum in the MARBLES cohort (Sethi et al, 2019), as well as highly detected in brain tissue (Chu et al, 2003;Corrigan et al, 1998;Dewailly et al, 1999;Li, Hefti, et al, 2022;Mitchell et al, 2012). Additionally, PCB 153 + 168 are the least lipophilic of this group, meaning they are more readily released from adipose tissue into the blood, potentially resulting in higher average serum levels (Louis et al, 2016).…”

“…Serum samples were extracted and analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis using published procedures (Li, Hefti, et al, 2022;Marek et al, 2014;Milanowski et al, 2010) in the Analytical Core of the Iowa Superfund Research Program. Briefly, tissue samples were homogenized in 3 mL isopropanol.…”

“…Helium was used as a carrier gas with a constant flow rate of 0.8 mL/min. The precursor-product ion transitions of all PCB analytes used for the MS/MS analysis have been reported previously (Li, Hefti, et al, 2022).…”