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

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.