Exposure to polychlorinated biphenyls (PCBs) is associated
with
developmental neurotoxicity and neurodegenerative disorders; however,
the underlying mechanisms of pathogenesis are unknown. Existing literature
has focused mainly on using neurons as a model system to study mechanisms
of PCB-mediated neurotoxicity, overlooking the role of glial cells,
such as astrocytes. As normal brain function is largely astrocyte-dependent,
we hypothesize that astrocytes play an important role in PCB-mediated
injury to neurons. We assessed the toxicity of two commercial PCB
mixtures, Aroclor 1016 and Aroclor 1254, and a non-Aroclor PCB mixture
found in residential air called the Cabinet mixture, all of which
contain lower chlorinated PCBs (LC-PCBs) found in indoor and outdoor
air. We further assessed the toxicity of five abundant airborne LC-PCBs
and their corresponding human-relevant metabolites in vitro models
of astrocytes, namely, the C6 cell line and primary astrocytes isolated
from Sprague–Dawley rats and C57BL/6 mice. PCB52 and its human-relevant
hydroxylated and sulfated metabolites were found to be the most toxic
compounds. No significant sex-dependent cell viability differences
were observed in rat primary astrocytes. Based on the equilibrium
partitioning model, it was predicted that the partitioning of LC-PCBs
and their corresponding metabolites in biotic and abiotic compartments
of the cell culture system is structure-dependent and that the observed
toxicity is consistent with this prediction. This study, for the first
time, shows that astrocytes are sensitive targets of LC-PCBs and their
human-relevant metabolites and that further research to identify mechanistic
targets of PCB exposure in glial cells is necessary.