Nicole M. Breese

Polychlorinated biphenyls (PCBs) persist in the environment as complex mixtures and undergo extensive biotransformation, yet the developmental toxicity of PCB metabolites remains poorly defined. We evaluated developmental, neurobehavioral, and molecular effects of parent PCBs, hydroxylated, methoxylated, and sulfated metabolites, and environmentally relevant mixtures using embryonic zebrafish. This study employed a high-throughput screening approach using nominal exposure concentrations to enable rapid hazard identification and prioritization across a large chemical series. Morphological abnormalities and photomotor behavior were assessed across early development, followed by targeted cyp1a reporter analysis and transcriptomic profiling for a subset of potent exposures. Most chemicals induced morphological effects, with hydroxylated and sulfated metabolites producing effects more frequently and at lower benchmark concentrations than parent congeners. Behavioral alterations were more prevalent in embryonic photomotor response than larval photomotor response and generally co-occurred with morphological effects. Environmental mixtures elicited broad phenotypic profiles comparable to highly active individual compounds. Transcriptomic analyses revealed minimal responses for parent PCBs but robust, exposure-specific gene expression changes for select metabolites, particularly 5-OH-PCB11, and mixtures. Differentially expressed genes were enriched for xenobiotic metabolism, immune signaling, and neuroactive pathways, alongside consistent downregulation of circadian regulators. Together, these results demonstrate contributions of PCB metabolites and mixtures to toxicity.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with neurodevelopmental toxicity, yet the effects of exposure during adolescence and adulthood remain underexplored. This scoping review evaluates the neurotoxic outcomes of post-weaning PCB exposure in rodent models. A comprehensive literature search was conducted across PubMed, Embase, and Scopus. Studies were screened according to PRISMA guidelines. Articles were included if they reported neurotoxic or behavioral outcomes in mice or rats exposed to PCBs during post-weaning stages. Thirty-five studies met the inclusion criteria, encompassing a variety of PCB congeners and mixtures administered via oral, inhalation, or intraperitoneal routes. Reported neurotoxic outcomes included histological and morphological brain changes, oxidative stress, disrupted calcium signaling, altered neurotransmitter systems, apoptosis, and gene expression alterations. These outcomes were assessed using diverse methodological approaches, including immunohistochemistry, biochemical assays, and gene expression profiling. Behavioral outcomes affected by PCB exposure included locomotion, anxiety-like behavior, learning and memory, motor coordination, and cognitive flexibility. Effects were often exposure-specific and sex-dependent, with limited female-focused studies and integrative molecular-behavioral assessments. These findings highlight the broad neurotoxic potential of PCBs following adolescent or adult exposure and underscore the need for further mechanistic, sex-specific research to inform health risk assessment and regulatory policy.