Motor Impairment and PCB+MEHG Exposure 1 Accepted for publication in Toxicological Sciences pending revisions MOTOR IMPAIRMENT IN RATS EXPOSED TO PCBS AND METHYLMERCURY DURING EARLY DEVELOPMENT

Epidemiological and laboratory studies indicate that PCBs and MeHg may have additive or interactive adverse effects on nervous system function. Prior studies have shown that high doses of MeHg target the cerebellum and impair balance and coordination, but the effects of PCBs on cerebellar function were unknown. In addition, the combined effects of PCBs and MeHg on cerebellar function have not been studied previously. Therefore, we investigated the effects of developmental exposure to PCBs, MeHg, or PCBs + MeHg on three motor tasks that involve cerebellar functions. Female Long-Evans rats were exposed to MeHg (0.5 ppm in drinking water), PCBs (6 mg/kg/d Aroclor 1254), PCBs + MeHg, or vehicle only, beginning 4 weeks prior to breeding, through pregnancy and continuing through postnatal day (PND) 16. Starting at approximately PND60, one male and one female from each litter were tested on three motor tasks that involve cerebellar function. PCB + MeHgexposed rats were impaired relative to controls on a task requiring them to traverse a rotating rod. Rats exposed to PCBs alone were also somewhat impaired relative to controls, whereas MeHg-exposed rats were not significantly different from controls. There were no statistically significant deficits related to PCB or MeHg exposure on a vertical rope-climbing test or a parallel bars test. Our results demonstrate that the possibility of additive neurotoxic effects of PCBs and MeHg needs to be seriously considered.