Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

In the present study the developmental neurotoxic effects ofthe PCB metabolite 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107)were compared with effects caused by a mixture of parent polychlorinatedbiphenyl (PCB) congeners (Aroclor 1254). Pregnant female Wistarrats were exposed to 0.5 or 5 mg 4-OH-CB107, or 25 mg Aroclor1254 per kg body weight from gestation days 10 to 16. Plasmathyroid hormone levels were significantly decreased in the offspringof all treatment groups at postnatal day 4 (PND 4). Behavioralexperiments using an open field paradigm revealed an impairedhabituation in male offspring of all treatment groups at PND130. Passive avoidance experiments indicated significant influenceson the time course of step-down latencies across trials in exposedmale rats. Catalepsy induced by haloperidol showed increasesin latencies to movement onset in female offspring exposed to0.5 mg 4-OH-CB107 compared to Aroclor 1254 treated offspringat PND 168–175. Male offspring exposed to 4-OH-CB107 orAroclor 1254 showed decreases in latencies compared to controlanimals. Brain stem auditory evoked potentials (BAEPs) measuredat PND 300–310 showed significant increases in auditorythresholds in the low frequency range between Aroclor 1254 and4-OH-CB107 (5 mg/kg bw) treated animals. Measurements of neurotransmitterlevels revealed effects of Aroclor 154 exposure on both thedopaminergic and the serotonergic systems, whereas 4-OH-CB107exposure affected dopaminergic and noradrenergic systems, withslight but not significant effects on the serotonergic system.These results indicate that 4-OH-CB107 is able to induce long-termeffects on behavior and neurodevelopment. The observed effectsfor 4-OH-CB107 are similar to, but in some aspects differentfrom, the effects observed after Aroclor 1254 exposure.