Modulation of neurotoxic behavior in F-344 rats by temporal disposition of benzo(a)pyrene.

The behavioral changes caused by benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, were monitored, and also its metabolite levels in cerebellum and cortex were measured in BaP treated rats to see if any relationship existed between these two aspects. Rats were administered 0, 25, 50, 100, and 200 mg/kg of BaP in peanut oil by oral gavage. Plasma, and brain tissue (cerebellum and cortex) samples were collected at 0, 2, 4, 6, 12, 24, 48, 72 and 96 h post administration. Neurotoxic effects peaked at 2 h after dosing and lasted 48 h after dosing for all dose groups. The metabolite levels remained the same from 2 to 4 h, reached a peak at 6 h post gavage and showed a gradual decline returning to baseline levels at 72 h when the motor activity of treatment groups also returned to control levels, indicating recovery from the effects of BaP. A significant (P<0.05) correlation between neurotoxic effects and BaP plasma, and brain metabolite concentrations suggests that metabolism plays an important role in modulating the neurobehavioral effects of BaP.