Neuropharmacologic and neuropathologic effect of fenvalerate in mice and rats

B6C3F1 mice and Sprague-Dawley rats displayed the characteristic signs of pyrethroid intoxication following single oral doses ranging from 56 to 320 and 133 to 1000 mg/kg fenvalerate, respectively. The LD50s for mice and rats were 180 and 776 mg/kg, respectively, with corn oil as the vehicle. Signs of neurologic deficit such as splayed gait, tremors, ataxia, and hind limb incoordination were observed at doses of greater than or equal to 100 mg/kg (mice) and greater than or equal to 133 mg/kg (rats) within 1-8 hr after dosing. These signs had disappeared in most animals within 72 hr. Slight peripheral nerve fiber damage was detected in surviving mice and rats sacrificed 10 days after dosing. The incidence and severity were dose related at doses greater than or equal to 56 and greater than or equal to 180 mg/kg; however, even at lethal doses, evidence was lacking for the presence of nerve lesions in several animals. Thus two distinct neurologic effects were observed: a reversible ataxia/incoordination and a neuropathologic effect manifested as sparse axonal damage in peripheral nerve.