Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin.

Rats were given various doses of chlordecone, 1,1,1-trichloro-2,2-bis(p-chloro-phenyl)ethane (DDT) and lindane and tested for neurobehavioral toxicity up to 24 hr postdosing. The organochlorines either had no effect or increased responsiveness to an acoustic stimulus at subconvulsant doses. Only chlordecone and p,p'-DDT produced tremor. For purposes of comparison, the neurobehavioral effects of permethrin were also studied; this pyrethroid insecticide produced tremor and hyperresponsiveness similar to that of p,p'-DDT. Pretreatment with phenytoin significantly reduced the tremor and hyperresponsiveness produced by p,p'-DDT and permethrin. On the other hand, pretreatment with phenytoin increased the responsiveness of animals dosed with chlordecone or lindane, suggesting that these agents differ in their mechanism of action from p,p'-DDT and permethrin. The results of our experiments also indicate that care should be taken in the choice of agents, particularly anticonvulsants, to be used to treat symptoms of insecticide toxicity.