A Comparison of the Acute Toxicity, Neuropathology, and Electrophysiology of N,N-Diethyl-m-toluamide and N,N-Dimethyl-2,2-diphenylacetamide in Rats

The insect repellent DEET and the structurally related herbicidediphenamid both cause ataxia associated with a spongiform myelinopathylargely confined to the cerebellar roof nuclei. This local myelinopathywas accompanied by the formation of neuronal cytoplasmic cleftsand was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide(DEET). These dose levels also produced a severe and often fatalprostration and clear electrophysiological signs of prolongedsuppressed seizure activity. Diphenamid produced an identicalmyelinopathy after doses of 0.8 to 1.5 g/kg but without thesevere prostration, suppressed seizures, or neuronal clefts.The effects of diphenamid were shown to be reversible over 3to 7 days by neuropathological, motor, and auditory evoked responseindices. Both compounds caused characteristic changes in auditoryevoked response which may be useful in clinical diagnosis. Sixother alkyl amides, two of which produce signs of CNS excitation,failed to produce myelinopathy at the maximum tolerated doses.Our findings show close parallels with a number of human casesof DEET poisoning and indicate that other amides, like diphenamid,also pose a potential hazard.