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 herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and 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 fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other 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 cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.
Verschoyle
R D
RD
MRC Toxicology Unit, Carshalton, Surrey, United Kingdom.
Brown
A W
AW
Nolan
C
C
Ray
D E
DE
Lister
T
T
D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000473:pathology; D003671:DEET / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004158:Diphenylacetic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D004158:Diphenylacetic Acids; D006540:Herbicides; D003671:DEET; C004840:diphenamid