Delayed neurotoxic and late acute effects of S,S,S-tributyl phosphorotrithioate on the hen: Effect of route of administration


Journal Article

This study compared the acute and delayed neurotoxic effects of S,S,S,-tributyl phosphorotrithioate (DEF) by oral ingestion and topical application with the effects of other compounds. Oral administration of a single dose of DEF caused immediate cholinergic effects in most treated hens; these symptoms were rapidly relieved by atropine sulfate treatment. Small single oral doses (100 to 400 mg/kg) caused gross ataxia in most treated hens. These neurologic symptoms regressed with time. Large oral doses, ranging between 500 and 1,000 mg/kg, caused a 'late acute' effect 24 to 48 hours after administration. The clinical signs of the 'late acute' effect were identical to those produced by n-butyl mercaptan (nBM), a hydrolytic product of DEF, and were not relieved by atropine sulfate. Some hens treated with large doses had clinical signs of the 'late acute' effect of DEF that coincided with the clinical signs of 'delayed neurotoxicity'. These hens died early, and no histological lesions in the central or peripheral nervous system were found. The effect of topical application of DEF differed from that of oral treatment. Delayed neurotoxicity with a typical delay period was consistently produced and degeneration of the central and peripheral nerve tissue could be shown. Tri-0-cresyl phosphate (TOCP) treated hens were used as controls in pathological studies. Degeneration of myelin and axons in the spinal cord of DEF-treated hens was identical to that found in TOCP-treated hens and was the most consistent histologic change. The administration of nBM did not result in neuropathologic lesions but resulted in slightly increased brain acetylcholinesterase (AChE) ad plasma butyrylcholinesterase (BuChE) activities. Topical administration of DEF caused a much more prolonged inhibition of plasma BuChE than the orally administered compound. Orally administered DEF is rapidly metabolized in the gastrointestinal tract to nBM. This metabolite causes the 'late acute' effect. Topically administered DEF is more stable in the body and caused 'delayed neurotoxicity'. Topical application may be an important method for evaluation of the neurotoxic effect of organophosphorus esters.

Duke Authors

Cited Authors

  • Abou-Donia, MB; Graham, DG; Timmons, PR; Reichert, BL

Published Date

  • January 1, 1979

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 425 - 447

International Standard Serial Number (ISSN)

  • 0161-813X

Citation Source

  • Scopus