Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male fischer 344 rats

Biochemical, neurobehavioral and neuropathological studies

Stephen G. Somkuti, Hugh A. Tilson, H. Roger Brown, Gerald Campbell, Daniel M. Lapadula, Mohamed B. Abou-donia

Research output: Contribution to journalArticle

Abstract

Lack of Delayed Neurotoxic Effect after Tri-o-cresyl Phosphate Treatment in Male Fischer 344 Rats: Biochemical, Neurobehavioral, and Neuropathological Studies. SOMKUTI, S. G., TIL-SON, H. A., BROWN, H. R., CAMPBELL, G. A., LAPADULA, D. M., AND ABOU-DONIA, M. B. (1988). Fundam. Appl. Toxicol. 10, 199-205. Tri-o-cresyl phosphate (TOCP), which produces a delayed neurotoxic syndrome in humans and some animal species, was given to Fischer 344 (F344) male (18 week old) rats to determine if it causes biochemical, sensorimotor, and neuropathological effects. Animals were given TOCP by gavage in doses ranging from 10 to 100 mg of TOCP/kg daily for a period of 63 days. The rats were subjected to a series of neurobehavioral tests including fore- and hindlimb grip strength, motor activity, tremor, and latency to respond to a thermal stimulus. Central and peripheral nervous tissues were examined for damage characteristic of organophosphorous compound-induced delayed neurotoxicity (OPIDN). Brain neurotoxic esterase and acetylcholinesterase activities were inhibited in a dose-dependent fashion. A group of three chickens treated with 100 mg of TOCP/kg/day for 18 days was included as the positive control for enzymatic and histopathological alterations associated with OPIDN. Rats showed no consistent neurobehavioral changes or evidence of neuropathological damage in nervous tissues associated with treatment. In contrast, chickens treated with TOCP developed delayed neurotoxicity characterized by ataxia, which progressed to paralysis. These neurological changes included swelling, fragmentation, and degeneration of the axon and myelin in both central and peripheral nervous tissues. This study concludes that the F344 rat is not sensitive to the delayed neurotoxic effects of TOCP. When studying OPIDN in rats, care must be exercised in choosing the experimental animal since some strains, e.g., F344, are not sensitive.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalToxicological Sciences
Volume10
Issue number2
DOIs
StatePublished - Feb 1988
Externally publishedYes

Fingerprint

Inbred F344 Rats
Rats
Nerve Tissue
Animals
Tissue
Therapeutics
Chickens
Forelimb
Hand Strength
Tremor
Ataxia
Acetylcholinesterase
Hindlimb
Myelin Sheath
tri-o-cresyl phosphate
Paralysis
Axons
Swelling
Brain
Motor Activity

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Toxicology

Cite this

Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male fischer 344 rats : Biochemical, neurobehavioral and neuropathological studies. / Somkuti, Stephen G.; Tilson, Hugh A.; Brown, H. Roger; Campbell, Gerald; Lapadula, Daniel M.; Abou-donia, Mohamed B.

In: Toxicological Sciences, Vol. 10, No. 2, 02.1988, p. 199-205.

Research output: Contribution to journalArticle

Somkuti, Stephen G. ; Tilson, Hugh A. ; Brown, H. Roger ; Campbell, Gerald ; Lapadula, Daniel M. ; Abou-donia, Mohamed B. / Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male fischer 344 rats : Biochemical, neurobehavioral and neuropathological studies. In: Toxicological Sciences. 1988 ; Vol. 10, No. 2. pp. 199-205.
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