Lack of Delayed Neurotoxic Effect after Tri-o-cresyl Phosphate Treatment in Male Fischer 344 Rats: Biochemical, Neurobehavioral and Neuropathological Studies

Lack of Delayed Neurotoxic Effect after Tri-o-cresyl PhosphateTreatment 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-cresylphosphate (TOCP), which produces a delayed neurotoxic syndromein 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 givenTOCP by gavage in doses ranging from 10 to 100 mg of TOCP/kgdaily for a period of 63 days. The rats were subjected to aseries of neurobehavioral tests including fore- and hindlimbgrip strength, motor activity, tremor, and latency to respondto a thermal stimulus. Central and peripheral nervous tissueswere examined for damage characteristic of organophosphorouscompound-induced delayed neurotoxicity (OPIDN). Brain neurotoxicesterase and acetylcholinesterase activities were inhibitedin a dose-dependent fashion. A group of three chickens treatedwith 100 mg of TOCP/kg/day for 18 days was included as the positivecontrol for enzymatic and histopathological alterations associatedwith OPIDN. Rats showed no consistent neurobehavioral changesor evidence of neuropathological damage in nervous tissues associatedwith treatment. In contrast, chickens treated with TOCP developeddelayed neurotoxicity characterized by ataxia, which progressedto paralysis. These neurological changes included swelling,fragmentation, and degeneration of the axon and myelin in bothcentral and peripheral nervous tissues. This study concludesthat the F344 rat is not sensitive to the delayed neurotoxiceffects of TOCP. When studying OPIDN in rats, care must be exercisedin choosing the experimental animal since some strains, e.g.,F344, are not sensitive.