TY - JOUR
T1 - Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male Fischer 344 rats
T2 - Biochemical, neurobehavioral, and neuropathological studies
AU - Somkuti, Stephen G.
AU - Tilson, Hugh A.
AU - Brown, H. Roger
AU - Campbell, Gerald A.
AU - Lapadula, Daniel M.
AU - Abou-Donia, Mohamed B.
PY - 1988/2
Y1 - 1988/2
N2 - 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.
AB - 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.
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U2 - 10.1016/0272-0590(88)90303-X
DO - 10.1016/0272-0590(88)90303-X
M3 - Article
C2 - 3356306
AN - SCOPUS:77957188420
SN - 0272-0590
VL - 10
SP - 199
EP - 205
JO - Fundamental and Applied Toxicology
JF - Fundamental and Applied Toxicology
IS - 2
ER -