Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male Fischer 344 rats: biochemical, neurobehavioral, and neuropathological studies.
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.
Somkuti
S G
SG
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Tilson
H A
HA
Brown
H R
HR
Campbell
G A
GA
Lapadula
D M
DM
Abou-Donia
M B
MB
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003408:Cresols / Q000633:toxicity*; D004950:Esterases / Q000097:blood; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D014317:Tritolyl Phosphates / Q000633:toxicity*
D003408:Cresols; D014317:Tritolyl Phosphates; D004950:Esterases; C025541:tri-o-cresyl phosphate