Electromyographic, neuropathologic, and functional correlates in the cat as the result of tri-o-cresyl phosphate delayed neurotoxicity.
To investigate the cat as a test animal for organophosphorous compound-induced delayed neurotoxicity, tri-o-cresyl phosphate (TOCP) was applied directly on the unprotected back of the neck of young adult cats. Single dermal doses, ranging from 250 to 2000 mg/kg TOCP, or subchronic daily administration of 1 to 100 mg/kg produced delayed neurotoxic effects in the cat. Severity of delayed neurotoxicity depended on the dose and duration. Clinical signs were characterized by hindlimb weakness, ataxia, and paresis. Electromyographic abnormalities resulting from acute denervation were observed in most cats that developed a neurologic deficit. No changes were seen in the motor nerve conduction, thus suggesting that the deficits were in the terminal branch rather than being diffuse lesions in the peripheral nerves. These results correlated well with histopathologic results showing lesions in the most distal portion of the longest tracts in both central and peripheral nervous systems. In the spinal cord, histopathologic studies showed that the ascending tracts of the upper cervical levels and descending tracts of the lumbosacral regions were affected most frequently. Although this study shows that the cat, like the chicken, is susceptible to TOCP-induced delayed neurotoxicity, it demonstrates two differences between the cat and the chicken: greater sensitivity of the cat to the acute effect of TOCP, and greater extent of recovery or improvement of the cat from delayed neurotoxicity. This recovery was demonstrated by: improvement of clinical signs, gain in body weight, disappearance of electromyographic abnormalities, and regeneration of peripheral nerves. Dermal administration of a single 100-mg/kg dose or subchronic 0.5-mg/kg doses of TOCP did not produce delayed neurotoxicity.
Abou-Donia, MB; Trofatter, LP; Graham, DG; Lapadula, DM
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