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Electromyographic, neuropathologic, and functional correlates in the cat as the result of tri-o-cresyl phosphate delayed neurotoxicity.
Abou-Donia MB; Trofatter LP; Graham DG; Lapadula DM
Toxicol Appl Pharmacol 1986 Mar; 83(1):126-141
A dose/response study of the effects of dermal administration of tri- o-cresyl-phosphate (78308) (TOCP) was conducted in cats. Adult male cats obtained from random sources were used. Doses ranging from 100 to 2,000 milligrams per kilogram (mg/kg) were applied at clipped areas on the back of the neck of six different groups of animals. Animals treated with 1,000ppm and higher received subcutaneous injections of atropine-sulfate (55481) and pyridine-2-aldoxime- methylchloride (51150) (PAM) immediately after TOCP administration and from 1 to 3 times daily until the period of acute cholinergic effects ended. Cats that survived were observed for 120 days; animals treated with lower doses were kept for 90 days. Additional groups of animals received subchronic doses of either 0.5, 1, 5, or 100mg/kg TOCP for 90 days and survivors were observed for an additional 30 days. Animals were sacrificed at the end of the test period. Animals were examined daily for signs of neurotoxicity and were weighed weekly. Tissues from the nervous system were taken from all cats for histopathological examination. Selected animals were studied electromyographically. Animals that received a single dermal dose of TOCP ranging from 250 to 1,000ppm showed an initial dose dependent weight loss followed by a weight gain. All animals treated with 1,000, 1,500, or 2,000ppm TOCP developed signs of cholinergic poisoning that were dose dependent. Daily doses of 5 to 100mg/kg also produced signs of an acute effect after a dose dependent delay period. Electromyographic changes were detected in cats given single doses ranging from 250 to 1,000mg/kg, but not in cats that received 100mg/kg. Early histopathologic changes in the spinal cord were seen in cats that died 25 days after a single dose of TOCP. The authors conclude that single or daily dermal applications of TOCP produce delayed neurotoxicity in the cat.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Laboratory-animals; Toxic-effects; Biological-effects; Histopathology; Analytical-methods; Neurotoxic-effects; Chemical-composition; Tissue-disorders; Clinical-symptoms; Dose-response
Pharmacology Duke University Medical Center Box 3813 Durham, NC 27710
78-30-8; 55-48-1; 51-15-0
Issue of Publication
Pulmonary-system-disorders; Neurotoxic Disorders; Neurotoxic-effects
Toxicology and Applied Pharmacology
Duke University, Durham, North Carolina
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