Neurologic manifestations of tri-o-cresyl phosphate delayed neurotoxicity in cats.
Abou-Donia-MB; Jensen-DN; Lapadula-DM
Neurobehav Toxicol Teratol 1983 Aug; 5(4):431-442
Neurotoxic effects of tri-o-cresyl-phosphate (78308) (TOCP) were studied in cats. Median lethal doses were determined for dermal and oral administration of TOCP to random bred cats at doses from 100 to 5000 milligrams per kilogram (mg/kg). TOCP was dermally applied to cats to study delayed neurotoxic effects at doses of 100, 250, 500, 1000, or 1500mg/kg. Cats given 1000 or 1500mg/kg were also given (51150) to protect against acute cholinergic effects for 14 days. These and untreated cats were observed for 90 days for acute and delayed signs of toxicity. Neurological signs of toxicity were tested through examination of specific reflexes and postural reactions. Central and peripheral nervous systems were examined histopathologically in cats that died, and in cats killed after 90 days. The dermal median lethal dose was determined to be 1500mg/kg while the oral median lethal dose was 3000mg/kg. Despite prophylactic treatment, all cats developed signs of acute poisoning if given 1000 or 1500mg/kg. Acute symptoms included salivation, pupil constriction, vomiting and diarrhea, and weakness in all four limbs. Delayed neurotoxicity was limited to rear leg functions. Cats given any dose over 100mg/kg developed leg weakness 15 to 28 days after application. Mild ataxia was seen at these doses. At doses of 500mg/kg and above severe ataxia appeared with abnormal spinal cord reflexes and postural reactions. Only cats given 1500mg/kg progressed to paresis at 55 days after dosing. All cats showed some degree of recovery by 90 days. Lesions were found in the spinal cords of animals with delayed toxicity. These included swelling, vacuolation and fragmentation of axonal and myelin sheaths. Lesions were found in peripheral nerves of animals receiving 500mg/kg and above. The authors conclude that the neurological indications of toxicity correlate well with histopathological lesions seen. Improvement apparently resulted from regeneration in the peripheral nerves that would not be expected in the central nervous system.
NIOSH-Publication; NIOSH-Grant; Histopathology; Poisons; Nerve-damage; Laboratory-animals; Nervous-system; Nerve-tissue; Nerve-function; Neurotoxicity; Physiology; Toxicology; Neurotoxicology
Pharmacology Duke University Department of Pharmacology Durham, NC 27710
78-30-8; 55-48-1; 51-15-0
Neurobehavioral Toxicology and Teratology
Duke University, Durham, North Carolina