Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male Fischer 344 rats: biochemical, neurobehavioral, and neuropathological studies.
Somkuti SG; Tilson HA; Brown HR; Campbell GA; Lapadula DM; Abou-Donia MB
Fundam Appl Toxicol 1988 Feb; 10(2):199-205
Delayed neurotoxic effects of tri-o-cresyl-phosphate (78308) (TOCP) were studied in rats. Male Fischer-344-rats were given 0, 10, 50, or 100mg/kg TOCP by oral gavage daily for 63 days. Chickens were treated with 100mg/kg TOCP daily for 18 days as a positive control. The animals were observed for clinical signs of toxicity. Neurobehavioral tests including tests of fore and hindlimb strength, motor activity, and thermal sensitivity were administered to the rats at the end of the study. The animals were then killed, the brains were removed, and assayed for acetylcholinesterase (AChE) and neurotoxic esterase (NTE) activity. Sections from the cervical, thoracic, and lumbosacral areas of the spinal cord and peripheral nerves were taken for histopathological examination. Only occasional signs of acute cholinergic toxicity, such as diarrhea, salivation, and ocular discharge, were seen in rats given 50 or 100mg/kg TOCP. No signs of delayed neurotoxicity were seen. Chickens treated with TOCP developed the ataxia and paralysis characteristic of delayed neurotoxicity by the seventh day of dosing. TOCP induced few consistent effects on the tested neurobehavioral parameters. Brain AChE and NTE activity were decreased in a dose dependent manner in rats. AChE and NTE activity were also decreased in the chickens. Rats showed no evidence of neuropathological damage that could be attributed to exposure. TOCP treated chickens showed changes characteristic of degeneration in the dorsal and lateral column in the cervical spinal cord and in lateral columns below the cervical regions. The authors conclude that the rat is not a suitable animal model for studying organophosphate induced delayed neurotoxicity.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Organo-phosphorus-compounds; In-vivo-studies; Laboratory-animals; Enzyme-activity; Nerve-damage; Cholinesterase-inhibitors; Histopathology; Clinical-symptoms
Pharmacology Duke University Department of Pharmacology Durham, NC 27710
Neurotoxic Disorders; Neurotoxic-effects
Fundamental and Applied Toxicology
Duke University, Durham, North Carolina