Clinical, biochemical, electrophysiologic, and histologic assessment of chlorpyrifos induced delayed neuropathy in the cat.
The ability of a supralethal dose of chlorpyrifos to produce delayed neuropathy was examined using assessments of clinical signs, electromyography (EMG), motor nerve conduction velocity (MNCV), lymphocyte neuropathy target esterase activity (LNTE), and histologic changes in nervous system tissues. Cats were exposed to a single, im injection of corn oil (vehicle control), DFP (positive control) at 5.0 mg/kg, or chlorpyrifos at 300 mg/kg and observed for 60 days. Atropine and 2-PAM were administered to chlorpyrifos exposed cats one to two times a day for 14 to 24 days in response to the appearance of cholinergic signs. Anorectic cats during the acute toxicosis were force fed by hand and hydration was maintained by administering fluids sc. Onset of ataxia (mean +/- SD) for the positive control and chlorpyrifos exposed cats were 16.2 +/- 1.8 days (range of 14-19 days) and 19.0 +/- 1.4 days (range of 17-21 days), respectively. Functional deficits for both groups were confined to the hindlimbs and characterized by a crouched-waddling gait, hypermetria, and proprioceptive deficits. Maximal inhibition of LNTE activity was 96% at 24 hr postdosing in the positive control group and 46% at 7 days postdosing in the chlorpyrifos group. No EMG or MNCV abnormalities were detected in any of the treatment groups. Axonal degeneration was similar for the positive control and chlorpyrifos exposed cats. Ascending tracts of the cervical spinal cord and descending tracts of the thoracic and lumbar spinal cord were most severely affected and peripheral nerves were only mildly affected. The clinical and histologic effects produced indicate that chlorpyrifos can cause delayed neuropathy in the domestic cat. The moderate but prolonged inhibition of LNTE produced by chlorpyrifos is atypical of classic organophosphorus delayed neurotoxicants.
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D001285:Atropine / Q000627:therapeutic use; D002265:Carboxylic Ester Hydrolases / Q000097:blood*; D002415:Cats; D004390:Chlorpyrifos / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D003975:Diazepam / Q000627:therapeutic use; D004576:Electromyography; D007531:Isoflurophate / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects*; D011220:Pralidoxime Compounds / Q000627:therapeutic use; D013997:Time Factors
D000931:Antidotes; D011220:Pralidoxime Compounds; D007531:Isoflurophate; D001285:Atropine; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002802:Cholinesterases; D004390:Chlorpyrifos; C028797:pralidoxime; D003975:Diazepam