Short-Term Clinical and Neuropathologic Effects of Cholinesterase Inhibitors inRats

摘要

Adult male Long Evans rats were given a single administration of 3 dosage levelsof the organophosphorus compounds tri-ortho-tolyl phosphate (TOTP), diisopropyl fluorophosphate (DFP), phenyl saligenin phosphate (PSP), mipafox, malathion, and dichlorvos or the carbamate carbaryl. Acetylcholinesterase and neurotoxic esterase activities were inhibited in a dose-dependent manner, with the highest dosages of all these compounds inhibiting activities of these enzymes in brain by at least 37% and 64%, respectively, at 4 and 48 hours after administration. Rats given the high doses of TOTP (1000 mg/kg), DFP (3 mg/kg), malathion (2000 mg/kg), and carbaryl (160 mg/kg) weighed significantly less than control rats 14 days after administration. A functional observational battery (FOB) was used to screen for neurotoxic effects 1, 2, and 3 weeks after exposure. All 7 test compounds were capable of causing changes in parameters indicative of behavioral and central nervous system excitability. In addition, dose-related alterations in response to approach were seen in rats given DFP, malathion, dichlorvos, and carbaryl.