Delayed neuropathy and acute toxicity studies with pirimiphos-methyl in the hen.
This paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21-day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg-1 pirimiphos-methyl, which was followed by a repeated dose after 21 days. Tri-o-cresyl phosphate (TOCP), 500 mg kg-1, was used as a positive control. All pirimiphos-methyl-treated hens received prophylactic doses of N-methylpyridinium-2-aldoxime methanesulphonate (P2S) and atropine sulphate. Hens dosed with pirimiphos-methyl had very low AChE activities (less than 20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP-treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos-methyl-treated hens were identical to those in the controls, while they were profoundly inhibited (greater than 80%) in the TOCP-treated hens. All hens dosed with pirimiphos-methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP-treated hens developed clinical signs of neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Lock
E A
EA
Biochemical Toxicology Section, ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Johnson
M K
MK
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002645:Chickens; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000633:toxicity
D007306:Insecticides; D009946:Organothiophosphorus Compounds; D014317:Tritolyl Phosphates; C014153:pirimiphos methyl; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; C025541:tri-o-cresyl phosphate