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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosfolan, chlorpyrifos, and stirophos when applied to white mice at sublethal doses did not induce any delayed neurotoxic effect. On the other hand, Leptophos and EPN when administered orally at sublethal or lethal levels clearly produced a delayed neurotoxic ataxia in treated mice. The five tested organophosphorus insecticides were compared for their ability to inhibit cholinesterase, neurotoxic esterases and monoamine oxidase. I50 values were estimated for each case. The results revealed that all five compounds were inhibitors of cholinesterase, but only Leptophos and EPN were shown to be potent inhibitors for both neurotoxic esterase and monoamine oxidase in the mouse brain. Additional particular properties of both Leptophos and EPN were found in their ability to cause delayed neurotoxic ataxia in chickens and sheep fed once on sublethal doses of these compounds. It is believed that the phosphonate ester configuration of EPN and Leptophos has a specific mode of toxic action which is mainly located at the central nervous system. It is also postulated that these delayed neurotoxic agents might inhibit postganglionic sympathetic neurons, thus resulting in chronic paralytic effects.
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PMID:Neurotoxicity of organophosphorus insecticides Leptophos and EPN. 7 68

Cyanofenphos (surecide)(R), 25% E.C., O-ethyl O-(4-cyanophenyl) phenylphosphonothioate, was orally administered to one year old lambs at sublethal doses of 1 mg, 2 mg and 4 mg active ingredient kg-1 day-1 for time intervals 60, 45 and 30 days respectively. Irreversible paralytic ataxia symptoms of delayed neuropathy appeared at about 80, 50 and 30 days respectively. In weekly blood samples, AChE (acetylcholine-sterase) and MAO (monoamine oxidase) activities were inhibited depending upon level of dosing and time interval. However no significant correlation was found between the extent of plasma AChE and MAO inhibition and the onset of ataxia symptoms. In brain samples from ataxiated animals, AChE, MAO and NTE (neurotoxic esterase) activities were assayed simultaneously with untreated animal. Direct correlation was shown between in vivo NTE inhibition and the occurrence of delayed neuropathy. Cyanofenphos is the third compound of the phenyl phosphonothioate type on the market showing delayed neuropathy together with Leptophos and EPN.
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PMID:Delayed neuropathy in sheep by the phosphonothioate insecticide cyanofenphos. 43 64

Fourteen organophosphorus esters (OPs) were evaluated for their potential to cause organophosphorus ester induced delayed neurotoxicity (OPIDN) when administered dermally and/or orally to white leghorn hens. The compounds were chlorpyrifos, DEF, dichlorvos, dimethoate, EPN, ethoprop, fenthion, isofenphos, leptophos, merphos, ronnel, tetrachlorvinphos, terbufos, and trichlorfon. DEF induced ataxia if given dermally or orally at over 21 mg/kg/day for up to 90 days. Hens treated with EPN developed irreversible ataxia after repeated exposure to as little as 1.3 mg/kg dermally or 5 mg/kg/day orally, while leptophos was neurotoxic at doses of 6-7 mg/kg/day dermally and 10 mg/kg/day orally. Multiple treatments of chlorpyrifos, terbufos, dichlorvos and dimethoate caused death after varying periods of increasing debility; although birds had difficulty walking, they did not display typical symptoms of OPIDN. Fenthion and isofenphos induced drastic weight loss in hens at low levels of treatment; Isofenphos treated hens developed OPIDN, but died soon afterwards. Dichlorvos given at greater than 6 mg/kg/day po or dermally at 1 mg/kg/day produced cholinergic symptoms and most hens died before the end of the treatment period. At lower levels, dichlorvos did not induce overt ataxia. None of the other compounds in this series induced consistent ataxia whether administered orally or dermally. Ethoprop, with an acute oral LD50 near 5 mg/kg and an acute dermal LD50 of approximately 3 mg/kg, was the most toxic compound tested and could not be fully evaluated for its potential to cause OPIDN.
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PMID:Toxicity of organophosphorus esters to laying hens after oral and dermal administration. 398 23

Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B-receptor binding activity with 3H-norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B-receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in-vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.
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PMID:Biochemical interaction of six OP delayed neurotoxicants with several neurotargets. 616 54

The delayed neurotoxic effects of tri-o-cresyl-phosphate (TOCP), O-methyl-O-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (leptophos), and O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN) at 5, 5, and 1 mg/kg/day, respectively, on male sheep were studied during 6 months of daily oral treatment under field conditions. A vehicle-control group of sheep given corn oil (0.1 ml/kg/day) only was used for comparison. All sheep were killed 24 h after the 180th daily treatment. Blood, brain, spinal cord, and sciatic nerve tissues were taken for histological and/or biochemical examinations. The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment. TOCP produced either mild ataxia or lameness in two of four sheep during the last week of experiment. On the other hand, none of the EPN-treated sheep showed clinical signs of neurotoxicity during the course of the experiment at the dosage tested. These clinical results were supported by histological findings and also by biochemical results with neurotoxic esterase (NTE) measurements. In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains. Similar but somewhat less numerous lesions were noted in sheep treated with TOCP. No histological changes were observed in similar tissues taken from EPN-treated sheep. The results also indicated that, for chronic exposure to these neurotoxic organophosphorus compounds in sheep, a threshold in excess of 60-70% prolonged inhibition of brain NTE, or 50-60% inhibition of spinal cord NTE must be exceeded to initiate clinical and/or histological neurotoxic effects.
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PMID:Six-month daily treatment of sheep with neurotoxic organophosphorus compounds. 619 47

Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.
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PMID:Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards. 620 72