Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute toxicity of oxamyl, an insecticide and nematicide, has been evaluated to establish proper handling guides. The material is highly toxic when given as a single oral dose; its LD50 is in fasted rats 2.5 to 3.1 mg/kg, 2.3 to 3.3 mg/kg in fasted mice, and 7 mg/kg in guinea pigs. A beagle dog given 30 mg/kg died, while 15 mg/kg was not lethal. In all species, clinical signs of cholinesterase inhibition (lacrimation, salivation, tremors) were observed. Cholinesterase activity was depressed in rats treated with a single oral dose. Atropine, when given immediately after oxamyl, was antidotal. When given by intraperitoneal injection, oxamyl was highly toxic to rats, mice, and guinea pigs. The material is a mild eye irritant with the reaction limited to the conjunctiva and iris, but systemic absorption via eye contact makes use of protective equipment essential. Oxamyl produces mild skin irritation and the dermal absorption toxicity in rats (LD50 is greater than 1,200 mg/kg) and rabbits (740 mg/kg) is relatively high suggesting limited absorption. No sensitization was produced when tested in guinea pigs. Oxamyl is highly toxic via inhalation with the 1-hr LC50 value in rats being 0.17 mg/liter (male) and 0.12 mg/liter (female). The corresponding 4-hr value is 0.064 mg/liter for male rats which indicates that concentration X time is a constant through the time periods tested. Repeated-dose studies, orally in rats and dermally in rabbits, showed oxamyl to be noncumulative, with the target system being the nervous system mediated through cholinesterase inhibition. No specific tissue or organ pathology was seen in either species tested.
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PMID:Acute toxicity studies with oxamyl. 369 28

Oxamyl (methylN',N'-dimethyl-N-[(methylcarbamoyl)oxy]-1-thiooxam imidate; CAS 23135-22-0) was tested for oral toxicity in the rat and dog (90-day and 2-year feeding studies) and in the mouse (2-year feeding study). Teratogenic potential was evaluated in the rat and rabbit and functional reproductive capacity was studied in the rat in a one- and a three-generation reproduction study. Rats fed a diet containing oxamyl at 500 ppm showed clinical signs of cholinesterase inhibition and body weight loss within 2 days. Feeding of either 100 or 150 ppm oxamyl for 90 days produced a reduced rate of weight gain without other signs of response, and no effects were detected at 50 ppm. An oxamyl feeding period of 2 years also showed depressed body weight gains in rats fed either 100 or 150 ppm. Cholinesterase activity was depressed only during the first week of feeding and only in the 150-ppm group. All other indices of response, including the type and distribution of tumors, were similar in the test and control rats and it was concluded that the no-observed-effect level was 50 ppm (equivalent to approximately 5 mg/kg). Mice fed oxamyl at 100 ppm for 6 weeks showed signs of cholinesterase inhibition and some mortalities, so the dietary concentration was reduced to 75 ppm in the 2-year study. Body weights of mice fed oxamyl at 50 or 75 ppm were lower than controls during the first 6 months of the study. No other signs of a toxic response to oxamyl were seen in mice and a no-observed-effect level of 25 ppm (approximately 2.5 mg/kg) was assigned to this compound. No evidence of a tumorigenic response was obtained. Dogs fed oxamyl at 150 ppm for 2 years showed marginal increases in serum alkaline phosphatase activity and cholesterol concentration but no tissue pathology was seen. No evidence of cholinesterase inhibition was seen. It was concluded that the no-observed-effect level for oxamyl in the dog was 100 ppm (approximately 2.5 mg/kg). In the one- and three-generation reproduction studies, litter sizes were somewhat lower in rats fed oxamyl at 100 or 150 ppm oxamyl with normal values seen at 50 ppm. Weanling body weights were normal in rats in the 50-ppm group for three generations but were reduced in the one-generation study. Pup body weights were lower in rats in both the 100- or 150-ppm groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic toxicity, reproductive, and teratogenic studies with oxamyl. 373 61

The concept of B-esterase buffering against anti-cholinesterase (ChE) insecticide toxicity has been extensively researched in mammalian species. Presumably due to relatively low levels of anti-ChE detoxifying enzyme activity in birds, however, avian species are often more susceptible to the toxic effects of these compounds. We quantified B-esterase buffering of organophosphate (diazinon and methyl parathion) and carbamate (aldicarb and oxamyl) toxicity in nestling European starlings (Sturnus vulgaris). The differential toxicities were studied using mortality, behavioral observation, and inhibitor affinity data. The toxicities of diazinon, methyl parathion, and oxamyl were affected by the removal of butyrylcholinesterase (BChE) using the specific inhibitor tetraisopropylpyrophosphoramide (iso-OMPA). When BChE was absent, aldicarb toxicity was not affected. Theoretically, compounds affected by BChE removal would have a higher affinity for BChE or carboxylesterase (CaE) than acetylcholinesterase (AChE). However, this was only the case for diazoxon, which had a 1,000-fold higher affinity for plasma BChE and CaE than AChE. Methyl paraoxon and aldicarb had a higher affinity for plasma AChE than for BChE or CaE. Oxamyl had similar IC50 values for all three enzymes studied. The generation of IC50 curves for each inhibitor revealed the presence of nonsensitive forms of CaE in both the plasma and brain. Based on the results of this research, there appears to be no strict correlation between mortality data and inhibitor affinities for each esterase that alone can explain the differential toxicities of these compounds.
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PMID:Differential toxicities of organophosphate and carbamate insecticides in the nestling European starling (Sturnus vulgaris). 1087 26