Methamidophos metabolites

Pathway a in Fig. 9.15 is one of amide hydrolysis mediated by a carboxy-amidase. The metabolite thus produced is methamidophos, the toxic species formed predominantly in insects and far less in mammals. Pathways b and c lead to an O-demethyl and a demethylthio metabolite, respectively. The re-... 

Fig. 9.15. Metabolism of acephate (9.82) in mammals [156]. Pathway a leads to toxification by producing methamidophos. Pathways b-d are reactions of detoxification that lead to an O-demethyl, a demethylthio, and a deacetylamino metabolite, respectively.

M. Mahajna, G. B. Quistad, J. E. Casida, Acephate Insecticide Toxicity Safety Conferred by Inhibition of the Bioactivating Carboxyamidase by the Metabolite Methamidophos , Chem. Res. Toxicol. 1997, 10, 64-67. 

CASRN 30560-19-1 molecular formula C4H10NO3PS FW 183.16 Soil. lu aerobic aud auaerobic soils, methamidophos aud carbou dioxide were ideutified as major soil metabolites (Hartley aud Kidd, 1987). The estimated half-life iu soil is 3 d (Wauchope, 1988). 

Animals. Metabolized to methamidophos q.v.). Plants Residual activity lasts for c. 10-15 days. The major metabolite is methamidophos (q.v.). 

Soil. Readily biodegraded and non-persistent soil DTJ0 2 days (aerobic) to 7 days (anaerobic). Methamidophos (q.v.) has been identified as a soil metabolite... 

Alachlor, benzene hexachloride, cycloodines, aldrin, chlordane, dieldrin, endrin, endosulfan, heptachlor, isodrin, telodrin and toxaphene, DDT and metabolites, dicofol, dimethoate, lindane, methoxychlor, mirex, pentachlorophenol, perthane Azinphosmethyl, bromophos ethyl, chlorpyrifos, crotoxyphos, demeton, diazinon, dichlorvos, ethion, fenitrothion, fensulfothin, fenthion, flusulfothin, methamidophos, mevinphos monocrotophos and dichrotophos, oxamyl, phorate, parathion (ethyl), parathion (methyl), phosphomidon, quinolphos temephos Aldicarb, benomyl, carbaryl, chlorpropham, fenvalerate, methomyl... 

Mahajna, M., Quistad, G.B., and Casida, J.E., Acephate insecticide Safety conferred by inhibition of the bioactivating carboxyamidase by the metabolite methamidophos, Chem. Res. Toxicol., 10, 64,1997. 

Acephate is converted to another organophosphorus compound, methamidophos, in the body. Studies with " C-acephate in mammals have shown 75% of the parent compound eliminated in the urine. Other major metabolites include 0,S-dimethyl phosphor-othioate (DMPT, 5%) and S-methyl acetyl phos-phoramidothioate (5%). 

Acephate is moderately toxic to mammals with an acute oral LD50 of 850-950 mg kg in rats, whereas its metabolite methamidophos is highly toxic to mammals. The common symptoms of acephate poisoning include salivation, nasal discharge, vomiting, diarrhea, nausea, blurred vision, difficulty in breathing, headache, and muscle weakness. Convulsions, coma, and death may occur in cases of severe acute poisoning. 

Both acephate and its metabolite, methamidophos, pose a high acute and chronic risk to birds. Studies in insects have shown that acephate is highly toxic to honey bees and other beneficial insects. Methamidophos is also very highly toxic to freshwater invertebrates. 

Glutathione conjugation. The involvement of glutathione transferases in OP metabolism was realized in the early 1960 s (35. 361. It was difficult to establish this fact because of similarities between glutathione transferase-and carboxylesterase-produced metabolites. Induction of glutathione transferase activity in the fall armyworm caused a 2- to 3-fold decrease in the toxicity of diazi-non, methamidophos, and methyl parathion (37.) This shows indirectly the importance of glutathione transferase activity in the detoxification of these OPs. 

Acephate is an organophosphate with high activity toward insects, but it seems to have low toxicity to other animals. It is systemic and is metabolized in plants to metamidophos, which has a much higher toxicity. But this activation does not seem to be so important in mammals. Methamidophos is also used as an insecticide/nematicide. Table 8.5 shows the high difference in toxicity toward acephate and its metabolite. 

Tomaszewaska and Hebert (2003) reported a method for the analysis of ( , -dimethyl hydrogen phosphorothioate (0,5-DMPT) in urine. 0,5-DMFT is a specific metabolite of methamidophos, The urine sample was extracted with a CIS column, and the sample was lyophilized at low temperature to prevent loss of highly volatile and thermally unstable metabolite (0,5-DMPT). The lyophilized residue was derivattzed using MTBSTFA and 1% terl-butyl-dimethylchlorosilane in acetonitrile. After filtration, the derivatized product was analyzed with GC/FPD (pulse FPD) in the phosphorus mode. The limit of detection for the method is reported as 0.004 ppm, with a mean recovery of 108%. 

Acephate and methamidophos are two OPs that do not produce DAPs. Acephate produces methamidophos on degradation thus, it is considered a metabolite of acephate. Olsson etal. (2003) included both acephate and metha-midopho.s in their analytical scheme for. specific metabolites. Chang and Lin (1995) reported a HPLC method for the determination of 3-mcthyl-4 nitrophenol in urine of rats orally dosed with fenitrothion. 

We should also mention that LiChrolut EN was successfully used for SPE pre-concentration of 90 pesticides from water—acetone extracts of fresh frxtits and vegetables with a subsequent pesticide analysis by GC-MS [285]. Only the most polar pesticides (methamidophos, acephate, and omethoate) could not be determined by this technique. Finally, a simple, fast, and sensitive method of determining a mycotoxine potuline (a metabolite of many moulds Penicillium and Aspergillus) in fruits and fruit juices was developed [286]. The method includes SPE pre-concentration of the toxin on Purosep 200 and its quantification by normal-phase FIPLC and provides recoveries over 90%, with LOD five times lower than the allowed tolerance Hmit, 50 Xg/kg. 

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