Dichlorvos activity

In the body, metrifonate converts to the active metaboUte dichlorvos, (2,2-dichlorovinyl dimethyl phosphate), which is responsible for the inhibition of the enzyme acetylcholinesterase in the susceptible worm. This effect alone is unlikely to explain the antischistosomal properties of metrifonate (19). Clinically, metrifonate is effective only against infection caused by S. haematobium. Metrifonate is administered in three doses at 2-wk intervals (17). The dmg is well tolerated. Side effects such as mild vertigo, nausea, and cramps are dose-related. This product is not available in the United States. The only manufacturer of metrifonate is Bayer A.G. of Leverkusen, Germany. 

Dichlorvos (9.50) is an insecticide of reportedly wide use, the metabolites of which in humans include dichloroethanol and dimethyl phosphate. Like paraoxon, dichlorvos is hydrolyzed by human serum. However, the enzyme activities hydrolyzing the two substrates were shown to differ by a number of criteria [114], Clearly large gaps remain in our understanding of the human metabolism of organophosphorus insecticides and other toxins. A bacterial phosphodiesterase appears as a promising tool to understand the catalytic mechanisms of organophosphoric acid triester detoxification [115-117],... 

Chloroform has been used as a carrier or solvent for some pesticides (HSDB 1996). It is still used as a carrier for at least one pesticide formulation with dichlorvos as the active ingredient (Retrelli et al. 1993). Application of pesticides using chloroform in the carriers could have resulted in releases of chloroform to the land. It is impossible to quantify the magnitude of such releases, and the chloroform could be expected to be transported to either the atmosphere through volatilization or, if dissolved in water, carried into surface waters or groundwater. 

Metrifonate is an organophosphorous compound that is effective only in the treatment of S. haematobium The active metabolite, dichlorvos, inactivates acetylcholinesterase and potentiates inhibitory cholinergic effects. The schistosomes are swept away from the bladder to the lungs and are trapped. Therapeutic doses produce no untoward side effects except for mild cholinergic symptoms. It is contraindicated in pregnancy, previous insecticide exposure, or with depolarizing neuromuscular blockers. Metrifonate is not available in the United States. 

Metrifonate, an organophosphate compound, is rapidly absorbed after oral administration. After the standard oral dose, peak blood levels are reached in 1-2 hours the half-life is about 1.5 hours. Clearance appears to be through nonenzymatic transformation to dichlorvos, its active metabolite. Metrifonate and dichlorvos are well distributed to the tissues and are completely eliminated in 24-48 hours. 

In this application, the use of wild-type electric eel AChE and a recombinant AChE, specifically selected as very sensitive to dichlorvos, was compared. The effect of the matrix extract was determined by using various sample solvent ratios, 1 2.5, 1 5, 1 10, and 1 20. The optimal extraction ratio, considering the electrochemical interferences and the effect on enzyme activity and bioavailability of the pesticide, was 1 10. 

The method was calibrated both in buffer and durum wheat extract. The LODs in durum wheat samples were 0.45 mg/kg for the wild-type AChE and 0.07 mg/kg for rAChE. These characteristics allowed the detection of contaminated samples at the legal MRL, which is 2 mg/kg [4]. Moreover, fortified samples of durum wheat were obtained with both dichlorvos and the commercial product Didivane, which contains dichlorvos as active molecule. At all the tested levels, the occurrence of contaminant was detected with an average recovery of 75%. The total assay time, including the extraction step, was 30 min. Because several extractions as well as most of the assay steps can be run simultaneously, the throughput for one operator is 12 determinations per hour. In Table 29.1, we summarize the results obtained for the fortified samples. 

Biocides most often found in the indoor environment are chlorinated hydrocarbons like chlordane, DDT, dieldrin, lindane, heptachlor and methoxychlor, pyrethroids like cyfluthrin, cypermethrin, and permethrin, organophosphates like chlorpyrifos, diazinon, dichlorvos, isofenfos, and malathion, carbamates like ben-diocarb, carbaryl and propoxur and chlorophenols like pentachlorophenol (PCP), chlorocresol (4-chloro-3-methylphenol) and o-phenylphenol. Residues formed in house dust may vary in different countries (Butte, 2003), but biocides like chlorpyrifos, DDT, methoxychlor, permethrin, pentchlorophenol and propoxur seem to be the active compounds in biocide formulations even in different continents, as they are found equally in house dust samples form Germany and the USA (Becker et al., 2002 Butte, 2003 Camann, Colt and Zuniga, 2002). Concentrations of biocides in house dust are mostly in the milligram per kilogram range, they seldom exceed a microgram per cubic meter in indoor air. 

Until now, many substances including pesticides, extracts of plants, and microbial metabolites have been bioassayed to find inhibitory activity on AF production. Organophosphorus insecticides with cholinesterase inhibitory activity, such as dichlorvos (116 in Figure 26), can inhibit AF production by inhibiting the esterase... 

T ichlorvos (DDVP, dichlorovinyldimethyl phosphate) was first syn-thesized in the late 1940s, but active investigation of its insecticidal properties was not initiated until 1954. Investigations at that time revealed that low concentrations of the vapor of dichlorvos were toxic to adult mosquitoes and flies and that there appeared to be a relatively wide margin of safety between the insecticidal dose and the concentration required to affect man. 

Inhibition of the cholinesterase activity of the blood is the most sensitive means now available, with the possible exception of the inhibition of the esterase activity of the liver, for detecting the absorption of an organic phosphorus compound that is known to be capable of inducing this effect. The values indicative of cholinesterase activity are shown in Tables III and V. All subjects were exposed to the recommended dosage (one Vaporizer per 1000 cubic feet) except subjects 15 and 16, who were exposed to resin strips that contained no dichlorvos. 

Carboxylamidase activity toward p-nitroacetanilide has been detected in different insect species from the orders Lepidoptera, Orthoptera, and Dictyoptera. The carboxylamidase from fall army worm larvae has been purified. The purified enzyme is a monomer with a molecular weight of 59,000-60,000 Da. The enzyme is inhibited by the hydrolase inhibitors paraoxon, triphenyl phosphate, eserine, and phenylmethylsulfonyl fluoride, showing I50 values of 4.7 iM, 0.2 mM, 16 iM, and 90 iM, respectively. Activity is also completely inhibited by the organophosphorus insecticides profenfos and dichlorvos at 0.1 mM. The enzyme is active toward other amides, such as acetanilide and phenacetin, and various a- and p-naphtholic esters. Based on the purification factor, substrate specificity, and sensitivity to hydrolase inhibitors, the carboxylamidase appears to be different from carboxy-lesterases in the fall army worm (Yu and Nguyen, 1998). 

A report published thirty years ago (Ref. 164) outlined the potential insecticidal activity of 2,2-dichlorovinyl carbamates and carbonates. However, progress in this area has been stifled because 2,2-dihalovinyl chloroformates were unknown. For the preparation of the phosphonato ester (A) assumed to exhibit interesting insecticidal properties as compared to the well known insecticide Dichlorvos, we needed the heretofore unknown 2,2-dichlorovinyl chloroformate [see scheme 113]. 

Since 1917, only 11 new endoparasiticides have been developed for use in the horse. Many of the early compounds had very narrow spectra of activity and/or high potential for toxicity such that they have become obsolete. Febantel, levamisole, trichlorfon, dichlorvos, phenothiazine and carbon disulfide are no longer used routinely in the horse (Lyons et al 1999). 

Dichlorvos is of moderate acute toxicity, with an oral LD50 value in rodents from 50 to 150mgkg. While the LC50 for inhibiting mammalian brain acetylcholinesterase is similar between dichlorvos and paraoxon (i.e., the active metabolite of parathion), the acute LD50 values for these agents are considerably different, due in part to the more rapid metabolism and elimination of dichlorvos. 

In humans, the plasma cholinesterase appears more sensitive than erythrocyte cholinesterase to inhibition by dichlorvos thus, discrimination between these two activities may be warranted during assessment of exposures. 

In soil, dichlorvos is generally not active, and has low persistence, with a half-life of 7 days. 

Trichlorfon is primarily an indirect inhibitor of AChE, that is, it is converted in the body to the active chemical inhibitor dichlorvos. In fact, trichlorfon is considered to be a slow release cholinesterase inhibitor, transformed nonenzymatically to dichlorvos. This leads to irreversible AChE inhibition by phosphorylation, primarily at the synapses of the nervous system and at the neuromuscular junctions. Dichlorvos is... 

Bluegill and catfish were both able to hydrolyze DFP, dichlorvos, and dimethyl 2,2,2-trichloro-l-n-butyryloxyethyl phosphonate (butonate). Catfish enzymes were also able to hydrolyze paraoxon and methyl 3-hydroxy-alpha-cronate dimethyl phosphate (mevinphos) although at a very slow rate. Kms calculated for the enzymes of both species indicated that each had a greater affinity for DFP than dichorvos. Sulfhydryl reagents and Cu2+ were found to inhibit the enzymatic activity of both organisms. Paraoxon had no effect. Cleavage products were identified as dimethyl phosphate and 2,2-dichloroacetaldehyde from dichlorovos hydrolysis and diisopropyl phosphate from the hydrolysis of DFP. 

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