Organophosphate insecticide metabolites

Organophosphate insecticide metabolites Breakdown products of organophosphate insecticides. Have been found in urine of adult farmworkers and children exposed to the organophosphate residues. 

Within this context, an interesting methodology using UPLC-QTOE-MS has been developed to achieve this purpose. Hernandez et al. [117] were able to evaluate the potential of the UPLC-MS technique for the characterization of phosmet (organophosphate insecticide) metabolites in VOO positives samples. 

As discussed in Section 2.5.1, the detection of certain thiophosphate esters in human urine may indicate exposure to disulfoton and/or other organophosphate insecticides. Several methods are available for the quantitation of organophosphorus metabolites from urine (Bradway et al. 1981 Daughton et al. 1976 Lores and Bradway 1977 Shafik et al. 1973). 

Still another experimental route to introducing otherwise excluded molecules into the brain is to chemically modify them so that they are lipophilic and therefore can passively diffuse. The brain, just as most other organs and tissues of the body, has enzymes to metabolize or biotransform metabolites in order to use and then get rid of them. Many of these pathways are oxidative. A reduced species or derivative which is lipophilic can enter the brain by simple passive diffusion there to be oxidatively transformed into an active state. Compounds which have been tested in animals include derivatives of 2-PAM (an antidote for organophosphate insecticide poisoning) and phenylethylamine (similar to amphetamine type molecules). Figure 5 illustrates the general concept behind this method. 

In a study of biomarkers of exposure to organophosphate insecticides, the urine of 6- and 7-year-old Italian children was analyzed for dimethyl- and diethyl- phosphates, thiophosphates, and dithiophosphates, such as the examples shown in Figure 18.11. Levels of these metabolites were found to correlate well with insecticide applications inside or outside the homes where the children... 

Tarbah FA, Kardel B. Pier S, Temme O, Daldrup T. Acute poisoning with phosphamidon determination of dimethyl phosphate (DMP) as a stable metabolite in a case of organophosphate insecticide intoxication. J Anal Toxicol 2004 28 198-203. 

Tarbah, F. A., Kardel, B., Pier. S Temme, 0 and Daldrup, T. (2004). Acute poisoning with phosphamidon Determination of dimethyl phosphate (DMP) a.s a stable metabolite io a ca.se of organophosphate insecticide poisoning. J. Anal. Toxicol- 28, 198-203. 

Esterase activity is important in both the detoxication of organophosphates and the toxicity caused by them. Thus brain acetylcholinesterase is inhibited by organophosphates such as paraoxon and malaoxon, their oxidized metabolites (see above). This leads to toxic effects. Malathion, a widely used insecticide, is metabolized mostly by carboxylesterase in mammals, and this is a route of detoxication. However, an isomer, isomalathion, formed from malathion when solutions are inappropriately stored, is a potent inhibitor of the carboxylesterase. The consequence is that such contaminated malathion becomes highly toxic to humans because detoxication is inhibited and oxidation becomes important. This led to the poisoning of 2800 workers in Pakistan and the death of 5 (see chap. 5 for metabolism and chap. 7 for more details). 

The action spectrum for DDT and its structural analogs is known to be quite broad and cannot be attributed to simple enzyme inhibition, as in the case of the carbamates or the organophosphates. The presence of chloroaryl moieties, as well as steric effects at receptor sites, both appear to be factors affecting insecticidal activity. In addition to DDT itself, its metabolites DDE and DDA and DDD have some activity. Efforts to overcome insect resistance and to produce more biodegradable analogs led to the introduction of substituents other than chlorine for... 

Figure 9.17. Organophosphate inhibitors of acetylcholinesterase. a The catalytic mechanism, shown here for diiso-propylfluorophosphate(DFP).b Stmcturesof soman and tabun. Like DFP, these were developed during world war II as nerve gases , c Stractures of the insecticides parathion and malathion, and of paraoxon, which is the achve metabolite of parathion. (Malathion likewise requires conversion to malaoxon.) The arrow above the malathione stmcture indicates the esterase cleavage sites in its leaving group esterase cleavage occurs in human plasma and renders the molecule non-toxic.

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. 

The purpose of Experiments 3 and 4 is to present methods for the TLC determination of pesticides. Experiment 3 describes procedures for the separation and detection of organochlorine (OCl), organophosphorus or organophosphate (OP), and Ai-methylcarbamate insecticides and metabolites (Sherma and Bloomer, 1977 Sherma et al., 1977, 1978 Sherma, 1978). Experiment 4 describes the quantitative TLC determination of three classes of herbicides after isolation from water by conventional separatory funnel extraction or solid-phase extraction (SPE) (Sherma, 1986c Sherma and Boymel, 1983). 

Human serum paraoxonase (PON 1) is an esterase that is physically associated with high-density lipoprotein (HDL) and is also distributed in tissues such as liver, kidney, and intestine [38,39]. Activities of PON 1, which are routinely measured, include hydrolysis of organophosphates, such as paraoxon (the active metabolite of the insecticide parathion) hydrolysis of arylesters, such as phenyl acetate and lactonase activities. Human serum paraoxonase activity has been shown to be inversely related to the risk of cardiovascular disease [40,41], as shown in atherosclerotic, hypercholester-olemic, and diabetic patients [42-44]. In 1998 HDL-associated PON 1 was shown to protect LDL, as well as the HDL particle itself, against oxidation induced by either copper ions or free radical generators [45,46], and this effect could be related to the hydrolysis of the specific lipoproteins oxidized lipids such as cholesteryl linoleate hydroperoxides and oxidized phospholipids. Protection of HDL from oxidation by PON 1 was shown to preserve... 

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