Hydroxy diazinon

Diazinon is rapidly biotransformed and excreted in mammals. Estimated half-times of diazinon persistence were 6 to 12 h in rats (Anonymous 1972) and dogs (Iverson et al. 1975). Most of the diazinon metabolites were excreted in the urine as diethyl phosphoric add and diethyl phosphorothioic acid in dogs (Iverson et al. 1975), and as hydroxy diazinon and dehydrodiazinon in sheep (Machin et al. 1974). 

More in-depth profiling of the in vitro hepatic metabolism of diazinon was carried out in carp, dace (Tribolodon hakonensis), channel catfish, rainbow trout and yellowtail (Seriola quinqueradiata)2S. All fish were able to catalyze the desulfuration of diazinon to the oxon. In freshwater fish, the predominant metabolites were isopropenyl diazinon and hydroxypyrimidine. In the carp, dace and catfish, hydroxy diazinon was observed, while hydroxymethyl diazinon was the major metabolite in the yellowtail. In rainbow trout and catfish, isopropenyl diazoxon was observed. In the freshwater fish, more than 70% of diazinon was converted to metabolites with 50% of the metabolites being the nontoxic hydroxypyrimidine. However, in yellowtails, more than 70% of diazinon remained as toxic P-containing esters including the oxon. It was hypothesized that yellowtails had approximately 50% of the CYP levels of carp and rainbow trout and were not capable of converting diazinon to the other metabolites. 

Diazinon is an example of an organophosphorus compound that can undergo photoisomerization reactions (see Fig. 4.5), in addition to the formation of diazoxon and hydroxy diazinon (Mansour et al., 1999). In the environment, the presence of other compounds can also result in additional mechanisms, such as photosensitization (either by interaction with a chromophore or by reaction with reactive oxygen species), or photo-catalytic reactions in the presence of metal ions or on particle surfaces. 

Plant. Diazinon was rapidly absorbed by and translocated in rice plants. Metabolites identified in both rice plants and a paddy soil were 2-isopropyl-4-methyl-6-hydroxypyri-midine (hydrolysis product), 2-(l -hydroxy-l -methyl)ethyl-4-methyl-6-hydroxypyrimi-dine and other polar compounds (Laanio et al., 1972). Oxidizes in plants to diazoxon (Ralls et al., 1966 Laanio et al., 1972 Wolfe et al., 1976) although 2-isopropyl-4-methyl-6-pyrimidin-6-ol was identified in bean plants (Kansouh and Hopkins, 1968) and as a hydrolysis product in soil (Somasundaram et al., 1991) and water (Suffet et al., 1967). Five days after spraying, pyrimidine ring-labeled C-diazinon was oxidized to oxodiazinon which was then hydrolyzed to 2-isopropyl-4-methylpyrimidin-6-ol which in turn, was further metabolized to carbon dioxide (Ralls et al., 1966). Diazinon was transformed in field-sprayed kale plants to form hydroxy diazinon (9,0-diethyl-0-[2-(2 -hydroxy-2 -pro-pyl)-4-methyl-6-pyrimidii5rl] phosphorothioate which was not previously reported (Par-due et al., 1970). 

We also enconnter tautomerism in hydroxy- and amino-diazines, and the preference for one tautomeric form over the other follows what we have seen with the pyridine derivatives. Thus, with the exception of 5-hydroxypyrimidine, all the mono-oxygenated diazines exist predominantly in the carbonyl tan-tomeric form. We term these amide-like tautomers diazinones. 5-Hydroxypyrimidine is analogous to 3-hydroxypyridine, in that the hydroxyl is wrongly positioned for tautomerism. 

Diazinon is the Ciba-Geigy Corporation trademark name for the active ingredient 0,0-diethyl-0-(2-[l-methylethyl]-4-methyl-6-pyrimidinyl) phosphorothioate. This insecticide is produced commercially by reacting 2-isopropyl-4-hydroxy-6-methylpyrimidine and 0,0-diethyl phosphorochloridothioate (HSDB... 

Soil (diazinon, diazoxon, 2-isopropyl-4-methyl-6-hydroxy-pyrimidine)... 

Extraction of soil with hexane acetone (1 1), centrifugation, separation of hexane from acetone/water layer. Extraction of acetone/water phase with chlorofornrdiethyl ether (1 1), solvent exchanged to methanol. Hexane layer contained diazinon, chloroform/diethyl ether fraction contained 2-isopropyl-4-methyl-6-hydroxy-pyrimidine. 

Methods for Determining Biomarkers of Exposure and Effect. Section 2.6.1 reported on biomarkers used to identify or quantify exposure to diazinon. Some methods for the detection of the parent compound in biological samples were described above. The parent chemical is quickly metabolized so the determination of metabolites can also serve as biomarkers of exposure. The most specific biomarkers will be those metabolites related to 2-isopropyl-6-methyl-4-hydroxypyrimidine. A method for this compound and 2-(r-hydroxy-l -methyl)-ethyl-6-methyl-4-hydroxypyrimidine in dog urine has been described by Lawrence and Iverson (1975) with reported sensitivities in the sub-ppm range. Other metabolites most commonly detected are 0,0-diethylphosphate and 0,0-diethylphosphorothioate, although these compounds are not specific for diazinon as they also arise from other diethylphosphates and phosphorothioates (Drevenkar et al. 1993 Kudzin et al. 1991 Mount 1984 Reid and Watts 1981 Vasilic et al. 1993). Another less specific marker of exposure is erythrocyte acetyl cholinesterase, an enzyme inhibited by insecticidal organophosphorus compounds (see Chapter 2). Methods for the diazinon-specific hydroxypyrimidines should be updated and validated for human samples. Rapid, simple, and specific methods should be sought to make assays readily available to the clinician. Studies that relate the exposure concentration of diazinon to the concentrations of these specific biomarkers in blood or urine would provide a basis for the interpretation of such biomarker data. 

Diazinon persisted for about 15 days in a flooded soil (pH 6,6) that had been treated previously with the insecticide but, in a flooded soil that had never been exposed to diazinon, it persisted for about 60 days. Similarly, water from a diazinon-treated rice field inactivated the insecticide within 5 days after incubation. Microorganisms that developed in response to insecticide application accelerated its hydrolysis and the subsequent mineralization of the hydrolysis product, 2-isopropyl-6-methyl-4-hydroxy pyrimidine, to COg. A Fla-vobacterium sp., isolated from water of a treated rice field, had exceptionally high capability to metabolize diazinon as sole carbon source. This provides unequivocal evidence that microbes are involved in the rapid inactivation of diazinon in rice fields. 

Figure 2. Formation of hydrolysis product, 2-isopropyl-6 methyl-4 hydroxy pyrimidine (H) from C-diazinon (D) incubated with water from a rice field treated previously with diazinon (19)...

In this report tests of operator exposure were conducted with the Nice N Green Company and ChemLawn Corporation. Studies to evaluate potential applicator exposure to diazinon (0,0-diethyl 0-[methyl-2-(I-methyl ethyl)-4-primidinyl]phosphorothioate) insecticide were made on 3 August, 18 and 28 September, 1979 and for the insecticide trichlorfon (dimethyl 2,2,2, trichloro-I-hydroxy-ethyl) phosphonate) on 5 September, 1979. 

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