Alkyl phosphate metabolites

Shafik T, Bradway DE, Enos HF, et al. 1973. Human exposure to organophosphorus pesticides modified procedure for the gas-liquid chromatographic analysis of alkyl phosphate metabolites in urine. J Agric Food Chem 21 625-629. 

Knaak, J. B. Maddy, K. T. Khalifa, S. Alkyl phosphate metabolite levels in the urine of field workers giving blood for cholinesterase test in California. Bull. Environm. Contam. Toxicol., 1979, 21, 375. 

The detection of pesticide metabolites in the urine of workers indicates prior exposure. However, it is difficult to relate this level of urinary metabolite to the actual worker exposure, and it is equally difficult to Interpret the toxicological significance of the level. A preliminary study conducted in rats exposed dermally to 100, 200 and 400 ug of azinphos-methyl showed a significant linear correlation between the dermal dosage and the urinary alkyl phosphate metabolite levels (19). Further studies are being conducted in other species to determine whether a similar type of relationship occurs and to develop a standard curve in which urinary metabolite levels could be utilized to estimate the amount of dermal exposure. 

Human Exposure to Organophosphorus Pesticides. Modified Procedure for the Gas Chromatographic Determination of Alkyl Phosphate Metabolites in Urine... 

Davies JE, Peterson JC. 1997. Surveillance of occupational, accidental, and incidental exposure to organophosphate pesticides using urine alkyl phosphate and phenolic metabolite measurements. Aim NY Acad Sci 837 257-268. 

In urine, OPFR metabolites have been detected, but the median concentrations of the diaryl and dialkyl phosphates remained mostly below the quantification limit. Ranges of concentrations of dialkyl and diaryl phosphates are shown in Table 4. In the study of Schindler et al. [302, 303], the detection frequency was highest for BCEP (50%), followed by DPP (30%), BCPP (12%), and DBP (3%). Di-w-cresyl and di-/7-cresyl phosphate were not found in any sample, probably due to lower exposure in the indoor environment. Reemtsma et al. [304] found also monoaryl and alkyl phosphates in human urine, of which the monobutyl phosphate was the... 

Exposure to organophosphate pesticides is often measured by determination of alkyl phosphate or phenol metabolites in the urine. Determination of blood cholinesterase activity can be a valuable indicator of exposure if pre-exposure cholinesterase activity is known (3, 5). Since normal cholinesterase levels... 

In addition to the above-described alkyl phosphates, a few less common metabolites can be mentioned, e.g. 3,5,6-trichloro-2-pyridinol (TCP). TCP is a major product of esterase cleavage of the OPi chlorpyrifos and chlopyrifos-methyl." ° Urinary TCP, like other... 

In addition to the determination of the unmetabolized compounds to confirm exposure, the quantification of their metabolites, e.g. alkyl phosphate metabohtes or other characteristic metabolites, is a possibility. The most commonly used analytical methods for the... 

Gosselin et ai (2005) developed a multicompartment model to describe the kinetics of parathion and it,s metabolites. p-nitrophenol and alkyl phosphates, in order to as.scss worker exposure and health risks. For percutaneous... 

Measurement of alkyl phosphates in the urine is a widely used biomarker of exposure to OPs but it is not suitable for diagnostic purposes. Alkyl phosphates can generally be metabolites of more than one OP, an exception being prope-tamphos, whose metabolite methylethylphosphoramidothioate, is more or less... 

Stone). In the last-named situation, where there will be likely exposure to a mixture of OPs, there is a serious problem in that the biological significance of the findings will be unclear. Furthermore, alkyl phosphates may be present in the environment (presumably from biotic or abiotic degradation of OPs) so it cannot be assumed that all alkyl phosphate seen in human urine is derived from metabolism of OPs in humans. Substance-specific urinary metabolites can be measured as an alternative to, or in addition to alkyl phosphates,and one such is discussed above in relationship to propetamphos. Unlike the metabolite of propetamphos, which is an unusual alkyl phosphate, these are generally metabolites of the leaving group and include 2-isopropyl-6-methyl-pyrimidin-4-ol, a metabolite of diazinon, and 3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos. For a list of substance-specific urinary analytes available for seleeted OPs, see Jain. ... 

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

Many organic chemicals are analyzed by RPC. These include various arylhydroxylamines as the N-hydroxyurea derivative with methyl isocyanate (614) alkyl- and alkoxy-disubstituted azoxybenzenes (6t5), n-alkyl-4-nitrophenylcarbonate esters ranging in length from methyl to octyl (616), 4-nitrophenol in the presence of 4-nitrophenyl phosphate (617), ben-zilic acid, and benactyzine-HCI using ion-pair chromatography (618), as well as aniline and its various metabolites (619), stereoisomers of 4,4 -dihydroxyhydrobenzoin (620), and aldehydes and ketones as the 2,4-dinitrophenylhydrazones (621). The technique has also been used to analyze propellants and hydrazine and 1,1-dimethylhydrazine were quantitita-vely determined (622, 623). 

These studies have been extended by Pearson et al. (1993a,b), who showed that a number of metabolites contribute to protein binding in addition to 2-bromoacrolein. The major metabolic pathw ay leading to protein binding is C-2 oxidation of the 2,3-dibromo-propyl groups, giving a reactive a-bromoketone which might either alkylate proteins directly or be hydrolysed to bis(2,3,-dibromopropyl) phosphate and an a-bromo-a -hydroxyketone w hich could mediate the alkylation of protein. 

Recently, several nucleophilic reagents have been used to establish the mode of action of the metabolites of polycyclic aromatic hydrocarbons (PAH). Among them, several phosphodiesters have been examined to clarify the possibility of reaction of PAH epoxides with the phosphate groups(P-alkylation) of nucleic acids (22). In this context we have studied the reaction of 3,4-epoxyprecocene II with dibenzyl phosphate under a variety of conditions. In all cases, instead of the formation of phenol or phosphotriesters observed with PAH epoxides, we obtained predominantly dimer XI. This compound was also the main component of the mixtures obtained by reaction of the above precocene epoxide with other acid catalysts, along with dimers XII and XII. Dimer XII was formed almost exclusively by thermal treatment. The structure and configuration for compound XII has been established by spectral and X-ray diffraction analyses (23). 

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