Biomarkers organophosphorus compounds

Although analysis of urine samples for the presence of these metabolites represents a potential means of assessing recent human exposure to diazinon, these metabolites can originate from exposure to other organophosphorus compounds and, therefore, are not specific for diazinon exposure. Additionally, these studies do not report a quantitative association between metabolite levels and exposure to diazinon in humans. Thus, these biomarkers are only indicative of exposure to diazinon (or other organophosphorus compounds) and are not specifically useful for diazinon exposure nor for dosimetric analysis. Further studies designed to refine the identification of metabolites specific to diazinon and provide dosimetric data will be useful in the search for a more dependable biomarker of diazinon exposure. 

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. 

Makhaeva, G.F., Sigolaeva, L. V., Zhuravleva, L.V., Eremenko, A. V., Kurochkin, I.N., Malygin, V. V., and Richardson, R.J. Biosensor detection of Neuropathy Target Esterase in whole blood as a biomarker of exposure to neuropathic organophosphorus compounds. J. Toxicol. Environ. Health, Part A, 66, 599-610,2003. 

Marsillach, J., Costa, L.G., Furlong, C.E., 2013. Protein adducts as biomarkers of exposure to organophosphorus compounds. Toxicology 307,46-54. 

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