Organophosphorus compounds exposure

Funk, K. A., Liu. C. H., Higgins, R. J.. and Wilson, B. W. (1994). Aviaii embryonic brain reaggregatc culture system. II, NTE activity discriminiues between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure. Toxicol. Appl. Pharmacol. 124, 159-163. 

Cholinesterase inhibitor a severely acute toxicant delayed effects may be observed after several hours toxic symptoms similar to other organophosphorus compounds exposure may cause headache, dizziness, blurred vision, and muscle spasms. Other toxic symptoms include vomiting, abdominal pain, diarrhea, seizures, and shortness of breath ingestion of 5-10 g could be fatal to adult humans oral LD50 value (mice) 15 mg/kg, rats 7 mg/kg LC50 inhalation (rat) 69 mg/m /1 h... 

Sigolaeva, L., Makhaeva, G., Rudakova, E., et al., 2010. Biosensor analysis of blood esterases for organophosphorus compounds exposure assessment approaches to simultaneous determination of several esterases. Chem. Biol. 

Larsen K-0, Hand HK. 1982. Effect of exposure to organophosphorus compounds on S-cholinesterase in workers removing poisonous depots. Scand J Work Environ Health 8 222-226. 

Organophosphate Ester Hydraulic Fluids. A number of studies have been conducted on organophosphate ester hydraulic fluids because of the well known neurotoxic effects caused by organophosphorus insecticides, organophosphorus nerve gases, and tri-ort/w-cresyl phosphate (TOCP). The following manifestations of acute exposure to organophosphorus compounds have been described ... 

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. 

With irreversible interactions, however, a single interaction will theoretically be sufficient. Furthermore, continuous or repeated exposure allows a cumulative effect dependent on the turnover of the toxin-receptor complex. An example of this is afforded by the organophosphorus compounds, which inhibit cholinesterase enzymes (see Aldridge (7) and chap. 7). 

For example, no difference in the toxicity of organophosphorus compounds to larvae of the midge Chrironomus riparius was observed between pulsed and continuous exposures (Kallander et al. 1997). In the same study, however, two 1-hour pulses caused significantly fewer symptoms of intoxication than 2 hours of continuous exposure to carbamate compounds, when animals were placed in clean water for at least 2 to 6 hours between treatments (Kallander et al. 1997), suggesting that detoxification or elimination of the toxicant during the toxicant-free period can reduce the toxic effects of the earlier exposures. 

Plasma or serum cholinesterase (pseudocholinesterase) is inhibited by a munber of compounds and can also be decreased in ftie presence of liver impairment. Erythrocyte cholinesterase (true cholinesterase) reflects more accurately the cholinesterase status of the central nervous system. However, pseudocholinesterase activity responds more quickly to an inhibitor and returns to normal more rapidly than eiythrocyte-cholinesterase activity. Thus, measurement of pseudocholinesterase activity is quite adequate as a means of diagnosing acute exposure to organophosphorus compounds, but cases of illness which may be due to chronic exposure to these compounds should also be investigated by determining the erydirocyte-cholinesterase activity. A colorimetric method for this purpose has been reported (K.-B. Augustinsson et ah, Clinica chim. Acta, 1978, 89, 239-252). 

Miller, J.K., Lenz, D.E. (2001). Development of an immunoassay for diagnosis of exposure to toxic organophosphorus compounds. J. Appl. Toxicol. 21 S23-6. 

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