Blood cholinesterases determination

Laboratory tests are of value but must be interpreted with care because of possible false results. Our experience notes that these tests are only helpful when certain precautions are taken into consideration, and the results correctly interpreted. For example, taking blood specimens too early or too late, or not containing them in proper temperatures (as in the case of erythrocyte cholinesterase determination), can give very misleading results. The tim-... 

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 a practical way, the best appreciation of cholinesterase was performed using individual norms for RBC AChE. It seems to be the most sensitive parameter for monitoring cholinesterase changes in exposed workers, followed by a sensitivity for whole blood hemolysate. Plasma BuChE activity is not so specific and is a sensitive parameter. A decrease of 30% of individual norms seems to be critical for further consideration. In conclusion, cholinesterase determination in blood (especially RBC AChE) is a good parameter for monitoring and laboratory examination of... 

The methods for determination of blood cholinesterases inhibition (AChE and BuChE) do not allow identification of the OP and do not provide reliable evidence for exposure at inhibition levels less than 20%. Moreover, they are less suitable for retrospective detection of exposure due to de novo synthesis of enzymes. A method has been developed which is based on reactivation of phosphylated cholinesterase and carboxylesterase (CaE) by fluoride ions. Treatment of the inhibited enzyme with fluoride ions can inverse the inhibition reaction, yielding a restored enzyme and a phos-phofluoridate which is subsequently isolated and quantified by gas chromatography and phosphorus-specific or mass spectrometric detection (Dll, Pll). Human (and monkey) plasma does not contain CaE but its BuChE concentration is relatively high [70-80 nM (M25, D8)], much higher than the concentration of AChE in blood [ca. 3 nM (H5)]. The plasma of laboratory animals, such as rats and guinea pigs, contains considerable concentrations... 

The actual biological monitoring of workers to detect evidence of exposure such as a drop in blood cholinesterase levels or the presence of a urinary metabolite is superior to the indirect techniques employed in this study. Realizing the difficulties in accurately determining the dermal exposures of mixers, loaders, and applicators to pesticides, the employment of simpler monitoring techniques than the ones performed by CDFA in this report might... 

Several medical tests can determine whether you have been exposed to methyl parathion. The first medical test measures methyl parathion in your blood or measures 4-nitrophenol, which is a breakdown product of methyl parathion, in your urine. These tests are only reliable for about 24 hours after you are exposed because methyl parathion breaks down quickly and leaves your body. These tests cannot tell whether you will have harmful health effects or what those effects may be. The next medical test measures the levels of a substance called cholinesterase in your blood. If cholinesterase levels are less than half of what they should be and you have been exposed to methyl parathion, then you may get symptoms of poisoning. However, lower cholinesterase levels may also only indicate exposure and not necessarily harmful effects. The action of methyl parathion may cause lower cholinesterase levels in your red blood cells or your blood plasma. Such lowering, however, can also be caused by factors other than methyl parathion. For example, cholinesterase values may already be low in some people, because of heredity or disease. However, a lowering of cholinesterase levels can often show whether methyl parathion or similar compounds have acted on your nerves. Cholinesterase levels in red blood cells can stay low for more than a month after you have been exposed to methyl parathion or similar chemicals. For more information, see Chapters 3 and 7. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

Most of the signs and symptoms resulting from diazinon poisoning are due to the inhibition of an enzyme called acetylcholinesterase in the nervous system. This enzyme is also found in your red blood cells and a similar enzyme (serum cholinesterase) is found in blood plasma. The most common test for exposure to many organophosphorus insecticides, including diazinon, is to determine the level of cholinesterase activity in the red blood cells or plasma. This test requires only a small amount of blood and is routinely available in your doctor s office. It takes time for this enzyme to completely recover to normal levels following exposure. Therefore, a valid test may be conducted a number of days following the suspected exposure. This test indicates only exposure to an insecticide of this type. It does not specifically show exposure to diazinon. 

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. 

In California, mixer-loaders and spray applicators who work with toxicity category I and II organophosphates or N-methyl carbamates more than 30 hours per 30-day period are required to have medical supervision. Supervision consists of an interview and a medical examination to determine if a medical condition exists which would make the worker unusually susceptible to poisoning due to cholinesterase inhibition, and to caution the individual about the use of certain drugs such as the pheno-thiazine tranquilizers vdtich potentiate the effects of cholinesterase (ChE) inhibition. Two blood samples, taken several days apart, are analyzed to determine the individual s preexposure plasma and red blood cell (RBC) ChE activity (baseline value). The physician arranges a routine ChE testing program and provides for extra ChE tests should the worker be accidently exposed to OP s. If ChE activity is depressed to 50 percent of the baseline value, the physician may ask the employer to place the worker on... 

The Department has developed methods for monitoring the exposure of workers exposed to organophosphate and carbamate pesticides. These methods utilize the determination of plasma and red blood cell cholinesterase activities and urinary alkyl phosphates. Studies are reported vrti ich show that these methods have proven useful in evaluating the safety effectiveness of closed-transfer systems and in determining reentry times for field workers. 

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