Cholinesterase in blood

Disulfoton and its breakdown products can be measured in the blood, urine, feces, liver, kidney, or body fat of exposed people. In cases of occupational or accidental exposure to disulfoton, the breakdown products are often measured in the urine. The breakdown products are relatively specific for disulfoton and a few other similar organophosphate pesticides and can be detected in urine for up to one week after people were last exposed. Because disulfoton inhibits cholinesterase in blood and in blood cells, inhibition of this enzyme activity may also suggest exposure to disulfoton. Cholinesterase activity in blood and in blood cells may remain inhibited for as long as 1-2 weeks after the last exposure. Because other organophosphate pesticides also inhibit cholinesterase activity in blood and blood cells, this test is not specific for disulfoton. The measurement of cholinesterase in blood and blood cells and the amount of disulfoton breakdown products in the urine cannot always predict how much disulfoton you were exposed to. Your doctor can send samples of your blood or urine to special laboratories that perform these tests. Chapters 2 and 6 provide more information about medical tests. 

T. Yao, Flow Injection Analysis for Cholinesterase in Blood Serum by Use of a Choline-Sensitive Electrode as an Amperometric Detector. Anal. Chim. Acta, 153 (1983) 169. 

With some modifications, an electrode system can be made responsive to enzyme levels in test solution by surrounding the ion-sensitive membrane with substrate molecules. For example, an electrode that will measure the enzyme activity of cholinesterases in blood fractions has been described. GeneraUy, such electrodes must be designed to replenish the substrate since it is consumed in the reaction. 

Yao T. (1983) Flow injection analysis for cholinesterase in blood serum by use of a choline-sensitive electrode as an amperometric detector. Anal. Chim. Acta, 153, 169-174. 

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. 

Function in blood, eg, coagulation factors, cholinesterase Leakage from cells or tissues, eg, aminotransferases... 

Hydraulic fluids themselves cannot be measured in blood, urine, or feces, but certain chemicals in them can be measured. Aliphatic hydrocarbons, which are major components of mineral oil hydraulic fluids and polyalphaolefin hydraulic fluids, can be detected in the feces. Certain components of organophosphate ester hydraulic fluids leave the body in urine. Some of these fluids inhibit the enzyme cholinesterase. Cholinesterase activity in blood can be measured. Because many other chemicals also inhibit cholinesterase activity in blood, this test is not specific for organophosphate ester hydraulic fluids. This test is not available at most doctor s offices, but can be arranged at any hospital laboratory. See Chapters 2 and 6 for more information. 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

There are different types of cholinesterases in the human body, and they differ in their location in tissues, substrate affinity, and physiological function. The main ones are ACHE, present in nervous tissue and red blood cells (RBC-ACHE), and plasma cholinesterases (PCHE), present in glial cells, plasma, and liver. The physiological functions of RBC-ACHE and PCHE, if any, are unknown. 

T Anders, LA Svensson. Bambuterol, a carbamate ester prodrug of terbutaline, as inhibitor of cholinesterases in human blood. Drug Metabol Dispos 16(5) 759-763,... 

All groups seemed normal at day 150 no difference in blood or serum cholinesterase activity... 

Presently available methods to diagnose and biomonitor exposure to anticholinesterases, e.g., nerve agents, rely mostly on measurement of residual enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in blood. More specific methods involve analysis of the intact poison or its degradation products in blood and/or urine. These approaches have serious drawbacks. Measurement of cholinesterase inhibition in blood does not identify the anticholinesterase and does not provide reliable evidence for exposure at inhibition levels less than 20 %. The intact poison and its degradation products can only be measured shortly after exposure. Moreover, the degradation products of pesticides may enter the body as such upon ingestion of food products containing these products. 

Thus a distinction was provided between simple esterases, such as fiver esterase, which catalysed the hydrolysis of simple aliphatic esters but were ineffective towards choline esters. The term 1 cholinesterase was extended to other enzymes, present in blood sera and erythrocytes of other animals, including man, and in nervous tissue, which catalysed the hydrolysis of acetylcholine. It was assumed that only one enzyme was involved until Alles and Hawes2 found that the enzyme present in human erythrocytes readily catalysed the hydrolysis of acetylcholine, but was inactive towards butyrylcholine. Human-serum enzyme, on the other hand, hydrolyses butyrylcholine more rapidly than acetylcholine. The erythrocyte enzyme is sometimes called true cholinesterase, whereas the serum enzyme is sometimes called pseudo-cholinesterase. Stedman,3 however, prefers the names a-cholinesterase for the enzyme more active towards acetylcholine, and / -cholinesterase for the one preferentially hydrolysing butyrylcholine. Enzymes of the first type play a fundamental part in acetylcholine metabolism in vivo. The function of the second type in vivo is obscure. Not everyone agrees with the designation suggested by Stedman. It must also be stressed that enzymes of one type from different species are not always identical in every respect.4 Furthermore,... 

The immediate clinical effects and simultaneous changes in blood-cholinesterase activity produced by an intramuscular injection of neostigmine were compared with those which resulted from an intramuscular injection of D.F.P. 

D.F.P. in small doses was administered for prolonged periods, and the clinical effects and concomitant changes in blood-cholinesterase activity were studied. 

Inhibition of the two principal human cholinesterases, acetylcholinesterase and pseudocholinesterase, may not always result in visible neurological effects (Sundlof et al. 1984). Acetylcholinesterase, also referred to as true cholinesterase, red blood cell cholinesterase, or erythrocyte cholinesterase is found in erythrocytes, lymphocytes, and at nerve synapses (Goldfrank et al. 1990). Inhibition of erythrocyte or lymphocyte acetylcholinesterase is theoretically a reflection of the degree of synaptic cholinesterase inhibition in nervous tissue, and therefore a more accurate indicator than pseudocholinesterase activity of inhibited nervous tissue acetylcholinesterase (Fitzgerald and Costa 1993 Sundlof et al. 1984). Pseudocholinesterase (also referred to as cholinesterase, butyrylcholinesterase, serum cholinesterase, or plasma cholinesterase) is found in the plasma, serum, pancreas, brain, and liver and is an indicator of exposure to a cholinesterase inhibitor. 

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. 

Workers exposed to carbaryl dust at levels that occasionally reached 40mg/m had slight depression in blood cholinesterase activity but no clinical symptoms. In general, cases of occupational poisoning by carbaryl are rare because mild symptoms appear long before a dangerous dose is absorbed, furthermore. 

Exposure to disulfoton can result in inhibition of cholinesterase activity in blood and at nerve synapses of muscles, secretory organs, and nervous tissue in the brain and spinal cord. Central nervous system signs and symptoms include anxiety, restlessness, depression of respiratory and circulatory centers, ataxia, convulsions, and coma. 

In humans, an oral dose of 3-5mg/kg is usually fatal. In a study of 115 workers exposed to parathion under varying conditions, the majority excreted significant amounts of p-nitrophenol (a metabolite of parathion) in the urine, whereas only those with heavier exposures had a measurable decrease in blood cholinesterase. Measurement of urinary p-nitrophenol can be useful in assessing parathion absorption in occupational or other settings. ... 

Eye exposure can produce visual disturbances without affecting blood cholinesterase levels. Exposed crop duster pilots, unable to judge distances, have been involved in accidents. Volunteers instilled with 2 drops of 0.1 % TEPP 30 minutes apart experienced maximal miosis without any change in blood cholinesterase. ... 

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