Cholinesterases plasma

Age/sex Plasma cholinesterase (mU per mL per minute) Erythrocyte cholinesterase (ApH/hour)"... 

Male rats exposed to 264 mg/m of methyl parathion by inhalation had 59% (range 53-61%) inhibition of blood (a combination of erythrocyte and plasma) cholinesterase 1 hour after exposure (EPA 1978e). These animals had typical cholinergic signs of toxicity salivation, exophthalmos, laerimation, spontaneous defecation and urination, and muscle fasciculation. Values for controls were not provided. Death was not correlated to the degree of eholinesterase inhibition in whole blood. 

Reductions in erythrocyte and plasma cholinesterase levels are considered biomarkers of neurological effects and not hematological effects as discussed in Sections 3.2.2.4 and 3.5.2. 

Mice that were exposed dermally to residues of methyl parathion in emulsifiable concentrate on foliage, and were muzzled to prevent oral intake, developed inhibition of plasma cholinesterase and erythrocyte cholinesterase after two 10-hour exposures (Skinner and Kilgore 1982b). For the organophosphate pesticides tested in this study, cholinergic signs generally were seen in mice with cholinesterase inhibition >50% results for this end point were not broken down by pesticide. 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Diagnosis of organophosphate poisoning (including methyl parathion) can be confirmed by evaluation of serum (plasma) cholinesterase and erythrocyte cholinesterase. However, cholinesterase inhibition is not specific for organophosphates. For example, carbamate insecticides also result in cholinesterase inhibition, which is usually transitory. Erythrocyte cholinesterase measurement is a specific test for... 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Women have exhibited significantly decreased plasma cholinesterase levels (De Peyster et al. 1994 ... 

Brock A. 1991. Inter and intraindividual variations in plasma cholinesterase activity and substance concentration in employees of an organophosphorus insecticide factory. Br J Ind Med 48 562-567. 

Evans RT, Wroe JM. 1980. Plasma cholinesterase changes during pregnancy. Anaesthesia 35 651-654. 

Fairbrother A, Bennett RS, Bennett JK. 1989. Sequential sampling of plasma cholinesterase in mallards (Anasplatyrh5Uichos) as an indicator of exposure to cholinesterase inhibitors. Environ Toxicol Chem 8 117-122. 

Howard JK, East NJ, Chaney JL. 1978. Plasma cholinesterase activity in early pregnancy. Arch Environ Health September/October 277-278. 

Moeller HC, Rider JA. 1959. The effects of various organic phosphate insecticides on RBC and plasma cholinesterase in humans [Abstract]. Fed Proc 18 424. 

Pope CN, Chakraborti TK. 1992. Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures. Toxicology 73 35-43. 

Venkataraman BV, Niyer GY, Narayanan R, et al. 1990. Er34hrocyte and plasma cholinesterase activity in normal pregnancy. Indian J Physiol Pharmacol 34 26-28. 

Released ACh is broken down by membrane-bound acetylcholinesterase, often called the true or specific cholinesterase to distinguish it from butyrylcholinesterase, a pseudo-or non-specific plasma cholinesterase. It is an extremely efficient enzyme with one molecule capable of dealing with something like 10000 molecules of ACh each second, which means a short life and rapid turnover (100 ps) for each molecule of ACh. It seems that about 50% of the choline freed by the hydrolysis of ACh is taken back into the nerve. There is a wide range of anticholinesterases which can be used to prolong and potentiate the action of ACh. Some of these, such as physostigmine, which can cross the blood-brain barrier to produce central effects and neostigmine, which does not readily... 

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

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. 

However, there are some data on interactions of phosphate esters with other compounds. Cocaine undergoes metabolism by three major routes one of these routes involves hydrolysis by liver and plasma cholinesterases to form ecgonine methyl ester. It has been suggested that cocaine users with serious complications tend to have lower plasma cholinesterase levels. Thus, it is possible that individuals with decreased plasma cholinesterase levels (such as resulting from organophosphate ester exposure) may be highly sensitive to cocaine (Cregler and Mark 1986 Hoffman et al. 1992). However, there are no experimental data to support this hypothesis. 

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