Cholinesterase levels

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. 

Developmental Effects. Adverse effects of methyl parathion on hirman fetal development have not been reported. Based on studies in animals, such effects appear to be possible if pregnant women were exposed during the first trimester to high concentrations of methyl parathion that resulted in significant depression of cholinesterase levels, particularly if concomitant signs and symptoms of organophosphate intoxication occur. Such an exposure scenario may occur with occupational exposure, exposure in homes or offices illegally sprayed with methyl parathion, or accidental exposure to methyl parathion, but is less likely as a result of low-level exposure. 

Neurological effects related to cholinesterase depression occurred in seven children acutely exposed to methyl parathion by inhalation as well as orally and dermally (Dean et al. 1984). The children were admitted to a local hospital with signs and symptoms of lethargy, increased salivation, increased respiratory secretions, and miosis. Two of the children were in respiratory arrest. Two children died within several days of each other. All of the children had depressed plasma and erythrocyte cholinesterase levels (Table 3-2). These effects are similar to those occurring in methyl parathion intoxication by other routes (see Sections 3.2.2.4 and 3.2.3.4). Three adults exposed in the same incident had normal plasma (apart from one female) and red blood cell cholinesterase, and urinary levels of 4-nitrophenol (0.46-12.7 ppm) as high as some of the ill children. 

Table 3-2. Plasma and Erythrocyte Cholinesterase Levels in Children Intoxicated by Methyl Parathion ...

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. 

M (44% decreased plasma and 25% decreased brain cholinesterase levels)... 

Neurologic signs did not occur over a 30-day period in male prisoner volunteers in California who ingested daily doses of methyl parathion ranging from 1.0 to 19 mg. There were no uniform changes in plasma or erythrocyte cholinesterase levels at any of these doses (Rider et al. 1969). By increasing concentrations of methyl parathion administered to the same experimental population and using the same protocol, a dose that inhibited cholinesterase values was established. These additional studies were published nearly 20 years ago in abstract form only therefore, they are not discussed in this section. 

When methyl parathion was given orally to rats at doses of 1.5 mg/kg and to guinea pigs at 50 mg/kg, plasma, erythrocyte, and brain cholinesterase activity was maximally inhibited within 30 minutes after administration. In rodents of both species that died after acute intoxication, brain cholinesterase levels decreased to 20% of control values and often to 5-7% (Miyamoto et al. 1963b). The species difference in susceptibility to orally administered methyl parathion is noted in Section 3.2.2.1. 

Erythrocyte cholinesterase levels were monitored in two men exposed dermally to methyl parathion after entering a cotton field that had been sprayed with this pesticide (Nemec et al. 1968). The field was entered on two separate occasions twice within 2 hours after an ultra-low-volume spraying and a third time within 24 hours after spraying. Dermal methyl parathion residues 2 hours after spraying were 2-10 mg on the arms dermal residues 24 hours after spraying were 0.16-0.35 mg on the arms. The exposed individuals did not have signs of cholinergic toxicity, but erythrocyte cholinesterase levels after the third exposure were 60-65% of preexposure levels. 

In a case-control study of pesticide factory workers in Brazil exposed to methyl parathion and formulating solvents, the incidence of chromosomal aberrations in lymphocytes was investigated (De Cassia Stocco et al. 1982). Though dichlorodiphenyltrichloroethane (DDT) was coformulated with methyl parathion, blood DDT levels in the methyl parathion-examined workers and "nonexposed" workers were not significantly different. These workers were presumably exposed to methyl parathion via both inhalation and dermal routes however, a dose level was not reported. The exposed workers showed blood cholinesterase depressions between 50 and 75%. However, the baseline blood cholinesterase levels in nonexposed workers were not reported. No increases in the percentage of lymphocytes with chromosome breaks were found in 15 of these workers who were exposed to methyl parathion from 1 week to up to 7 years as compared with controls. The controls consisted of 13 men who had not been occupationally exposed to any chemical and were of comparable age and socioeconomic level. This study is limited because of concomitant exposure to formulating solvents, the recent history of exposure for the workers was not reported, the selection of the control group was not described adequately, and the sample size was limited. 

Often, absorption occurs by multiple routes in humans. Dean et al. (1984) reported deaths and toxic effects as well as lowered blood cholinesterase levels and excretion of urinary 4-nitrophenol in several children who were exposed by inhalation, oral, and possibly dermal routes after the spraying of methyl parathion in a house. In the same incident (Dean et al. 1984), absorption was indicated in adults who also excreted 4-nitrophenol in the urine, though at lower levels than some of the children, and in the absence of other evidence of methyl parathion exposure. In this study, the potential for age-related differences in absorption rates could not be assessed because exposure levels were not known and the children may have been more highly exposed than the adults. Health effects from multiple routes are discussed in detail in Section 3.2. 

Most of the toxic effects caused by methyl parathion resulted from exposure by multiple routes, especially for workers in sprayed fields or formulating facilities, or people in homes. Dean et al. (1984) reported deaths and toxic effects in several children as well as lowered blood cholinesterase levels and excretion of urinary 4-nitrophenol (adults showing no adverse effects also excreted 4-nitrophenol). 

A classification of organophosphate poisoning has been proposed by Tafuri and Roberts (1987) modified from Namba et al. (1971). Clinical signs and symptoms of intoxication may occur when serum cholinesterase levels drop to below 50% of the normal value. Mild poisoning, with the patient still ambulatory, may occur when serum cholinesterase levels are 20-50% of normal moderate poisoning with inability to walk with levels 10-20% of normal and severe poisoning with respiratory distress and unconsciousness with serum cholinesterase levels <10% of normal. 

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 ... 

Nemec SJ, Adkisson PL, Dorough HW. 1968. Methyl parathion adsorbed on the skin and blood cholinesterase levels of persons checking cotton treated with ultra-low-volume sprays. J Econ Entomol 61 1740-1742. 

Most chemical agents are essentially cumulative in their effects. The reason is that the human body detoxifies them very slowly or not at all. For example, a 1-h exposure to HD or CG followed within a few hours by another 1-h exposure has about the same effect as a single 2-h exposure. Continued exposure to low concentrations of HD may cause sensitivity to very low concentrations of HD. Other chemical agents also have cumulative effects. For example, an initial exposure to a small (less than lethal) amount of Sarin (GB) would decrease cholinesterase levels a second quantity less than the FDS0... 

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. 

May cause severe and painful irritation of the eyes, nose, throat, and lungs. Severe exposure can cause accumulation of fluid in the lungs (pulmonary edema). Inhalation toxicity similar to hydrogen chloride and hydrogen fluoride. May cause second or third degree burns upon short contact with skin surfaces. Oral ingestion may result in tissue destruction of the gastrointestinal tract. Decreased blood cholinesterase levels have been reported in animals. 

Total bird numbers on treated plots decreased. Some of the decrease (2-3%) was due to death, but most represented movements of birds in reaction to a reduction in their arthropod food. Brain cholinesterase levels in several avian species were depressed 1 week posttreatment (Mullie and Keith 1993)... 

All doses inhibited erythrocyte cholinesterase levels by 45-95%. All groups tolerated 16.6 mg/kg BW. Severe toxicosis in the two high-dose groups (9 of 20) in bulls but not in heifers and steers 7 of the 9 bulls died or had to be euthanized necropsy showed severe pulmonary edema... 

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