Blood 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. 

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. 

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). 

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. 

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. 

On the skin, concentrated solutions may cause irritation and systemic intoxication. Allergic skin reactions are rare but have been reported. Men accidently exposed to 85% water-wettable powder as a dust complained of burning and irritation of the skin but recovered in a few hours without any treatment except bathing. Their blood cholinesterase levels were only slightly depressed. ... 

The relative safety of malathion to humans has been demonstrated repeatedly. In a group of workers with an average exposure of 3.3 mg/m for 5 hours (maximum of 56mg/m ), the cholinesterase levels in the blood were not significantly lowered and no one exhibited signs of cholinesterase inhibition. In a human experiment in which four men were exposed I hour daily for 42 days to 84.8 mg/m, there was moderate irritation of the nose and the conjunctiva, but there were no cholinergic signs or symptoms. ... 

ArterberryJD, Durham WF, ElliottJW, Wolfe HR Exposure to parathion—measurement by blood cholinesterase level and urinary -nitro-phenol excretion. Arch Environ Health 3 476-485, 1961... 

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. ... 

The judicious use of biological monitoring entails the scheduled administration of the test within the context of the exposure history. The usefulness of urinary concentrations of heavy metals, such as uranium, can be highly dependent upon the time between the collection of the specimen and the last exposure (12). The assessment of blood cholinesterase levels is similarly dependent upon the temporal relationship between the administration of the test and the exposure (13). The designation of an exposure or medical parameter as normal or abnormal can be made in relationship to the individuals baseline status 0,J ) or in reference to results from a statistically generated reference group (14,15). 

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... 

Callaway, S., D.R. Davies and J.P. Rutland. 1951. Blood cholinesterase levels and range of personal variation in a healthy adult population. Br. Med. J. 2 812-816. (Cited in Hayes, 1982)... 

An uncertainty factor of 10 is used for animal-to-human extrapolation because there is ample evidence that humans are more sensitive to GB than laboratory rodents. In humans, the single dose oral RBC-AChE 50 (dose required to lower red blood cell cholinesterase by 50%) is 0.01 mg/kg (Grob and Harvey, 1958), and an average daily dose of 0.034 mg/kg for three days resulted in moderate signs of toxicity. In comparison, rats receiving 0.3 mg GB Type Il/kg/day for 90 days exhibited decreases in blood cholinesterase levels but no signs of toxicity (Bucci and Parker, 1992). 

Goldman et al. (1988) administered VX subcutaneously to Sprague-Dawley rats on days 6-15 of gestation. The administered doses were 0, 0.25, 1.0, or 4.0 pg/kg/day. Body weight, frequency of visceral and skeletal abnormalites, litter size, and sex ratios were evaluated. There was no statistical evidence that VX affected any of the parameters studied. Blood cholinesterase levels were not monitored. 

Goldman et al. (1988) administered s.c. doses of 0, 0.25, 1.0 and 4.0 jig VX/kg/day to New Zealand white rabbits on days 6-19 of gestation. Animals were also observed daily for signs of toxicity. The does were sacrificed on day 29 of gestation. Body weight, fetal weights, fetal deaths, frequency of visceral and skeletal abnormalites, litter size, and sex ratios were evaluated. There was no statistical evidence that VX affected any of the parameters studied. Blood cholinesterase levels were monitored in a 7-day pilot study which also included a dose of 8 pg/kg. The 8 //g/kg dose was severely toxic to the rabbits (1/3 died, 2/3 ataxic). The dose of 0.25 pg/kg resulted in a level of RBC-AChE inhibition equal to 0.71 of the control value, but produced no signs of toxicity. 

Young, J.F., Gough, B.J., Suber, R.L., Gaylor, D.W. (2001). Correlation of blood cholinesterase levels with the toxicity of sarin in rats. J. Toxicol. Environ. Health A 62 161-74. 

The subjects blood cholinesterase levels were monitored continuously, along with EEC, EKG, respiratory rate and volume with pneumotact, and blood pressure. There were no significant changes In the parameters measured. Untreated subjects were asymptomatic at the dose levels given, and even though there was some drop In ChE (28Z of normal) in plasma, the RBC ChE was unaffected Subjects treated with atropine alone, or with PAMCl, responded well to relief of severe parasympathomimetic reactions. No residual effects of the drug reportedly were observed In any of the subjects tested. 

Deroetth A Jr, Dettbarn WD, Rosenberg P, Wilensky JG, Wong A. Effect of phosphohne iodide on blood cholinesterase levels of normal and glaucoma subjects. Am J Ophthalmol 1965 59 586-92. 

Barnes JM, Davies DR. Blood cholinesterase levels in workers exposed to organo-phosphorus insecticides. BMJ 1951 4735 816-9. 

The onset of miosis is within seconds to minutes following aerosol or vapor exposure but may not be maximal for up to 1 h, especially at low concentrations. The duration of miosis varies and is dependent on the extent of exposure. The ability of the pupil to dilate maximally in darkness may not return for up to 6 weeks. There is no correlation between miosis and blood cholinesterase levels. 

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