Cholinesterases exposure

Plasma and Erythrocyte Cholinesterase Eevels in Children Intoxicated by Methyl Parathion 3-3. Eevels of Significant Exposure to Methyl Parathion - Oral 3-4. Eevels of Significant Exposure to Methyl Parathion - Dermal 3-5. Genotoxicity of Methyl Parathion In Vivo... 

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. 

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. 

Routine gross and histopathological examinations revealed no treatment-related effects on the nervous system of dogs exposed to 0.03, 0.1, or 0.3 mg/kg/day methyl parathion in the diet for 1 year (Suba 1981). In addition, there were no treatment-related effects on cholinesterase activity in plasma, red blood cells, or brains in dogs under these exposure conditions. These data are in agreement with the NOAEL established above for dogs exposed to these levels for 13 weeks. 

Mean plasma, erythroc54e, and brain cholinesterase activities were significantly reduced by 67-88%, 9-20%, and 76-79%, respectively, in rats of both sexes following 2-year exposures to 2.5 mg/kg/day methyl parathion (Suba 1984). This effect did not occur in rats exposed to either 0.025 or 0.25 mg/kg/day methyl parathion. 

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. 

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. 

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). 

Based on the rapid appearance of clinical signs and cholinesterase inhibition, methyl parathion appears to be readily absorbed by humans and animals following inhalation, oral, and dermal exposure. Following oral administration of methyl parathion to animals, the extent of absorption was at least 77-80% (Braeckman et al. 1983 Hollingworth et al. 1967). No studies were located regarding the extent of absorption following inhalation and dermal exposure, or the mechanism of absorption. 

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. 

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

De Peyster A, Willis WO, Molgaard CA, et al. 1993. Cholinesterase and self-reported pesticide exposure among pregnant women. Arch Environ Health 48 348-352. 

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. 

Larsen K-0, Hand HK. 1982. Effect of exposure to organophosphorus compounds on S-cholinesterase in workers removing poisonous depots. Scand J Work Environ Health 8 222-226. 

Nigg HN, Knaak JB. 2000. Blood cholinesterases as human biomarkers of organophosphorus pesticide exposure. Rev Environ Contam Toxicol 163 29-112. 

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. 

TharrD. 1998. Rapid assessment of organophosphate-induced cholinesterase depression A comparison of laboratory and field kit methods to detect human exposure to organophosphates. Appl Occup Environ Hyg 13 265-268. 

Other additional studies or pertinent information that lend sunnort to this MRL Methyl parathion affects the nervous system by inhibiting acetylcholinesterase activity. Cholinesterase inhibition and neurological effects have been observed in humans and animals, for all exposure routes and durations (for example. Dean et al. 1984 Desi et al. 1998 EPA 1978e Gupta et al. 1985 Nemec et al. 1968 Suba 1984). 

Case Studies in Environmental Medicine Taking an Exposure History—The importance of taking an exposure history and how to conduct one are described, and an example of a thorough exposure history is provided. Other case studies of interest include Reproductive and Developmental Hazards Skin Lesions and Environmental Exposures Cholinesterase-Inhibiting Pesticide Toxicity and numerous chemical-specific case studies. 

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