Cholinesterase depression, blood

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. 

Jones, R. D.. Hastings, T. F., and Landes. A. M. (1999). Absence of neurovisual effects due to tissue and blood cholinesterase depression in a chronic disulfoion feeding study in dogs. Toxicol Uu. 106, 181-190. 

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. 

Most displayed decreased blood cholinesterase activity. Many were observed to have affective syndromes (anxiety, fear, aggression), sometimes accompanied by symptoms of depression. Disruption of memory was noted. Vision problems are also caused by long-term contact with OPPs [A64]. In cotton growing regions with intensive OPP use, the number of spontaneous miscarriages and stillbirths was higher than elsewhere [3]. 

At the 2 lowest doses, significant depression from day 2 through day 14 blood cholinesterase normal at day 21. At 60.75 mg/kg, blood cholinesterase decreased for entire 49-day posttreatment. No outward signs of organophosphate intoxication and normal food intake and demeanor At 24 h, whole milk had 0.24 mg famphur/L of which 76% was in the butterfat fraction after 72 h, residues in milk were <0.008 mg/L... 

Rations containing 1,3, or 25 mg famphur/kg for as many as 90 days At 90 days, all groups had depressed plasma cholinesterase, although growth and appetite seemed normal. Whole-blood cholinesterase was depressed in the 3- and 25-mg/kg groups brain cholinesterase was significantly reduced in the 25-mg/kg group 24... 

Blood Cholinesterase activity Rapid, available in the field Does not identify the OP False positive results Only relatively high levels of activity depression are detectable... 

Nervous system effects may occur in humans after occupational exposure to disulfoton (Wolfe et al. 1978). In this study, mean disulfoton concentrations of 0.460.633 mg/m caused a 22.8% depression in erythrocyte cholinesterase activity in workers at a pesticide-fertilizer mixing operation. The workers were exposed to disulfoton for 9 weeks, and there were no reports of adverse clinical signs due to disulfoton exposure. The study was limited in that baseline blood cholinesterase activities were obtained 2 weeks after the initial exposure and were compared with cholinesterase activities at 9 weeks. Therefore, the actual depression in cholinesterase activity over a 9-week period was probably >22.8%. In addition, these workers were also dermally exposed to disulfoton (see Section 2.2.3.4) therefore, the 22.8% depression in cholinesterase activity was probably due to both inhalation and dermal exposure. Despite these limitations, the study concluded that because this depression in cholinesterase activity was only associated with dry mixing operations, the wet mixing operations are less hazardous to workers. 

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. 

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. ... 

A reentry study 12 hr after application in Arizona cotton, exposing volunteers to methyl parathion, ethyl parathion, or monocrotophos for 5 hr produced no clinical signs of poisoning. However, cholinesterase depression averaged 147., and both ethyl-and methyl-parathion were found in the blood as well as p-nitrophenol (PNP) in the urine. These workers were not judged in jeopardy as cholinesterase depression was less than 307. and the PNP excretion was less than 4 mg following exposure (22). 

The Army s interim RfD for VX is 6 x 10 mg/kg per day (0.0006 pg/kg per day). ORNL (1996) calculated that value on the basis of the lowest oral dose of VX that cansed significant depression in blood-cholinesterase (ChE) activity in sheep. The lowest-observed-adverse-effect level... 

Blood Cholinesterase Inhibition as a Critical Toxic Effect. Because nerve agents function primarily as AChE inhibitors, and because changes in blood ChE are a measure of potential toxic effects, an exposure or dose level that results in no significant depression in blood ChE activity can be used to establish maximum acceptable exposure limits. The use of this endpoint is, however, complicated by two factors (1) the natural variability in blood ChE activity levels of individuals and (2) the fact that, at low doses, blood ChE can be inhibited significantly without any clinical signs of toxicity. 

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... 

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