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Cholinesterase Inhibition |
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A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. Major support and funding was provided by the USDA/Extension Service/National Agricultural Pesticide Impact Assessment Program.
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Human exposure to cholinesterase inhibiting chemicals can result from inhalation, ingestion, or eye or skin contact during the manufacture, mixing, or applications of these pesticides.
Let us look at a typical synapse in the body's nervous system, in which a muscle is being directed by a nerve to move. An electrical signal, or nerve impulse, is conducted by acetylcholine across the junction between the nerve and the muscle (the synapse) stimulating the muscle to move. Normally, after the appropriate response is accomplished, cholinesterase is released which breaks down the acetylcholine terminating the stimulation of the muscle. The enzyme acetylcholine accomplishes this by chemically breaking the compound into other compounds and removing them from the nerve junction. If acetylcholinesterase is unable to breakdown or remove acetylcholine, the muscle can continue to move uncontrollably.
Electrical impulses can fire away continuously unless the number of messages being sent through the synapse is limited by the action of cholinesterase. Repeated and unchecked firing of electrical signals can cause uncontrolled, rapid twitching of some muscles, paralyzed breathing, convulsions, and in extreme cases, death. This is summarized below.
Exposure to:
May result in:
Organophosphate insecticides include some of the most toxic pesticides. They can enter the human body through skin absorption, inhalation and ingestion. They can affect cholinesterase activity in both red blood cells and in blood plasma, and can act directly, or in combination with other enzymes, on cholinesterase in the body. The following list includes some of the most commonly used OPs:
Carbamates, like organophosphates, vary widely in toxicity and work by inhibiting plasma cholinesterase. Some examples of carbamates are listed below:
Signs and symptoms of cholinesterase inhibition from exposure to CMs or OPs include the following:
Unfortunately, some of the above symptoms can be confused with influenza (flu), heat prostration, alcohol intoxication, exhaustion, hypoglycemia (low blood sugar), asthma, gastroenteritis, pneumonia, and brain hemorrhage. This can cause problems if the symptoms of lowered cholinesterase levels are either ignored or misdiagnosed as something more or less harmful than they really are.
The types and severity of cholinesterase inhibition symptoms depend on:
Although the signs of cholinesterase inhibition are similar for both carbamate and organophosphate poisoning, blood cholinesterase returns to safe levels much more quickly after exposure to CMs than after OP exposure. Depending on the degree of exposure, cholinesterase levels may return to pre-exposure levels after a period ranging from several hours to several days for carbamate exposure, and from a few days to several weeks for organophosphates.
When symptoms of decreased cholinesterase levels first appear, it is impossible to tell whether a poisoning will be mild or severe. In many instances, when the skin is contaminated, symptoms can quickly go from mild to severe even though the area is washed. Certain chemicals can continue to be absorbed through the skin in spite of cleaning efforts.
If someone experiences any of these symptoms, especially a combination of four or more of these symptoms during pesticide handling or through other sources of exposure, they should immediately remove themselves from possible further exposure. Work should not be started again until first aid or medical attention is given and the work area has been decontaminated. Work practices, possible sources of exposure, and protective precautions should also be carefully examined.
The victim of poisoning should be transported to the nearest hospital or poison center at the first sign(s) of poisoning. Atropine and pralidoxime (2-PAM, Protopam) chloride may be given by the physician for organophosphate poisoning; atropine is the only antidote needed to treat cholinesterase inhibition resulting from carbamate exposure (9).
When a cholinesterase blood test is taken, two types of cholinesterase can be detected. Physicians find plasma cholinesterase readings helpful for detecting the early, acute effects of organophosphate poisoning, while red blood cell readings are useful in evaluating long-term, or chronic, exposure (8).
The cholinesterase test is a blood test used to measure the effect of exposure to certain or cholinesterase-affected insecticides. Both plasma (or serum) and red blood cell (RBC) cholinesterase should be tested. These two tests have different meanings and the combined report is needed by the physician for a complete understanding of the individual's particular cholinesterase situation.
Laboratory methods for cholinesterase testing differ greatly, and results obtained by one method cannot be easily compared with results obtained by another. Sometimes there is also considerable variation in test results between laboratories using the same testing method. Whenever possible, cholinesterase monitoring for an individual should be performed in the same laboratory, using a consistent testing method.
The approved methods are: Michel, microMichel, pH stat, Ellman, micro-Ellman, and certain variations of these. Micro methods have the advantage of not necessitating venipuncture, the drawing of blood from a vein by puncturing the vein with a needle attached to a collecting tube. The Ellman technique is considered better for detecting cholinesterase inhibition caused by carbamates. Many of the various "kit" methods in use are not satisfactory, particularly those which can be used only for plasma (or serum) determinations.
The extent of potential pesticide poisoning can be better understood if cholinesterase tests taken after exposure to the cholinesterase inhibiting pesticides can be compared to the individual's baseline, pre-exposure measurement. Workers that receive routine exposure to organophosphate or carbamate pesticides should be offered an initial pre-employment check of their blood cholinesterase levels to establish "baseline values" prior to any exposure to these agrochemicals. If no pre-exposure value was obtained, however, the earliest cholinesterase value recorded can be used for later comparison. Excessive exposure to OPs and CMs depresses the cholinesterase so markedly that a diagnosis can also be made without previous baseline testing. If an individual's cholinesterase levels drop 30 percent below the original baseline level, immediate retesting should be done.
While there is no set formula for deciding the frequency of cholinesterase testing, in general, the initial baseline test should be followed by subsequent cholinesterase testing on a regular (usually monthly) basis. This testing should be done weekly during the active season, however, when workers are employed full-time and regularly using OPs and CMs labelled "DANGER." The test should be repeated any time a worker becomes sick while working with OPs, or within 12 hours of his/her last exposure.
Several factors should be considered in deciding how often someone should have his/her cholinesterase levels tested:
Baseline blood samples should be taken at a time when the worker has not been exposed to organophosphate and carbamate pesticides for at least 30 days. Establishing a stable baseline requires a minimum of two pre-exposure tests taken at least 3 days but not more than 14 days apart. If these two tests differ by as much as 20 percent, a third sample should be taken and the two closest values averaged and considered the true baseline.
While carbamates (CMs) cause a depression in cholinesterase levels, the enzyme levels may return to baseline levels within hours of exposure, perhaps before test results are returned. When the effects of over-exposure to CMs are being checked, blood must be drawn during actual exposure or not more than 4 hours thereafter. If the drawing of blood and the actual completion of the laboratory test is delayed for more than 4 hours, reactivation of the enzyme will have taken place in the blood. This situation makes it hard for the physician to know the extent to which cholinesterase was inhibited, and to fully assess the seriousness of any safety problems which might exist in the work environment.
A reported change in an individual's cholinesterase level may result from something other than a pesticide exposure, or it may be the result of laboratory error, but this should never be assumed to be the case. If the report shows a worker's cholinesterase level has dropped 20 percent below his/her baseline in either plasma or RBC, he/she should be retested immediately. If the second test repeats the same low values, faulty work practices should be carefully looked for and steps should be taken to correct them.
A 30 percent drop below the individual's baseline of RBC cholinesterase or plasma cholinesterase means that the individual should be removed from all exposure to organophosphates and carbamates, with the individual not being allowed to return until both levels return to the pre-exposure baseline range. Removal from exposure means avoidance of areas where the materials are handled or mixed and avoidance of any contact with open containers or with equipment that is used for mixing, dusting or spraying organophosphates or carbamates. A worker removed from exposure to cholinesterase inhibitors may be employed at other types of work.
The 1986 estimates on the cost of individual cholinesterase tests range from $7.00 to $60.00, with the average test costing approximately $35.00. The quality of tests will improve and prices will be lowered if and when testing methods are standardized and automated.
Cooperative Extension Service in your area.
Pesticide Unit, Epidemiological Studies Laboratory, California Department of Health, 2151 Berkeley Way, Berkeley, CA. 94704. Telephone: (415)-540-3063.
Worker Health and Safety Branch, Department of Food and Agriculture, 1220 N Street, Sacramento, CA. 95814. Telephone: (916)-445-8474.
Davies, J.E. and V.H. Freed (eds.). 1981. An agromedical approach to pesticide management Some health and environmental considerations. Consortium for International Crop Protection. Berkeley, CA.
Goh, Kean, W.G. Smith, R.F. Pendleton. 1985. Pesticide safety for IPM field scouts. Chemicals Pesticides Program. Cornell University, Ithaca, NY.
Golz, H.H. and C.B. Shaffer. 1960. Toxicological information on cyanamid Insecticides. American Cyanamid Co., Princeton, NJ.
Paul, Jane. 1987. Commercial pesticide applicators may get mandatory blood tests. Agrichemical Age. March.
Smith, William G. 1983. Cholinesterase. Chemicals Pesticide Program. Cornell Cooperative Extension Information. New York State College of Agriculture and Life Sciences, Cornell University, Ithaca, NY.
Van Driesche, R G. 1985. Cholinesterase testing information. Pesticide Facts. Cooperative Extension Service, University of Massachusetts, Amherst, MA. June 7, 1985.
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