Background

Organophosphates are inhibitors of cholinesterase. Cholinesterase is the enzyme that causes the metabolism of acetylcholine. Acetylcholine is the neurotransmitter at parasympathetic and myoneural junctions, in autonomic ganglia, and in the brain. Poisoning from organophosphates results when the inhibition of cholinesterase leads to an accumulation of acetylcholine at the nerve synapses, causing overstimulation. If the process continues, there is eventual paralysis of neural transmission. Workers who apply and mix pesticides are at risk of systemic poisoning. Agricultural workers are also at risk from exposure to these pesticides in the field. Both acute and chronic poisoning may occur. Biological monitoring is useful in assessing the effectiveness of personal protective equipment, including respirators; it is also useful in assessing work practices and compliance with safety procedures.

Designing a Monitoring Program

A comprehensive medical monitoring program for potential exposure to organophosphate pesticides would include physical examinations, air sampling, measurement of post-exposure urinary alkylphosphates, and determination of acetylcholinesterase levels. However, such a comprehensive program may be too expensive or otherwise impractical for many companies. Therefore, medical monitoring should adhere to the following recommended hierarchy:

Monitoring Cholinesterase

Measurement of the pesticide itself in blood is not useful for monitoring because of the rapid metabolism of the pesticide. Organophosphates are hydrolyzed by the liver within minutes to hours of exposure. Instead, measurement of cholinesterase activity in blood is the established procedure for monitoring organophosphate exposure. Although there is a wide range of cholinesterase levels in a population, each individual maintains a relatively stable level of cholinesterase activity in blood unless there are interfering factors to upset that stable level. There are several different laboratory methods available to measure cholinesterase activity in blood, and different units of measurement are utilized by different laboratories. Whatever laboratory you use, I strongly recommend that you verify that all determinations are made using the same units of measurement.

Monitoring Urinary Alkylphosphates

Measurement of alkylphosphate metabolites in urine is perhaps the most sensitive measurement of organophosphate exposure. The most common metabolites found in urine are diethylphosphate (DEP), diethylphosphorothioate (DETP), diethylphos-phorodithioate (DEDTP), dimethylphosphate (DMP), dimethylphosphorothioate (DMTP), and dimethylphos-phorodithioate (DMDTP). These metabolites are found at peak levels about three days after exposure and they may be detected in urine up to six or seven days after exposure. Although measuring alkylphosphate metabolites in urine is a sensitive method of assessing exposure, there is an innate difficulty in using this method as the base form of monitoring because of the sophisticated analytical method required. In some situations this technique can be utilized with impressive results, but it does not replace cholinesterase monitoring.

Monitoring of Workers

Chronic exposure to organophosphate pesticides may cause symptoms that are nonspecific and resemble illnesses like flu, simple fatigue, or heat exhaustion. A clinical picture of weakness, loss of appetite, malaise, or "orange pickers’ disease" (a severe dermatitis), is cause for evaluation of the work environment and work practices. Small, repeated exposures to organophosphates may gradually depress cholinesterase activity to relatively low levels, with little, or no, symptomatology. In general, symptoms for acute poisoning occur after the serum cholinesterase is depressed to 50% of normal. In mild poisoning, the cholinesterase activity is depressed to 20–50%; in severe poisoning, activity is 10% or less of normal. Depression of an individual’s cholinesterase activity to 70% of baseline indicates significant exposure. If depression of activity is 60% of baseline, the individual must be removed from exposure and must be monitored medically until activity levels return to 80%. For cases of acute poisoning, treatment is started based on clinical findings and patient history and should not be delayed until cholinesterase determinations are available. Continuing clinical decisions, however, need to be based on the current cholinesterase level compared to the individual’s baseline. Because of the need for such information, we recommend that individuals with potential exposure to organophosphate carry their baseline cholinesterase level with them, and we issue a small laminated card with the individual’s baseline cholinesterase levels for this purpose. The card is kept in a wallet or purse and is immediately available if needed. This provides a solution to the ubiquitous problem of trying to find someone’s baseline cholinesterase levels in the company’s files or the doctor’s office, particularly after hours, or on weekends, etc.

Regulations for organophosphate pesticides vary from state to state, but there is no OSHA standard, per se, for these materials. It is important to check your own state regulations in regard to monitoring and reporting requirements. Perhaps the strongest regulations are found in California, where workplace monitoring is required if a worker’s RBC or plasma cholinesterase falls below 80% of normal.

The growing use of organophosphate pesticides has given rise to a growing need for biological monitoring for workers with potential exposure to organophosphate pesticides. Now is the time to establish medical monitoring procedures for workplace exposures.

Happy Monitoring!