PRINCIPLES OF TOXICOLOGY - Biology East Borneo

15.1 ORGANOPHOSPHATE AND CARBAMATE INSECTICIDES 351Plasma cholinesterase, while susceptible to the inhibitory actions of organophosphate insecticides,has no known biological use in the body. Plasma cholinesterase can vary in an individual based on anumber of disease states or conditions (e.g., decreased plasma cholinesterase levels in liver diseasesuch as cirrhosis and hepatitis, multiple metastases, during pregnancy). Plasma cholinesterase isproduced by the liver, and this enzyme is found in the nervous tissue, heart, pancreas, and white matterof the brain. Plasma cholinesterase levels typically decline and regenerate more rapidly than red bloodcell cholinesterase levels. Plasma cholinesterase levels typically regenerate at the rate of 25 percent inthe first 7–10 days. Following organophosphate intoxication, plasma cholinesterase levels may remaindepressed for a period of 1–3 weeks.The enzyme in red blood cell cholinesterase is the same enzyme that is present in the nervoussystem. Red blood cell cholinesterase regenerates at the rate of approximately 1 percent per day in thebody and is dependent on the synthesis of new red blood cells in the body. As mentioned earlier, insevere intoxications from organophosphate pesticide exposure, red blood cell cholinesterase could takeas long as 3 months to regenerate.The measurement of cholinesterase activity in cases of carbamate intoxication are not useful, dueto quick reactivation of cholinesterase following carbamate overexposures.Treatment for Organophosphate and Carbamate SymptomatologyThere are two effective treatments for organophosphate intoxication: atropine and pralidoxime.Atropine competes with muscarinic sites, and treatment ameliorates symptoms of nausea, vomiting,abdominal cramps, sweating, salivation, and miosis. Atropine treatment has no effect on the nicotinicsigns, such as muscle fasciculations and muscle weakness. Atropine does not affect muscle weaknessof respiratory failure. Additionally, atropine does not reactivate cholinesterase.The second therapeutic agent, pralidoxime (also called 2-PAM), is a medication that reactivates theorganophosphate-inhibited cholinesterase enzyme by the removal of the phosphate group that is boundto the esteratic site. However, 2-PAM should be given fairly soon after exposure because the agedenzyme cannot be reactivated. 2-PAM is effective in improving the symptoms of respiratory depressionand muscle weakness. Individuals suffering from carbamate intoxication should not be treated with2-PAM possibly because the reversal of the carbamate inhibitor could add insult to injury.Decontamination of the individual should include the removal of any contaminated clothing (rubbergloves should be worn to avoid contact with contaminated clothing and materials) and thoroughwashing of the contaminated skin with soap and water.Regulatory Information on Organophosphates and CarbamatesOSHA PELs and ACGIH TLVs exist for some of the organophosphate and carbamate insecticides.Biological exposure indices (BEIs) also exists for exposure to parathion (see Table 15.2). There is anACGIH BEI p-nitrophenol levels (metabolite of parathion) in urine as well as a BEI for cholinesteraseactivity for workers exposed to organophosphate cholinesterase inhibitors.TABLE 15.2 1999 ACGIH Biological Exposure Indices (BEI)Pesticide Determinant Sampling Time BEIOrganophosphorus cholinestease inhibitorsCholinesterase activity in red cells Discretionary 70% of individual’s baselineParathionTota l p-nitrophenol in urine End of shift 0.5 mg/g creatinineCholinesterase activity in red cells Discretionary 70% of individual’s baseline