PRINCIPLES OF TOXICOLOGY

15.1 ORGANOPHOSPHATE AND CARBAMATE INSECTICIDES 351
Plasma 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 a
number of disease states or conditions (e.g., decreased plasma cholinesterase levels in liver disease
such as cirrhosis and hepatitis, multiple metastases, during pregnancy). Plasma cholinesterase is
produced by the liver, and this enzyme is found in the nervous tissue, heart, pancreas, and white matter
of the brain. Plasma cholinesterase levels typically decline and regenerate more rapidly than red blood
cell cholinesterase levels. Plasma cholinesterase levels typically regenerate at the rate of 25 percent in
the first 7–10 days. Following organophosphate intoxication, plasma cholinesterase levels may remain
depressed for a period of 1–3 weeks.
The enzyme in red blood cell cholinesterase is the same enzyme that is present in the nervous
system. Red blood cell cholinesterase regenerates at the rate of approximately 1 percent per day in the
body and is dependent on the synthesis of new red blood cells in the body. As mentioned earlier, in
severe intoxications from organophosphate pesticide exposure, red blood cell cholinesterase could take
as long as 3 months to regenerate.
The measurement of cholinesterase activity in cases of carbamate intoxication are not useful, due
to quick reactivation of cholinesterase following carbamate overexposures.
Treatment for Organophosphate and Carbamate Symptomatology
There 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 nicotinic
signs, such as muscle fasciculations and muscle weakness. Atropine does not affect muscle weakness
of respiratory failure. Additionally, atropine does not reactivate cholinesterase.
The second therapeutic agent, pralidoxime (also called 2-PAM), is a medication that reactivates the
organophosphate-inhibited cholinesterase enzyme by the removal of the phosphate group that is bound
to the esteratic site. However, 2-PAM should be given fairly soon after exposure because the aged
enzyme cannot be reactivated. 2-PAM is effective in improving the symptoms of respiratory depression
and muscle weakness. Individuals suffering from carbamate intoxication should not be treated with
2-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 (rubber
gloves should be worn to avoid contact with contaminated clothing and materials) and thorough
washing of the contaminated skin with soap and water.
Regulatory Information on Organophosphates and Carbamates
OSHA 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 an
ACGIH BEI p-nitrophenol levels (metabolite of parathion) in urine as well as a BEI for cholinesterase
activity for workers exposed to organophosphate cholinesterase inhibitors.
TABLE 15.2 1999 ACGIH Biological Exposure Indices (BEI)
Pesticide Determinant
Organophosphorus cholinestease inhibitors
Sampling Time BEI
Cholinesterase activity in red cells
Parathion
Discretionary 70% of individual’s baseline
Tota l p-nitrophenol in urine End of shift 0.5 mg/g creatinine
Cholinesterase activity in red cells Discretionary 70% of individual’s baseline