Plasma cholinesterases pesticides

Mice that were exposed dermally to residues of methyl parathion in emulsifiable concentrate on foliage, and were muzzled to prevent oral intake, developed inhibition of plasma cholinesterase and erythrocyte cholinesterase after two 10-hour exposures (Skinner and Kilgore 1982b). For the organophosphate pesticides tested in this study, cholinergic signs generally were seen in mice with cholinesterase inhibition >50% results for this end point were not broken down by pesticide. 

The purpose of this chapter is not to discuss the merits, or lack thereof, of using plasma cholinesterase inhibition as an adverse effect in quantitative risk assessments for chlorpyrifos or other organophosphate pesticides. A number of regulatory agencies consider the inhibition of plasma cholinesterase to be an indicator of exposure, not of toxicity. The U.S. Environmental Protection Agency, at this point, continues to use this effect as the basis for calculating the reference doses for chlorpyrifos, and it is thus used here for assessing risks. 

Potter WT, Garry VF, Kelly JT, et al. 1993. Short Communication Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota. Toxicol Appl Pharmicol 119 150-155. 

In addition to being found in the nervous system, acetylcholinesterase also occurs in the blood where it is bound to the surface of red blood cells (termed RBC-ChE or RBC-AChE). RBC-AChE activity, as well as the activity of a second type of cholinesterase found in blood plasma (butyrylchoUnesterase, or plasma cholinesterase) have been used to monitor exposure to organophosphate compounds (pesticides and nerve agents). Both RBC-AChE and plasma-ChE activity have been used as bioindicators of potential toxic effects. There is some evidence that RBC-AChE is as sensitive as brain ChE to the effects of nerve agents. Grob and Harvey (1958) reported that the in vitro concentrations producing 50% depression of brain-ChE and RBC-AChE activity were the same in the case of GA (1.5 x 10 mol/L),... 

Duncan, R. C-, Griffith, J.. and Konctal. J. (1986). Comparison of plasma cholinesterase depression among workers occupationally exposed to organophosphorus pesticides as reported by various Studies, / Toxicol. Environ, Health 18, 1-1). 

Mason, H. J., Waine, E., Stevenson, A., and Wilson, H. K. (1993). Aging and spontaneous reactivation of human plasma cholinesterase activity after inhibition by organophosphorus pesticides. Hum. Exp. Toxicol. 12, 497-503. 

In a study of 135 workers in the ehemical industry who handle methyl parathion, the methyl parathion concentration in plasma, the 4-nitrophenol concentration in urine, and the cholinesterase and acetylcholinesterase activities were determined to assess the pesticide burden in such workers (Leng and Lewalter 1999). The mean concentration of methyl parathion in the plasma of the workers was 233 pg/L no clinical symptoms were reported by the workers. In an additional group of 19 workers handling methyl parathion, who were also exposed to the pyrethroid cyfluthrin, the mean concentrations of methyl parathion in plasma were 269 and 241 pg/L (for groups without and with clinical S5miptoms, respectively), and 7 of the workers exhibited skin paraesthesia, while none of the 427 workers exposed only to the pyrethroid experienced the symptom (Leng and Lewalter 1999). 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

Iyaniwura TT. 1991. Relative inhibition of rat plasma and erythrocyte cholinesterases by pesticide combinations. Vet Hum Toxicol 33 166-168. 

The Department has developed methods for monitoring the exposure of workers exposed to organophosphate and carbamate pesticides. These methods utilize the determination of plasma and red blood cell cholinesterase activities and urinary alkyl phosphates. Studies are reported vrti ich show that these methods have proven useful in evaluating the safety effectiveness of closed-transfer systems and in determining reentry times for field workers. 

While the depression of plasma and/or RBC cholinesterase may be detected after exposure to very large amounts of carbamates, enzyme activity usually recovers rapidly--within minutes to hours. Hence these tests can be misleading unless one of the rapid methods for testing cholinesterase activity has been employed. A more sensitive and specific absorption test for several of the carbamate pesticides is the measurement of their metabolites in the urine within 48 hours of exposure. Carbamate pesticides are sufficiently acutely toxic that those attending the victim must avoid contact with contaminated apparel or vomitus, and should wear rubber gloves during decontamination of hair and skin of the victim. 

ORGANOPHOSPHORUS PESTICIDES There are no simple direct chemical tests for organophosphorus compounds. The toxic effects e usually associated with depression of the cholinesterase activity of the body, and measurement of the plasma or serum cholinesterase can be used, therefore, as an indication of organophosphorus poisoning. 

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