Pesticide poisoning cholinesterases

With an excessive, single exposure, the result will be either a systemic pesticide poisoning or a topical lesion frequently observed on the skin or in the eyes. Since most acute intoxications are from the carbamate and organoposphate insecticides, the systemic manifestations are cholinergic and are due to the inhibition of acetyl cholinesterase and the resultant accumulation of the neurotransmitter acetylcholine, at the synapse. Topical effects, in contrast, either are the result of the irritant properties of the chemicals in the formulation or have an allergenic basis for their occurrence (3). However, topical effects are not necessarily exclusively the result of exposure to the active ingredient in the formulation but may result from a reaction to one or more inerts as well. 

Pralidoxime (2-PAM) Pralidoxime is a commonly used oxime and is rccom-mended for all cases of moderate-to-severe nerve agent poisoning. The optimal dosage is dependent on the nerve agent, time since exposure and the cholinesterase activity of the victim, i here has been considerable experience with pralidoxime and other oximes over many years in the treatment of OP pesticide poisoning. 

Many pesticides are neurotoxicants poisoning the nervous system. A number of pesticides are acetyl cholinesterase inhibitors (Serat and Mengle 1973). Generally, pesticides determination has been performed by GC since the 1960 s (Morrison and Durham 1971 Fournier et al. 1978). There are no reference materials for pesticides in urine or serum, although as with PAHs there are a number biological matrices certified for the content of various pesticides available for environmental food and agriculture analysis and which may have some application in clinical chemistry. 

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... 

Stone, W.B. and P.B. Gradoni. 1986. Poisoning of birds by cholinesterase inhibitor pesticides. Wildl. Rehabil. 5 12-28. 

Presently available methods to diagnose and biomonitor exposure to anticholinesterases, e.g., nerve agents, rely mostly on measurement of residual enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in blood. More specific methods involve analysis of the intact poison or its degradation products in blood and/or urine. These approaches have serious drawbacks. Measurement of cholinesterase inhibition in blood does not identify the anticholinesterase and does not provide reliable evidence for exposure at inhibition levels less than 20 %. The intact poison and its degradation products can only be measured shortly after exposure. Moreover, the degradation products of pesticides may enter the body as such upon ingestion of food products containing these products. 

Cholinesterase inhibitors are a very important class of compounds related to cholinomimetics. Besides their therapeutic importance, a few of them are used as pesticides in agriculture, and the most toxic are used as chemical poisoning agents. Use of these substances is based on changes that take place after inactivation of cholinesterase or pseudocholinesterase (a less specific enzyme), i.e. effects observed as a result of acetylcholine buildup in neuro-effector compounds. Cholinesterase inhibitors are classified both by their chemical structure as well as by the type of their chemical reaction with the enzyme, which determines their temporary action. 

Organophosphate and carbamate cholinesterase inhibitors (see Chapter 7) are widely used to kill insects and other pests. Most cases of serious organophosphate or carbamate poisoning result from intentional ingestion by a suicidal person, but poisoning has also occurred at work (pesticide application or packaging) or, rarely, as a result of food contamination or terrorist attack (eg, release of the chemical warfare nerve agent sarin in the Tokyo subway system in 1995). 

Machin AF, Anderson PH, Hebert CN. 1974. Residue levels and cholinesterase activities in sheep poisoned experimentally with diazinon. Pesticide Science 5 49-56. 

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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