Organophosphates and cholinesterase

TharrD. 1998. Rapid assessment of organophosphate-induced cholinesterase depression A comparison of laboratory and field kit methods to detect human exposure to organophosphates. Appl Occup Environ Hyg 13 265-268. 

Dieter MP, Ludke JL. 1975. Studies on the combined effects of organophosphates and heavy metals in birds. I. Plasma and brain cholinesterase in Cotumix quail fed methyl mercury and orally dosed with parathion. Bull Environ Contam Toxicol 13 257-262. 

Organophosphate and carbamate pesticides are potent inhibitors of the enzyme cholinesterase. The inhibition of cholinesterase activity by the pesticide leads to the formation of stable covalent intermediates such as phosphoryl-enzyme complexes, which makes the hydrolysis of the substrate very slow. Both organophosphorus and carbamate pesticides can react with AChE in the same manner because the acetylation of the serine residue at the catalytic center is analogous to phosphorylation and carbamylation. Carbamated enzyme can restore its catalytic activity more rapidly than phosphorylated enzyme [17,42], Kok and Hasirci [43] reported that the total anti-cholinesterase activity of binary pesticide mixtures was lower than the sum of the individual inhibition values. 

Dieter, M.P. and J.L. Ludke. 1978. Studies on combined effects of organophosphates or carbamates and morsodren in birds. II. Plasma and cholinesterase in quail fed morsodren and orally dosed with parathion or carbofuran. Bull. Environ. Contam. Toxicol. 19 389-395. 

Hill, E.F. 1992. Avian toxicology of cholinesterases. Pages 272-294 in B. Ballantyne and T.C. Marrs (eds.). Clinical and Experimental Toxicology of Organophosphates and Carbamates. Butterworth-Heinemann, Boston. 

In the 1960s and 1970s, the organophosphate and carbamate compounds replaced the chlorinated hydrocarbons as the most prominently used insecticides. These two families of insecticides share a common toxicological mechanism, the inhibition of cholinesterase enzymes in the nervous systems of... 

Two important classes of cholinesterase inhibitors are the organophosphates and the carbamates, a few of which are widely used insecticides. Two such insecticides are chloropyrifos and carbaryl (structures shown). They are highly effective insecticides and, if used properly, appear to be without significant risk to humans (although the use of chloropyrifos and some other members of the class is somewhat controversial). 

Acetyl cholinesterase activity AChE,. brain Neurotoxic parameter Organophosphate and carbamate pesticides Brain tissue 13-15... 

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). 

The coupling of HPLC with a cholinesterase-inhibition AutoAnalyzer for the determination of organophosphate and carbamate insecticides has much potential for the routine screening of residues of these compounds [58]. 

Method. A diagram of the apparatus is shown in Fig.4.29. Any suitable liquid chromatograph may be used. The AutoAnalyzer is modified such that the liquid sampler is fitted to the end of the chromatographic column. The proportioning pump is by-passed. The set-up of the AutoAnalyzer is the same as that for normal measurements of cholinesterase. The application of this technique to the determination of CGA 18809 in plum-leaf extract is shown in Fig.4.30. A comparison is made with UV analysis of the same extract. The limit of detection for CGA 18809 is c . 20 ng at a 3 1 signal to noise ratio. The relative inhibitions of several organophosphates and carbamates are compared in Table 4.9. Diazoxon may be detected in low picogram quantities. 

CHOLINESTERASE INHIBITION (RELATIVE TO CGA 18809) OF SOME ORGANOPHOSPHATES AND CARBAMATES USING BUTYRYLTHIOCHOLINE AND HUMAN PLASMA... 

The detection of organophosphate and other pesticides based on the inhibition of the enzyme acetylcholinesterase by these compounds has received considerable attention primarily due to high specificity and sensitivity [1,7-16]. Cholinesterases, such as acetylcholinesterase,... 

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. 

The acute toxic effects of the cholinesterase inhibitors, like those of the direct-acting agents, are direct extensions of their pharmacologic actions. The major source of such intoxications is pesticide use in agriculture and in the home. Approximately 100 organophosphate and 20 carbamate cholinesterase inhibitors are available in pesticides and veterinary vermifuges used in the USA. 

Insecticides fall largely into three main chemical groups 1) the organochlorines whose action is primarily on the peripheral nervous system 2) organophosphates, and 3) carbamates. The latter two classes are cholinesterase inhibitors. 

Radic, Z., Taylor, P. (2006). Stmcture and function of cholinesterases. In Toxicology of Organophosphate and Carbamate Compounds (R.C. Gupta, ed.), pp. 161-86. Academic Press, Amsterdam. 

---