Insecticides, organo-phosphorus compounds

As mentioned above, to apply to insects a conclusion drawn directly from tests on mammals may sometimes be misleading.3 For instance, American cockroaches have a remarkably high tolerance for acetylcholine,4 but, on the other hand, a substance showing some of the pharmacological properties of acetylcholine does accumulate in flies and cockroaches poisoned with D.D.T. Similarly, Hopf, working with locusts, was unable to demonstrate any increase in toxicity of eserine or T.E.P.P. resulting from the subsequent injection of acetylcholine. From this, Lord and Potter infer that acetylcholine may not be directly involved in the insecticidal action of organo-phosphorus compounds, either because the enzymes which hydrolyse acetylcholine are not inhibited to any considerable extent in vivo or because the functions performed by acetylcholine in mammals are performed by another substance in insects. 

These authors claim, therefore, that it cannot safely be assumed that the toxic action of organo-phosphorus insecticides to insects is due to the inhibition of cholinesterase, although in the case of some insect species there is considerable evidence that an enzyme capable of hydrolysing acetylcholine may be important in the toxic action of the organo-phosphorus compounds.5 Further evidence on this point6 showed that with... 

While carrying out early experiments with D.F.P. and related compounds on small animals, we frequently noticed that extremely small quantities of these materials caused the death of flies in the room. It was this observation that led us during the war to claim the use of certain phosphorus compounds as insecticides. Schrader describes phosphorus-containing compounds made by the I.G. Farbenindustrie in Germany. Many similar compounds were also made (independently) by British and German research workers. It turned out, however, that systemic insecticides based on organo-phosphorus compounds were first commercially produced in England. ... 

The widespread use of these compounds in commerce as insecticides, oil additives, plasticisers, etc., coupled with the possibilities of studying phosphate metabolism in nucleic acids, lecithins and similar products, has stimulated a good deal of work in this field, and a number of correlations are now available. These have been summarised in correlation charts for (a) inorganic phosphorus links [22], and (b) organo phosphorus compounds [23] by Corbridge, and by Thomas and Chittenden [36]. Useful reviews of P=0 frequencies have been given by Hudson [37], and by Thomas [59]. 

The industrial uses of phosphorus compounds in recent years has grown rapidly. Phosphorus compounds are used in food manufacture and water treatment, as additives in the oil industry, and as detergents, insecticides, and solvent extractants (ore processing). It is in the field of solvent extraction that many of the organo-phosphorus compounds have made valuable contributions of late. 

The pure compound is a pale yellow, nearly odourless oil, soluble in organic solvents, but almost insoluble in water. Averell and Norris2 describe the detection of minute quantities of parathion (20 /ig.) in spray and dust, by reduction with zinc, diazotization and coupling with an amine to give an intense magenta colour. It is effective (at concentrations of 25-600 p.p.m.) against many insect species, but of course, like the majority of organo-phosphorus insecticides, it is toxic to man and to animals. 

Many pesticides are esters or amides that can be activated or inactivated by hydrolysis. The enzymes that catalyze the hydrolysis of pesticides that are esters or amides are esterases and amidases. These enzymes have the amino acid serine or cysteine in the active site. The catalytic process involves a transient acylation of the OH or SH group in serin or cystein. The organo-phosphorus and carbamate insecticides acylate OH groups irreversibly and thus inhibit a number of hydrolases, although many phosphorylated or carbamoylated esterases are deacylated very quickly, and so serve as hydrolytic enzymes for these compounds. An enzyme called arylesterase splits paraoxon into 4-nitrophenol and diethyl-phosphate. This enzyme has cysteine in the active site and is inhibited by mercury(ll) salts. Arylesterase is present in human plasma and is important to reduce the toxicity of paraoxon that nevertheless is very toxic. A paraoxon-splitting enzyme is also abundant in earthworms and probably contributes to paraoxon s low earthworm toxicity. Malathion has low mammalian toxicity because a carboxyl esterase that can use malathion as a substrate is abundant in the mammalian liver. It is not present in insects, and this is the reason for the favorable selectivity index of this pesticide. 

During the last decade parathion has been the most used organo-phosphorus insecticide. It has been proved to be valuable in crop protection 27). However, using this compound so much has also resulted in numerous accidental intoxications, and many have been lethal 28). In aquatic environments parathion hydrolyzes to yield p-nitro-phenol or oxidizes to yield paraoxon (25, 26). Baker (29) has shown that substituted phenols aflFect the odor quality of drinking water. p-Nitrophenol may be chlorinated at a water treatment plant to produce an odorous product. The U. S. Public Health Service has adopted 1 /xg/liter as a limit for phenolic compounds in water (10). Paraoxon is more toxic to insects and mammals than the parent compound parathion (27). The lethal dose (LD50) for male white rats is 14 mg/kg for parathion while that determined for paraoxon is only 3 mg/kg (30). Bioassay studies with fathead minnows indicated a Median Tolerance Limit (TLni) (96 hours) for parathion of 1.4 mg/liter and 0.3 mg/liter for paraoxon. 

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