Organo-phosphorus pesticides, toxicity

Mileson BE, Chambers JE, Chen WL, et al. (1998) Common mechanism of toxicity A case study of organo-phosphorus pesticides. Toxicological Sciences 41 8-20. 

Barson, G. (1983) The effect of temperature and humidity on the toxicity of three organo-phosphorus insecticides to adult Oryzaephilus surinamensis. Pesticide Science 14, 145-152. 

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. 

A succession of books and articles have dealt with the effects of toxic chemicals on people and the environment, a hazard that accompanies industrialization. If there is any doubt that these compounds can be lethal, the horror that descended upon Bhopal, India, during the early morning hours of December 3, 1984, should be recalled. (It confirms that a large quantity of any toxic material should never be stored as such. The presumably nontoxic or less toxic reactants should instead be stored apart, to be mixed and reacted only as needed. Or better yet, manufacture the stuff from scratch only as needed.) Regarding the hypertoxic nerve gases from which organo/phosphorus/sulfur pesticides are derived, there is the unpublicized fact that a person only has about one minute to wash a drop from his skin before death intervenes. 

Hydroxy-l,2,4-thiadiazoles readily form esters with phosphoric acid and its various analogs. Because of the pesticidal properties of these organo-phosphorus compounds, and their reported relatively low toxicity to warmblooded animals, a large volume of preparative work has been undertaken. The patent literature exemplifies almost the full range of possible phosphoric and phosphonic acid derivatives, and their thio analogs. For their production, a hydroxy-1,2,4-thiadiazole is condensed with the phosphoro- or phosphono-chloridic ester (426 or 429), in the presence of a base.332-336 Alternatively, a halogeno-1,2,4-thiadiazole is allowed to react with the appropriate free acid (424 or 427).337-341 The use of mercapto-l,2,4-thiadiazoles, or of the... 

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