Organophosphate compounds insecticides

Crop protection chemicals are an important group of contaminants that exhibit biologically mediated transformation in aerobic or anaerobic subsurface environments. We consider two well-known contaminants the insecticide parathion, which is an organophosphate compound, and the herbicide atrazine, from the triazine group. 

Tetraethylpyrophosphate (TEPP) was the first organophosphate compound to be used as an insecticide. This compound was developed in Germany during World War II and was substituted for nicotine as an insecticide. It is a white to amber hygroscopic liquid (bp, 155°C) that readily hydrolyzes in contact with water. Because of its tendency to hydrolyze and its extremely high toxicity to mammals, TEPP was used for only a very short time as an insecticide, although it is a very effective one. It was typically applied as an insecticidal dust formulation containing 1% TEPP. 

A number of synthetic organophosphate compounds have the capacity to bind covalently to acetylcholinesterase. The result is a long lasting increase in acetylcholine at all sites where it is released. Many of these drugs are extremely toxic and were developed by the military as nerve agents. Related compounds such as parathion are employed as insecticides. 

The inhibition by other organophosphate compounds of the carboxylesterase which hydrolyzes malathion is a further example of xenobiotic interaction resulting from irreversible inhibition because, in this case, the enzyme is phosphorylated by the inhibitor. A second type of inhibition involving organophosphorus insecticides involves those containing the P=S moiety. During CYP activation to the esterase-inhibiting oxon, reactive sulfur is released that inhibits CYP isoforms by an irreversible interaction with the heme iron. As a result, these chemicals are inhibitors of the metabolism of other xenobiotics, such as carbaryl and fipronil, and are potent inhibitors of the metabolism of steroid hormones such as testosterone and estradiol. 

Although examples are known in which synergistic interactions take place at the receptor site, the majority of such interactions appear to involve the inhibition of xenobiotic-metabolizing enzymes. Two examples involve the insecticide synergists, particularly the methylenedioxyphenyl synergists, and the potentiation of the insecticide malathion by a large number of other organophosphate compounds. 

Pesticides used around the house and garden include insecticides, herbicides, rodenticides, fungicides, and fumigants. Toxic chemicals contained in pesticides include organochlorine and organophosphate compounds, carbamates, and arsenicals. The solvents used as carriers for these include aliphatic and aromatic hydrocarbons, alcohols, and glycol ethers. I34l... 

Psychomotor performance has been evaluated after exposure to insecticides. Rowntree et al60 found that daily administration of an organophosphate compound caused slowness in thought and decreased performance speed. Metcalf and Holmes59 noted slowed thinking and calculation in patients who had been exposed to insecticides more than a year previously. 

In summary, studies intended to examine the neuropsychiatric effects of organophosphate compounds vary in their adequacy, and in some instances the results are contradictory. Most studies agree, however, that acute neuropsychiatric effects result from exposure to both insecticides and nerve agents. These effects include inability to concentrate, memory problems, sleep disturbances, anxiety, irritability, depression, and problems with information processing and psychomotor tasks. With pesticides, these effects do not occur in the absence of the conventional signs of poisoning. 

Organophosphate compounds (e.g., IX, XXX, XXXVII, XXXIX in Table 9.5), carbamates (e.g VII) and pyrethroids (e.g., XIII) have been used as insecticides for many years. The pyrethroids are synthetic modifications of pyrethrin I (cf Formula 9.1), the main active agent of pyrethmm. Pyrethmm is isolated from the capitulum of different varieties of chrysanthemums and used as a natural insecticide. 

FIGURE 2.12 Relative toxicides of various substances commonly expressed in units of milligrams dose per kilogram of body mass required to kill 50% of test subjects (LD50). Also shown is a comparison of the toxicity of insecticidal parathion to that of another organophosphate compound, nerve gas sarin, in which the toxic dose of parathion is represented by the area of the large circle and that of sarin by the area of the small dot. 

Pesticides are further subdivided into classes of compounds. Historically, insecticides included the organochlorine, methyl carbamate, and organophosphate classes of pesticides. Herbicides comprise about 10—12 principal classes of compounds. Within each class of pesticide there may be several hundred active ingredients. 

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