Dimethoate toxicity

Mechanism of action can be an important factor determining selectivity. In the extreme case, one group of organisms has a site of action that is not present in another group. Thus, most of the insecticides that are neurotoxic have very little phytotoxicity indeed, some of them (e.g., the OPs dimethoate, disyston, and demeton-5 -methyl) are good systemic insecticides. Most herbicides that act upon photosynthesis (e.g., triaz-ines and substituted ureas) have very low toxicity to animals (Table 2.7). The resistance of certain strains of insects to insecticides is due to their possessing a mutant form of the site of action, which is insensitive to the pesticide. Examples include certain strains of housefly with knockdown resistance (mutant form of Na+ channel that is insensitive to DDT and pyrethroids) and strains of several species of insects that are resistant to OPs because they have mutant forms of acetylcholinesterase. These... 

The organophosphorons insecticides dimethoate and diazinon are mnch more toxic to insects (e.g., housefly) than they are to the rat or other mammals. A major factor responsible for this is rapid detoxication of the active oxon forms of these insecticides by A-esterases of mammals. Insects in general appear to have no A-esterase activity or, at best, low A-esterase activity (some earlier stndies confnsed A-esterase activity with B-esterase activity) (Walker 1994b). Diazinon also shows marked selectivity between birds and mammals, which has been explained on the gronnds of rapid detoxication by A-esterase in mammals, an activity that is absent from the blood of most species of birds (see Section 23.23). The related OP insecticides pirimiphos methyl and pirimiphos ethyl show similar selectivity between birds and mammals. Pyrethroid insecticides are highly selective between insects and mammals, and this has been attributed to faster metabolic detoxication by mammals and greater sensitivity of target (Na+ channel) in insects. 

In addition to ester bonds with P (Section 10.2.1, Figures 10.1 and 10.2), some OPs have other ester bonds not involving P, which are readily broken by esteratic hydrolysis to bring about a loss of toxicity. Examples include the two carboxylester bonds of malathion, and the amido bond of dimethoate (Figure 10.2). The two carboxylester bonds of malathion can be cleaved by B-esterase attack, a conversion that provides the basis for the marked selectivity of this compound. Most insects lack an effective carboxylesterase, and for them malathion is highly toxic. Mammals and certain resistant insects, however, possess forms of carboxylesterase that rapidly hydrolyze these bonds, and are accordingly insensitive to malathion toxicity. 

Amidases can be found in all kinds of organisms, including insects and plants [24], The distinct activities of these enzymes in different organisms can be exploited for the development of selective insecticides and herbicides that exhibit minimal toxicity for mammals. Thus, the low toxicity in mammals of the malathion derivative dimethoate (4.44) can be attributed to a specific metabolic route that transforms this compound into the nontoxic acid (4.45) [25-27]. However, there are cases in which toxicity is not species-selective. Indeed, in the preparation of these organophosphates, some contaminants that are inhibitors of mammalian carboxylesterase/am-idase may be present [28]. Sometimes the compound itself, and not simply one of its impurities, is toxic. For example, an insecticide such as phos-phamidon (4.46) cannot be detoxified by deamination since it is an amidase inhibitor [24],... 

T. Uchida, R. D. O Brien, Dimethoate Degradation by Human Liver and Its Significance for Acute Toxicity , Toxicol. Appl. Pharmacol. 1967, 10, 89-94. 

Chemical/Physical. On heating, dimethoate is converted to the O.S-dimethyl analog (Worthing and Hance, 1991). Burns readily in contact with flame releasing toxic fumes of phosphorus, nitrogen and sulfur oxides (Sax and Lewis, 1987). 

Another example is dime thoate, the toxicity of which is related to its rate of hydrolysis. Those species, which are capable of metabolizing the insecticide, are less susceptible than those species, which are poor metabolizers. The metabolism of dimethoate is shown in Figure 5.13. Studies on the metabolism in vitro of dimethoate have shown that sheep liver produces only the first metabolite, whereas guinea pigs produce only the final product (Fig. 5.13). Rats and mice metabolize dimethoate to both products. The toxicity is in the descending order sheep>dog>rat>cattle>guinea pig>mouse. 

The hydrolysis of esters by esterases and of amides by amidases constitutes one of the most common enzymatic reactions of xenobiotics in humans and other animal species. Because both the number of enzymes involved in hydrolytic attack and the number of substrates for them is large, it is not surprising to observe interspecific differences in the disposition of xenobiotics due to variations in these enzymes. In mammals the presence of carboxylesterase that hydrolyzes malathion but is generally absent in insects explains the remarkable selectivity of this insecticide. As with esters, wide differences exist between species in the rates of hydrolysis of various amides in vivo. Fluoracetamide is less toxic to mice than to the American cockroach. This is explained by the faster release of the toxic fluoroacetate in insects as compared with mice. The insecticide dimethoate is susceptible to the attack of both esterases and amidases, yielding nontoxic products. In the rat and mouse, both reactions occur, whereas sheep liver contains only the amidases and that of guinea pig only the esterase. The relative rates of these degradative enzymes in insects are very low as compared with those of mammals, however, and this correlates well with the high selectivity of dimethoate. 

Dimethoate Cancer, mutagenicity, reproductive toxicity, birth defects... 

P.R.S. Chen, and W.C. Dauterman, Studies on the toxicity of dimethoate analogs and their hydrolysis by sheep liver amidase. Pestic. Biochem. Physiol. 1 340, 1971. 

Some of the toxicants present in foods (93) are endrin, DDT, toxaphine, aldrin and dieldrin, heptachlor, diazinon, parathion, chlorobenzilate, dithiocarbimate, dalapon, dimethoate and many other compounds employed for various purposes. Besides novel food compounds directly added by agriculture, many industrial compounds such as polychlorinated biphenols have found their way into our food supply. Some of the compounds of common occurrence in today s food are illustrated in Figure 11. These compounds and similar derived products are assumed to detract from the... 

Dimethoate exerts toxicity through inhibition of acetylcholinesterase. The oxidative metabolite (i.e., omethoate) is two to three orders of magnitude more potent in inhibiting acetylcholinesterase than the parent compound. The N-demethylated omethoate may be the most potent inhibitor of cholinesterases. The enzyme in red blood cells may be more sensitive to inhibition than plasma enzyme following dimethoate exposure. 

Dimethoate shows moderate toxicity after absorption through oral, dermal and inhalation routes. 

Respiratory ailments, recent exposure to cholinesterase inhibitors, impaired cholinesterase production, or liver malfunction may potentiate the toxicity of dimethoate. Also, high environmental temperatures or exposure of dimethoate to light (visible or UV) may enhance its toxicity. 

The half-life of dimethoate in river water is 8 days. It does not bioaccumulate in aquatic organisms, nor does it adsorb to suspended particles in water. Dimethoate undergoes significant hydrolysis, especially under alkaline conditions. However, losses by photolysis and evaporation from open waters are not expected to be significant. Dimethoate is not toxic to plants. 

In birds, dimethoate is moderately to very highly toxic. Acute oral LD50 values of 41.7mgkg in mallards and 20 mg kg in pheasants have been reported. Since birds are unable to metabolize dimethoate as rapidly as mammals, it shows greater toxicity in these species. 

Dimethoate produces moderate toxicity in fish, with reported LC50 values of 6.2mgl in rainbow trout and 6.0mgl in bluegill sunfish. However, it is much more toxic to aquatic invertebrate species like stoneflies and scuds. Dimethoate is highly toxic to honeybees. The 24 h topical LD50 for dimethoate in bees is 0.12 pg per bee. 

The toxic effects of some pesticide mixtures are additive, particularly when their toxic mechanisms are identical. The additive effects of the organophosphates chlorpyrifos and diazanon were demonstrated in one study. T Another study found the s-triazine herbicides atrazine and cyanazine to show additive toxic effects. Not all mixtures of similar pesticides produce additive effects, however. In one study, mixtures of five organophos-phate pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion) were shown to produce greater than additive effects when administered to laboratory animals. Another article discusses nonsimple additive effects of pyrethroid mixtures. Despite the similarities in their chemical structure, pyrethroids act on multiple sites, and mixtures of these produce different toxic effects. 10 ... 

In a study using a human neuroblastoma cell line, mixtures of three different organophosphates (azinphos-methyl, diazanon, and dimethoate), and mixtures of an organic phosphate (pirimiphos-methyl) and a benzim-idizole fungicide (benomyl) showed greater toxicity toward protein synthesis than the individual pesticides. I21 The authors of the study concluded that it is not feasible to predict the toxicities of pesticide mixtures on the basis of the toxicities of the single components. 

---