Paraoxon insecticide

The rat LD qS are 13, 3.6 (oral) and 21, 6.8 (dermal) mg/kg. Parathion is resistant to aqueous hydrolysis, but is hydroly2ed by alkah to form the noninsecticidal diethjlphosphorothioic acid and -nitrophenol. The time required for 50% hydrolysis is 120 d ia a saturated aqueous solution, or 8 h ia a solution of lime water. At temperatures above 130°C, parathion slowly isomerizes to 0,%diethyl 0-(4-nitrophenyl) phosphorothioate [597-88-6] which is much less stable and less effective as an insecticide. Parathion is readily reduced, eg, by bacillus subtilis ia polluted water and ia the mammalian mmen to nontoxic 0,0-diethyl 0-(4-aminophenyl) phosphorothioate, and is oxidized with difficulty to the highly toxic paraoxon [511-45-5] diethyl 4-nitrophenyl phosphate d 1.268, soluble ia water to 2.4 mg/L), rat oral LD q 1.2 mg/kg. 

The reactivity of the individual O—P insecticides is determined by the magnitude of the electrophilic character of the phosphoms atom, the strength of the bond P—X, and the steric effects of the substituents. The electrophilic nature of the central P atom is determined by the relative positions of the shared electron pairs, between atoms bonded to phosphoms, and is a function of the relative electronegativities of the two atoms in each bond (P, 2.1 O, 3.5 S, 2.5 N, 3.0 and C, 2.5). Therefore, it is clear that in phosphate esters (P=0) the phosphoms is much more electrophilic and these are more reactive than phosphorothioate esters (P=S). The latter generally are so stable as to be relatively unreactive with AChE. They owe their biological activity to m vivo oxidation by a microsomal oxidase, a reaction that takes place in insect gut and fat body tissues and in the mammalian Hver. A typical example is the oxidation of parathion (61) to paraoxon [311-45-5] (110). 

Degraeve N, Moutschen J. 1984. Absence of genetic and cytogenetic effects in mice treated by the organophosphorus insecticide parathion, its methyl analogue, and paraoxon. Toxicology 32 177-183. 

Although the inhibition-based biosensors are sensitive, they are poor in selectivity and are rather slow and tedious since the analysis involves multiple steps of reaction such as measuring initial enzyme activity, incubation with inhibitor, measurement of residual activity, and regeneration and washing. Biosensors based on direct pesticide hydrolysis are more straightforward. The OPH hydrolyzes ester in a number of organophospho-rus pesticides (OPPs) and insecticides (e.g. paraoxon, parathion, coumaphos, diazinon) and chemical warfare agents (e.g. sarin) [53], For example, OP parathion hydrolyzes by the OPH to form p-nitrophenol, which can be measured by anodic oxidation. Rainina... 

MWNTs favored the detection of insecticide from 1.5 to 80 nM with a detection limit of InM at an inhibition of 10% (Fig. 2.7). Bucur et al. [58] employed two kinds of AChE, wild type Drosophila melanogaster and a mutant E69W, for the pesticide detection using flow injection analysis. Mutant AChE showed lower detection limit (1 X 10-7 M) than the wild type (1 X 10 6 M) for omethoate. An amperometric FIA biosensor was reported by immobilizing OPH on aminopropyl control pore glass beads [27], The amperometric response of the biosensor was linear up to 120 and 140 pM for paraoxon and methyl-parathion, respectively, with a detection limit of 20 nM (for both the pesticides). Neufeld et al. [59] reported a sensitive, rapid, small, and inexpensive amperometric microflow injection electrochemical biosensor for the identification and quantification of dimethyl 2,2 -dichlorovinyl phosphate (DDVP) on the spot. The electrochemical cell was made up of a screen-printed electrode covered with an enzymatic membrane and combined with a flow cell and computer-controlled potentiostat. Potassium hexacyanoferrate (III) was used as mediator to generate very sharp, rapid, and reproducible electric signals. Other reports on pesticide biosensors could be found in review [17],... 

T.T. Bachmann and R.D. Schmid, A disposable multielectrode biosensor for rapid simultaneous detection of the insecticides paraoxon and carbofuran at high resolution. Anal. Chim. Acta 401, 95-103 (1999). 

Chemicals. Insecticides, at least 95% pure, were prepared as acetone solutions p-p DDT, lindane, parathion, paraoxon, malathion, malaoxon, propoxur, carbaryl, LandrinR, aminocarb, mexacarbate, allethrin (90%), piperonyl butoxide (PBO) and sesamex. Aldrin was 98.5% and dieldrin was 99+% pure. 

Dieldrin, the oxidative metabolite of aldrin, was the most toxic of all insecticides in this study but was only slightly more toxic than its parent compound. The oxidative metabolites of parathion and malathion, paraoxon and malaoxon, were slightly less toxic than their parent compounds. 

Insecticides of the phosphoric acid triester class include paraoxon (9.49) and dichlorvos (9.50). The phosphorothioate derivative parathion is a relatively non-toxic insecticide that undergoes monooxygenase-catalyzed oxidative desulfuration to paraoxon [105] (see also Chapt. 7 in [59] see Sect. 9.3.6). Paraoxon itself, like its congeners and the P-halide nerve gases, is highly toxic through its potent inactivation of acetylcholinesterase [69]. 

Dichlorvos (9.50) is an insecticide of reportedly wide use, the metabolites of which in humans include dichloroethanol and dimethyl phosphate. Like paraoxon, dichlorvos is hydrolyzed by human serum. However, the enzyme activities hydrolyzing the two substrates were shown to differ by a number of criteria [114], Clearly large gaps remain in our understanding of the human metabolism of organophosphorus insecticides and other toxins. A bacterial phosphodiesterase appears as a promising tool to understand the catalytic mechanisms of organophosphoric acid triester detoxification [115-117],... 

The discovery of prontosil was fortuitous and was not based on rationale design. There are a large number of pesticides which fall in the same category as prontosil, i.e., they are active by virtue of their susceptibility to metabolic or chemical modification to active intermediates. The classical example of an insecticide of this type is parathion, a phosphorothionate ester which in animals or plants is oxidatively desulfurated to the potent anticholinesterase paraoxon O). The insecticidal activity of parathion was known for several years before the purified material was shown to be a poor anticholinesterase and that metabolic activation to paraoxon was necessary for intoxication. 

The pesticides methyl and ethyl parathion were determined in run-off water er preconcentration on XAD-2. This allowed analyses of these compounds at the parts per billion level (497). Parathion and paraoxon obtained from leaf extracts and orchard soil have also been determined (492). The separation of 30 carbamate pesticides by RPC has been described (493). Various modes of postcolumn fluorometric detection of carbamate insecticides have been reported including post-colun)n reaction between o-phthalaldehyde and methylamine, a carbamate hydrolysis... 

The discovery in the early years of the 20 century that certain phosphate esters possess mammahan toxicity and insecticidal properties heightened interest in this class of compounds, both in agriculmre and as potential agents in chemical warfare. Parathion became the practical choice as a broad-spectrum insecticide because of its greater stability and lower mammalian toxicity compared to its P=0 analogue, paraoxon . 

Myristicin has not been reported to possess antifungal activity, and therefore is not a phytoalexin according to the standard interpretation of this term (1 ). It does, however, potentiate the activity of the insecticide, paraoxon, in flies by inhibiting its degradation (2), and may in similar manner potentiate the action of phytoalexins of carrot root (falcarinol, falcarindiol,... 

It Is well known that phosphorothlonate insecticides such as parathlon (, 0-diethyl p-nitrophenyl phosphorothloate) and malathion [0, -dimethyl -(l,2 -dlcarbethoxy)ethyl phosphoro-dithioate] are Intrinsically poor inhibitors of acetylcholinesterase and in vivo activation to the respective anticholinesterases paraoxon and malaoxon is required before animals exposed to the phosphorothionates are intoxicated. Since metabolic activation is essential to the biological activity of these thiono sulfur-containing organophosphorus insecticides, compounds of this type may be considered as propesticides or, more specifically, prolnsectlcldes. 

Organophosphorsus inhibitors have been developed as insecticides (paraoxon, parathion) and for chemical warfare (soman, tabun, sarin). They are extremely toxic and lethal either by cardiac arrest of general paralysis and subsequent suffocation. 

Desulfuration. Replacement of sulfur by oxygen is known to occur in a number of cases, and the oxygenation of the insecticide parathion to give the more toxic paraoxon is a good example of this (Fig. 4.25). This reaction is also important for other phosphorothionate insecticides. 

Esterase activity is important in both the detoxication of organophosphates and the toxicity caused by them. Thus brain acetylcholinesterase is inhibited by organophosphates such as paraoxon and malaoxon, their oxidized metabolites (see above). This leads to toxic effects. Malathion, a widely used insecticide, is metabolized mostly by carboxylesterase in mammals, and this is a route of detoxication. However, an isomer, isomalathion, formed from malathion when solutions are inappropriately stored, is a potent inhibitor of the carboxylesterase. The consequence is that such contaminated malathion becomes highly toxic to humans because detoxication is inhibited and oxidation becomes important. This led to the poisoning of 2800 workers in Pakistan and the death of 5 (see chap. 5 for metabolism and chap. 7 for more details). 

Fish have a relatively poor ability for oxidative metabolism compared with the commonly used laboratory animals such as rats and mice. Insects such as flies have microsomal enzymes, and these are involved in the metabolism of the insecticide parathion to the more toxic paraoxon as discussed in the previous chapter (chap. 4, Fig. 25). 

Figures 1A, 2A and 3A give representative dissipation curves for parathion, azinphosmethyl and methidathion on orange trees in California (6). Parathion dissipates with the formation of considerable amounts of paraoxon. Low volume application (100 gal/acre) of these insecticides results in high levels of OP residues and thus longer dissipation times to safe levels. Azinphosmethyl does not dissipate as rapidly as parathion under field conditions. Azinphosmethyl oxon is formed during the process and dissipates slowly with time. Azinphosmethyl oxon levels were determined only for azinphosmethyl at 6.0 lb AI per 100 gal/acre. Methidathion dissipates on citrus also with the formation of its oxon.

Desulfuration is the term given to removal of sulfur from a molecule. One of the most common desulfuration reactions occurs with sulfur bonded to phosphorus. A common desulfuration reaction is the enzyme-mediated conversion of parathion to paraoxon (see discussion of organophosphate insecticides in Section 18.7) ... 

Figure 18.8 shows some organophosphate insecticides based on the phosphate esters. These compounds do not contain sulfur. One of the more significant of these compounds is paraoxon,... 

An example of biotoxification is the formation of paraoxon from the insecticide parathion via sulfoxidation. The simple substitution of an oxygen atom for a sulfur atom in the molecule results in a cholinesterase inhibitor with several times more potency. Similarly, the toxic action of methanol in producing blindness is the result of its metabolism to formaldehyde. Examples of bioactivation and biotoxification reactions are shown in Figure 3.2. 

The first of the organophosphorus insecticides to gain widespread use was parathion which is still an important commercial pesticide. This compound (Figure 9) is converted to the S-ethyl isomer by heating whereas paraoxon, a more toxic compound, is formed by enzymic action in plants. In animals, the additional products, p-nitrophenol and p-amino-phenol, are also formed. At present, little information appears to be available regarding the decomposition products of parathion in soils. 

Table 6.3 shows penetration rates of four insecticides dimethoate, paraoxon, dieldrin, and DDT, through cockroach cuticle. It is seen that the rates of penetration are inversely related to their partition coefficient in the olive oil-water system. In other words, the compound with the best solubility in water, as indicated by its partition coefficient, moved through the cuticle most rapidly. In this experiment, the insecticides were applied to the cuticle as acetone solutions, and it was suggested by the authors that this may have neutralized or canceled any barrier presented by the epicuticle. Thus, the data indicate the... 

Organophosphate insecticides with the P=S group are oxidatively desulfurated by cytochrome P450 monooxygenases of insects to their corresponding P=0 analogs. This reaction results in activation (increased toxicity), because the product, P=0, binds more tightly to the acetylcholinesterase than the parent compound and, thus, to more potent acetylcholinesterase inhibitors. For example, parathion is oxidatively desulfurated to paraoxon. 

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