Toxicity paraoxon

Costa, L.G., Richter, R.J., Murphy, S.D., Omenn, G.S., Moml-sky, A.G., Furlong, C.E. (1987). Species differences in serum paraoxonase correlate with sensitivity to paraoxon toxicity. In Toxicology of Pesticides Experimental Clinical and Regulatory Perspectives (L.G. Costa, C.L. Galli, S.D. Murphy, eds), pp. 263-6. Springer-Verlag, Heidelberg. 

Krutak-Krol H and Domino EF (1985). Comparative effects of diazepam and midazolam on paraoxon toxicity in rats. Toxicol Appl Pharmacol, 81, 545-550. 

Pharmacological manipulation of eCB signaling has been shown to affect both acute and long-term toxicity of OPs. The CBl receptor agonist WIN 55,212-2 (1.5mg/kg, i.p.) reduced acute paraoxon toxicity with a... 

Rosenberg, Y.J., Gearhart, J., Mao, L., et al, 2013. Protection against paraoxon toxicity by an intravenous pretreatment with polyethyleneglycol-conjugated recombinant butyrylcholinesterase in macaques. Chem. Biol. Interact. 210C, 20-25. 

Rosenberg, Y.J., Laube, B., Mao, L.J., et ah, 2013. Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques. Chem. Biol. Interact. 203,167-171. Rosenberg, Y.J., Gearhart, J., Mao, L., et al., 2014. Protection against paraoxon toxicity by an intravenous pretreatment with polyethylene-glycol-conjugated recombinant butyrylcholinesterase in macaques. Chem. Biol. Interact. 210, 20-25. Rotundo, D., 2011. Peptides that enhance acetylcholinesterase expression. US Patent No. 2011/0183922 Al. 

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. 

Acetaminophen, which depletes hepatic glutathione, does not potentiate the toxicity of methyl parathion in mice. A possible mechanism of action may be competition between acetaminophen and methyl parathion for mixed function oxidases and subsequent prevention of activation of methyl parathion to methyl paraoxon (Costa and Murphy 1984). Diethyl maleate, an agent that depletes cytosolic glutathione and is not an enzyme inducer, potentiates toxicity of methyl parathion in mice (Mirer et al. 1977). 

Practically all toxicokinetic properties reported are based on the results from acute exposure studies. Generally, no information was available regarding intermediate or chronic exposure to methyl parathion. Because methyl parathion is an enzyme inhibitor, the kinetics of metabolism during chronic exposure could differ from those seen during acute exposure. Similarly, excretion kinetics may differ with time. Thus, additional studies on the distribution, metabolism, and excretion of methyl parathion and its toxic metabolite, methyl paraoxon, during intermediate and chronic exposure are needed to assess the potential for toxicity following longer-duration exposures. 

Sultatos LG, Huang GJ, Jackson O, et al. 1991. The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse. Toxicol Lett 55 77-83. 

Previously, we have shown that functional secretion of OPH molecules into the periplasmic space induced about 2.8-fold higher specific whole cell OPH activity [10]. From the detail reaction kinetic studies in this work, we showed that this periplasmic space-secretion strategy provided much improved bioconversion capability and efficiency ( 1.8-fold) for Paraoxon as a model organophosphate compound. From these results, we confirmed that Tat-driven periplasmic secretion of OPH can be successfully employed to develop a whole cell biocatalysis system with notable enhanced bioconversion efficiency and capability for environmental toxic organophosphates. 

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]. 

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 . 

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. 

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