Organophosphorus toxicity

It is important to note that the computed potential energy surface reveals a facile reactivation via Scheme 7, with low energy barriers both in the gas phase and in aqueous solution" . This accords with experimental findings on oximates as reactivators following poisoning by organophosphorus toxics. 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

Li, B., Schopfer, L.M., Hinrichs, S.H., Masson, P., Lockridge, O. (2007). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411. Anal. Biochem. 361 263-72. 

Peeples ES, Schopfer LM, Duysen EG et al. (2005). Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometry. 

D5. Das Gupta, S., In vitro assessment of antidotes to organophosphorus toxicity. Arch. Toxicol. (Suppl. 14), 3-7 (1991). 

Liyasova, M.S., Schopfer, L.M., Lockridge, O., 2012. Cresyl saligenin phosphate, an organophosphorus toxicant, makes covalent adducts with histidine, lysine, and tyrosine residues of human serum albumin. Chem. Res. Toxicol. 25 (8), 1752-1761. 

Casida, J.E., Quistad, G.B., 2005. Serine hydrolase targets of organophosphorus toxicants. Chem. Biol. Interact. 157-158, 277-283. 

Many organophosphorus compounds are highly toxic and frequently lethal. They have been actively developed for herbicides, pesticides and more sinister purposes such as nerve gases which disorient, harass, paralyse or kill. ... 

DOT/UN/NA/IMCO shipping Methyl parathion, liquid (DOT) Methyl parathion mixture, dry (DOT) methyl parathion, solid (DOT) UN 3017 organophosphorus pesticides, liquid, toxic, flammable, not otherwise specified HSDB 1999 RTECS 1989... 

Thompson HM, Langton SD, Hart ADM. 1995. Prediction of inter-species differences in the toxicity of organophosphorus pesticides to wildlife—a biochemical approach. Comp Biochem Physiol 111C 1-12. 

All the enzymes discussed above belong to the class of dimetalloenzymes. In this context, it should be mentioned that serine-type hydrolases are irreversibly inhibited by organophosphorus esters, among them highly toxic chemical warfare agents. However, in some cases, for example of human butyrylcholi-noesterase, the inhibited enzyme could be reactivated by proper mutations." Moreover, such mutahons were found to confer phosphotriesterase activity in this... 

Brief notes are added on phosphorofluoridates even though their destruction by microbial activity— though clearly possible—is limited by their toxicity to the requisite microorganisms. One of the motivations for their inclusion is the fact that the hydrolytic enzyme(s) responsible for defluorination—organophosphorus acid anhydrase (OPA)—is widespread, and is found in a number of bacteria (Landis and DeFrank 1990). The microbial hydrolysis of organophosphorus pesticides and cholinesterase inhibitors is accomplished by several distinct enzymes, which are collectively termed organophosphorus acid anhydrases (OPAs). These have been reviewed (DeFrank 1991), so that only a few additional comments are necessary. 

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