Organophosphorus nerve agent toxicity

Organophosphorus nerve agents are potent cholinesterase inhibitors, specifically acetylcholinesterase (AChE), the 

Compound LD50 inhalation (mg per person) LCt5o skin (mg-min m ) CAS number 

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Most organophosphorus nerve agents decompose slowly in water. Raising the pH of an aqueous solution of these agents significantly increases the rate of decomposition. Reaction with dry bleach may produce toxic gases. 

Pyridostigmine bromide competitively binds to nerve tissue AchE. The binding is reversible and has been shown to protect AchE against irreversible inhibition by organophosphorus nerve agents. Pyridostigmine is a quarternary compound and does not readily cross the blood-brain barrier. Thus, it is not expected to affect or protect brain AchE. Cholinesterase inhibition, which is a mechanism of action, is also responsible for toxicity. 

Solberg Y and Belkin M (1997). The role of excito-toxicity in organophosphorus nerve agents central poisoning. Trends Pharm Sci, 18, 183-185. 

Cell culture based bioassays are used in the agricultural field to screen for harmful contaminants such as mycotoxins. The chick embryo neuron culture system is very sensitive to the anticholinesterase activity of organophosphorus nerve agents, in a manner which parallels toxicities in animals the sensitivity to sarin was around 100 pg . The bioassay was used successfully to detect sarin at low ppm levels spiked into soil. 

Technical experts generally agree that sea-dumped CW should be left undisturbed, because any attempt to move them could result in an explosion or other rupture of the munitions, thereby spilling the contents into the environment. Organophosphorus nerve agents hydrolyze readily in sea water into essentially benign degradation products of low toxicity. The primary environmental and human health threats are posed... 

Table 2.1 Toxicity values for organophosphorus nerve agents. Table taken from Reference [5] with permission from Environmental Health Perspectives...

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. 

John H, Worek F, Thiermann H (2008) LC-MS based procedures for monitoring of toxic organophosphorus compounds and the verification of pesticide and nerve agent poisoning. Anal Bioanal Chem 391 97-116... 

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