Tabun toxicity

Gupta, R.C., Patterson, G.T., Dettbam, W-D. (1988). Acute tabun toxicity biochemical and histochemical consequences in brain and skeletal muscle of rat. Toxicology 46 329-42. 

Autoinjectors (AtroPen , Mark I , Combopen MC ) are atropine or atropine and pralidoxime combinations available for human use. They are not used in veterinary medicine as they are not adjustable for different sized patients. Experimental vaccines against nerve agent VX, and monoclonal antibodies which protect against soman, sarin, and tabun toxicity have been produced and are being tested (Dunn and Sidell, 1989 Somani et al, 1992). 

Contrary to these findings of decreased CarbE activity increasing the toxicity of many OPs, there are also data showing that increased CarbE activity can decrease toxicity of OPs. Activity of CarbE can be increased by about 80% after repeated administration of phenobarbital to rats and mice by a mechanism of enzyme induction which caused a decrease in soman and tabun toxicity by two-fold, while... 

Raveh, L., Segall, Y., Leader, H., Rothschild, N., Levanon, D., Henis, Y., Ashani, Y. (1992). Protection against tabun toxicity in mice by prophylaxis with an enzyme hydrolyzing organophosphate esters. Biochem. Pharmacol. 44 397 00. 

Raveh, L. et al. Protection against tabun toxicity in mice by prophylaxis with an enzyme hydrolyzing organophosphate esters, Biochem. Pharmacol, 44, 397, 1992. 

Gupta RC, Patterson GT and Dettbarn W-D (1987a). Acute tabun toxicity biochemical and histochem-ical consequences in brain and skeletal muscles of rats. Toxicology, 46, 329-341. 

Obidoxime is normally second line freotment for nerve agent treatment in UK after pralidoxime. However, it is more efficacious with known Tabun toxicity or when pralidoxime does not work. 

The carbamate and OP insecticides and the organophosphorous nerve gases soman, sarin, and tabun all act as anticholinesterases, and most of their toxicity is attributed to this property. The naturally occurring carbamate physostigmine, which has been used in medicine, is also an anticholinesterase. Some OP compounds can cause relatively long-lasting inhibition of the enzyme because of the phenomenon of... 

Human toxicity values have not been established or have not been published. However, based on available information, this agent appears to be less than half as toxic as Tabun (C01-A001). 

Fire Tabun reacts with steam and water to produce toxic and corrosive vapors. Any personnel not fighting a fire of sarin should immediately be evacuated from the area. Respiratory protection is required (positive pressure, full face piece, NIOSH-approved SCBA will be worn). When response personnel respond to handle rescue or reconnaissance, they will wear Level A protection that should be worn when the highest level of respiratory, skin, eye, and mucous membrane protection is needed. This level consists of a fully-encapsulated, vapor-tight, chemical-resistant suit, chemical-resistant boots with steel toe and shank, chemical-resistant inner/outer gloves (butyl rubber glove M3 and M4 Norton, chemical protective glove set), coveralls, hard hat, and self-contained (positive pressure) breathing apparatus (SCBA). 

GB Sarin, a nerve agent, more toxic than tabun or soman. 

Nerve Agent Substances that interfere with the central nervous system. Organic esters of phosphoric acid used as a chemical warfare agent because of their extreme toxicity (tabun-GA, sarin-GB, soman-GD, GF, and VX). All are potent inhibitors of the enzyme, acetylcholinesterase, which is responsible for the degradation of the neurotransmitter, acetylcholine in neuronal synapses or myoneural junctions. Nerve agents are readily absorbed by inhalation and/or through intact skin. 

Acoustic wave sensors are also used to detect nerve and blister agents. The surface acoustic wave chemical agent detector (SAW Mini-CAD) is a commercially available, pocket-sized instrument that can monitor for trace levels of toxic vapors of sulfur-based mustard agents (e.g., distilled mustard) and G nerve agents (e.g., tabun, sarin, soman) with a high degree of specificity. Colorimetric tubes are the... 

Ethyl dimethylphosphoramidofluoridate (VIII) was prepared by a similar method and proved to be a very toxic liquid. Its l.d. 50, on intravenous injection into rabbits and also on subcutaneous injection into mice, was 2-5 mg./kg. Toxicity was also determined by inhalation and a Ct ((7 = concentration, <=10 min.) of 200 mg./min./cu.m. killed seven out of a batch of eleven rabbits, guinea-pigs, rats and mice a Ct of 100 mg./min./cu.m. killed four out of eleven. The compound also possessed myotic properties. Other compounds that we made in this series were much more toxic and it will be seen that they bear some resemblance to tabun and sarin now about... 

B. 0. Holmstead1 has carried out investigations on the rate of hydrolysis of cyano-phosphorus compounds. First of all, mention may be made of the hydrolysis of diethyl phosphorocyanidate2 which proceeds rapidly in a buffer solution at pH 7-2 giving rise to the CN ion. Some 90 per cent hydrolysis takes place at this pH in 1 hr. Under similar conditions tabun is also hydrolysed to cyanide to the extent of about 80 per cent in 12 hr. There is a concurrent diminution of toxicity as the hydrolysis proceeds. Even in distilled water 50 per cent of the cyanide is split off in 9 hr. This instability would seem to render this compound ineffective as a toxic agent for use on a large scale. 

Bleaching powder destroys tabun, but it gives rise to cyanogen chloride, CNC1, which is also toxic. 

It is an odourless, colourless, hygroscopic liquid, completely miscible with water in which it is hydrolysed at an appreciable rate with the loss of fluorine and loss of toxicity. It is about three times as toxic as tabun to most animal species. Its boiling-point, 147° with decomposition, classifies it as a semi-persistent gas. It is hydrolysed extremely rapidly by dilute aqueous... 

As stated previously (pp. 62 etseq.) there is often correlation between anticholinesterase activity in vitro and gross mammalian toxicity. The toxicity of O.M.P.A. is not very muoh less than that of tabun, D.F.P. and T.E.P.P., yet the anti-cholinesterase activity of O.M.P.A. in vitro is negligible (50 per cent inhibition, 4-5x10 2m). On the other hand, O.M.P.A. produces all the symptoms of acetylcholine poisoning when administered to animals. Moreover, the serum cholinesterase of such animals is almost completely inhibited. Another anomaly of O.M.P.A. is that toxic action is slower than that of D.F.P. or tabun, an hour s delay being usual compared to the very quick knock-out action of D.F.P., etc. (see p. 2). 

The P-atom in sarin (9.84), soman (9.85), and tabun (9.87) is a stereogen-ic center, allowing for stereoselective enzymatic hydrolysis [162], This aspect has been extensively investigated for soman, which exists as four stereoisomers by virtue of the presence of a second stereogenic center (C-atom). These stereoisomers are usually designated as C(+)P(-), C(-)P(+), C(+)P(+), and C(-)P(-), where C(+/-) refers to the 1,2,2-trimethylpropyl moiety and P(+/ ) to the P-atom. Such a nomenclature may be convenient but has no implication for the absolute configuration. The C(+)P( ) and Cf-)P(-) epimers are the more active toward acetylcholinesterase and, hence, the more toxic ones. In contrast, the C(+)P(+) and C(-)P(+) epimers are preferentially hydrolyzed... 

During the Second World War, even before the mechanism of toxicity had been established, related compounds including sarin and tabun were developed for use as so-called nerve gases. These compounds possess exceptionally high mam-... 

Organophosphorons componnds snch a zarin, zoman, and tabun are some of the most toxic chemical componnds known that are nsed as poisonons snbstances in weapons. They cause rapid deterioration of enzymes and cannot nndergo reactivation. Therefore, there is no appropriate therapy for the treatment of snch poisons. 

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. 

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. 

---