Sarin.

Description

Sarin, also known as "nerve agent Gas B" or GB, is an organophosphorus compound, a colourless and odourless liquid, and a potent inhibitor of the cholinesterase enzyme. Sarin reacts with steam or water to produce toxic and corrosive gases. Sarin is incompatible with tin, magnesium, cadmium-plated steel, and some aluminium and reacts with copper, brass, and lead. Sarin is the most volatile of the nerve agents, which means that it can easily and quickly evaporate from a liquid into a vapour and spread into the environment. People can be exposed to the vapour even if they do not come in contact with the liquid form of sarin.

Chemical Properties

Sarin (GB), a nerve agent, is one of the most toxic of the known chemical warfare agents. Exposure to sarin can cause death in minutes. A fraction of an ounce (1 to 10 mL) of GB on the skin can be fatal. GB is an odorless, colorless, tasteless, nonflammable liquid @ 15 ℃ and 1 atm. GB has no warning properties, especially when pure, and it can take away your sense of smell.

Uses

Sarin is a synthetic OP compound developed to be used in chemical warfare and terrorism.

Uses

Chemical warfare agent.

Definition

ChEBI: Isopropyl methylphosphonofluoridate is a phosphinic ester that is the isopropyl ester of methylphosphonofluoridic acid. It is a phosphinic ester and a fluorine molecular entity.

General Description

A colorless, odorless liquid. Almost no odor in pure state. Used as a quick-acting military chemical nerve agent. Chemical warfare agent.

Air & Water Reactions

Hydrolyzed by water, rapidly hydrolyzed by dilute aqueous sodium hydroxide. Water alone removes Fluoride atom producing nontoxic acid [Merck 11th ed. 1989].

Reactivity Profile

Acidic conditions produce hydrogen fluoride; alkaline conditions produce isopropyl alcohol and polymers. When heated to decomposition or reacted with steam, Sarin. emits very toxic fumes of fluorides and oxides of phosphorus. Slightly corrosive to steel. Hydrolyzed by water [EPA, 1998].

Health Hazard

Sarin is one of the most toxic compounds ever synthesized. It is a very powerfulinhibitor of acetylcholinesterase enzyme. It exhibits systemic toxicity to the central nervous system. The liquid can be absorbed readily through the skin. One drop so absorbed can be fatal to humans (Manahan 1989). It is extremely toxic by inhalation and oral intake. The toxic symptoms are similar to those of the insecticide parathion but more severe than the latter.
In humans the toxic effects from sarin may be manifested at an oral dose as low as 0.002–0.005 mg/kg with symptoms of nausea, vomiting, muscle weakness, bronchiolar constriction, and asthma. A lethal dose may be as low as 0.01 mg/kg. A LC50 value from 10-minute exposure may be 100-150 mg/m³ for most animals; and the oral LD50 value for rats should be within the range of 0.5 mg/kg.
Mioduszewski et al. (2001) estimated the probability of sarin vapor-induced lethality in Sprague-Dawley rats exposed to various combinations of exposure concentration and duration in a whole-body dynamic chamber. In this study, the onset of clinical signs and changes in blood cholinesterase activity were measured with each exposure. Miosis was the initial clinical sign observed at the start of the exposure. The authors have reported that the interaction of LC50× time (LCT 50) values increased with each exposure duration and found poor correlation of cholinesterase inhibition to exposure conditions or to the severity of clinical signs.
Bide and Risk (2004) studied the inhalation toxicity of sarin in mice from longer exposures to low-level concentrations in an effort to establish toxicity estimates for humans. The exposure period ranged from 20 minutes to 12 hours in their study. The LCT 50 values for 20-, 60-, 180-, 360-, and 720minute exposures were 430, 540, 900, 1210, and 2210 mgDmin/m³, respectively, corresponding to LC50 values 21.5, 9.0, 5.0, 3.4, and 3.1 mg/m³, respectively. The authors reported their data did not fit Haber’s rule LCT50＝CT in predicting the toxicity for longer exposures. The LC50 and LCT 50 values for 3－12 h were progressively higher (toxicity lower) than those predicted either by Haber’s rule or the “toxic load model”. The 20- and 60-minute data fit the “toxic load model” established previously from historical data for 0.17-30 min sarin exposures in mice.
In a study on the toxicity of sarin, soman, and tabun in brain acetylcholinesterase activity in mice, Tripathi and Dewey (1989) observed differential potencies between lethality and inhibition of acetylcholinesterase. These investigators conclude that there were more factors involved than simply the inhibition of acetylcholinesterase within the brain, causing lethality of these nerve agents. An LD50 value by intravenous administration for sarin was reported as 0.109 mg/kg. The acute toxicity of sarin based on behavioral test models indicated that certain species, such as marmosets, showed greater sensitivity to the lethal action of sarin than rodents and rabbits (D’Mello and Duffey 1985). Doses in the range 33–55% LD50 produced 88% or more inhibition of erythrocyte acetylcholinesterase and disrupted the performance of a foodreinforced visually guided reaching response.
Acute neurotoxic investigation using perfused canine brain indicated that 400 μg of sarin caused seizure in 5.6 minutes after stimulation of cerebral metabolic activity (Drewes and Singh 1987). Inhalation of sarin and soman in amounts of 30 and 13.14 μg/kg, respectively, caused irregular pulse rate, development of apnea, and a significant decrease in mean blood pressure in baboons (Anzueto et al. 1990). These effects were reversed with atropine.
Yokoyama et al. (1998) have evaluated the chronic neurobehavioral effects related to post-traumatic stress disorder induced by exposure to sarin in male and female patients in the Tokyo subway incident in 1995. Nakajima et al. (1998) conducted an epidemiological study and discussed the muscarinic and nicotinic signs in the victims of sarin poisoning in Matsumoto City, Japan, in 1994.
Goldman et al. (1987) evaluated mutagenic potential of sarin and soman in vitro and in vivo. Both these nerve agents gave no significant evidence of mutagenicity.

Health Hazard

Extremely toxic; lethal dose in humans may be as low as 0.01 mg/kg. Extremely active cholinesterase inhibitor. Toxic effects similar to, but more severe than those of parathion. Death within 15 minutes after fatal dose is absorbed.

Fire Hazard

Non-flammable. Acidic conditions produce hydrogen fluoride; alkaline conditions produce isopropyl alcohol and polymers. When heated to decomposition or reacted with steam, Sarin. emits very toxic fumes of fluorides and oxides of phosphorus. Slightly corrosive to steel. Hydrolyzed by water.

Potential Exposure

GB is used as a quick-acting chemical warfare nerve agent; nerve gas. Both the liquid and the vapor can kill you. Very small amounts can hurt you in one minute or less, and can quickly lead to death. A single drop, if vaporized, can kill everyone in a room ! Sarin is 26 times more deadly than cyanide gas and 20 times more deadly than Potassium cyanide.

Shipping

UN2810 Toxic liquids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poison Inhalation Hazard, Technical Name Required. Driver shall be given full and complete information regarding shipment and conditions in case of emergency. AR 50-6 deals specifically with the shipment of chemical agents. Shipments of agent will be escorted in accordance with AR 740-32. Passenger aircraft/rail: FORBIDDEN; Cargo aircraft only: FORBIDDEN. The packaging and shipping of samples are subject to strict regulations established by the Department of Transportation (DOT), Center for Disease Control, United States Postal Service, OSHA, and International Air Transport Association). Military driver shall be given full and complete information regarding shipment and condi- tions in case of emergency. AR 50-6 deals specifically with the shipment of chemical agents. Shipments of agent will be escorted in accordance with AR 740-32.

Toxicity evaluation

Sarin and other nerve agents are irreversible cholinesterase inhibitors. Clinical effects of exposure result primarily from inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Normally, AChE is responsible for degradation of the neurotransmitter acetylcholine in both the peripheral and central nervous systems (CNS). Acetylcholine stimulates contraction of skeletal muscles, and hydrolysis by AChE prevents continual overstimulation of the acetylcholine receptors. Inhibition of AChE blocks degradation of acetylcholine, resulting in an accumulation of acetylcholine and cholinergic overstimulation of the target tissues. AChE inhibition can have muscarinic, nicotinic, and CNS effects, resulting in a variety of symptoms, including involuntary muscle contractions, seizures, and increased fluid secretion (e.g., tears, saliva). The cause of death is typically respiratory dysfunction resulting from paralysis of the respiratory muscles, bronchoconstriction, buildup of pulmonary secretions, and depression of the brain’s respiratory center.
Cholinesterases in the blood are often used to approximate AChE tissue levels following exposure to a nerve agent. Red blood cell cholinesterase (RBC-ChE) is found on erythrocytes and BuChE in blood plasma. Affinities of cholinesterase inhibitors for BuChE or RBC-ChE vary. The turnover rate for RBC-ChE enzyme activity is the same as that for red blood cell turnover at w1% per day. Tissue AChE and plasma BuChE activities return with synthesis of new enzymes, the rate of which differs between plasma and tissues as well as between different tissues.
Binding of nerve agents to AChE is generally considered to be irreversible unless removed by therapy. Oximes are used as therapeutics to reactivate the enzyme prior to ‘aging’ or the point at which the agent–enzyme complex is covalently linked and the enzyme cannot be reactivated. Spontaneous reactivation in the absence of oximes is possible but is unlikely to occur at a rate sufficient to be clinically important. The time required for 50% of the enzyme to become resistant to reactivation varies by nerve agent. For sarin, the t1/2 for AChE is w3 h and for RBC-ChE w5 h.
It is known that OP cholinesterase inhibitors exert their toxic effects through mechanisms other than AChE inhibition. A 1978 study by Van Meter, Karczamar, and Fiscus showed that administering a second dose of sarin to rabbits still induced seizures even though the brain AChE was already inhibited by the previous dose of sarin. Further, pretreatment protection of AChE with physostigmine still resulted in death after high-dose treatment with nerve agent. Finally, it has been shown that mice lacking AChE are actually more sensitive to OP poisoning (including sarin) than wild type mice, supporting that fact that inhibition of AChE is not the only cause of toxic effects.
One of the noncholinergic effects resultant from treatment with OP nerve agents is changes in the levels of neurotransmitters other than acetylcholine. These include g-amino-butyric acid (GABA), dopamine, serotonin, and norepinephrine. While the exact mechanism by which nerve agent exposure alters the levels of these neurotransmitters is not known, it is thought that these changes may be due to a compensatory mechanism in response to overstimulation of the cholinergic system, direct action of the OP on the proteins responsible for noncholinergic neurotransmission, or perhaps both. Nerve agents have also been shown to inhibit a family of enzymes called serine esterases, which play an important role in the metabolism and persistence of neuropeptides such as endorphins and enkephalins. Neuroinflammation as a result of nerve agent exposure is another possible mechanism for noncholinergic toxicity effects. OPs have also been shown to have direct toxic effects on cells via induction of cellular oxidative stress and mitochondrial dysfunction.

Incompatibilities

Attacks tin, magnesium, cadmium plated steel; and some aluminums. GB decomposes tin, magne- sium, cadmium-plated steel, and aluminum. Slightly corro- sive to brass, copper, and lead. No attack on 1020 steel, Inconel, and K-Monel. Hydrolyzed by water. In acid condi- tions, GB hydrolyzes, forming hydrofluoric acid (HF). Rapidly hydrolyzed by dilute aqueous sodium hydroxide (NaOH), or sodium carbonate, forming relatively nontoxic products of polymers and isopropyl alcohol. Contact with metals may evolve flammable hydrogen gas.

Waste Disposal

It is dissolved in a combustible solvent and burned in a chemical incinerator equipped with an afterburner and scrubber. Sarin may also be destroyed by the Shultz process of molten metal reduction (Shultz 1987). Molten aluminum, aluminum alloys, recovered scrap metal, or eutectic melts may be used at 780－1000°C (1436-1832°F). Sarin is reduced to phosphorus, alkenes, and hydrogen. The hydrocarbon products may be used in preheating the feed.
Worley (1989) reported decomposition of sarin,soman,VX,andother chemicalwarfare agentsbyoxidizingwith1,3-dibromo-4,4,5,5tetramethyl-2-imidazolidinoneorotherN,N0dihalo-2-imidazolidinone. The reaction is carriedoutinanaqueousemulsioncontaining tetrachloroethylene or a similar organic solvent.
Sarin and other nerve agents may be removed from cleaning organic solvents (trichlorotrifluoroethane and its mixtures) by such adsorbents as Fuller’s earth, activated alumina, silica gel, and silica gel impregnated with a metal salt (Fowler and McIlvaine 1989). Hydrolysis with water or dilute alkaliesshould yieldproductsof low toxicity. .