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Cyclosarin (GF) is a liquid nerve agent/organ- ophosphate containing fluoride. GF is a colorless liquid. The odor is variously described as nondescript, sweet, fruit- like. Odor threshold is about 12 milligram per cubic meter.

Colorless liquid, odorless to fruity.

Likely hydrolyzed by water, rapidly hydrolyzed by dilute aqueous sodium hydroxide.

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

Median lethal dose (mg-min/m3): 2500 by skin (vapor) or 350 (liquid); 35 inhaled. Median incapacitating dose: 25 inhaled. Eye/skin toxicity: Very high. Rate of action: Very rapid. Physiological action: Cessation of breath-death may follow. Detoxification rate: Low. (ANSER)

A quick-acting and lethal cholinester- ase inhibitor and casualty agent. Females appear to be more susceptible to nerve agent effects. Small percentages of general population have genetic traits that may increase susceptibility.

The immediate treatment for nerve agent intoxi- cation is intravenous injection of 2 mg atropine sulfate (intramuscular injection should be considered if the patient is hypoxic and ventilation cannot be initiated, as there is a risk of ventricular fibrillation). This should be followed by additional injections of atropine at 10 15 minute intervals, continuing until bradycardia has been reversed (e.g., until the heart rate is at 90 beat/minute or less). If breathing has stopped, a mechanical respirator should be used to ventilate the patient. Do not attempt mouth-to-mouth resuscitation.If possible, oxygen or oxygen-enriched air should be used for ventilation. If possible, monitor cardiac activity.br Notes for physician and medical personnel: Oximes (prali- doxime salts, obidoxime) may be of use in restoring acetyl- cholinesterase activity. Obidoxime may be used to treat GF intoxication; however, it may cause liver damage. Animal studies indicate that the oxime Hi-6 may be significantly superior to other oximes in the treatment of GF intoxica- tion, but it is not widely available. Therefore pralidoxime salts should be used, with a slow intravenous infusion of 500 mg. to 1 g. being given initially. Diazepam may be administered to control convulsions. It also has value in controlling the victim’s fear. An initial dose of 5 mg may be followed by additional doses at 15-minute intervals up to a total of 15 mg .br Other effective antidote: National Response Team (NRT) lists atropine and (if more severe) 2-PAM Chloride injec- tions; atropine eye drops .

UN2810 Toxic liquids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Fairly stable. Cyclo-sarin (GF) is hydro- lyzed by water; rapidly hydrolyzed in the presence of heat and alkalies; by dilute solution of aqueous sodium hydrox- ide. Contact with alkaline conditions produce isopropyl alcohol and polymer substances. Contact with acid condi- tions produce HF; alkaline conditions produce isopropyl alcohol and polymers. Reasonably stable when stored in steel at normal temperatures; slightly corrosive to steel when heated.

Cyclosarin was the fourth of the G-series of nerve agents to be described following the development of tabun (GA), the first G-agent to be discovered in 1938. Cyclosarin was given the designation GF, reflective of the order in which it was discovered.
As with the other G-agents, after learning of its properties the German Ministry of Defense began studying cyclosarin along with the United States and United Kingdom following World War II. Cyclosarin, unlike other G-agents, was not selected for mass production by any nations at that time possibly due to the cost of reagents required for cyclosarin production. After the Gulf War, it was discovered that Iraq had stockpiled G-agents including cyclosarin. Rockets containing both sarin and cyclosarin were found and destroyed by the US forces at the Khamisiyah weapons depot resulting in exposure to these two agents. One possible reason why Iraq stockpiled cyclosarin despite the fact that no other nation had done so, is that the precursor chemicals for sarin production, but not cyclosarin were embargoed making it a more desirable selection. Additionally, cyclosarin is the most persistent of the G-agents potentially making it a greater threat.
In 1997, the Chemical Weapons Convention (CWC) was enacted that banned the production, stockpiling, and use of chemical weapons (including cyclosarin) and called for the destruction of existing chemical weapons stockpiles. The CWC is administered by the Organisation for the Prohibition of Chemical Weapons, of which nearly all world nations are a part.

Principles and methods for destruction of chemical weapons: “Destruction of chemical weapons” means a process by which chemicals are con- verted in an essentially irreversible way to a form unsuitable for production of chemical weapons, and which in an irreversible manner renders munitions and other devices unusable as such. Each nation shall determine how it shall destroy chemical weapons, except that the following processes may not be used: dumping in any body of water, land burial or open-pit burning. It shall destroy chemical weapons only at specifically designated and appropriately designed and equipped facilities. Each nation shall ensure that its chemical weapons destruction facilities are con- structed and operated in a manner to ensure the destruction of the chemical weapons; and that the destruction process can be verified under the provisions of this Convention. (Organization for the Prohibition of Chemical Weapons; Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and Their Destruction). Grossly liquid-contaminated materials should be decontaminated and containerized and labeled in accordance with DOT and EPA requirements as a hazwaste. Wastewater solution from decon should be analyzed to ensure no residual agent is present. The National Response Plan, ESF-3 designates United States Army Corps of Engineers (USACE) as the primary agency to manage con- taminated debris. USACE and the Department of Defence (DOD) typically use safety procedures prior to transport that include “head space” (off gas) monitoring around containers prior to shipment to ensure no leakage/off-gassing. Typically waste will be transported in accordance with state require- ments to a designated disposal facility, such as a RCRA- permitted hazardous waste facility (typically an incinerator). Wastewater solution from the decontamination process will be analyzed to ensure no residual agent is present. It is likely that the solution will not contain residual agents and there- fore not need to be classified as a hazardous waste but sam- pling must be used to verify. Chlorinated wastewater may need to be treated/neutralized prior to disposal . United States munitions stockpiles of G-agent are/have undergone destruction/disposal in the states of Utah, Oregon, Arkansas, Alabama, and Kentucky. State/local plans to address poten- tial releases from United States Army properties are in place at these sites.

Cyclosarin is a synthetic organophosphate (OP) compound used in chemical warfare and terrorism.

A highly toxic colourlessliquid, C₇H₁₄FO₂P; r.d. 1.13; m.p.–30°C; b.p. 239°C. it is a fluorinatedorganophosphorus compound,(fluoromethylphosphoryl)oxycyclohexane.Cyclosarin was discovered in1949 and belongs to the G-series ofnerve agents (GF).

Reasonably stable in steel at normal temperatures.Prior to working with this chemical you should be trainedon its proper handling and storage. Store in tightly closedcontainers in a cool, well-ventilated area away from strongoxidizers. Where possible, automatically transfer materialfrom drums or other storage containers to process containers. Sources of ignition, such as smoking and open flames,are prohibited where this chemical is handled, used, orstored. Metal containers involving the transfer of this chemical should be grounded and bonded. Wherever this chemical is used, handled, manufactured, or stored, useexplosion-proof electrical equipment and fittings.

Cyclosarin 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 the degradation of 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 cyclosarin, the t1/2 for AChE is ～7 h and for RBC-ChE is ～2.2 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 upon 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 the fact that inhibition of AChE is not the only cause of toxic effects.
One of the noncholinergic effects that results from treatment with OP nerve agents is changes in the levels of neurotransmitters other than acetylcholine. These include g-amino-butyric acid, 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. Specifically, OP-induced disruption of mitochondrial oxidative phosphorylation occurs through a variety of mechanisms including reduction of electron transport chain enzyme complexes, reduction in ATP synthesis, increased hydrolysis of ATP, and disruption of the mitochondrial membrane potential. Accumulation of reactive oxygen species induces oxidative damage and cell death via caspase-induced apoptosis.
The pharmacological and toxicological effects of the nerve agents are dependent on their stability, rates of absorption by the various routes of exposure, distribution, ability to cross the blood–brain barrier, and rate of reaction.