Ｏ－シクロヘキシル＝メチルホスホノフルオリダート

Protection: Evacuation: Immediately isolate an area around any liquid or solid contamination for at least 700 feet in all directions. If possible, identify the agent and develop a downwind hazard diagram (see Table 3.2). Adjust the initial isolation distance as appropriate. Based on the type of release, amount of material aerosolized, persistence of the agent and local conditions (e.g., weather, population density, time of day), shelter in place until the initial cloud passes may be the most appropriate course of action since timely evacuation of the threatened downwind population may not be possible. Depending on the persistence of the agent and the potential for condensation of agent from the cloud, evacuation of the threatened population after passage of the initial cloud may be appropriate. /"G" Series Nerve Agents/

Principles and methods for destruction of chemical weapons: ... "Destruction of chemical weapons" means a process by which chemicals are converted 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 State Party 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 State Party shall ensure that its chemical weapons destruction facilities are constructed 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.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

Responders should be trained and appropriately attired before entering the Hot Zone. If the proper personal protective equipment (PPE) is not available, or if the rescuers have not been trained in its use, call for assistance in accordance with local Emergency Operational Guides (EOG). ... /in the decontamination zone, rescuers/ should continue to wear the same level of protection as required in the Hot Zone. /Nerve Agents/

Victims whose skin or clothing is contaminated with liquid nerve agent can contaminate rescuers by direct contact or through off-gassing vapor.... Before transport, all casualties must be decontaminated. ...Rapid decontamination is critical to prevent further absorption by the patient and to prevent exposure to others. Decontaminable gurneys and back boards should be used if possible when managing casualties in a contaminated area. ... All victims must be decontaminated properly before entering the Support Zone. /Nerve Agents/

If contaminated patients arrive at the Emergency Department, they must be decontaminated before being allowed to enter the facility. Decontamination can only take place inside the hospital if there is a decontamination facility with negative air pressure and floor drains to contain contamination. Personnel should wear the same level of protection required in the Hot Zone. /Nerve Agents/

For more Preventive Measures (Complete) data for CYCLOSARIN (6 total), please visit the HSDB record page.

0.00020 [ppm]

0.0024 [ppm]

0.018 [ppm]

For information on chemical warfare nerve agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

Nerve agent vapor is readily absorbed by inhalation and ocular contact and produces rapid local and systemic effects. The liquid is readily absorbed thorough the skin; however, effects may be delayed for several minutes to up to18 hours. Respiratory Protection: Pressure-demand, self-contained breathing apparatus (SCBA) is recommended in response situations that involve exposure to any nerve agent vapor or liquid. Skin Protection: Chemical-protective clothing and butyl rubber gloves are recommended when skin contact is possible because nerve agent liquid is rapidly absorbed through the skin and may cause systemic toxicity. /Nerve agents/

Recommendations for Personal Protective Equipment /PPE/ should be based on a site-based job hazard analysis of possible hazards including skin contact, air concentrations, heat stress, etc. All PPE should be used with appropriate additional administrative controls including medical surveillance, employee training, respirator fit-testing, and decontamination procedures to limit the potential for unforeseen adverse effects. /Nerve agents/

Personal Protective Requirements: "G" series nerve agents pose both a severe respiratory and severe contact hazard. Wear appropriate fully encapsulating protective gear with positive pressure self contained breathing apparatus (SCBA). Structural firefighters' protective clothing is recommended for fire situations only; it is not effective in spill or release events. Thickened agents pose a less significant vapor hazard but a much more significant contact hazard. /"G" Series Nerve Agents/

Protective equipment (self-contained breathing equipment or gas mask, barrier suit) must be used. ... Latex gloves are not adequate protection.

AEGL 1: Notable discomfort, irritation, or certain asymptomatic non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure (Unit: ppm [mg/m3])

0.00049 [0.0035]

0.00028 [0.0020]

0.00020 [0.0014]

0.00010 [0.00070]

0.000070 [0.00050]

The toxicity of agents GB and GF were basically additive when administered together by subcutaneous injection to mice.

The combined toxicity of sarin and cyclosarin does not indicate synergism...

Rhesus monkeys administered five times the LD50 but treated with atropine, pyridostigmine, and either 2-PAM or HI6 oxime all lived and had minimal nervous system changes.

A computer program (Q-test) was used to evaluate the combined toxic effects of nerve agent GF and its combined form with sarin (GB/GF) in mice. Efficacy of Jielin Injection, the 2-PAM-containing antidote used successfully in China for the treatment of organophosphate pesticide poisoning, was also evaluated and compared with HI-6 against single and combined poisonings. The two agents were basically additive in toxicity when combined. However, toxic signs (convulsions) appeared later in combined poisoning than after exposure to each agent alone. The protective ratio of Jielin Injection against GF poisoning was low but significantly higher when against poisoning by GB or combined agent. When HI-6 was substituted for 2-PAM, the antidote was more effective against poisoning by both single and combined agents. Results of in vitro reactivation of GF-inhibited human erythrocyte acetylcholinesterase by these oximes agreed with the in vivo antidotal efficacy.

For more Interactions (Complete) data for CYCLOSARIN (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 56(SRC), determined from a structure estimation method(2), indicates that cyclosarin is expected to have high mobility in soil(SRC). Volatilization of cyclosarin from moist soil surfaces may be an important fate process(SRC), given an estimated Henry's Law constant of 2.8X10-6 atm cu m/mol(SRC), derived from its vapor pressure, 0.044 mm Hg(3) and water solubility of 3,700 mg/L(3). Volatilization from dry soil, moist soil, snow and other solid surfaces has been observed to occur with other similar G-type nerve agents (tabun, sarin and soman)(4-6) which indicate, by analogy, that volatilization is expected to be an important fate process for cyclosarin (nerve agent GF)(SRC). Cyclosarin hydrolyzes in water forming hydrofluoric and cyclohexylmethylphosphonic acids(7); although hydrolysis rates in soil are not available, estimated water hydrolysis half-lives on the order of a few hours-to-several days at 25 °C and pH 5-8(2) suggest that hydrolysis in moist soil will be an important fate process(SRC). Biodegradation data in soil were not available(SRC, 2013); however, biodegradation has been demonstrated under controlled conditions(8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 56(SRC), determined from a structure estimation method(2), indicates that cyclosarin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water may be an important environmental fate process(3), given an estimated Henry's Law constant of 2.8X10-6 atm cu m/mol(SRC), derived from its vapor pressure, 0.044 mm Hg(4) and water solubility of 3,700 mg/L(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives from a model river and model lake are 18 and 132 days, respectively(SRC). If released into natural waters or water systems, cyclosarin will likely degrade rapidly (less than 2 days) depending on cyclosarin volume and other environmental conditions(5). Cyclosarin hydrolyzes in water with the hydrolysis products being hydrofluoric and cyclohexylmethylphosphonic acids(6) which are unlikely to persist for more than a few days in an unprotected environment(6). Using a structure estimation method(6), the hydrolysis half-life of cyclosarin at 25 °C can be estimated to be 5 days at pH 6, 19 hours at pH7 and 2 hours at pH 8(SRC); these estimated half-lives are on the same order of magnitude as measured hydrolysis rates for sarin(7). According to a classification scheme(8), an estimated BCF of 6(SRC), from an estimated log Kow of 1.67(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013); however, biodegradation has been demonstrated under controlled conditions(9). [

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cyclosarin, which has a vapor pressure of 0.044 Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase cyclosarin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 6 hours(SRC), calculated from its rate constant of 6.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The UV absorption spectrum of the structurally similar sarin in cyclohexane solution does not exhibit any absorption above 290 nm(4); therefore, by anaology cyclosarin is not expected to be susceptible to direct photolysis by sunlight(SRC).

Routine laboratory studies for all admitted patients include CBC, glucose, and serum electrolyte determinations. Chest X-ray and pulse oximetry (or ABG measurements) are recommended for severe exposures. Symptomatic and asymptomatic patients suspected of significant exposure should have determinations of red blood cell (RBC) cholinesterase activity, the most useful test for nerve agent poisoning. Severe symptoms of toxicity are usually present when more than 70% of RBC cholinesterase is inhibited. However, there is no correlation between cholinesterase activity and severity of topical signs and symptoms (e.g., miosis, rhinorrhea, dyspnea). If this test is not available, plasma cholinesterase can be measured. /Nerve Agents/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cyclosarin can be estimated to be 56(SRC). According to a classification scheme(2), this estimated Koc value suggests that cyclosarin is expected to have high mobility in soil(SRC).

/SIGNS AND SYMPTOMS/ Children present a clinical picture that can be very different to that observed in adults. Children in cholinergic crisis may not necessarily manifest with miosis (constriction of pupils)... In fact one case series demonstrated absence of myosis in 43% of pediatric victims. Studies involving pediatric exposure to organophosphates /OP/ have suggested the appearance of isolated CNS effects (such as stupor, coma) in the absence of peripheral muscarinic effects. Pediatric victims of OP intoxication display sigmificant muscular weakness and hypotonia in the absence of glandular secretions in 70-100% of cases involving moderate to severe levels of exposure... For adults, a presentation of central intoxication (weakness and hypotonia) from OPs without peripheral muscarinic signs and symptoms would be extremely atypical. /Nerve agents/

/SIGNS AND SYMPTOMS/ The chemical-warfare agents /including cyclosarin/ ... are highly toxic organophosphate ester derivatives of phosphonic acid. They are commonly termed nerve agents as a consequence of their anticholinesterase properties and subsequent adverse effects on smooth and skeletal muscle function as well as the central nervous system. Although the inhibition of cholinesterases within neuroeffector junctions or the effector itself is thought to be responsible for the major toxic effects of nerve agents, these compounds can apparently affect nerve impulse transmission by more direct processes as well

/SIGNS AND SYMPTOMS/ Nerve Agent Effects. Vapor Exposure. Mild: eyes - small pupils (miosis), dim vision; headache; nose - runny nose (rhinorrhea); mouth - salivation; lungs - tightness in the chest; time of onset: seconds to minutes after exposure. Self-aid: 1 MARK I Kit. Buddy-aid: stand by. Severe: all of the above, plus severe breathing difficulty or cessation of respiration; generalized muscular twitching, weakness, or paralysis; convulsions; loss of consciousness; loss of bladder, bowel control. Time of onset: seconds to minutes after exposure. /Nerve agents/

/EPIDEMIOLOGY STUDIES/ More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, /the authors/ reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner. Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (beta=-0.11, p=0.02) and WM (beta=-0.14, p=0.03) volumes, and number of CPT omission errors (beta=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, /the authors/ did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans. These findings confirm previous reports ...of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure.

An estimated BCF of 6 was calculated for cyclosarin(SRC), using an estimated log Kow of 1.67(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for cyclosarin is estimated as 2.8X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 0.044 mm Hg(1), and water solubility, 3,700 mg/L(1). This Henry's Law constant indicates that cyclosarin is expected to volatilize from moist soil and water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 18 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 132 days(SRC). Volatilization from dry soil, moist soil, snow and other solid surfaces has been observed to occur with other similar G-type nerve agents (tabun, sarin and soman)(3-5) which indicate, by analog, that volatilization is expected to be an important fate process for cyclosarin (nerve agent GF)(SRC).

/LABORATORY ANIMALS: Acute Exposure/ ...Pupil area decrement was measured from electronic flash photographs of dark-adapted eyes for which baseline pupil area had been previously determined. The nominal cumulative exposure (Cts) necessary to produce 50% and 90% decrement in total pupil area were determined and compared for GB vapor (46 eye measurements from 14 rabbits), GD vapor (153 eye measurements from 48 rabbits), and T-2715 (GF analog) vapor (85 measurements on 19 rabbits). The cumulative exposure needed to produce miosis sufficient to generate 90% pupil area decrement was 2.71 mg-min/cu m (95% CI = 1.84- 4.00 mg-min/cu m) for agent GB, 2.19 mg-min/cu m (95% CI = 1.45-3.29 mg-min/cu m) for agent GD, and 1.79 mg-min/cu m (95% CI = 1.40-2.29 mg-min/cu m) for agent GF. The cumulative exposure needed to produce miosis sufficient to generate 50% pupil area decrement was 1.32 mg-min/cu m (95% CI = 1.05-1.67 mg-min/cu m) for agent GB, 0.59 mg-min/cu m (95% CI = 0.49-0.70 mg-min/cu m) for agent GD, and 0.75 mg-min/cu m (95% CI = 0.65-0.87 mg-min/vu m) for agent GF.

/LABORATORY ANIMALS: Acute Exposure/ When inhaled, cyclosarin reportedly is less toxic than GB in rats and mice, similarly toxic in rabbits, and 6 to 12 times less toxic than soman in non-human primates. GF is approximately four times more toxic than GB by dermal exposure, most likely because it is a less volatile, more lipid soluble /compound/.

/LABORATORY ANIMALS: Acute Exposure/ Changes in serum biochemical and hematological parameters were studied in 20 male rhesus monkeys following acute poisoning by the organophosphate nerve agent cyclohexylmethylphosphonofluoridate (CMPF or GF). Animals were challenged with 5 x LD50 GF (233 ug/kg, IM) following pretreatment with pyridostigmine (0.3-0.7 mg/kg/24 hr) and treated with atropine (0.4 mg/kg, IM) and either 2-PAM (25.7 mg/kg, IM) or HI6 (37.8 mg/kg, IM) at the onset of clinical signs or at 1 min after exposure. Muscle fasciculations, tremors, or convulsions occurred in 19 of 20 animals. Serum biochemical and hematologic parameters were analyzed 2 days and 7 days after exposure and compared to pre-exposure baseline values. Significant increases in creatine kinase (CK), lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase (ALT) and potassium ion (K+), associated with damage to striated muscle and metabolic acidosis, occurred in both oxime-treated groups 2 days after exposure. Total protein, albumin, red blood cell (RBC) count, hemoglobin concentration (Hb) and hematocrit (Hct), were decreased in both oxime-treated groups at 7 days.

/LABORATORY ANIMALS: Acute Exposure/ Cyclohexylmethylphosphonofluoridate (CMPF) is an organophosphate cholinesterase inhibitor with military significance. The purpose of these studies was 1) to determine the acute toxicity of CMPF in the male rhesus monkey, 2) to evaluate the efficacy of pyridostigmine (PYR) pretreatment plus atropine and oxime (2-PAM or H16) treatment, and 3) to evaluate the pathological consequences of acute poisoning. An im LD50 of CMPF was estimated using an up-and-down dose selection procedure and 12 animals. The 48-hr and 7-day LD50 was 46.6 ug/kg, im In the protection experiments, pyridostigmine (0.3-0.7 mg/kg/24 hr) was administered by surgically implanted osmotic minipumps for 3-12 days resulting in 21-65% inhibition of erythrocyte acetylcholinesterase activity. Animals were challenged with 5 x L50 CMPF (233 ug/kg) and treated with atropine (0.4 mg/kg) and either 2-PAM (25.7 mg/kg) or HI6 (37.8 mg/kg) at the onset of signs or 1 min after challenge. Osmotic pumps were removed within 30 min after agent challenge. Pyridostigmine, atropine, and either 2-PAM or HI6 were completely effective against CMPF, saving ten of ten animals in each group. In comparison, three of five animals challenged with 5 x LD50 of soman and treated with atropine and 2-PAM survived 7 days. The primary histologic lesions in the acute toxicity group were neuronal degeneration/necrosis and spinal cord hemorrhage. The CMPF treated groups (total of 20 animals) had minimal nervous system changes with no significant lesion difference resulting from the different oxime therapies. The primary non-neural lesions were degenerative cardiomyopathy and skeletal muscle degeneration which occasionally progressed to necrosis and mineralization.

Children have several vulnerabilities putting them at increased toxicity from this class of chemical agents. A child's smaller mass alone reduces the dose needed to cause symptoms or lethality. For volatile nerve agents, children are especially at risk for respiratory toxicities due to their anatomic differences compared to adults. Their smaller airways can become compromised by the large amount of secretions and the bronchospasm caused by the agents. Also, a greater dose of nerve agent will be inhaled in children due to their higher respiratory rate and minute volumes. /Nerve Agents/

The rate constant for the vapor-phase reaction of cyclosarin with photochemically-produced hydroxyl radicals has been estimated as 6.7X10-11 cu cm/molecule-sec at 25 °C(SRC), using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 hours(SRC) at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). If released into natural waters or water systems, cyclosarin will likely degrade rapidly (less than 2 days) depending on cyclosarin volume and other environmental conditions(2). Degradation in water occurs through hydrolysis with the hydrolysis products being hydrofluoric and cyclohexylmethylphosphonic acids(3) which are unlikely to persist for more than a few days in an unprotected environment(3). Using a structure estimation method(1), the hydrolysis half-life of cyclosarin at 25 °C can be estimated to be 5 days at pH 6, 19 hours at pH7 and 2 hours at pH 8(SRC); these estimated half-lives are on the same order of magnitude as measured hydrolysis rates for sarin(4). The UV absorption spectrum of the structurally similar sarin in cyclohexane solution does not exhibit any absorption above 290 nm(5); therefore, cyclosarin is not expected to degrade through direct photolysis in the environment(SRC).