Methanesulfonyl Fluoride

Toxic Gases & Vapors -> Acid Halides

Corrosives

255 °F at 760 mmHg (EPA, 1998)

123.5 °C

124 °C @760 [mm Hg]

10.9 [mmHg]

10.9 mm Hg at 20 °C

10 [mm Hg] @25 °C

Methanesulfonyl fluoride is a liquid. (EPA, 1998)

Liquid; [CAMEO] Colorless liquid with a pungent odor; [MSDSonline]

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P264, P270, P271, P280, P284, P301+P316, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P320, P321, P330, P363, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 40 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

Highly corrosive; May cause serious injury to skin, eyes, mucous membranes, and upper respiratory tract; Inhalation may cause chemical pneumonitis and pulmonary edema; A selective inhibitor of CNS acetylcholinesterase; Sex-specific changes in brain development were observed in rats chronically exposed in utero; [HSDB] Reacts with water evolving hydrogen fluoride gas; Corrosive; Highly toxic by inhalation; [CAMEO] Effects in high-dose animal studies include inhibition of true cholinesterase and degenerative changes to brain; [RTECS]

METHANESULFONYL FLUORIDE is corrosive, toxic liquid. Vigorous reaction with water, steam, alkali. A dangerous storage hazard. On contact with moisture it produces highly corrosive and toxic fumes of hydrogen fluoride gas. When heated to decomposition it emits toxic fumes of fluoride, and oxides of sulfur [M. K.]. May react vigorously or explosively if mixed with diisopropyl ether or other ethers in the presence of trace amounts of metal salts [J. Haz. Mat., 1981, 4, 291].

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Methanesulfonyl fluoride is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.

Acute Tox. 2 (100%)

Acute toxicity (Oral) - Category 1

Corrosives

Biological Exposure Indices (BEI) [ACGIH] - Fluorides in urine = 2 mg/L prior to shift or 3 mg/L at end of shift; (Repeated measurements recommended.)

1.0 [mg/m3], as F, inhalable fraction[German Research Foundation (DFG)]

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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.

0.00081 [ppm]

0.0089 [ppm]

0.053 [ppm]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

TERRESTRIAL FATE: A spontaneous hydrolysis rate constant of 1X10-4/sec at a pH of 8.75 observed for methanesulfonyl fluoride(1) indicates that adsorption in soil and volatilization from moist soil surfaces will not be important environmental fate processes(SRC). Biodegradation data were not available(SRC, 2007).

AQUATIC FATE: A spontaneous hydrolysis rate constant of 1X10-4/sec at a pH of 8.75 observed for methanesulfonyl fluoride(1) indicates that adsorption to suspended solids and sediments, bioconcentration, and volatilization from water surfaces will not be important environmental fate processes(SRC). Biodegradation data were not available(SRC, 2007).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methanesulfonyl fluoride, which has a vapor pressure of 10.9 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase methanesulfonyl fluoride 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 15 days(SRC), calculated from its rate constant of 1.1X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Methanesulfonyl fluoride does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

/SIGNS AND SYMPTOMS/ Extremely destructive to tissues of the mucous membranes and upper respiratory tract, eyes and skin. Inhalation may be fatal as a result of spasm, inflammation and oedema of the larynx and bronchi, chemical pneumonitis and pulmonary edema

Methanesulfonyl fluoride's production and use as an experimental drug for the treatment of Alzheimer's disease(1) may result in its release to the environment through various waste streams. Its former production and use as a fumigant insecticide(2) may have resulted in its direct release to the environment(SRC).

A spontaneous hydrolysis rate constant of 1X10-4/sec at a pH of 8.75 observed for methanesulfonyl fluoride(1) indicates that volatilization from moist soil and water will not be an important environmental fate process(SRC). The potential for volatilization of methanesulfonyl fluoride from dry soil surfaces may exist(SRC) based upon a vapor pressure of 10.9 mm Hg(1).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The effects of exposure to methane sulfonylfluoride ... at concentrations of 20 or 100 ppb for a total of 61 exposures of 7 hr each were studied in male and female rats. The control and exposed groups did not differ in appearance, behavior, weight gain or food consumption. There was no effect on plasma cholinesterase. Red blood cell cholinesterase was significantly depressed in the high-level male and female exposure groups. There was no significant accumulation of F- in either the liver or blood at either exposure level.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ /The authors/ have previously confirmed that a single in utero exposure to MSF at clinically appropriate doses inhibits AChE activity in fetal rat brain by 20%, and when administered throughout gestation, MSF achieves a 40% level of inhibition. Here, /it is shown/ that rats chronically exposed in utero to MSF display marked sex-specific differences in morphological development of the cerebral cortical layers compared with controls at 7 days of age. Forebrain size and cortical thickness were increased in females and decreased in males. An analysis of gene expression in neonate brain on the day of birth revealed sex-specific differential expression of over 25 genes, including choline acetyltransferase (ChAT), which were affected by prenatal MSF exposure. Many of these genes are associated with sexual differentiation and brain development, while others are involved in more generalized cellular and metabolic processes. The changes observed in cortical morphology and gene expression suggest a critical developmental role for AChE in the fetal nervous system, most likely through its effect on cholinergic neurotransmission.[Byers DM et al; Brain Res Dev Brain Res 158 (102): 13-22 (2005)]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, /the authors/ investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 +/- 10%) and significantly prolonged acquisition (398 +/- 62 s) and shortened retention (79 +/- 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 +/- 8%), they performed significantly better in the passive avoidance task (255 +/- 36 s and 145 +/- 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task.[Borlongan CV et al; Brain Res 1038 (1): 50-8 (2005)]

/ALTERNATIVE and IN VITRO TESTS/ The purpose of this study was to investigate the functional impact of acute irreversible inhibition of acetylcholinesterase (AChE) on the fatigability of medial gastrocnemius and plantaris muscles of Sprague-Dawley rats. After treatment with methanesulfonyl fluoride (a lipid-soluble anticholinesterase), which reduced their AChE activity by >90%, these muscles were subjected to an in situ indirect stimulation protocol, including a series of isolated twitch and tetanic contractions preceding a 3-min fatigue regimen (100-ms trains at 75 Hz applied every 1.5 s). During the first minute of the fatigue regimen, the effects of AChE inhibition were already near maximal, including marked reductions in peak tension and the force-time integral (area), as well as a decrement of compound muscle action potential amplitudes within a stimulus train. Neuromuscular transmission failure was the major contributor of the force decreases in the AChE-inhibited muscles. However, despite this neuromuscular transmission failure, muscles of which all AChE molecular forms were nearly completely inhibited were still able to function, although abnormally, during 3 min of intermittent high-frequency nerve stimulation.[Panenic R et al; J Appl Physiol 87 (4): 1455-62 (1999)]

The rate constant for the vapor-phase reaction of methanesulfonyl fluoride with photochemically-produced hydroxyl radicals has been estimated as 1.1X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 15 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A spontaneous hydrolysis rate constant of 1X10-4/sec at a pH of 8.75 was observed for methanesulfonyl fluoride(2). This corresponds to a half-life of 2 hrs(SRC). Methanesulfonyl fluoride does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(3).

Methanesulfonyl fluoride's production and use as an experimental drug for the treatment of Alzheimer's disease may result in its release to the environment through various waste streams. Its former production and use as an fumigant insecticide may have resulted in its direct release to the environment. If released to air, a vapor pressure of 10.9 mm Hg at 20 °C indicates methanesulfonyl fluoride will exist solely as a vapor in the atmosphere. Vapor-phase methanesulfonyl fluoride will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 15 days. Methanesulfonyl fluoride does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, a spontaneous hydrolysis rate constant of 1X10-4/sec at a pH of 8.75 (half-life of 2 hrs) indicates that adsorption in soil and volatilization from moist soil surfaces will not be important environmental fate processes. Biodegradation data were not available. If released into water, its hydrolysis rate constant indicates that adsorption to sediment, volatilization from water, and bioconcentration will not be important environmental fate processes. Occupational exposure to methanesulfonyl fluoride may occur through inhalation and dermal contact with this compound at workplaces where methanesulfonyl fluoride is produced or used. (SRC)

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Aggressive airway control may be needed. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... Monitor for shock and treat if necessary ... Anticipate seizures and treat if necessary ... For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... /Organophosphates and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously and consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... Administer atropin Correct hypoxia before giving atropine ... Administer pralidoxime chloride (2 PAM). USE UNDER DIRECT PHYSICIAN ORDERS ONLY ... Treat seizures with adequate atropinization and correction of hypoxia. In rare cases diazepam or lorazepam may be necessary ... Watch for signs of fluid overload ... Use proparacaine hydrochloride to assist eye irrigation ... /Organophosphates and related compounds/

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Methanesulfonyl fluoride is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.

The chemical properties of methanesulfonyl-fluoride (MSF) were determined for comparison with the properties of the acetylcholinesterase inhibitors sarin and diisopropyl-phosphorofluoridate (DFP). MSF was subject to a series of chemical reactions and physical measurements which could be compared with those in the literature for sarin and DFP. The results reported have relevance toward the mechanism of inhibitor complex formation and reaction with the AChE esteratic site. The chemical reactivity of MSF and isopropyl-methylphosphonofluoridate (GB) or DFP was similar only with the strong nucleophiles such as oxime and hydroxamic-acid reactions and with the base catalyzed hydrolysis. Dissimilar chemical reactivity was noted with reactions involving weaker amine nucleophiles, phenolic hydrogen bonding, cupric complex coordination bonding, and acid catalyzed hydrolysis. The beta scale hydrogen bond acceptor measurement was shown to be an easy one and may be useful as a tool for probing reactivity differences of enzyme inhibitors. /The/ finding of interest was that the extremely weak basicity of MSF could account for the sulfonyl-fluoride/phosphoryl-fluoride reactivity divergence which may relate to the acetylcholinesterase inhibition and reactivation differences.

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Used formerly as fumigant insecticide; Used in medical research; [HSDB]

Farming (Pesticides) [Category: Industry]

Fumigant insecticide /Former/

High-purity /methanesulfonyl fluoride/ is prepared by treatment of /methanesulfonyl chloride/ with fluorides and /water/, distillation of the reaction mixture ... and phase separation of the distillate.

Heat methanesulfonyl chloride with /ammonium fluoride/ at 95-100 °C with continuous mixing ... cool, wash with water, and separate the methanesulfonyl fluoride. Dry it over /calcium chloride/ and distill at 122-4 °C. The preferred synthesis is the one in which hyposulfite, /dimethyl sulfate/ and /chlorine/ are used as the starting materials.

Methanesulfonyl fluoride: ACTIVE

Currently being developed and tested for the treatment of Alzheimer's disease.

Formerly marketed by Bayer AG as trade mark Fumette.