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Methyl methanesulfonate

Methyl methanesulfonate structure

Methyl methanesulfonate 

structure
  • CAS No:

    66-27-3

  • Formula:

    C2H6O3S

  • Chemical Name:

    Methyl methanesulfonate

  • Synonyms:

    Methanesulfonic acid,methyl ester;Methyl methanesulphonate;MMS;Methyl methanesulfonate;Methyl methylsulfonate;NSC 50256;Methyl mesylate

  • Categories:

    Pharmaceutical Intermediates  >  Bulk Drug Intermediates

Description

colourless liquid Clear, colorless to amber liquid.


Methyl methanesulfonate is a colorless to amber liquid. (NTP, 1992)


Methyl methanesulfonate is a colorless to amber liquid. (NTP, 1992)|Methyl methanesulfonate is a methanesulfonate ester resulting from the formal condensation of methanesulfonic acid with methanol. It has a role as an alkylating agent, a genotoxin, a carcinogenic agent, a mutagen and an apoptosis inducer.|Methyl Methanesulfonate is a stable, colorless, combustible liquid that emits toxic fumes of sulfoxide when heated to decomposition. Methyl methanesulfonate is used for laboratory purposes as a catalyst in chemical synthesis and has been tested clinically as a cancer chemotherapeutic agent. This substance is an alkylating agent and acts as a mutagen by altering and damaging DNA and is reasonably anticipated to be a human carcinogen. (NCI05)|An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.

Methyl methanesulfonate Basic Attributes

110.13

110.13

200-625-0

AT5C31J09G

50256

2922

DTXSID7020845

C44399

Colorless liquid

29051900

Characteristics

51.8

-0.4

Methyl methanesulfonate is a colorless to amber liquid. (NTP, 1992)

1.2943 g/cm3 @ Temp: 20 °C

20 °C

203 °C @ Press: 753 Torr

104.4±0.0 °C

1.406

200 g/L (20 ºC)

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should b

0.8 hPa (59 °C)

LD50 orally in Rabbit: 225 mg/kg

Henry's Law constant = 4.0X10-6 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 2.3X10-13 cu cm/molecule-sec at 25 °C (est)|... decompose on distillation at normal pressure ... darken when stored in the absence of light ... form hydrates, are hygroscopic, and dissolve readily in water /Alkanesulfonic acids/

Water soluble.

Sulfonates, Phosphonates, and Thiophosphonates, Organic

METHYL METHANESULFONATE is incompatible with strong oxidizing agents, strong acids and strong bases. (NTP, 1992)

Safety Information

6.1(b)

2810

3

6.1

S53-S26-S45-S36/37/39

PB2625000

T:Toxic;

Stable. Combustible. Incompatible with strong oxidizing agents, strong acids, strong bases.

P201-P261-P301 + P310-P305 + P351 + P338-P308 + P313

H301-H315-H319-H335-H350

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.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for METHYL METHANESULFONATE (7 total), please visit the HSDB record page.

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Methyl Methanesulfonate (66-27-3) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s110meme.pdf]

This chemical is combustible. (NTP, 1992)

|Danger|H301 (99.56%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P272, P273, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 225 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material at ambient temperatures and away from oxidizers. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves. RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). Splash proof safety goggles should be worn while handling this chemical. Alternatively, a full face respirator, equipped as above, may be used to provide simultaneous eye and respiratory protection. (NTP, 1992)|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for METHYL METHANESULFONATE (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

Tire leachate water, obtained from tire cores exposed to water for 40 days, did not contain methyl methanesulfonate at concentrations greater than the detection limit of 1.0 ug/L(1). Methyl methanesulfonate was not detected over a two-year period, from 1989-1991, from the incinerator stack gas(both particulate and vapor), the turbine stack gas(both particulate and vapor), offgas from wastewater treatment, or the sweet syngas of a Louisiana gasification plant; GC/MS was used for detection(2).

Toxicity

The combined effects of methyl methanesulfonate and ethyl methanesulfonate on the induction of 6-thioguanine resistant mutants and chromosome aberrations were examined in Chinese hamster V79 cells. Cells were simultaneously treated with ethylmethanesulfonate at a concentration of D20 /SRP: D20 = concentration required to reduce cell survival to 20%/ and methyl methanesulfonate at various concentrations for 3, 6 or 9 hr. In other experiments cells were simultaneously treated with methyl methanesulfonate at a concentration of D20 and ethyl methanesulfonate at various concentrations for 3, 6 or 9 hr. The mathematical analysis of the combined effects of both chemicals for cell killing (cytotoxicity) and 6-thioguanine resistant mutations indicates that synergistic interactions were observed for both cell killing and mutations induced by methyl methanesulfonate and ethyl methanesulfonate. The frequency of chromosome aberrations induced by simultaneous treatment with methyl methanesulfonate at a concentration of D20 and ethyl methanesulfonate at various concentrations for 3 hr was additive. However, the frequency of chromosome aberrations induced by ethyl methanesulfonate at a concentration of D20 and methyl methanesulfonate at various concentrations for 3 hr was not significantly different from those induced by methyl methanesulfonate alone.|Ethanol itself did not induce any apparent chromosome aberrations in Chinese hamster ovary cells. However, post-treatment with ethanol potentiated the chromosome aberrations induced by ... methyl methanesulfonate. ... Chromatid exchanges were predominantly increased in cultures treated with ... methyl methanesulfonate ... and then with ethanol. ... Post-treatment with acetaldehyde, the major metabolite of ethanol, also potentiated the chromosome aberrations induced by ... methyl methanesulfonate. ... The main types of aberrations potentiated by posttreatment with acetaldehyde were similar to those by posttreatment with ethanol. /Methyl methanesulfonate/

LD50 Rat oral 225 mg/kg|LD50 Rat ip 140 mg/kg|LD50 Rat sc 125 mg/kg|LD50 Rat iv 175 mg/kg

Methyl methanesulfonate's former production and use as a research chemical(1) may have resulted in its limited release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that methyl methanesulfonate is expected to have very high mobility in soil(SRC). Volatilization of methyl methanesulfonate from moist soil surfaces may occur SRC) given an estimated Henry's Law constant of 4.0X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). However, hydrolysis of methyl methanesulfonate is expected to be the major fate process in moist soil based on measured half-lives in water of 4.56 hours(5), 9.66 hours(6), and 77 hours(7). Methyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.3 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2007).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that methyl methanesulfonate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.0X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 6 and 74 days, respectively(SRC). However, the rapid hydrolysis of methyl methanesulfonate, with half-lives of 4.56 hours(9), 9.66 hours(10), and 77 hours(11) in water, indicates that hydrolysis, and not volatilization, will be the major fate process for this compound in aquatic environments. According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -0.7(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(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), methyl methanesulfonate, which has an estimated vapor pressure of 0.3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase methyl methanesulfonate 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 70 days(SRC), calculated from its rate constant of 2.3X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Methyl methanesulfonate does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of methyl methanesulfonate with photochemically-produced hydroxyl radicals has been estimated as 2.3X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 70 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Measured hydrolysis half-lives in water of 4.56 hours at 25 °C(2), 9.66 hours at an unknown temperature(3), and 77 hours at 20 °C(4), have been reported for methyl methanesulfonate. Methyl methanesulfonate does not contain chromophores that absorb at wavelengths >290 nm(5) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for methyl methanesulfonate(SRC), using an estimated log Kow of -0.7(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of methyl methanesulfonate can be estimated to be 12(SRC). According to a classification scheme(2), this estimated Koc value suggests that methyl methanesulfonate is expected to have very high mobility in soil.

The Henry's Law constant for methyl methanesulfonate is estimated as 4.0X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that methyl methanesulfonate is expected to volatilize from 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 6 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 73 days(SRC). However, the rapid hydrolysis of methyl methanesulfonate(4-6) indicates that hydrolysis, and not volatilization, will be the major fate process for this compound in water. Methyl methanesulfonate's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Methyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.3 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to methyl methanesulfonate may have occurred through inhalation and dermal contact with this compound at former workplaces where methyl methanesulfonate was produced or used. (SRC)

Drug Information

Therapeutic application of total doses of between 2.8-800 mg/kg bw over period of up to 350 days to 13 cancer patients led to significant GI and hepatic toxic effects.

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)|Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. (See all compounds classified as Mutagens.)

In rats, approximately 30% of the radioactivity injected as (14)CH3 methyl methanesulfonate was exhaled as (14)CO2 within 30 hr, and an additional 20% was recovered from urine. In mice given a single ip dose ... approximately 34% ... was recovered from urine and 27% as (14)CO2.|In mice and rats methyl methanesulfonate is rapidly distributed throughout the body, including the CNS. In pregnant rats (21st day of gestation), transplacental passage into fetuses occurred within 2 min after iv injection. Following iv injection of 100 mg/kg body weight to rats, no detectable amount of methyl methanesulfonate were found in blood serum after 2 hr.|... If administered intraperitoneally, it reaches the excretion mechanism readily in activated form.

Various urinary metabolites (methylmercapturic acid sulfoxide, 2-hydroxy-3-methylsulfinylpropionic acid, methylsulfinylacetic acid and a mixture of methylmercapturic acid and N-(methylthioacetyl)glycine) were identified in rats after iv administration of (14)CH3-methyl methansulfonate during the first 16 hr. About 80% of the excreted radioactivity was accounted for by these metabolites, resulting from an initial methylation of cysteine residues by methyl methanesulfonate.

Monofunctional, methylating agents, such as methyl methanesulfonate, produce primarily 7-methyl-guanine, an adduct that is believed to be innocuous due to its inability to block nucleic acid synthesis or cause misincorporation of bases in newly synthesized DNA. This altered base, however, has been postulated to be indirectly deleterious to cells due to the increased lability of the /glycosyl/ bond, leading to the formation of noninstructive apurinic sites in the DNA template. Another abundant lesion formed is 3-methyladenine. This product has been shown to block nucleic acid synthesis, but direct evidence that it is a lethal moiety in mammalian cells is lacking. The primary promutagenic lesions formed by methylating agents are O6-methylguanine and O-4-methylthymine, both of which can cause base transitions in newly synthesized DNA. O-Methylguanine is formed to a higher extent than O-4-methylthymine, and it has been demonstrated that guanines preceded at 5' by adenine are twice as likely to be methylated at the O6 position as those preceded by thymine, indicating the existence of base sequence effects on adduct formation. Another lesion formed by methylating agents is the methylphosphotriester. This persistent adduct clearly slows nucleic acid synthesis in cell-free systems, but its effect on gene expression or mutagenesis in cells is not clear. ... Longer chain alkylating agents produce similar spectra of damage, but the relative proportions of the adducts formed are significantly different. The lesions formed in the greatest quantities are the alkylphosphotriesters, which represent more than 50% of the total damage to the DNA. The promutagenic lesion that becomes increasingly important with these agents is O4-alkylthymine. It is produced in amounts five- to tenfold greater than occur with methylating agents, and, although it is slowly removed from DNA, its half-life is significantly longer than that for O6-alkylguanine, making it potentially more important in causing point mutations following DNA synthesis.

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the eyes, skin, mucous membranes, nose and respiratory tract. It can cause dermatitis and nausea. Large doses ingested over nearly a year produced gastrointestinal and hepatic toxic effects. ACUTE/CHRONIC HAZARDS: This chemical causes irritation of the skin. It is corrosive. It may cause eye, nasal, respiratory and mucous membrane irritation. It is harmful if swallowed, inhaled or absorbed through the skin. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and sulfur oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. Corrosive chemicals will destroy the membranes of the mouth, throat, and esophagus and, in addition, have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. Transport the victim IMMEDIATELY to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist respirations 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 ... . 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. Activated charcoal is not effective ... . Do not attempt to neutralize because of exothermic reaction. Cover skin burns with dry, sterile dressings after decontamination ... . /Organic acids 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. Early intubation, at the first sign of upper airway obstruction, may be necessary. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as 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. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic acids and related compounds/

/HUMAN EXPOSURE STUDIES/ Therapeutic application of total doses of between 2.8-800 mg/kg body weight over a period of up to 350 days to 13 cancer patients led to significant gastrointestinal and hepatic toxic effects.|/EPIDEMIOLOGY STUDIES/ Sixty-one xeroderma pigmentosum patients living in the Federal Republic of Germany were investigated. Clinical symptoms were correlated with DNA repair parameters measured in fibroblasts grown from skin biopsies. Classification according to the international complementation groups revealed that of the 61 patients 3 belonged to group A, 26 to group C, 16 to group D, 3 to group E, and 2 to group F; 11 were of the xeroderma pigmentosum variant type. A striking clinical aspect was the frequency of histogenetically different skin tumors varying from one xeroderma pigmentosum complementation group to the other: squamous and basal cell carinomas predominated in xeroderma pigmentosum group C; lentigo maligna melanomas were most frequent in group D; basal cell carcinomas occurred preferentially in group E and xeroderma pigmentosum variants. Three DNA repair parameters were determined for 46 fibroblast strains: colony forming ability; DNA repair synthesis; and DNA incising capacity. Dose response experiments with up to 13 dose levels were performed throughout to achieve sufficient experimental accuracy. DNA damaging treatments included UV light, the UV like carcinogen N-acetoxy-2-acetylaminofluorene, and the alkylating carcinogens methyl methanesulfonate and N-methyl-N-nitrosourea. Comparison of clinical signs and repair data was made on the basis of colony forming ability, DNA repair synthesis, and DNA incising capacity values of both individual cell strains and weighted means of xeroderma pigmentosum complementation groups. Despite considerable clinical and biochemical heterogeneity within complementation groups distinctive features emerged. In general, colony forming ability, DNA repair synthesis, and DNA incising capacity values of all xeroderma pigmentosum strains investigated, including xeroderma pigmentosum variants, were found to be reduced upon treatment with UV light or N-acetoxy-2-acetylaminofluorene. After treatment with UV light or N-acetoxy-2-acetylaminofluorene, cell strains in which DNA incising capacity was reduced also showed a similar reduction in both colony forming ability and DNA repair synthesis. Consequently, the weighted mean colony forming ability, DNA repair synthesis, and DNA incising capacity values of complementation groups and xeroderma pigmentosum variants correlated with each other. Furthermore, the onset of both early dermatological symptoms of xeroderma pigmentosum and tumor growth correlated with the extent of DNA repair defects. Of 45 xeroderma pigmentosum fibroblast strains checked for colony forming ability after treatment with methyl methanesulfonate only 3 cell strains from group D were found to be more sensitive than normal controls, suggesting that overall repair in xeroderma pigmentosum strains was equal to that in controls. Weighted means of DNA repair synthesis of xeroderma pigmentosum complementation groups, however, showed reductions hinting at impaired excision of distinct alkylated bases. This held true for complementation groups, D, A, E, and F. Upon treatment with N-methyl-N-nitrosourea, the weighted mean DNA repair synthesis values of the complementation groups did not differ significantly from that of controls, ... However, the weighted mean colony forming ability value of complementation group D was significantly reduced, ...|/ALTERNATIVE and IN VITRO TESTS/ Nine human tumor cell lines derived from both epithelial and mesenchymal tumors exhibited either an anchorage independent growth non-tumorigenic phenotype or an anchorage independent tumorigenic phenotype. Transformed epithelial cell lines with the non-tumorigenic phenotype could be converted to a progressively growing tumor phenotype following treatment with either methylmethane sulfonate or N-methyl-N'-nitro-N-nitrosoguanidine. In contrast, sarcoma derived cell lines with a non-tumorigenic phenotype could be converted to a progressively growing tumor phenotype only with N-methyl-N'-nitro-N-nitrosoguanidine. SV40 immortalized HET-1A non-tumorigenic phenotype cells could be converted to a progressively growing tumorigenic phenotype, infrequently, when treated with N-methyl-N'-nitro-N-nitrosoguanidine, but not methylmethane sulfonate. Progressively growing tumors produced by either methylmethane sulfonate or N- methyl-N'-nitro-N-nitrosoguanidine treated non-tumorigenic phenotypes exhibited metastatic potential in nude mice. Chemically treated HET-1A cells acquired the abilty to produce tumor in mice but the tumor did not exhibit metastatic potential. In contrast, populations of tumorigenic cells were not rendered more biologically aggressive after treatment with either methylmethane sulfonate or N-methyl-N'-nitro-N-nitrosoguanidine; ie, the latency period for tumor development was not accelerated and the tumors did not exhibit metastatic potential. ...|/ALTERNATIVE and IN VITRO TESTS/ Squamous epithelial carcinoma is a predominant form of skin cancer in man and, in theory, human epidermal keratinocytes present an appropriate target cell to employ as an in vitro system to study epidermal carcinogenesis. Keratinocytes were serially cultivated from adult human skin samples and maintained in culture for at least 3 passages. Tertiary cultures, isolated from 3 separate individuals, were exposed to the direct acting experimental carcinogen, methyl methanesulfonate. DNA repair was assessed by a quantitative autoradiographic technique. Methyl methanesulfonate elicited a dose related increase in unscheduled DNA synthesis in cultures prepared from each individual. Inter-individual variation in the response was observed.|For more Human Toxicity Excerpts (Complete) data for METHYL METHANESULFONATE (8 total), please visit the HSDB record page.

Dimethylsulfonate

Methyl methanesulfonate Use and Manufacturing

Methods of Manufacturing

Reaction of mesyl chloride with methanol in anhydrous pyridine.|... Prepared from action of methyl iodide upon methyl sulfite. No indications ... That methyl methanesulfonate is produced commercially ... .

Uses

Experimentally as mutagen, teratogen, brain carcinogen.

Production

(1977) NOT PRODUCED COMMERCIALLY IN US|(1979) NOT PRODUCED COMMERCIALLY IN US

Essentially 100% as a research chemical

Methanesulfonic acid, methyl ester: ACTIVE

EPA Method 8250. Packed Column GC/MS Technique for the determination of semivolatile organic compounds in extracts prepared from all types of solid waste matrices, soil, and groundwater. This method is applicable to quantify most neutral, acidic, and basic organic compounds that are soluble in methylene chloride and capable of being eluted with derivatization as sharp peaks from a gas chromatographic packed column. Under the prescribed conditions, methyl methanesulfonate detection limit not determined. Precision and method accuracy were found to be directly related to the concentration of the analyte and essentially independent of the sample matrix.|EPA Method 3540. Soxhlet Extraction. A solid sample is mixed with anhydrous sodium sulfate and extracted using an appropriate solvent in a Soxhlet extractor. The sample is then dried and concentrated using a Kuderna-Danish apparatus. This is a procedure for extracting nonvolatile and semivolatile organic compounds from solids such as soils, sludges, and waste.|EPA Method 3550. Sonication Extraction. A 2- to 3-g solid sample is mixed with anhydrous sodium sulfate to form a free-flowing powder, then solvent extracted using a horn-type sonicator, followed by vacuum filtration or centrifugation for organic components of equal or less than 20 mg/kg. This method is applicable to the extraction of nonvolatile and semivolatile organic compounds from solids such as soils, sludges, and waste. Interferences include chlorofluorocarbons and methylene chloride.|Method: EPA-EAD 1625; Procedure: gas chromatography/mass spectrometry; Analyte: methanesulfonic acid, methyl ester; Matrix: water; Detection Limit: not provided.|For more Analytic Laboratory Methods (Complete) data for METHYL METHANESULFONATE (10 total), please visit the HSDB record page.

Computed Properties

Molecular Weight:110.13
XLogP3:-0.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:110.00376522
Monoisotopic Mass:110.00376522
Topological Polar Surface Area:51.8
Heavy Atom Count:6
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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