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Ethyl methanesulfonate

Ethyl methanesulfonate structure

Ethyl methanesulfonate 

structure
  • CAS No:

    62-50-0

  • Formula:

    C3H8O3S

  • Chemical Name:

    Ethyl methanesulfonate

  • Synonyms:

    Methanesulfonic acid,ethyl ester;EMS;Ethyl methanesulfonate;Ethyl methanesulphonate;NSC 26805;Ethyl mesylate;O-Ethyl methylsulfonate;101946-08-1

  • Categories:

    Pharmaceutical Intermediates  >  Bulk Drug Intermediates

Description

colourless liquid Ethyl methane sulfonate is a clear liquid.


Ethyl methanesulfonate is a clear colorless liquid. Denser than water. (NTP, 1992)


Ethyl methanesulfonate is a clear colorless liquid. Denser than water. (NTP, 1992)|Ethyl methanesulfonate is a methanesulfonate ester resulting from the formal condensation of methanesulfonic acid with ethanol. It has a role as an alkylating agent, an antineoplastic agent, a carcinogenic agent, a genotoxin, a mutagen and a teratogenic agent.|Ethyl Methanesulfonate is a sulfonoxyalkane with carcinogenic and teratogenic properties. Ethyl methanesulfonate ethylates DNA, thereby damaging DNA and leading to genetic mutations, single-stranded breaks in DNA, and chromosomal aberrations. Ethyl methanesulfonate may be used experimentally in biomedical research. (NCI04)|An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.

Ethyl methanesulfonate Basic Attributes

124.16

124.16

773969

200-536-7

9H154DI0UP

26805

3082

DTXSID6025309

C29820

Colorless liquid

29041000

Characteristics

51.75000

-0.03

liquid

1.1452 g/cm3 @ Temp: 22 °C

<25 °C

213-213.5 °C @ Press: 761 Torr

100 °C

1.416

Miscible with water.

2-8°C

0.27 hPa (25 °C)

Henry's Law constant = 5.4X10-10 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 4.0X10-16 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.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

ETHYL METHANESULFONATE alkylates nucleophiles such as hydroxy, amino and sulfhydryl groups in model and biological materials. Is hydrolyzed by excess aqueous alkali to non-corrosive and non-toxic products. Is hydrolyzed by water to a highly corrosive product (NTP, 1992).

Safety Information

II

6.1

2810

3

46-22-40-36/37/38-45

53-23-36/37/39-45-36/37-37/39-26

PB2100000

T

Stable. Combustible. Incompatible with water, alkalies, oxidizing agents.

P201-P301 + P312 + P330-P308 + P313

H302-H340-H351

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U197, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds.|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/|For more Disposal Methods (Complete) data for ETHYL METHANESULFONATE (8 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. Ethyl Methanesulfonate (62-50-0) 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/s088ethy.pdf]

This chemical is combustible. (NTP, 1992)

|Danger|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501|Aggregated GHS information provided by 50 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|H227: Combustible liquid [Warning Flammable liquids]|P201, P202, P210, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P370+P378, P403+P233, P403+P235, P405, and P501

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

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing 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 chemical under refrigerated temperatures, and protect it from moisture. (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 ETHYL 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/

The major hazards encountered in the use and handling of ethyl methanesulfonate stem from its toxicologic properties. Exposure to this colorless liquid may occur from its use as a mutagen in experimental biochemical research. Effects from exposure may include mutagenesis. Also, the International Agency for Research on Cancer (IARC) has designated ethyl methanesulfonate as a Group 2B carcinogen, meaning, "The agent is possibly carcinogenic to humans." Exhaust ventilation which employs a high-efficiency particulate arrestor (HEPA) or charcoal filter should be used to minimize airborne levels of this substance. In activities and situations where over-exposure may occur, wear a protective suit and a carefully fitted respiratory. If contact should occur, irrigate exposed eyes with copious amounts of tepid water for at least 15 minutes and wash exposed skin thoroughly with soap and water. Smoking, eating, and drinking should be prohibited in ethyl methanesulfonate work areas. Ethyl methanesulfonate should be stored in a securely sealed container which is enclosed in a second, unbreakable, leakproof container. Ethyl methanesulfonate is a potential candidate for fluidized bed, rotary kiln, and liquid injection forms of incineration.

U119; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802; The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

U119; As stipulated in 40 CFR 261.33, when ethyl methanesulfonate as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Tire leachate water, obtained from tire cores exposed to water for 40 days, did not contain ethyl methanesulfonate at concentrations greater than the detection limit of 1.0 ug/L(1). Ethyl methanesulfonate was not detected in four process waste streams (sweet syngas, turbine stack gas, incinerator stack gas, offgas from wastewater treatment) from the Dow syngas facility in Plaquemine, LA during 1991(2).

Toxicity

The antimutagenic effects of vitamins C, E, and A, and derivatives of vitamin C on ethyl methanesulfonate induced 6TG resistant mutations in Chinese hamster V79 cells were examined. Vitamin C was most effective in inhibiting ethyl methanesulfonate cytotoxicity and 6TG resistant mutations. In the presence of vitamin C at a concentration of 100 micrograms/ml, ethyl methanesulfonate induced mutations were reduced to about one-third or one-forth of those in control cultures treated with ethyl methanesulfonate alone. Dehydro-vitamin C and iso-vitamin C also inhibited ethyl methanesulfonate induced mutations to about ... one-half or one-third of the control level. ... Vitamin C may react directly with ethyl methanesulfonate as a desmutagen and thus inactivate its mutation-inducing activity in Chinese hamster V79 cells. Vitamin E had an additive cytotoxic effect on EMS-induced cytotoxicity. This vitamin enhanced the frequencies of 6TG-resistant mutations induced by ethyl methanesulfonate. Pretreatment with vitamin E before treatment with ethyl methanesulfonate resulted in no detectable effect in modifying the ethyl methanesulfonate induced mutations. On the contrary, vitamin A markedly enhanced ethyl methanesulfonate induced mutation frequencies.|The 1,4-dihydropyridine derivative 2,6-dimethyl-3,5-diethoxycarbonyl-4-(sodium carboxylate)-1,4-dihydropyridine was studied for antimutagenic effect in the dominant lethal test and in the sex-linked recessive lethal test of Drosophila melanogaster. ... 1,4-dihydropyridine reduces the frequency of ethyl methanesulfate induced genetic damage (point mutations and chromosome breakage). A reduction of the mutation rate induced by ethyl methanesulfate in adults could be observed independently of the developmental stages (larvae or imago) pretreated with 1,4-dihydropyridine. The protective effect of this ... antimutagen against the alkylating agent depended on both the 1,4-dihydropyridine dose and the level of the ethyl methanesulfonate induced mutation rate. The effect of 1,4-dihydropyridine was more pronounced than that of /cysteine and cysteamine/.|Rat and canine hepatocyte suspensions were exposed to toxic concentrations of ethyl methanesulfonate (EMS) and ionophore A-23187 in the presence and absence of extracellular calcium (Ca2+) and alpha-tocopheryl succinate (alpha-TS). The exogenous administration of alpha-TS (25 microM) completely protected hepatocytes from chemically- induced toxicity when exposed to physiological free extracellular calcium concentrations (0.8-1.5 mM). ... Hepatocytes exposed to unesterified alpha- tocopherol (alpha-T, 25 microM) or alpha-tocopheryl acetate (alpha-TA, 25 microM), however, were not protected from the toxic effect of chemicals even though these treatments resulted in the marked accumulation of cellular alpha-T (2.65 nml/10(6) cells) and alpha-TA (2.3 nmol/10(6) cells), respectively. Finding suggest that the supplementation of endogenous stores of alpha-T or alpha-TA does not promote protection against chemical toxicity and that alpha-TS cytoprotection results not from the accumulation of alpha-T but rather from the cellular presence of the intact alpha-TS molecule. Thus alpha-TS appears to possess cytoprotective properties that differ from other vitamin E congeners.|The combination of EMS and aureomycin was highly cytotoxic, but EMS alone inhibited the mitosis in Vicia fabia.|For more Interactions (Complete) data for ETHYL METHANESULFONATE (7 total), please visit the HSDB record page.

LD50 Mouse oral 470 mg/kg

/AQUATIC SPECIES/ The filamentous blue-green algae, Anabaena oryzae and Nostoc entophytum, were isolated from rice fields soil and clonal cultures were raised from a single filament. 10 mL suspensions of both algae were treated with 0.1 mL ethyl methanesulfonate (EMS) for 0, 15, 30 and 60 min. Observations were made for 14 days. EMS progressively decreased the fresh weight of Anabaena oryzae (except on 2nd day at 15 min time dose) over controls. Chlorophyll a decreased in all the days with increase in dose time. In Nostoc entophytum, growth rates in EMS treated cultures were significantly affected but the cells grew after a long lag-phase (as compared to controls). Chlorophyll a was consistently reduced (except on 4th and 6th day at 15 min time dose) over controls. Vegetative cell length and breadth for both algae were higher in treated cultures. Algae treated with 0.1 mL of EMS at pH 5 for 2 hr, grew after a much shorter lag phase than those treated at higher pH values (pH 6, 7, or 8). Breakage of filaments and cell lysis were observed in Anabaena oryzae at 30 and 60 min doses. Nostoc entophytum was even more strongly affected. The cells showed chlorosis and lysis with incr time doses. The filaments in control were greenish blue whereas in treated samples they were pale yellow.|/BIRDS and MAMMALS/ Juvenile Coturnix coturnix japonica males were injected intravenous with 2, 20 or 200 mg ethyl methanesulfonate/kg bw; and hematologic variables were measured at 0 (non-injected), 24 and 72 hr post-injection. Ethyl methanesulfate induced hemolytic anemia began within 24 hr post-injection. Recovery from anemia began within 72 hr post-injection of ethyl methanesulfate. Ethyl methanesulfate induced lymphocytopenia, monocytopenia and heterophilia. The anemia induced by ethyl methanesulfate was dissimilar from that induced by phenylhydrazine and that EMS affected leukopoiesis.

Ethyl 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 22(SRC), determined from a structure estimation method(2), indicates that ethyl methanesulfonate is expected to have very high mobility in soil(SRC). Volatilization of ethyl methanesulfonate from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 5.4X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). However, hydrolysis of ethyl methanesulfonate is expected to be the major fate process in moist soil based on measured half-lives in water of 46(5) and 96 hours(6). Ethyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.206 mm Hg(4). Biodegradation data were not available(SRC, 2007).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 22(SRC), determined from a structure estimation method(2), indicates that ethyl 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 5.4X10-6 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 5 and 60 days, respectively(SRC). However, the rapid hydrolysis of ethyl methanesulfonate, with half-lives of 46(8) and 96 hours(9), 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 -0.2(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), ethyl methanesulfonate, which has a vapor pressure of 0.206 mm Hg at 25 °C (2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase ethyl 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 17 days(SRC), calculated from its rate constant of 9.6X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Ethyl 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 ethyl methanesulfonate with photochemically-produced hydroxyl radicals has been estimated as 9.6X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 17 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A neutral hydrolysis rate constant of 1.58X10-2 per hour was measured for ethyl methanesulfonate; this corresponds to a half-life of 46 hours at pH 7 and 25 °C(2). In a second study, a reaction rate constant of 7.2X10-3 per hour was measured(3); this corresponds to a half-life of 96 hours at 20 °C(3). This compound is expected to be inert to reaction with naturally-occurring oxidants found in water (alkylperoxy radicals and singlet oxygen)(4). Ethyl 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 ethyl methanesulfonate(SRC), using an estimated log Kow of -0.2(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, provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ethyl methanesulfonate can be estimated to be 22(SRC). According to a classification scheme(2), this estimated Koc value suggests that ethyl methanesulfonate is expected to have very high mobility in soil.

The Henry's Law constant for ethyl methanesulfonate is estimated as 5.4X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that ethyl 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 5 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 60 days(SRC). Ethyl methanesulfonate's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Ethyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.206 mm Hg(3).

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

Drug Information

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.)

... Is rapidly distributed in the mammalian system and increases the excretion of methylnicotinamide.

... IS METAB ... BY REACTION WITH GLUTATHIONE TO GIVE ETHYLMERCAPTURIC ACID, & BY HYDROLYSIS TO ETHANOL ... .

... HALF-LIFE IN RAT BLOOD SERUM ... 6.5 HR.

/GENOTOXICITY/ The relative importance of different sites of alkylation on DNA was determined by comparing two ethylating agents. 1-Ethyl-1-nitrosourea ethylates DNA with a higher proportion of total adducts on ring oxygens than ethyl methanesulfonate, which ethylates with a higher proportion of total adducts on the N-7 of guanine. ... To determine the importance in germ-line mutagenesis of the O6-G site relative to the N-7 of guanine, dose-response curves were constructed for both 1-ethyl-1-nitrosourea and ethyl methanesulfonate, where dose was measured as total adducts per deoxynucleotide and response as sex-linked recessive lethals induced in Drosophila melanogaster spermatozoa. For both mutagens the dose response curve was linear and extrapolated to the origin. ... 1-Ethyl-1-nitrosourea is 1.9 times more efficient per adduct in inducing sex-linked recessive lethals mutations than EMS. In vitro studies showed that 1-ethyl-1-nitrosourea induced 9.5% of its total adducts on O6-G while EMS induced 2.0% of its adducts on O6-G. If O6-G was the sole genotoxic site, then 1-ethyl-1-nitrosourea should be 4.8 times more efficient per adduct than ethyl methanesulfonate. ... While O6-G was the principal genotoxic site, N-7 G made a significant contribution to germ-line mutagenesis.

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the skin, eyes, respiratory tract and mucous membranes, dermatitis, nausea, vomiting, central nervous system depression and fibrosis. It may cause decreased visual acuity. A related compound is corrosive to tissues. ACUTE/CHRONIC HAZARDS: This compound is an irritant of the skin, eyes and mucous membranes. When heated to decomposition it emits toxic fumes of sulfur oxides. A similar compound is corrosive. (NTP, 1992)|Carcinogens, Mutagens

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/

/GENOTOXICITY/ A single 24-hour treatment with ethyl methanesulfonate at a concentration >100 uM induced mutation more efficiently in human lymphoblasts than 20 daily treatments at concentrations below 16 uM.|/GENOTOXICITY/ In order to determine the relationships among the reduction in relative cloning efficiency, sister chromatid exchange formation, and interference with progression through the cell cycle, human teratocarcinoma derived (P3) cells were exposed to either ethyl methanesulfonate or to methyl methanesulfonate. The relationship between sister chromatid exchange and toxicity was quantified, the progression through the cell cycle was evaluated with flow cytometric methods, and the effects of these chemicals on cell growth and average generation time were determined. A strong correlation existed between relative cloning efficiency and sister chromatid exchange (r= -0.978, p< .001) which was accompanied by an inhibition of growth as evidenced by a significant (p< .0001) negative linear effect of concentration on the relative cell count from 24 to 72 hr after exposure and by a concentration dependent increase (p< .0001) in the average generation time. Delays in the transit through S-phase were evident 4 hr after exposure to toxic concentrations of either carcinogen and by 8 to 12 hr post-exposure at the lower concentrations. Increases in the percentage of nuclei in G2 + M, indicative of G2 arrest, occurred from 12 to 24 hr after exposure. ...|/GENOTOXICITY/ Frequencies of chromosomal damage in the peripheral leukocytes of patients with Down syndrome, on exposure to gamma rays (2Gy) or ethyl methane sulfonate (EMS, 1X10(-4) m), were assessed. Analysis of break points in the chromosomes of irradiated cells revealed a non-random occurrences. Six of the break points observed in EMS-treated cells were found to overlap with those recorded in irradiated cells. Thirteen break points observed were found to correlate with the location of cancer-specific break points and four of these coincided with the bands where oncogenes have been located. Two break points were localized to the some bands as that of known heritable fragile sites.

Ethyl Mesilate

Ethyl methanesulfonate Use and Manufacturing

Methods of Manufacturing

By reacting dimethyl sulfate with sodium thiosulfate, the resulting methanesulfonyl chloride is then esterified with ethanol to obtain ethyl methanesulfonate.

Uses

Experimentally as mutagen, teratogen and brain carcinogen.

Production

(1975) NOT PRODUCED COMMERCIALLY IN USA.|(1977) NOT PRODUCED COMMERCIALLY IN USA.

Methanesulfonic acid, ethyl ester: ACTIVE|S - indicates a substance that is identified in a final Significant New Use Rule.|REVERSIBLE MALE CHEMOSTERILANT FOR INSECTS & MAMMALIAN PESTS. /MONOESTERS OF METHANESULFONIC ACID/

Method 8250. "Gas Chromatography/Mass Spectrometry for Semivolatile Organics: Packed Column Technique". Gas Chromatography Mass Spectrometric Method with no detection limit specified.|Method: EPA-EAD 1625; Procedure: gas chromatography/mass spectrometry; Analyte: ethyl mesylate; Matrix: water; Detection Limit: not provided.|Method: EPA-OSW 8270D; Procedure: gas chromatography/mass spectrometry; Analyte: ethyl mesylate; Matrix: solid waste matrices, soils, air sampling media and water samples; Detection Limit: 20 ug/L.|Analyte: ethyl methanesulfonate; matrix: pharmaceutical preparation; procedure: capillary gas chromatography with flame ionization detection; limit of detection: 1 ug/g|For more Analytic Laboratory Methods (Complete) data for ETHYL METHANESULFONATE (8 total), please visit the HSDB record page.

Health Hazards -> Carcinogens, Mutagens

Computed Properties

Molecular Weight:124.16
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:124.01941529
Monoisotopic Mass:124.01941529
Topological Polar Surface Area:51.8
Heavy Atom Count:7
Complexity:118
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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