Isopropyl methanesulfonate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 35(SRC), determined from a structure estimation method(2), indicates that isopropyl methanesulfonate is expected to have very high mobility in soil(SRC). Volatilization of isopropyl methanesulfonate from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.1X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Isopropyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.43 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 35(SRC), determined from a structure estimation method(2), indicates that isopropyl 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 7.1X10-6 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 48 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.25(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis is expected to be rapid by analogy to methyl methanesulfonate, which has measured hydrolysis half-lives in water of 4.56 hours at 25 °C(8) and 77 hours at 20 °C(9). 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), isopropyl methanesulfonate, which has an estimated vapor pressure of 0.4 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 isopropyl 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 9 days(SRC), calculated from its rate constant of 1.8X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Isopropyl 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).

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of isopropyl methanesulfonate can be estimated to be 35(SRC). According to a classification scheme(2), this estimated Koc value suggests that isopropyl methanesulfonate is expected to have very high mobility in soil.

An estimated BCF of 3 was calculated in fish for isopropyl methanesulfonate(SRC), using an estimated log Kow of 0.25(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).

The Henry's Law constant for isopropyl methanesulfonate is estimated as 7.1X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that isopropyl 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 48 days(SRC). Isopropyl methanesulfonate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.436 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Six-wk-old female HSD:(ICR)BR mice were divided into three groups: 1) vehicle control (30 mice), 2) untreated control (60 mice), and 3) isopropyl methanesulfonate treated (32 mice). Group 1 received 0.05 mL trioctanoin subcutaneously once per week for 288 days, group 2 received no treatment, and group 3 received all injections of IMS in 0.05 mL trioctanoin once per week subcutaneously. The dose of isopropyl methanesulfonate was 2.8 mg (20 micromoles) for 63 days, 1.4 mg (10 micromoles) for the next 57 days, and then 0.7 mg (5 micromoles) for the final 82 days of treatment. Animals were necropsied when moribund. None of the group 1 or group 2 animals had died by day 288, when the report was written. By 63 days, 2 of 7 moribund animals in group 3 had lymphoid neoplasms (therefore the dose was halved); from 63 to 120 days, 10 of 15 treated mice had lymphoid neoplasms (again the dose was halved); and the remainder of the animals in group 3 were moribund by 202 days. Of group 3, 5 animals died with no evidence of neoplasia and 7 animals were too autolysed to autopsy. The mean survival time of tumor bearing animals was 118 days after initiation of treatment. Altogether 20 of 32 treated mice (group 3) developed lymphoid neoplasms of thymus origin.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Isopropyl methanesulfonate, a direct-acting SN1 alkylating agent, induced thymic lymphomas in 29 of 30 female Hsd: (ICR)BR mice by the 139th day following once a week subcutaneous injections at a dose of 10 umol/mouse. No such neoplasms were observed at the 450th day following 52 once a week subcutaneous injections (20 umol/mouse) of the borderline SN1/SN2 alkylating agent ethyl methanesulfonate. Local sarcomas were observed in 2 and pulmonary adenomas in 20 of the 30 ethyl methanesulfonate treated mice, 70% of which were alive at the 450th day. Neoplasms were not observed at local or at distant sites other than the thymus gland following treatment with isopropyl methanesulfonate.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Decreased fertility in female mice following single ip injection of isopropyl methanesulfonate has been observed ...

/GENOTOXICITY/ ... Isopropyl methanesulfonate ... /induces dominant lethal mutations/ in meiotic and premeiotic sperm /of mice and rats/.

/GENOTOXICITY/ Storage of isopropylmethanesulfonate-treated seeds at 30% water content resulted in recovery from induced mutagenic effects, while at 5% seed water content no significant changes in frequency of chromosome aberrations or in frequency of m2 chlorophyll mutants were detected.

The rate constant for the vapor-phase reaction of isopropyl methanesulfonate with photochemically-produced hydroxyl radicals has been estimated as 1.8X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolysis is expected to be rapid by analogy to methyl methanesulfonate, which has measured hydrolysis half-lives in water of 4.56 hours at 25 °C(3) and 77 hours at 20 °C(4). Isopropyl methanesulfonate does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Isopropyl methanesulfonate's former production and use as a catalyst may have resulted in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 0.43 mm Hg at 25 °C indicates isopropyl methanesulfonate will exist solely as a vapor in the atmosphere. Vapor-phase isopropyl methanesulfonate 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 9 days. Isopropyl methanesulfonate 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, isopropyl methanesulfonate is expected to have very high mobility based upon an estimated Koc of 35. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 7.1X10-6 atm-cu m/mole. Biodegradation data were not available. If released into water, isopropyl methanesulfonate is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is expected to be an important environmental fate process by analogy to methyl methanesulfonate, which has measured hydrolysis half-lives in water of 4.56 hours at 25 °C and 77 hours at 20 °C. Occupational exposure to isopropyl methanesulfonate may have occurred through inhalation and dermal contact with this compound at workplaces where isopropyl methanesulfonate was produced or used. (SRC)