Isopropyl methanesulfonate

• CAS: 926-06-7
• Catalog Number: ACM926067
• Category: Main Products
• Molecular Weight: 138.19
• Molecular Formula: C₄H₁₀O₃S
• Synonyms: 2-Propyl methanesulphonate;2-propylmethanesulphonate;IMS;Isopropyl mesylate;Isopropyl methane sulphonate;Isopropyl methanesulfate;isopropylmesylate;isopropylmethanesulphonate
• IUPAC Name: propan-2-ylmethanesulfonate
• SMILES: CC(C)OS(=O)(=O)C
• InChI Key: SWWHCQCMVCPLEQ-UHFFFAOYSA-N
• Boiling Point: 82°C (6 mmHg)
• Flash Point: 104°C
• Density: 1.145
• Appearance: clear, colorless liquid.
• EC Number: 213-132-0
• Exact Mass: 138.03500
• Hazard Statements: C
• Safety Description: 45-36/37/39-26
• Supplemental Hazard Statements: H302-H314-H341-H351
• Symbol: GHS05,GHS07,GHS08

Case Study

Study on the In Vivo Mutagenicity of Isopropyl Methanesulfonate in Acute and 28-Day Rat Studies

Coffing, Stephanie L., et al. Environmental and Molecular Mutagenesis 56.4 (2015): 322-332.

The in vivo mutagenicity of isopropyl methanesulfonate (IPMS), a pharmaceutically relevant alkyl ester impurity, was evaluated using the Pig-a mutation assay in mature male Wistar Han rats. Two exposure regimens were designed: acute exposure with a single intraperitoneal injection at doses of 3.5, 7, 14, 28, and 56 mg/kg, and subchronic exposure with daily intraperitoneal injections for 28 consecutive days at doses of 0.125, 0.25, 0.5, 1, 2 mg/kg/day in the first subchronic study and 0.1, 0.2, 0.3, 0.4, 1 mg/kg/day in the second low-dose subchronic study.
Blood samples were collected at specified time points via jugular venipuncture. The frequency of CD59-negative mutant reticulocytes (Ret) and red blood cells (RBC) was detected by flow cytometry after leukocyte depletion, antibody labeling, and magnetic column enrichment of mutant cells.
In the acute study, a statistically significant dose-related increase in mutant Ret and RBC frequencies was observed on all analysis days. The maximum mutant Ret response occurred on day 15, with a 58-fold increase over the control at the 56 mg/kg dose. The maximum mutant RBC response appeared on day 28, showing a 28-fold increase at the 56 mg/kg dose. A No Observed Effect Level (NOEL) of 7 mg/kg was determined for both mutant Ret and RBC induction. Toxicity was manifested as a statistically significant dose-related decrease in the percentage of Ret at doses of 14 to 56 mg/kg on day 15, along with a significant decreasing trend in body weight gain across the dose range.
In the first subchronic study, no dose-related statistically significant changes in the percentage of Ret were found, indicating no obvious RBC toxicity. The maximum mutant Ret response occurred on day 29, with a fivefold increase at the 2 mg/kg/day dose, and the NOEL for mutant Ret induction was 0.5 mg/kg/day. The maximum mutant RBC response was observed on day 56, showing an 11-fold increase at the 2 mg/kg/day dose, and the NOEL for mutant RBC induction was 0.25 mg/kg/day. In the second low-dose subchronic study, no statistically significant trend in mutant Ret frequency was detected on days 29 and 56, leading to a NOEL of 1 mg/kg/day for mutant Ret. A statistically significant dose-related increase in mutant RBC frequency was first observed on day 56 at doses of 0.4 and 1 mg/kg/day, with a NOEL of 0.3 mg/kg/day for mutant RBC induction.
A comparison of mutant RBC frequencies between the acute and subchronic studies suggested a potential sublinear dose response. The acute mutant RBC responses at doses of 28 and 56 mg/kg were four and threefold higher than the subchronic responses at the equivalent fractionated doses of 1 and 2 mg/kg/day, respectively. However, this sublinearity was not substantiated by statistical analysis using the Lutz and Lutz bilinear model. Based on the subchronic NOEL of 0.25 mg/kg/day for mutant RBCs and relevant safety factors, the calculated Permitted Daily Exposure (PDE) for a 50 kg human was 2.5 mg/day, which was not significantly higher than the Threshold of Toxicological Concern (TTC).
A comparison of the Swain Scott constant, SN1/SN2 reaction mechanism, and O6:N7 guanine adduct ratio indicated that IPMS had a mutagenic profile similar to ethyl nitrosourea (ENU). The NOEL of IPMS was consistent with that of ENU, which could be attributed to the fact that IPMS-induced bulky adducts are repaired more slowly than those induced by ENU, despite ENU having a higher O6:N7 guanine adduct ratio and carcinogenic potential.

Study on DNA Repair Induction in Mouse Early Spermatids by Isopropyl Methanesulfonate (IMS)

Sega, Gary A, et al. Mutation Research 36 (1976): 193-212

This study investigated the DNA repair-inducing effect of isopropyl methanesulfonate (IMS) in early spermatid stages of male mice, with methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and propyl methanesulfonate (PMS) as homologous controls. The unscheduled incorporation of [methyl-³H] thymidine ([³H]dT) into germ cell DNA was used to evaluate the level of DNA repair, and the purification of sperm DNA verified that [³H]dT was indeed incorporated into the DNA. IMS was administered to (C3Hf×101) F₁ male mice via intraperitoneal injection, and [³H]dT was injected into the testes either simultaneously with IMS or 0.5, 1, 2 and 3 days after IMS treatment. Early spermatids treated with IMS were recovered from the caudal epididymides 16 days after chemical treatment, and the level of DNA repair was measured by liquid scintillation counting and autoradiography of sperm heads.
Within the tested dose range of 10-170 mg/kg, IMS induced a linear increase in DNA repair level in early spermatids with increasing dose. At equimolar doses, the effectiveness of the four alkyl methanesulfonates in inducing DNA repair was ranked as MMS > EMS > IMS > PMS. When [³H]dT was injected simultaneously with IMS, the unscheduled incorporation of [³H]dT into early spermatid DNA reached the maximum level, indicating that IMS could reach the DNA of early spermatids and induce repairable lesions within 1 hour after treatment. The duration of DNA repair in early spermatids after IMS treatment was further studied. The level of DNA repair decreased rapidly in the first 0.5 days after treatment, and then remained relatively stable from 0.5 to 3 days after treatment. At 3 days post-treatment, the DNA repair level of IMS-treated group was about twice that of the control group. The detection sensitivity of DNA repair induced by IMS in mouse germ cells was 5-10 times higher than that of genetic endpoints such as dominant lethal mutations and translocations. The autoradiographic results showed that the grain distribution over IMS-treated sperm heads was the closest to the Poisson distribution among the four chemicals, reflecting the biological variability of germ cell populations in response to chemical mutagens. These studies demonstrate that IMS can effectively induce DNA repair in mouse early spermatids in vivo, and the DNA repair detection method has high sensitivity in evaluating the mutagenic potential of IMS. The in vivo DNA repair effect of IMS was verified in mouse early spermatids by detecting the unscheduled incorporation of [³H]dT. (C3Hf×101) F₁ male mice aged 10-14 weeks were used in the experiment. IMS was formulated with Hanks' balanced salt solution and injected intraperitoneally, with a dose volume of 0.5 ml per 30 g mouse. [³H]dT with a specific activity of 43 Ci/mmol was injected into the testes at a dose of 32 Ci per testis. Sperm heads were purified from the caudal epididymides 16 days after treatment, and the [³H]dT activity in the sperm heads was determined by liquid scintillation counting. The autoradiography of sperm head smears was performed using NTB₂ nuclear track emulsion, and 100-150 sperm heads were scored for the number of overlying grains per slide.

Study on the Induction of Specific-Locus and Dominant Lethal Mutations in Mice by Isopropyl Methanesulfonate (iPMS)

Ehling, U.H., et al. Mutation Research 328 (1995): 73-82

This study investigated the mutagenic activity of isopropyl methanesulfonate (iPMS) in male mice, focusing on its induction of specific-locus and dominant lethal mutations, with n-propyl methanesulfonate (nPMS) as a control. iPMS was dissolved in Hanks' balanced salt solution and administered to (102/El × C3H/El) F₁ male mice via intraperitoneal injection at doses ranging from 20 to 100 mg/kg body weight. Dominant lethal mutations were evaluated by sequential mating with virgin hybrid females, and the frequency was calculated based on the number of live embryos, dead implants, and corpora lutea. Specific-locus mutations were detected using test-stock females homozygous for seven recessive markers, with offspring examined for variant phenotypes at birth and weaning, followed by genetic confirmation.
iPMS showed dose-dependent induction of dominant lethal mutations: a low dose of 20 mg/kg only induced mutations in spermatocytes (mating interval 25-28 days post-treatment), while 100 mg/kg induced mutations in all postspermatogonial germ cell stages (spermatozoa, spermatids, spermatocytes). A sterile phase starting 37 days post-treatment was observed at doses ≥40 mg/kg, indicating cytotoxicity to stem-cell spermatogonia. For specific-locus mutations, 50 mg/kg iPMS induced mosaic or non-mosaic mutations in spermatozoa, spermatids, and spermatocytes (1-28 days post-treatment), with 80% of mutations being mosaics. Most iPMS-induced mutations were viable in homozygous condition, suggesting intragenic mutations as the main mechanism. In contrast, nPMS only induced mutations in spermatozoa and spermatids, with no sterile phase. These studies demonstrate that iPMS exhibits distinct mutagenic characteristics compared to nPMS, including dose-dependent germ cell stage sensitivity, induction of sterility in stem-cell spermatogonia, and a high proportion of mosaic mutations. The in vivo mutagenic effect of iPMS was verified through dominant lethal and specific-locus tests in mice. (102/El × C3H/El) F₁ male mice aged 9-14 weeks were divided into different dose groups.

Mutations Induced in Male Germ Cells of Transgenic Mice by Isopropyl Methanesulfonate (iPMS)

Katoh, M., et al. Mutation Research 341 (1994): 17-28

This study investigated the mutagenic effect of isopropyl methanesulfonate (iPMS) in male germ cells of transgenic Muta Mouse (MM) carrying 80 copies of the bacterial lacZ gene as mutation targets, with ethylnitrosourea (ENU) and X-ray as controls. iPMS (CAS No. 926-06-7) was freshly dissolved in isotonic sodium chloride solution and administered to male MM mice via a single intraperitoneal injection at a dose of 200 mg/kg. Mice were sacrificed at 3 and 12 days post-treatment to collect vasa deferential sperm, caudal epididymal sperm, and whole testes, corresponding to different spermatogenic stages (spermatozoa, early spermatids, and all spermatogenic stages). Genomic DNA was extracted from the collected tissues, and mutation analysis at the lacZ locus was performed using phage packaging, plating, and plaque counting methods. The spontaneous lacZ mutant frequency in control mice was 5.2-13.4×10⁻⁶, while iPMS treatment increased the mutant frequency by 3-5 times across all tested germ cell stages. Specifically, the mutant frequency in vasa deferential sperm (spermatozoa stage) at 3 days post-treatment was 20.2×10⁻⁶, in caudal epididymal sperm (early spermatids stage) at 12 days post-treatment was 17.9×10⁻⁶, and in whole testes at 12 days post-treatment was 27.6×10⁻⁶. iPMS induced more colored mutant plaques (light blue) in early spermatids, while colorless and colored mutant plaques were approximately equally distributed in testes. Compared with the specific locus test, the lacZ mutant frequency induced by iPMS in postmeiotic stages was relatively low, and the transgenic mouse assay showed lower resolution power. These studies demonstrate that iPMS can induce mutations in multiple spermatogenic stages of transgenic mice, with distinct mutant plaque phenotype distributions among different germ cell stages. The in vivo mutagenic effect of iPMS was verified using the transgenic MM mouse assay. Male MM mice were divided into treatment and control groups, with the treatment group receiving 200 mg/kg iPMS intraperitoneally and the control group receiving the same volume of isotonic sodium chloride solution. Tissue samples were collected at specified time points post-treatment, and genomic DNA was extracted following Sega's procedure with modifications. Phage packaging, titering, and lacZ⁻ mutant plaque screening were conducted according to the Muta Mouse assay protocol. Mutant frequencies were calculated by counting total plaques and mutant plaques, and statistical analysis was performed using the Chi-square test with Yates's correction to compare differences between groups.

Custom Q&A

What is the molecular formula of Isopropyl methanesulfonate?

The molecular formula of Isopropyl methanesulfonate is C4H10O3S.

What are some synonyms for Isopropyl methanesulfonate?

Some synonyms for Isopropyl methanesulfonate are Isopropyl mesylate and propan-2-yl methanesulfonate.

What is the molecular weight of Isopropyl methanesulfonate?

The molecular weight of Isopropyl methanesulfonate is 138.19 g/mol.

What is the IUPAC name of Isopropyl methanesulfonate?

The IUPAC name of Isopropyl methanesulfonate is propan-2-yl methanesulfonate.

What is the InChIKey of Isopropyl methanesulfonate?

The InChIKey of Isopropyl methanesulfonate is SWWHCQCMVCPLEQ-UHFFFAOYSA-N.

What is the CAS number of Isopropyl methanesulfonate?

The CAS number of Isopropyl methanesulfonate is 926-06-7.

What is the European Community (EC) number of Isopropyl methanesulfonate?

The European Community (EC) number of Isopropyl methanesulfonate is 213-132-0.

What is the UNII of Isopropyl methanesulfonate?

The UNII of Isopropyl methanesulfonate is T0K2TXY26B.

What is the boiling point of Isopropyl methanesulfonate?

The boiling point of Isopropyl methanesulfonate is 82 °C at 6 mm Hg.

What is the physical description of Isopropyl methanesulfonate?

Isopropyl methanesulfonate is described as a clear colorless liquid.