Methyl methanesulfonate

Numbers used in this cycle AG° for dissociation of methyl methanesulfonate to methanesulfonylinm ion and methoxide, assumed to be the same as for dimethyl sulfate, estimated above AG° for ionization of methanol. )... 

Lee, T.C., S. Wang-Wuu, R.Y. Huang, K.C.C. Lee, and K.Y. Jan. 1986b. Differential effects of pre-and posttreatment of sodium arsenite on the genotoxicity of methyl methanesulfonate in Chinese hamster ovary cells. Cancer Res. 46 1854-1857. 

Liotta and Grisdale (1975) have reported on the relative nucleophilicities of anions whose potassium salts were solubilized into acetonitrile by 18-crown-6 [3]. The results (Table 28) show the sequence Nj > OAc- > CN- > F- > Cl-x Br- > I- > SCN-, which is very different from the reactivity scale in water CN- > I- >SCN- > Nj > Br- > Cl- > OAc- > F-. Furthermore, the relative nucleophilicities in acetonitrile vary only by a factor of 30, whereas in water they differ by as much as a factor of 1000. The fact that gas-phase nucleophilicities also span a narrow range led the authors to conclude that anion solvation is much less important in acetonitrile than in water. The values recently reported by Lemmetyinen et al. (1978) for the relative nucleophilicities of anions towards methyl methanesulfonate in benzene show the same sequence as in protic solvents, however. The authors offered no explanation for this peculiar behaviour. 

H. G. Ramjit, M. M. Singh and A. B. Coddington, Gas chromatographic/mass spectro-metric analysis of methyl methanesulfonate and ethyl methanesulfonate in the bismesy-late salt of DPI 201-106, a positive inotropic agent for the treatment of heart failure. Journal of Mass Spectrometry, 31(8), 867-872.1996. 

W. Li, Trace analysis of residual methyl methanesulfonate, ethyl methanesulfonate and isopropyl methanesulfonate in pharmaceuticals by capillary gas chromatography with flame ionization detection. Journal of Chromatography A, 2004,1046(1-2), 297-301. 

Brown, R.V. 1960. The effects of intracistemal sarin and pyrldine-2-aldoxime methyl methanesulfonate In anaesthetized dogs. Brit. J. Pharmacol. Chemotherap. 15 170-174. 

D-2 P2S methyl methanesulfonate derivative of 2-PAM pralidoxime methanesulfonate Protopam methanesulfonate 154-92-2 95... 

Few split-dose experiments have been performed with chemicals. Popescu et aL (1984) observed that with split doses of carcinogen separated by 2 to 24 hours only N-acetoxy-2-fluorenylacetamide enhanced transformation of Syrian hamster embryo ceUs while doses of N-methyl-N -nitro-N-nitrosoguanidine, mitomycin C or ultraviolet light were less effective than single doses, and no effect of dose fractionation was observed with methyl methanesulfonate. 

No indication was found that methyl methanesulfonate is produced commercially, although it has been produced for research purposes. Information available in 1995 indicated that it was produced in one country (India) (Chemical Information Services, 1995). 

Groups of 20 female NMRI mice, seven weeks of age, received a single skin application of either (o) 100 nmol 7,12-dimethylbenz[fl]anthracene (DMBA), (Z ) 100 pmol methyl methanesulfonate or (c) 400 piuol methyl methanesulfonate (highest tolerated dose). One week later, all were treated with 10 nmol 12-i9-tetradecanoylphorbol 13-acetate twice weekly for 24 weeks. While 90% of the DMBA group had skin tumours after 15 weeks, no methyl methanesulfonate-initiated mice had skin tumours after 24 weeks (Fiirstenberger et al., 1989). 

Groups of 20 female NMRI mice were treated with DMBA as above and subsequently treated with o ) acetone (the vehicle used for all substances in the experiment) 6 h before 10 nmol 12-G-retinoylphorbol 13-acetate, b) 100 jmol methyl methanesulfonate 6 h before acetone, (c) 100 pmol methyl methanesulfonate 6 h before 10 nmol 12-G-retinoylphorbol 13-acetate, (<7) 10 p,mol methyl methanesulfonate 6 h before 10 nmol 12-i9-retinoylphorbol 13-acetate or (e) 10 nmol 12-G-tctradecanoylphorbol 13-acetate 6 h before acetone. Two weeks after DMBA treatment, all groups received 10 nmol 12-i9-retinoylphorbol 13-acetate once a week for 23 weeks. At the end of the experiment, > 90% of the mice were alive. The numbers of papillomas per survivor at 24 weeks [figures read from a graph] were (a 0.4, (/>) 1.6, (c) 1.7, (<7) 2.9 and (e) 3.0 (Fiirstenberger etal., 1989). 

Following a single intraperitoneal injection of 120 mg/kg bw to an unspecified number of four-week-old AKR mice, all of the methyl methanesulfonate-treated mice had developed thymomas after 50 weeks versus 50% tumour incidence in the controls (Warren et al., 1990). [The Working Group noted the inadequate reporting.]... 

Groups of female Fischer 344 rats, six to eight weeks old, were either left untreated (group A) or received a single intravesicular instillation of 0.3 mg A-methyl-A-nitroso-urea (group B), six intravesicular instillations of 2.5 mg methyl methanesulfonate at 14-day intervals (group C) or sequential treaments with 0.3 mg A-methyl-A-nitrosourea followed by six intravesicular instillations of 2.5 mg methyl methanesulfonate at 14-day intervals (group D). The numbers of rats with bladder tumours were (A) 0/25, (B) 7/29 (24%), (C) 2/27 (7%) and (D) 19/33 (58%) (Tudor et al., 1984). 

Methyl methanesulfonate is rapidly distributed throughout the body of mice and rats, including the central nervous system, and rapidly crosses the placenta. After intravenous injection of 100 mg/kg bw methyl methanesulfonate to rats, none was detected in serum after 2 h (lARC, 1974). 

Urinary metabolites recovered within the first 16 h and representing 80% of the excretion products resulted from an initial methylation of cysteine residues by methyl methanesulfonate. These were mcthylmercapturic acid sulfoxide, 2-hydroxy-3-methyl-sulfmylpropionic acid, methylsulfmylacetic acid, methylmercapturic acid and 7V-(methyl-thioacetyl)glycine. Glutathione conjugation has been shown to occur in rat liver (lARC, 1974). 

Methyl methanesulfonate (250 iM) induced neurite formation in 71% of mouse neuroblastoma N-18 cells, when cell growth was inhibited by 83% (Yoda et al., 1982). 

Methyl methanesulfonate induced DNA single-strand breaks and alkali-labile sites in human lymphocytes in vitro. It induced unscheduled DNA synthesis in human epidermal keratinocytes and in oral epithelial and fibroblast cell cultures. Methyl methanesulfonate induced gene mutations in human lymphoblasts at the hprt locus and sister chromatid exchanges and micronuclei in HepG2 human liver cells in vitro. 

Methyl methanesulfonate induced DNA strand breaks in mouse kidney and spermatozoa and DNA fragmentation in rat brain cells following in-vivo treatment. 

Table 1. Genetic and related effects of methyl methanesulfonate...

Methyl methanesulfonate is a laboratory chemical that has been produced for research purposes. No infonnation was available to the Working Group on potential human exposures. 

Methyl methanesulfonate caused an increased Ifequency of resorptions and con-... 

No epidemiological data relevant to the carcinogenicity of methyl methanesulfonate were available. 

There is sufficient evidence in experimental animals for the carcinogenicity of methyl methanesulfonate. 

Methyl methanesulfonate is probably carcinogenic to humans (Group 2A). 

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