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EC number: 200-625-0 | CAS number: 66-27-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- toxicity to reproduction
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from peer-reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- A time-course characterizaton of male rerpocuctive toxicity in rats treated with Methyl methanesulphonate (MMS)
- Author:
- Kazuya Kuriyama, Ryohei Yodoi, Kazuya Kobayashi, satoshi Suda, Morimichi Hayashi, Shigenari ozawa, Junji kuroda and Hirotada Tsulii
- Year:
- 2 005
- Bibliographic source:
- The journal of toxicology sciences, vol 30, no.2, 91-102, 2005
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Reproductive toxicity study of Methyl methanesulphonate (MMS) in rat
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- Not spcified
Test material
- Reference substance name:
- Methyl methanesulphonate
- EC Number:
- 200-625-0
- EC Name:
- Methyl methanesulphonate
- Cas Number:
- 66-27-3
- Molecular formula:
- C2H6O3S
- IUPAC Name:
- methyl methanesulfonate
- Test material form:
- other: Solid
- Details on test material:
- - Name of test material (as cited in study report): Methyl methanesulphonate (MMS)
- Molecular formula (if other than submission substance): C2H6O3S
- Molecular weight (if other than submission substance): 110.1324 g/mole
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): 00.1 %
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Methyl methanesulphonate (MMS)
- Molecular formula (if other than submission substance): C2H6O3S
- Molecular weight (if other than submission substance): 110.1324 g/mole
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): 00.1 %
Test animals
- Species:
- rat
- Strain:
- other: Crj:CD (SD), SPF
- Details on species / strain selection:
- Not spcified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles river Japan, Inc (kanagawa, Japan)
- Age at study initiation: (P) x wks; (F1) x wks: P: 10 weeks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g: No data available
- Fasting period before study: No data available
- Housing: Animals were housed in a stainless mesh individual cage (sized 260 X 230 X 180 mm
- Diet (e.g. ad libitum): Pellet diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 17 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.8 to 24.6˚C
- Humidity (%):40.9 to 57.0 %
- Air changes (per hr): 11.13 times/hr ventilation
- Photoperiod (hrs dark / hrs light): 12 hr light/12hr dark
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Remarks:
- Distilled
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: MMS were administrated in water
VEHICLE
- Justification for use and choice of vehicle (if other than water): Water
- Concentration in vehicle: 0, 20, 30 and 40 mg/kg bw
- Amount of vehicle (if gavage): 5 ml / kg bw
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- - M/F ratio per cage: 1:1 ratio
- Length of cohabitation: Overnight
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Plug observed in the following morning were considered to be Day 0 of gestation.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)] Yes, male that fail to copulate were allowed to pair up to 3 consecutive night for overnight in 1:1 ratio
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 5 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 20 mg/kg bw/day
- Dose / conc.:
- 30 mg/kg bw/day
- Dose / conc.:
- 40 mg/kg bw/day
- No. of animals per sex per dose:
- Total : 220
0 mg/kg body weight/day: 55 male
20 mg/kg body weight/day: 55 male
30 mg/kg body weight/day: 55 male
40 mg/kg body weight/day: 55 male
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose and route od administration was selsected based on previous study. in which testicular toxicity was observed after 2 to 4 weeks treatment
- Positive control:
- not specified
Examinations
- Parental animals: Observations and examinations:
- Mortality , clinical sign and body weight were observed
- Oestrous cyclicity (parental animals):
- Any irregularities in the estrous cycle were investigated.
- Sperm parameters (parental animals):
- Sperm mortality, sperm morphological and caudal epodidymal sperm count were examined
- Litter observations:
- Number of live embreyos and Number of dead embreyos were observed
- Postmortem examinations (parental animals):
- Gross abnormalities were examined.
Number of implantation sites and number of corpora lutea was examined. - Postmortem examinations (offspring):
- not specified
- Statistics:
- All quantitative data were tested for equal variance. If equal variance was found, one-way analysis of variance was used. If not, the Kruskal-Wallis procedure for nonparametric analysis was used. If not, the Kruskal-Wallis procedure for nonprametric analysis was used. When significant inter-group differences were found, the Dunnett multiple comparison tests or the Dunnett rank test was applied for the analysis of copulation index and fertility index and fertility index, the chi square test was employed. For the analysis of implantation index and post-implantation loss Wilcoxon test was used. Probabilities less than 5% were considered statistically significant.
- Reproductive indices:
- Fertility index, gestation index and implantation index were examined.
- Offspring viability indices:
- not specified
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs of toxicity were observed in treated rat as compare to control.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality were observed in reated rats
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg slight but statistically significant decrease in body weight was observed on 5 day of treatment which is at the end of recovery period almost comparable to control.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg/day , significant decreased were observed in number of corpora lutea and number of implants on 1 day of treatment and in 1,2 and 3 week of recovry.
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg, slightly decreased sperm counts were observed throughout the study period. Chronological change such as tailless sperm followed by no-hook head sperm in caput epididymis was also observed.
During recovery: The frequency of morphologically abnormal sperm in caput epididymis increased in 2 and 3 week which recovered in 4 week
When treated with 30 mg/kg, significantly increased frequencies of morphologically abnormal sperm in cauda epididymis were observed from week 3 to 5.
During recovery
Significantly increased frequencies of tailless sperm in 4 week and no-hook sperm in 4and 5 week were observed as compared to control in recovery. - Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in no. of dead embryos, no. of corpora lutea and decreased in no. of live embryos in first week were observed in 40 mg/kg body weight/ day treated rat as compared to control.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- organ weights and organ / body weight ratios
- gross pathology
- reproductive function (oestrous cycle)
- reproductive function (sperm measures)
- reproductive performance
- Remarks on result:
- other: No effect observed
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs of toxicity were observed in treated rat as compare to control.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality were observed in treated rats
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg slight but statistically significant decrease in body weight was observed on 5 day of treatment which is at the end of recovery period almost comparable to control.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg, significant decreased were observed in absolute epididymis weight in 1 and 5 week of recovery in male as compare to control.
When treated with 30 mg/kg, significant decreased were observed in absolute epididymis weight in 4 week of recovery as compare to control. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- During recovery
Number of cauda epidiymis was significantly decreased in 1 week and significant increase in frequencies of morphologically abnormal sperm in cauda epididymis were observed from week 3 to 5 as compared to control. - Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg/day , significant decreased were observed in number of corpora lutea and number of implants on 1 day of treatment and in 1,2 and 3 week of recovery.
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 40 mg/kg, slightly decreased sperm counts were observed throughout the study period. Chronological change such as tailless sperm followed by no-hook head sperm in caput epididymis was also observed.
During recovery: The frequency of morphologically abnormal sperm in caput epididymis increased in 2 and 3 week which recovered in 4 week
When treated with 30 mg/kg, significantly increased frequencies of morphologically abnormal sperm in cauda epididymis were observed from week 3 to 5.
During recovery
Significantly increased frequencies of tailless sperm in 4 week and no-hook sperm in 4and 5 week were observed as compared to control in recovery. - Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in no. of dead embryos, no. of corpora lutea and decreased in no. of live embryos in first week were observed in 40 mg/kg body weight/ day treated rat as compared to control.
Effect levels (P1)
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- organ weights and organ / body weight ratios
- gross pathology
- reproductive function (oestrous cycle)
- reproductive function (sperm measures)
- reproductive performance
- Remarks on result:
- other: No effect observed
Target system / organ toxicity (P1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- other: not specified
- Generation:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not specified
Effect levels (F2)
- Dose descriptor:
- other: not specified
- Generation:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
Target system / organ toxicity (F2)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no-observed-adverse-effect-level (NOAEL) was considered to be 20 mg/kg/day for P generation when Crj:CD (SD), SPF male and female rat were exposed to Methyl methanesulphonate (MMS) orally for 5 days.
- Executive summary:
In a reproductive toxicity study, male and female Crj:CD (SD), SPF rat were exposed Methyl methanesulphonate (MMS) orally in the concentration 0, 20, 30 and 40 mg/kg/day. In the parental generation, decreased in body weight and absolute epididymis weight were observed in 30 and 40 mg/kg/day treated rat as compare to control. In addition, significant decreased in number of corpora lutea and number of implants, Chronological change such as tailless sperm followed by no-hook head sperm in caput epididymis were observed in male and female rat. Effect on number of cauda epidiymis, significant increased in number of dead embryos, number of corpora lutea and decreased in number of live embryos during recovery was observed when treated with 40 and 30 mg/kg body weight/day. Therefore, the no-observed-adverse-effect-level (NOAEL) is considered to be 20 mg/kg body weight/day for P generation when rats are exposed to Methyl methanesulphonate (MMS) orally for 5 days.
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