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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
Carcinogenicity
Administrative data
Description of key information
Carcinogenic LOAEC was considered to be 50 mg/L (50000 mg/m3) when Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS) by whole-body inhalation for 30 days.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via inhalation route
Link to relevant study records
- Endpoint:
- carcinogenicity: inhalation
- 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
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Principles of method if other than guideline:
- Subacute repeated dose inhalation toxicity study of Methylmethane sulfonate in rat
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Methyl methanesulfonate
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mole
- Smiles notation: COS(=O)(=O)C
- InChl: 1S/C2H6O3S/c1-5-6(2,3)4/h1-2H3
- Substance type:Organic
- Physical state: Liquid - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: 11 to 12-week-old
- Weight at study initiation: 325 ± 16.8 g,
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): Purina Lab Chow, ad libitum, except during exposure periods.
- Water (e.g. ad libitum): Water, ad libitum, except during exposure periods.
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Test atmospheres of the chemicals were generated by passing an airstream over the liquids in a generating flask and then feeding the effluent vapor into the chamber air supply.
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Air, as it is a inhalation study.
- Concentration in vehicle: 0 and 50 ppm (5 mg/kg)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data available
- Duration of treatment / exposure:
- 30 days
- Frequency of treatment:
- 6 hr/day X 5 days/wk
- Post exposure period:
- No data available
- Dose / conc.:
- 50 mg/L air
- No. of animals per sex per dose:
- Total : 178
0 mg/L: 98
50 mg/L: 80 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: 50 ppm dose was used for MMS because of the cost of compound.
- Rationale for animal assignment (if not random): Animal was assigned to test group randomly. - Positive control:
- No data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included: Mortality
DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available
DERMAL IRRITATION (if dermal study): No data available
- Time schedule for examinations: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: Monthly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER: No data available - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organs examined :
Trachea, larynx, liver, kidneys, testes, and any other organs.
HISTOPATHOLOGY: Yes
A complete necropsy was performed on each animal. The nasal passages were flushed with 10% neutral buffered Formalin; then the entire head and other organs were fixed in the same fixative. The head was then decalcified; and stepwise cross-sections were taken in the dorsoventral plane perpendicular to the long axis of the skull, beginning just posterior to the nostrils and extending caudal as far as the orbit. Histologic sections were taken from each lobe of the lung and from the trachea, larynx, liver, kidneys, testes, and any other organs exhibiting gross pathology. Paraffin sections, 4-5 /µm thick, were prepared in the usual fashion and stained with hematoxylin-eosin and with special stains, if necessary.
Organs examined :
Nasal passages, entire head, lung, Trachea, larynx, liver, kidneys, testes, and any other organs were examined. - Other examinations:
- No data available
- Statistics:
- No data available
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- 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
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
- Details on results:
- Mortality: Cumulative mortality was observed in treated rat as compare to control.
Gross Pathology: Metastatic lesions in the lungs, Rhinitis, Squamous metaplasia, Polyp or papillomas lesions were observed in treated rat as compare to control.
Histopathology: neoplastic: Nasal epithelium, Squamous cell, Adeno- carcinoma. Mixed carcinoma, Osteo- genic sarcoma and tumors in larynx, trachea, adrenal, skin, thyroid, pancreas, mammary gland, salivary gland and parathyroid were observed in treated rat as compare to control. - Dose descriptor:
- LOAEL
- Effect level:
- 50 mg/L air
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- gross pathology
- histopathology: neoplastic
- mortality
- other: Effect observed
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 50 ppm
- System:
- other: Not specified
- Organ:
- adrenal glands
- larynx
- mammary gland
- oral cavity
- pancreas
- parathyroid gland
- salivary glands
- skin
- thyroid gland
- Treatment related:
- yes
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- Carcinogenic LOAEC was considered to be 50 mg/L (50000 mg/m3) when Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS) by whole-body inhalation for 30 days.
- Executive summary:
In a subacute carcinogenic study, Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS)bywhole-body inhalationin the concentrations of 0 and 50 ppm. The results showed thatMethylmethane sulfonate (MMS) wascarcinogenic. Carcinogenic changes were observed as cumulative mortality as the week of exposure increase and gross pathological changes such asmetastatic lesions in the lungs, Squamous metaplasia, Polyp or papillomas lesions and Adenomatous polyps in larynx and adenomatous polyps in trachea were observed. In addition, carcinogenic effect on the nasal epithelium and Squamous cell Adeno-carcinoma.Mixed carcinoma,Osteo-genic sarcoma and tumors in larynx, trachea, adrenal, skin, thyroid, pancreas, mammary gland, salivary gland and parathyroid were observed in treated rat as compare to control. Therefore, Carcinogenic LOAEC was considered to be 50 mg/L (50000 mg/m3) when Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS) by whole-body inhalation for 30 days.
Reference
Table: Median life-span and time of tumor appearance following exposure to alkylating agents
Treatment |
No. of animals |
Median life days |
Animals with tumors, No (%) |
Time of tumor appearance, days |
|
Median |
Range |
||||
5 mg/L X 30 exp |
80 |
495 |
47 (59) |
513 |
256-775 |
Table: Specific types of tumors and other lesions of the nasal mucosa in rats exposed to various alkylating agents
|
Treatment |
MMS, 5 mg/L X 30 exp |
|
No. of animals examined |
80 |
No. of tumors and other lesions of nasal mucosa |
Tumors bearing animals, No (%) |
47 (59) |
Rhinitis |
49 |
|
Squamous metaplasia |
5 |
|
Polyps or papillomas |
11 |
|
Squamous cell carcinoma |
33 |
|
Adenocarcinoma |
2 |
|
Mixec carcinoma |
2 |
|
Osteogenicsarcome |
- |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEC
- 50 000 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from peer-reviewed journal
- System:
- respiratory system: upper respiratory tract
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the above studies on Methyl methanesulphonate, it can be concluded that Methyl methanesulphonate is carcinogenic by inhalation. Thus, comparing this effect with the criteria of CLP regulation, Methyl methanesulphonate can be classified as “Category 2 carcinogen” by inhalation.
Additional information
Carcinogenicity: Inhalation
In different studies, Methyl methanesulphonate has been investigated for Carcinogenicity by inhalation to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for Methyl methanesulphonate.
In a study conducted by Sellakumaret al(J. Natl Cancer Inst, VOL. 79, NO.2, August 1987, page no. 285-289),Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS)bywhole-body inhalationin the concentrations of 0 and 50 ppm. The results showed thatMethylmethane sulfonate (MMS) wascarcinogenic. Carcinogenic changes were observed as cumulative mortality as the week of exposure increase and gross pathological changes such asmetastatic lesions in the lungs, Squamous metaplasia, Polyp or papillomas lesions and Adenomatous polyps in larynx and adenomatous polyps in trachea were observed. In addition, carcinogenic effect on the nasal epithelium, Squamous cell, Adeno-carcinoma.Mixed carcinoma,Osteo-genic sarcoma and tumors in larynx, trachea, adrenal, skin, thyroid, pancreas, mammary gland, salivary gland and parathyroid were observed in treated rat as compare to control. Therefore, Carcinogenic LOAEC was considered to be 50 mg/L (50000 mg/m3) when Sprague-Dawleymalerat were exposed toMethylmethane sulfonate (MMS)bywhole-body inhalation for 30 days.
In another study conducted by Carrollet al(Cancer Letter Vol. 33, pp 175-181, 1986), Sprague-Dawley male rat were exposed to Methylmethane sulfonate (MMS)bywhole-body inhalationin the concentrations of 0 and 50 ppm. The results showed that Methylmethane sulfonate (MMS) was carcinogenic. Carcinogenic changes were observed as cumulative mortality as the week after fist exposure increase. In addition, carcinogenic effect on the nasal mucosal macromolecules and abilities to bind to nasal mucosal DNA was also observed in treated rat as compare to control. Therefore, Carcinogenic lowest-observed-adverse-effect level (LOAEL) was considered to be50 mg/L (50000 mg/m3)when Sprague-Dawley male rat were exposed to Methylmethane sulfonate (MMS) by whole-body inhalation for 6 weeks.
Thus, based on the above studies on Methyl methanesulphonate, it can be concluded that Methyl methanesulphonate is carcinogenic by inhalation. Thus, comparing this effect with the criteria of CLP regulation, Methyl methanesulphonate can be classified as “Category 2 carcinogen” by inhalation.
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