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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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Inhalation Carcinogenesis of Various Alkylating Agents
- Author:
- Arthur R. Sellakumar, Carroll A. Snyder and Roy E. Albert
- Year:
- 1 987
- Bibliographic source:
- J. Natl Cancer Inst, VOL. 79, NO.2, AUGUST 1987, page no. 285-289
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Repeated dose inhalation toxicity study was performed to determine the toxic nature of Methylmethane sulfonate in rat upon repeated exposure
- GLP compliance:
- not specified
- Limit test:
- yes
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
- Details on test material:
- - Name of test material: Methylmethane sulfonate (MMS)
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mole
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): < 5 %
Constituent 1
- Specific details on test material used for the study:
- - Name of test material : Methylmethane sulfonate (MMS)
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mol
- Substance type: Organic
- Physical state: Liquid
- Purity: > 95%
- Impurities (identity and concentrations): < 5 %
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No data
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- 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
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Remarks on MMAD:
- MMAD / GSD: No data available
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic exposure Chambers
- Method of holding animals in test chamber: No data available
- Source and rate of air: Airstream
- Method of conditioning air: Airstream over the liquids in a generating flask and then feeding the effluent vapor into the chamber air supply.
- System of generating particulates/aerosols: 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.
- Temperature, humidity, pressure in air chamber: No data available
- Air flow rate: 1.0 m3 or 1.3 m3
- Air change rate: No data available
- Method of particle size determination: Wilks Miran infrared gas analyzer were use to determine the particle size.
- Treatment of exhaust air: No data available
TEST ATMOSPHERE
- Brief description of analytical method used: Chamber concentrations of the chemicals were analyzed at half-hour intervals during the daily exposures by means of a Wilks Miran infrared gas analyzer with the use of appropriate wavelength.
- Samples taken from breathing zone: No data available
VEHICLE (if applicable)
- Justification for use and choice of vehicle: Air
- Composition of vehicle: No data available
- Type and concentration of dispersant aid (if powder): No data available
- Concentration of test material in vehicle: 0 or 50 ppm (0 or 5 mg/L)
- Lot/batch no. of vehicle (if required): No data available
- Purity of vehicle: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 30 days
- Frequency of treatment:
- 6 hr/day X 5 days/wk
Doses / concentrations
- Remarks:
- 0 or 5 mg/L
- No. of animals per sex per dose:
- Total : 178
0 ppm (0 mg/L): 98
50 ppm (5 mg/L): 80 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: 50 ppm (5 mg/L) 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.
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available - Positive control:
- No data
Examinations
- 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
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:
- 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
Results and discussion
Results of examinations
- Clinical signs:
- 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
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality
Mortality: Cumulative mortality was observed in treated rat as compare to control.
Clinical signs: No data available
Body weight and weight gain: No data available
Food consumption and compound intake: No data available
Food efficiency: No data available
Water consumption and compound intake: No data available
Opthalmoscopic examination: No data available
Haematology: No data available
Clinical chemistry: No data available
Urinanalysis: No data available
Neurobehaviour: No data available
Organ weights: No data available
Gross pathology: Metastatic lesions in the lungs were noted in 2 animals dying of nasal squamous cell carcinomas, Squamous metaplasia, Polyp or papillomas lesions were observed in treated rat as compare to control.
Histopathology:
High incidences of nasal tumor, potent carcinogenic effect on the nasal epithelium, adenomatous polyps in larynx, adenomatous polyps in trachea, malignant lymphoma, adenoma in adrenal, adenocarcinoma in adrenal, papilloma in skin, adenomas in thyroid, islet cell adenoma in pancreas, fibro adenomas in mammary gland, adenocarcinoma in salivary gland, adenoma in salivary gland, lipomas in subcutaneous, fibromas in subcutaneous and adenoma in parathyroid.
47 (59%) developed tumors of the nasal mucosa with the first carcinoma being observed in animal dying at 256 days.
Effect levels
- Dose descriptor:
- LOAEC
- Effect level:
- 5 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Effect on Mortality, gross pathology and histopathology.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
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 |
- |
Applicant's summary and conclusion
- Conclusions:
- The low-observed-adverse-effect concentration (LOAEC) was considered to be 5 mg/L air (50ppm) when Sprague-Dawley male rat were exposed to Methylmethane sulfonate (MMS) upon repeated exposure for 30 days.
- Executive summary:
Repeated dose inhalation toxicity study was performed to determine the toxic nature of Methylmethane sulfonate (MMS) in rat upon repeated exposure. 11 -12 week old Male Sprague Dawley rat were exposed to MMS at a dose level of 0 or 5 mg/L for 30 days. All animals were observed daily, weighed monthly, and allowed to die spontaneously or sacrificed when moribund. A complete necropsy was performed on each animal. The nasal passages were flushed with 10% neutral buffered Formalin and 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 feom 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 for histologic examination. Cumulative mortality was noted in the test animals. Gross pathological examinations revealed the presence of metastatic lesions in the lungs in 2 animals dying of nasal squamous cell carcinomas, squamous metaplasia and polyp or papillomas lesions were observed in treated rat as compare to control. In addition, High incidences of nasal tumor, potent carcinogenic effect on the nasal epithelium, adenomatous polyps in larynx, adenomatous polyps in trachea, malignant lymphoma, adenoma in adrenal, adenocarcinoma in adrenal, papilloma in skin, adenomas in thyroid, islet cell adenoma in pancreas, fibro adenomas in mammary gland, adenocarcinoma in salivary gland, adenoma in salivary gland, lipomas in subcutaneous, fibromas in subcutaneous and adenoma in parathyroid were observed. 47 (59%) developed tumors of the nasal mucosa with the first carcinoma being observed in animal dying at 256 days. On the basis of observations made, the low-observed-adverse-effect concentration (LOAEC) was considered to be 5 mg/L air (50ppm) when Sprague-Dawley male rat were exposed to Methylmethane sulfonate (MMS) upon repeated exposure for 30 days.
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