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EC number: 212-480-0 | CAS number: 821-55-6
- 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: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- 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:
- Commercial-Grade Methyl Heptyl Ketone (5-Methyl-2-octanone) Neurotoxicity: Contribution-of 5Nonanone’
- Author:
- JOHN L. DONOGHUE, WALTER J. KRASAVAGE, GEORGE D. DIVINCENZO, AND DONALD A. ZIEGLER
- Year:
- 1 982
- Bibliographic source:
- TOXlCOLOGY AND APPLIED PHARMACOLOGY 62,307-316 (1982)
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- To evaluate the acute toxicity of Methyl heptyl ketone in COBS, CD (SD) BR male rats.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Nonan-2-one
- EC Number:
- 212-480-0
- EC Name:
- Nonan-2-one
- Cas Number:
- 821-55-6
- Molecular formula:
- C9H18O
- IUPAC Name:
- nonan-2-one
- Reference substance name:
- Methyl heptyl ketone
- IUPAC Name:
- Methyl heptyl ketone
- Test material form:
- other: colorless to pale yellow clear oily liquid
- Details on test material:
- - Name of test material (as cited in study report): Methyl heptyl ketone
- Molecular formula (if other than submission substance): C9H18O
- Molecular weight (if other than submission substance): 142.24g/mol
- Substance type: Organic
- Physical state: colorless to pale yellow clear oily liquid (est)
- Impurities (identity and concentrations): 27.7 %
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- - Name of test material: Methyl heptyl ketone
- IUPAC name: nonan-2-one
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): 27.7 %
Test animals
- Species:
- rat
- Strain:
- other: CD, COBS
- Details on species / strain selection:
- No data
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Lab; Wilmington, Mass
- Age at study initiation: No data available.
- Weight at study initiation: No data available.
- Fasting period before study: No data available.
- Housing: They were singly housed in solid floor cages covered by Ab-Sorb-Dri bedding to reduce the likelihood of wire mesh-induced pressure neuropathy.
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow 5001 was available ad libitum.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: No data available.
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:
- oral: gavage
- Details on route of administration:
- No data
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Methyl heptyl ketone was dissolved in water to give a dose level of 0, 1000, 2000 or 4000 mg/kg
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): Water
- Concentration in vehicle: 0, 1000, 2000 and 4000 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
- Duration of treatment / exposure:
- 3 Weeks
- Frequency of treatment:
- Once a day, 5 days per week
Doses / concentrations
- Remarks:
- 0, 1000, 2000 or 4000 mg/kg
- No. of animals per sex per dose:
- Total animals -18 male rats
0 mg/kg: 9 male rats
1000 mg/kg: 3 male rats
2000 mg/kg :3 male rats
4000 mg/kg :3 male rats - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data available.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked in table [No.?] were included: Clinical conditions were observed.
DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: On 0, 3,7,14 and 21 day of treatment.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes ,
Time schedule: 0, 3,7,14 and 21 day of treatment.
- 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 studies): No data available.
OPHTHALMOSCOPIC EXAMINATION: No data available.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the termination of study
- Anaesthetic used for blood collection: Yes, carbon dioxide were used
- Animals fasted: No data available.
- How many animals: All 18 rats were examined.
- Parameters checked in table [No.?] were examined: Hemoglobin concentration, haematocrits, and total and relative white blood cell counts were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of study
- Anaesthetic used for blood collection: Yes, carbon dioxide were used
- Animals fasted: No data available.
- How many animals: All 18 rats were examined.
- Parameters checked in table [No.?] were examined.-
Glutamic-oxaloacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (AP), and lactic dehydrogenase (LDH), Urea nitrogen and glucose were examined.
URINALYSIS: No data available.
NEUROBEHAVIOURAL EXAMINATION: No data available.
OTHER: Liver and kidney weights were recorded prior to fixation. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Gross abnormalities were examined.
Tissues were fixed in 10% buffered formalin (pH 7.0), embedded in paraffin, sectioned at 5 pm, stained with hematoxylin-eosin, and examined by light microscopy.
Eyes were fixed in a modified Zenker’s (Russell’s) fixative.
HISTOPATHOLOGY: Yes,
Organ examined:
Trachea, lungs, thymus, heart, tongue, salivary glands, esophagus, stomach, small intestine, large intestine, kidneys, urinary bladder, adrenal glands, pituitary, thyroids, parathyroids, pancreas, testes, epididymides, accessory sex glands, spleen, mesenteric lymph nodes, bone marrow, medulla oblongata, pons, cerebellum, cerebral cortex, thalamus, basal ganglia and eyes were examined. - Other examinations:
- No data
- Statistics:
- Statistical analyses included Bartlett’s test, one-way analysis of variance (ANOVA), and Duncan’s multiple range test as a significance level of 5%.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- 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
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality:
Mortality:
When treated with 4000 mg/kg/day, following two to four doses animals were died as compared to control.
Clinical signs:
When treated with 4000 mg/kg/day, sevear depression was observed in treated rats as compared to control.
Body weight and weight gain: When treated with 4000 mg/kg/day, significant decrease in body weight gain was observed in treated rats as compared to control.
When treated with 2000 mg/kg/day, slit decrease in body weight gain was observed in treated rats as compared to control.
Food consumption and compound intake: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Clinical chemistry: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Urinanalysis: No data
Neurobehaviour: No data
Organ weights: When treated with 1000 and 2000 mg/kg/day, significant increase in absolute and relative liver and relative kidney weight were observed in treated rats as compared to control.
Increased mean absolute kidney weights were considered to be not statistically significant.
Gross pathology: Vascular congestion and hemorrhage in major organ in 4000 mg/kg/day treated rats.
Histopathology: Moderate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated rats as compared to control.
Minor to moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No adverse effect on survival, body weight and body weight gain, food consumption, haematology, clinical chemistry, organ weight, gross pathology and histopathology.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table: TERMINAL BODY AND ORGAN WEIGHTS FOR RATS DOSED WITH COMMERCIAL-GRADE METHYL HEPTYL KETONE
Range finding study |
Terminal body weight (g) |
Liver |
Kidneys |
||
g |
% body weight |
g |
% body weight |
||
2000 mg/Kg |
302 a |
13.80b |
4.51b |
2.82 |
0.93b |
n: 3 |
23.2 |
0.770 |
0.178 |
0.412 |
0.064 |
1000 mg/Kg |
311 |
11.98b |
3.86b |
2.90 |
o.94b |
n: 3 |
26.0 |
0.805 |
0.064 |
0.189 |
0.087 |
Control |
320 |
9.79 |
3.06 |
2.51 |
0.78 |
n: 9 |
15.8 |
0.652 |
0.147 |
0.283 |
0.057 |
a Values are listed as X + SD.
b Indicates a statistically significant difference from control p Y 0.05, one-way ANOVA.
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
- Executive summary:
In a repeated dose toxicity study, CD, COBS male rats treated with Methyl heptyl ketone in the concentration of 0, 1000, 2000 and 4000 mg/kg/day orally by gavage for 3 weeks. Following two to four doses of 4000 mg/kg/day animals withsevear depressionwere died and significant decrease in body weight gain were observed in treated rats as compared to control. Slitdecrease in body weight gain in in 2000 mg/kg/day and significant increase in absolute and relative liver and relative kidney weight were observed in 1000 and 2000 mg/kg/day treated rats as compared to control. Increased mean absolute kidney weights were considered to be not statistically significantfor 1000 mg/kg/day dose group.In addition, Vascular congestion and hemorrhage in major organ andModerate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated ratsandminorto moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
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