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EC number: 203-550-1 | CAS number: 108-10-1
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented. According to acceptable guidelines.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
- Reference Type:
- secondary source
- Title:
- TOXICOLOGICAL REVIEW OF METHYL ISOBUTYL KETONE (CAS No. 108-10-1). In Support of Summary Information on the Integrated Risk Information System (IRIS)
- Author:
- EPA (U.S. Environmental Protection Agency)
- Year:
- 2 003
- Bibliographic source:
- http://www.epa.gov/iris/toxreviews/0173tr.pdf
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- - humidity was >70% in 2 instances
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 4-methylpentan-2-one
- EC Number:
- 203-550-1
- EC Name:
- 4-methylpentan-2-one
- Cas Number:
- 108-10-1
- Molecular formula:
- C6H12O
- IUPAC Name:
- 4-methylpentan-2-one
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): Methyl isobutyl ketone
- Lot/batch No.: A13A
- Stability under test conditions: Stable for at least 12 days at the concentrations tested
- Storage condition of test material: Stored in original container at room temperature and ambient humidity
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 7 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 250, or 1000 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 30/sex/dose
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- Non-fasted body weights recorded on Test Day 1 and weekly thereafter.
Individual food consumption data were collected on a weekly basis.
Moribundity/mortality checks were performed twice daily (morning and afternoon).
Test animals were examined once/week for clinical signs of toxicity.
Ophthalmology examinations were performed during the quarantine period and in Test Week 13.
Hematology, clinical chemistry, and urinalysis were performed on 10 rats/sex/dose during Test Week 7 (interim clinical pathology) and on Test Week 14. - Sacrifice and pathology:
- Necropsy evaluations were performed on 10 rats/sex/dose during Test Week 7 (interim necropsy) and on all remaining animals on Test Week 14.
Histological tissue examinations were conducted on the control and high-dose animals. - Statistics:
- Statistics: one-way ANOVA with Dunnett's t-test.
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):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Reversible lethargy was observed in rats of both sexes receiving 1000 mg/kg-day (but not at lower dose levels) for a few hours following dosing and reportedly decreased in incidence and severity during the study.
Two female rats administered 1000 mg/kg bw/d died during the study (one during Test Week 6 and the other during Test Week 13. These animals demonstrated mottled lungs at gross necropsy. In addition, the liver and kidneys were dark red for one of the animals). A control female also was found dead on Test Week 5.
BODY WEIGHT AND WEIGHT GAIN
Males in the high-dose group showed a slight (9%) but significantly decreased mean body weight gain as compared to controls during the last 2 weeks of exposure, whereas female body weight gain was significantly increased during 5 of the last 6 weeks of exposure.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Both male and female food consumption was significantly increased during the second half of the exposure period.
OPHTHALMOSCOPIC EXAMINATION
No ophthalmic lesions were noted.
HAEMATOLOGY
The only potentially exposure-related hematological effects observed were slight but statistically significant increases in hemoglobin (+6%) and hematocrit (+8%) at terminal sacrifice in females administered 1000 mg/kg-day and a 15% decrease in lymphocyte count in high-dose males at terminal sacrifice.
CLINICAL CHEMISTRY
250 mg/kg-day: increased (+39%) serum glutamic-pyruvic transaminase (SGPT) in female rats at the terminal sacrifice.
1000 mg/kg-day: increased SGPT (+73%, interim; +34%, terminal) in females as compared to controls, increased serum alkaline phosphatase (+84%, interim) in females, increased serum cholesterol in males (+30%, interim) and females (+59%, interim; +65%, final), decreased albumin/globulin ratio in males (-16%, interim), and minimally increased serum total protein in females (+9%, interim; +10%, terminal), increased blood-urea-nitrogen (BUN) in males (+37%, interim), increased serum potassium in males (+34%, terminal), decreased serum glucose in males (-27%, terminal), and a reported increase in urinary protein and ketones in males and females at terminal sacrifice (summary data were not provided).
URINALYSIS
Increased quantities of urinary protein and ketones and elevated specific gravity were generally seen for high-dose and, to a lesser extent, mid-dose animals of both sexes at both the interim and teminal kill periods. An elevated number of epithelial cells also occurred for high- and mid-dose males at the interim kills.
NEUROBEHAVIOUR
No data
ORGAN WEIGHTS
- 250 mg/kg bw/d
Liver: increased terminal absolute (+34%, males; +39%, females) and relative (+42%, males; +38%, females) weights
Kidneys: increased terminal absolute or relative kidney weights in males and females, ranging from 6 to 12% over controls
- 1000 mg/kg bw/d
Liver: increased terminal absolute (+34%, males; +39%, females) and relative (+42%, males; +38%, females) liver weights,
Kidneys: increased terminal absolute and relative kidney weights (from 25 to 34% in males and from 20 to 22% in females) as compared to controls
Adrenals: increased relative weights in male (+29%) and female (+11%) rats
Testis: slightly increased relative weights (+9%) in males
GROSS PATHOLOGY
Gross necropsy failed to suggest treatment-related lesions.
HISTOPATHOLOGY: NON-NEOPLASTIC
1000mg/kg bw/d: increased incidence of male rats with mild nephropathy (multifocally distributed swollen or hyperchromatic and flattened renal cortical tubular epithelial cells) at 1000 mg/kg-day (16/20) as compared to controls (4/20) but no increase in such lesions in females.
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: No treatment-related effects of any kind
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: Increases in relative kidney weights for male and females rats administered MIBK at doses of 250 mg/kg bw/d but without histological lesions
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: Based on kidney changes, hepatomegaly and alterations in clinical chemistry and urinalysis parameters
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The NOAEL was estimated to be 250 mg/kg bw/d, based on increases in relative kidney weights for male and female rats administered MIBK at doses of 250 mg/kg bw/d but without histological lesions. Effects at higher doses included kidney changes, hepatomegaly and alterations in clinical chemistry and urinalysis parameters. No treatment-related effects of any kind were observed at 50 mg/kg-day.
- Executive summary:
Groups of 30 male and 30 female Sprague-Dawley rats were administered MIBK by gavage in corn oil at daily dose levels of 0 (vehicle control), 50, 250, or 1000 mg/kg-day for 13 consecutive weeks and evaluated for exposure-related changes in body weight, food consumption, mortality, clinical signs, ophthalmological parameters, and terminal organ weights (heart, liver, spleen, brain, kidney, gonads, adrenals, thyroid, and parathyroid). The following evaluations were conducted in rats from each exposure level at interim (week 7) and final sacrifices: hematology, clinical chemistry, urinalysis, and comprehensive gross pathology. All tissue samples collected during gross necropsy in high-dose and control rats were evaluated for histopathologies, and kidney samples were also histologically evaluated in mid-dose rats.
Reversible lethargy was observed in rats of both sexes receiving 1000 mg/kg-day (but not at lower dose levels) for a few hours following dosing and reportedly decreased in incidence and severity during the study. Males in the high-dose group showed a slight (9%) but significantly decreased mean body weight gain as compared to controls during the last 2 weeks of exposure, whereas female body weight gain was significantly increased during 5 of the last 6 weeks of exposure. Both male and female food consumption was significantly increased during the second half of the exposure period. The only potentially exposure-related hematological effects observed were slight but statistically significant increases in hemoglobin (+6%) and hematocrit (+8%) at terminal sacrifice in females administered 1000 mg/kg-day and a 15% decrease in lymphocyte count in high-dose males at terminal sacrifice.
The lowest hepatic effect level that was observed in the oral exposure studies was 250 mg/kg-day for increased (+39%) serum glutamic-pyruvic transaminase (SGPT) in female rats at the terminal sacrifice. The following changes suggestive of adverse liver effects were observed at 1000 mg/kg-day at either interim and/or final sacrifice: increased SGPT (+73%, interim; +34%, terminal) in females as compared to controls, increased serum alkaline phosphatase (+84%, interim) in females, increased serum cholesterol in males (+30%, interim) and females (+59%, interim; +65%, final), increased terminal absolute (+34%, males; +39%, females) and relative (+42%, males; +38%, females) liver weights, decreased albumin/globulin ratio in males (-16%, interim), and minimally increased serum total protein in females (+9%, interim; +10%, terminal).
The only renal effect occurring at 250 mg/kg-day was increased terminal absolute or relative kidney weights in males and females, ranging from 6 to 12% over controls. The following changes suggestive of adverse kidney effects were observed at 1000 mg/kg-day: increased terminal absolute and relative kidney weights (from 25 to 34% in males and from 20 to 22% in females) as compared to controls, increased blood-urea-nitrogen (BUN) in males (+37%, interim), increased serum potassium in males (+34%, terminal), decreased serum glucose in males (-27%, terminal), and a reported increase in urinary protein and ketones in males and females at terminal sacrifice (summary data were not provided). Histological examination of kidney tissues revealed an increased incidence of male rats with mild nephropathy (multifocally distributed swollen or hyperchromatic and flattened renal cortical tubular epithelial cells) at 1000 mg/kg-day (16/20) as compared to controls (4/20) but no increase in such lesions in females.
Significantly increased relative adrenal weights in male (+29%) and female (+11%) rats and slightly increased relative testis weights (+9%) in males were also observed at 1000 mg/kgday. No exposure-related histopathologic lesions were evident in the liver or adrenal glands nor in any other tissue that was examined, aside from the kidney. The NOAEL was estimated to be 250 mg/kg bw/d, based on increases in relative kidney weights for male and female rats administered MIBK at doses of 250 mg/kg bw/d but without histological lesions. Effects at higher doses included kidney changes, hepatomegaly and alterations in clinical chemistry and urinalysis parameters. No treatment-related effects of any kind were observed at 50 mg/kg-day.
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