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EC number: 202-496-6 | CAS number: 96-29-7
- 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:
- supporting study
- Study period:
- 4-weeks
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- number and sex of animals, humidity, dosage
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Butanone oxime
- EC Number:
- 202-496-6
- EC Name:
- Butanone oxime
- Cas Number:
- 96-29-7
- Molecular formula:
- C4H9NO
- IUPAC Name:
- (NE)-N-butan-2-ylidenehydroxylamine
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Char1 es River Breeding Laboratories, Inc., Kingston, New York
- Age at study initiation: 7 weeks
- Weight at study initiation: 159.9-184.7
- Fasting period before study: no
- Housing: Animals were doubly housed in elevated stainless steel wire mesh cages during the first week of acclimation and individual1y housed
thereafter.
- Diet (e.g. ad libitum): Certi f i ed Rodent chow@, No. 5002; Purina Mills Inc., St. Louis, MO; ad libitum; fresh food presented weekly.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 15-62
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses to determine stability, homogeneity and concentration of the test and/or control materials with carriers under conditions of this study were performed.
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 15 males/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The study was designed to assess any potential peroxisome proliferation, or any potential changes in hepatic glutathione levels or serum testosterone levels after oral administration of MEKO.
- Positive control:
- A positive control group recieved clofibric acid, 250 mg/kg bw/day; at a dose volume of 10 mL/kg.
A negative control group received distilled water at a dose volume of 10 mL/kg.
Examinations
- Observations and examinations performed and frequency:
- Physical observations and body weight measurements were performed on all animals three times pretest and weekly during treatment period. Serum testosterone levels were determined on test days 8, 15, and 29.
After 7, 14, and 28 days of treatment, 5 animals/group were sacrificed, selected organs were weighed and relative organ weight as well as organ/brain weight ratios determined. Liver tissue samples were analysed by light and electron microscopy. Liver homogenates were assayed for protein content, cyanide-insensitive palmitoyl-CoA oxidation activity and for total, reduced, and oxidised glutathione content.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Hepatocellular hypertrophy was seen microscopically after 14 and 28 days.
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- MEKO did not produce any significant hepatic peroxisome proliferation in the rat, as indicated by a lack of effect on palmitoyl-CoA oxidation and by electron microscopy. The potential responsiveness of the animals used in this study was confirmed by the marked induction of palmitoyl-CoA in the rats treated with clofibric acid. No effects on testosterone levels were found.
While MEKO was not a peroxisome proliferator in the rat, significant increases in the levels of hepatic glutathione (primarily reduced glutathione) wereobserved in rats given 250 and 500 mg MEKO/kg bw/day for 14 days and 28 days. This lack of an effect after 7 days of dosing correlated with the hepatocellular hypertrophy which was seen microscopically after 14 and 28, but not 7 days of treatment.
Effect levels
- Dose descriptor:
- LOAEL
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Based on significant increases in hepatic glutathione (primarily reduced glutathione) observed after 14 and 28 days.
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- In rats administered oral doses of MEKO at levels up to 500 mg/kg bw/day for 4 weeks, MEKO did not induce peroxisome proliferation. A significant increase in peroxisomes was produced by clofibric acid demonstrating the ability of the analytical procedures to detect this effect. Similarly, MEKO had no effect on serum testosterone levels. While MEKO was not a peroxisome proliferator in the rat, significant increases i n the levels of hepatic glutathione (primarily reduced glutathione) were observed in rats given 250 and 500 mg MEKOlkglday for 14 days. This lack of an effect after 7 days of dosing correlated with the hepatocellular hypertrophy which was seenmicroscopically after 14 and 28 but not 7 days of treatment.
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