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EC number: 202-874-0 | CAS number: 100-64-1
- 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:
- 1985
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Equivalent to guidellne with limited documentation
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1985
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Cyclohexanone oxime
- EC Number:
- 202-874-0
- EC Name:
- Cyclohexanone oxime
- Cas Number:
- 100-64-1
- Molecular formula:
- C6H11NO
- IUPAC Name:
- cyclohexanone oxime
- Test material form:
- not specified
- Details on test material:
- - Name of test material (as cited in study report): cyclohexanone oxime
- Analytical purity: 99,5%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles
River Breeding Laboratories (Kingston, NY, USA)
- Housing: individually
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 5
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: with distilled water
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days (main study)
30, 60 days (satellite groups) - Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.25, 2.5 or 25 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 20 (main study)
10 (satellite groups) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Post-exposure recovery period in satellite groups: no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: days -14, 7, 0 (start of exposure), 1, 4, 7 and weekly thereafter
FOOD CONSUMPTION:
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: days -7, 7 and monthly thereafter
- Dose groups that were examined: all
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on morning of necropsy
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: all
- Parameters: white blood cells (WBC), red blood cells, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) , mean corpuscular hemoglobin concentration, white cell differential count, platelet count, and reticulocyte count
Osmotic fragilities determined in 5 animals per sex and group
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on morning of necropsy
- Animals fasted: Yes
- How many animals: all
- Parameters: calcium, chloride, blood urea nitrogen, glucose, total protein, albumin, total bilirubin, serum glutamicoxaloacetic transaminase, creatinine phosphokinase, lactate dehydrogenase, sodium, potassium, phosphorus
URINALYSIS: Yes
- Time schedule for collection of urine: 19 h sample prior to necropsy
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters: volume, sodium, potassium, chloride, pH, protein, glucose, specific gravity, phosphorus, and osmolality
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: daily
- Dose groups that were examined: all
- Battery of functions tested: observational screen - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Complete necropsy
HISTOPATHOLOGY: Yes
Brain (three levels), eyes with optic nerves, pituitary, cervical spinal cord, major salivary glands, cervical lymph nodes, heart, thymus and mediastinal contents, larynx with thyroid and parathyroid, trachea, lungs, esophagus, stomach, duodenum, ileum, lymph nodes, adrenals, pancreas, liver, spleen, kidneys, bladder, testes with epididymis, prostate, ovaries, uterus, femur with marrow, sternebrae with marrow, and skeletal muscle from proximal hind limb - Other examinations:
- Organ weights: brain, lung with trachea, heart, liver, spleen, each kidney, each testis with epididymis, and each ovary. Organ and terminal body weights were used to calculate organ/body weight ratios
- Statistics:
- Continuous variables: Bartlett's homogeneity of variance, analysis of variance, and Duncan's multiple range test.
If Bartlett's test indicated heterogeneous variance or where data were ranked or suspected to be nonparametric, Kruskall-Wallis nonparametric analysis of variance and Wilcoxan rank sum tests were used.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results below
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- see details on results below
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results below
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results below
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results below
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results below
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Through the first 9 weeks of the study: Highest dose males: persistent red nasal discharge, chromodacryorrhea and swollen conjuntiva (also mid dose), the effects gradually subsided and had disappeared by the end of the study
Females after 2 weeks of exposure: chromodacryorrhea (high dose) and corneal opacity (high and mid dose), which both gradually subsided but persisted at study termination
Three females of the high dose died (additionally on female of low dose group due to dosing accident)
OPHTHALMOSCOPIC EXAMINATION
Corneal opacity (transiently in males of all treated groups, persistent in females at >= 2.5 mg/kg bw /day))
HAEMATOLOGY
Dose-related decreases in erythrocyte counts, haemoglobin, increase in MCV, nucleated erythrocytes, lymphocytes (significant at highest dose in both sexes), increased white blood cell counts (significant at >= 2.5 mg/kg bw/day in males, at highest dose in fermales)
Increase in reticulocyte counts and Howell-Jones bodies, anisocytosis and poikilocytosis (significant in all treated males, at highest dose in females)
ORGAN WEIGHTS
Increased spleen weights in males and kidney weights in females (significant at highest dose)
GROSS PATHOLOGY
Splenomegaly in high dose males
HISTOPATHOLOGY: NON-NEOPLASTIC
Spleen: increased haemosiderin pigmentation, extramedullary haematopoesis; increased erythropoesis also in bone marow, all treated males
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Remarks:
- 90-days study
- Effect level:
- 0.25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Haematotoxicity, extramedullary erythropesis in spleen, increased erythropoesis in bone marrow
- Dose descriptor:
- LOAEL
- Remarks:
- 60-days study
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Haematotoxicity, increased spleen weight
- Dose descriptor:
- NOAEL
- Remarks:
- 60-days study
- Effect level:
- 2.5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- LOAEL
- Remarks:
- 30-days study
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Haematotoxicity, increased spleen weight
- Dose descriptor:
- NOAEL
- Remarks:
- 30-days study
- Effect level:
- 2.5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Similar effects were oberved in the satellite groups with 30 or 60 days of exposure, but to a lesser extent. However, the increase in spleen weight was also significant in the male animals of the highest dose group; significant haematological alterations were restricted to the highest dose group. Therefore the LOAEL and NOAEL of the 30- and 60 -days studies are 25 and 2.5 mg/kg bw/day, respectively.
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study the test substance was haematotoxic at all dose levels, especially in males (LOAEL 0.25 mg/kg bw/day).
- Executive summary:
Groups of F-344 rats (20 per sex per dose) were treated by oral gavage with the test substance for 5 days/w for 90 days at doses of 0, 0.25, 2.5 or 25 mg/kg body weight. Satellite groups with 10 animals per sex and dose were exposed for 30 and 60 days. The 30-days study revealed increased spleen weights and haematotoxicity at the highest dose, with a NOAEL of 2.5 mg/kg bw/day. In the main study, there were no significant effects on either body weight or food consumption; mortality occurred at the highest dose (3 female rats). In males, treatment-related clinical effects were observed (red nasal discharge, highest dose only; chromodacryorrhea and swollen conjunctiva (2.5 mg/kg bw/day and above), and corneal opacity (all doses)). These effects gradually subsided and disappeared by the end of the study. In females, clinical signs included chromodacryorrhea (high dose) and corneal opacity (high and mid dose), both of which gradually subsided but persisted at study termination. There was a dose-related decrease in erythrocytes, hemoglobin and hematocrit, accompanied by an increase in circulating reticulocytes and nucleated erythrocytes, the appearance of Howell-Jones bodies, anisocytosis and poikilocytosis. This was confirmed by the observation of haemosiderose, extramedullary erythropoesis in all exposed males and splenomegaly at the highest dose. According to the authors, all observed effects are a compensatory increase in erythropoesis following erythrocyte destruction, were considered "to be not severe and recovery could be expected". No other organs or tissues were adversely affected, including reproductive organs.
Based on dose-related haematotoxic effects, observable at all dose levels, the LOAEL of this 90-days study is 0.25 mg/kg bw/day and a NOAEL could not be determined.
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