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EC number: 461-290-6 | CAS number: 167374-38-1
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study performed in compliance with GLP regulations
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- - Name of test material (as cited in study report): MEOE
- Physical state: solid, powder/light beige
- Analytical purity: 96.8g/100g
- Storage condition of test material: ambient (RT); no direct sunlight; avoid temperature above 40°C; protect against humidity
Test animals
- Species:
- rat
- Strain:
- other: Crl:WI(Han)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Sulzfeld, Germany
- Age at study initiation: 42 ± 1 days
- Weight at study initiation: Does not exceed +/- 20% of the mean weight of each sex
- Housing: The rats were housed together (5 animals per cage) in H-Temp polysulfonate cages supplied by TECNIPLAST, Hohenpeißenberg, Germany (floor area about 2065 cm2).
- Diet (e.g. ad libitum): Kliba maintenance diet mouse/rat “GLP”, meal, supplied by Provimi Kliba SA, Kaiseraugst, Switzerland.
- Water (e.g. ad libitum): Food and drinking water (from water bottles) were available ad libitum.
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: drinking water containing 1% carboxymethylcellulose
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
MEOE was applied as a suspension. To prepare this suspension, the appropriate amount of test substance was weighed out depending on the desired concentration. Then, drinking water containing 1% carboxymethylcellulose was filled up to the desired volume, subsequently released manually. During administration of the test substance, preparations were kept homogeneous by stirring with a magnetic stirrer. The test substance preparations were produced once a week.
For details see table 1 below. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in drinking water containing 1% carboxymethylcellulose at room temperature for a period of 7 days was demonstrated before the start of the administration period.
Concentration control analyses of the test-substance preparations were performed in samples of all concentrations at the start of the administration period. Each 3 samples were taken from the lowest and highest and one sample from the mid concentration for homogeneity analysis; these samples were used as a concentration control at the same time.
Method: Quantitative H-NMR spectroscopy - Duration of treatment / exposure:
- MEOE was administered daily for 28 days.
- Frequency of treatment:
- MEOE was administered daily for 28 days.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 1, 3 and 6 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
A check for moribund and dead rats was made twice daily on working days and once daily on Saturdays, Sundays and public holidays. If rats were in a moribund state, they were sacrificed and necropsied. All rats were checked daily before and within 2 hours as well as within 5 hours after the administration for any clinically abnormal signs. Abnormalities and changes were documented for each rat.
DETAILED CLINICAL OBSERVATIONS: Yes
Detailed clinical observations (DCO) were performed in all rats prior to the administration period and thereafter at weekly intervals. The findings were ranked according to the degree of severity, if applicable. The rats were transferred to a standard arena (50 × 37.5 cm with sides of 25 cm high). The following parameters were examined:
1. abnormal behavior during “handling”
2. fur
3. skin
4. posture
5. salivation
6. respiration
7. activity/arousal level
8. tremors
9. convulsions
10. abnormal movements
11. impairment of gait
12. lacrimation
13. palpebral closure
14. exophthalmus
15. feces (appearance/ consistency)
16. urine
17. pupil size
BODY WEIGHT: Yes
Body weight was determined before the start of the administration period in order to
randomize the rats. During the administration period the body weight was determined on day 0 (start of the administration period) and thereafter at weekly intervals. The difference between the body weight on the respective day of weighing and the body weight on day 0 was calculated as body weight change.
OPHTHALMOSCOPIC EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: end of study
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: 5 per sex and dose
- Parameters checked: Leukocyte count, Erythrocyte count, Hemoglobin, Hematocrit, Mean corpuscular volume, Mean corpuscular hemoglobin, Mean corpuscular hemoglobin concentration, Platelet count, Differential blood count, Reticulocytes, Prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: end of study
- Animals fasted: Yes
- How many animals: 5 per sex and dose
- Parameters checked: Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase, γ-Glutamyltransferase, sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, triglycerides, cholesterol, magnesium, bile acids,
URINALYSIS: Yes
- Time schedule for collection of urine: day 23
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked: pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, specific gravity, sediment, color, turbidity, volume
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- verious statistical tests
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No rat died prematurely in the present study. Respiration sounds were observed in female No. 34 of test group 2 (3 mg/kg bw/d). This finding was observed from study day 21 onwards. This finding was assessed as being incidental and not related to the test substance.
BODY WEIGHT AND WEIGHT GAIN
No test substance-related changes of body weight and body weight gain were observed in any test group.
Body weight change was significantly increased in female animals of test group 1 (1 mg/kg bw/d) from study day 14 onwards (maximum +46.34% on study day 14). These changes were assessed as being incidental and not related to treatment.
When compared to control group 0 (set to 100%), the terminal body weight was significantly increased (+11%) in females of test group 1 (1 mg/kg bw/d). Because there was no doseresponse relationship the increase of the terminal body weight was regarded to be incidental. The mean absolute duodenum weight in test groups 1-3 (1, 3 and 6 mg/kg bw/d) did not show significant differences when compared to test group 0 (control).
FOOD CONSUMPTION
No test substance-related effects on food consumption were obtained.
WATER CONSUMPTION
No test substance-related findings were observed.
HAEMATOLOGY
No treatment-related, adverse changes among hematological parameters were observed.
In females of test group 3 (6 mg/kg bw/d) the absolute lymphocyte and, therefore, also the total white blood cell (WBC) counts were, although not significantly, higher compared to controls. The total white blood cell counts in the mentioned test group were within the historical control range whereas the absolute lymphocyte counts were slightly above the upper border of the historical control range (WBC: 3.06-5.03 Giga/L, absolute lymphocyte
counts: 2.66-3.85 G/L). Because these findings were single changes in clinical pathology of this test group, they were regarded as not adverse (ECETOC Technical Report No 85, 2002).
CLINICAL CHEMISTRY
No treatment-related, adverse changes among clinical chemistry parameters were observed.
In males of test group 1 (1 mg/kg bw/d) the serum calcium levels were lower and the glucose concentrations were higher compared to controls. Both parameters were not changed dosedependently and, therefore, this alteration was regarded as incidental and not treatmentrelated.
URINALYSIS
No treatment-related changes among urinalysis parameters were measured.
ORGAN WEIGHTS
The mean relative duodenum weight in test groups 1-3 (1, 3 and 6 mg/kg bw/d) did not show significant differences when compared to the control group 0.
GROSS PATHOLOGY
No treatment-related gross lesions were observed.
HISTOPATHOLOGY:
No histopathological findings were observed.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 6 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: highest dose tested
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Executive summary:
In conclusion the oral administration of MEOE by gavage over a period of 4 weeks revealed no signs of toxicity in male and female Wistar rats at dose levels up to 6 mg/kg bw/d. In addition, no increase of duodenum weight was observed at any dose level. Therefore, under the conditions of the present study, the no observed adverse effect level (NOAEL) was ≥6 mg/kg bw/d for male and for female Wistar rats.
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