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EC number: 264-513-3 | CAS number: 63843-89-0
- 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
- Study period:
- 2011-2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant study. Specific target organ investigations performed as part of an OECD 421 study.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 421
- Deviations:
- yes
- Remarks:
- extra investigation of known endpoints (haematology, histopathology of spleen, liver, intestine), etc
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
- EC Number:
- 264-513-3
- EC Name:
- Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate
- Cas Number:
- 63843-89-0
- Molecular formula:
- C42H72N2O5
- IUPAC Name:
- bis(1,2,2,6,6-pentamethylpiperidin-4-yl) 2-butyl-2-[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]propanedioate
- Details on test material:
- - Substance type: powder
- Physical state: white solid
- Analytical purity: HPLC: approx. 99 area-% (220 nm)
- Expiration date of the lot/batch: 21 Feb 2014
- Stability under test conditions: stable
- Storage condition of test material: room teperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld
- Age at study initiation: 10-11 weeks; males/ females
- Weight at study initiation: ca 250 g (females), ca 300g (males)
- Fasting period before study: overnight
- Housing: single (except for mating)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2011-10-11 To: 2011-12-06
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% aqueous CMC and 5% Cremophor EL
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
To prepare the suspension, the appropriate amount of test substance was weighed out depending on the desired concentration. Then,
drinking water containing 1% carboxymethylcellulose and 5 mg/ 100 mL Cremophor EL was filled up to the desired volume, subsequently released with a magnetic stirrer. During administration of the test substance preparations were kept homogeneous by stirring with a magnetic stirrer. The test substance preparations were produced at least once a week and were stored at room temperature. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- HPLC-method
- Duration of treatment / exposure:
- 28 days (males)
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.5, 2 and 10 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on range-finder study
- Positive control:
- not required
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least once daily for any signs of morbidity, pertinent behavioral changes and signs of overt toxicity.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Detailed clinical observations (DCO; including palpation) were performed in all animals prior to the administration period and thereafter at weekly intervals.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD EFFICIENCY:
- 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: Yes
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study (males: study day 36, females: study days 45, 49 and 50)
- Anaesthetic used for blood collection: Yes (isoflurane anesthesia)
- Animals fasted: Yes
- How many animals: 10
- Parameters were examined:
Leukocyte count (WBC)
Erythrocyte count (RBC)
Hemoglobin (HGB)
Hematocrit (HCT)
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin concentration (MCHC)
Platelet count (PLT)
Differential blood count
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All groups: All gross lesions, jejunum, spleen, liver, Mesenteric lymph nodes, ovaries
Control and high dose group: testes, epididymides - Other examinations:
- Organ weights: Epididymides, Testes
- Statistics:
- yes
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Male animal Nos. 33 and 34 of test group 3 (10.0 mg/kg bw/d) showed unsteady gait and swelling of limbs from study day 35 until sacrifice. Poor general state was noted for male animal Nos. 33, 34 and 36 of test group 3 (10.0 mg/kg bw/d) towards the end of the application period. Piloerection was observed in male animal No. 36 of test group 3 (10.0 mg/kg bw/d) from study day 29 onwards as well as in male animal Nos. 33, 34 and 37 on study day 36. No clinical findings were observed for any female animal in test groups 0-3 (0, 0.5, 2.0 and 10.0 mg/kg bw/d).
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Male animal Nos. 33 and 34 of test group 3 (10.0 mg/kg bw/d) showed unsteady gait and swelling of limbs from study day 35 until sacrifice. Poor general state was noted for male animal Nos. 33, 34 and 36 of test group 3 (10.0 mg/kg bw/d) towards the end of the application period. Piloerection was observed in male animal No. 36 of test group 3 (10.0 mg/kg bw/d) from study day 29 onwards as well as in male animal Nos. 33, 34 and 37 on study day 36. No clinical findings were observed for any female animal in test groups 0-3 (0, 0.5, 2.0 and 10.0 mg/kg bw/d).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight change values were significantly lower in male animals of test group 3 (10.0 mg/kg bw/d) from study week 4 to 5 as well as study week 0 to 5.
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- increases in white blood cells at 10 mg/kg bw
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- only investigated for testes and epididymides
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Details on results:
- Findings at 10 mg/kg bw:
Thickened Jejunum in 15 of 20 animals
Foci in liver in 6/20 animals
Enlarged mesenteric lymph nodes in 17/20 animals
Two animals with enlarged iliac lymph nodes
Enlarged spleen in 4/20 animals, two with foci
multifocal random liver necrosis in males, granulomatous liver inflammation for both sexes
foam cell aggregates in the lamina propria of intestinal villi, in 3 females granulomatous inflammation in the intestinal wall
mesenteric lymph nodes: granulomatous inflammation with necrosis
Increased total white blood cell counts
Increased absolute and relative neutrophils counts
Increased absolute and relative monocytes counts
Increased absolute eosinophils counts
Decreased HGB
Decreased relative lymphocytes counts
Findings at 2 mg/kg bw:
Thickened jejunum in 2 females and 1 male
accumulation of eosinophilic slightly vacuolated histiocytes mostly in the cortex of the mesenteric lypmh node.
Findings at 0.5 mg/kg bw:
Thickened jejunum in 1 animal
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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