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EC number: 204-844-2 | CAS number: 127-47-9
- 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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented study which meets basic scientific principles.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 984
- Report date:
- 1984
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:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Retinyl acetate
- EC Number:
- 204-844-2
- EC Name:
- Retinyl acetate
- Cas Number:
- 127-47-9
- Molecular formula:
- C22H32O2
- IUPAC Name:
- (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl acetate
- Details on test material:
- Vitamin A acetate (CAS No. 127-47-9) (dry powder), technical grade; purity was 535000 IU Vitamin A/g (ca. 180 mg/g or 18%)
composition:
gelatine, 31%
Vitamin A acetate, 20%
water, 3%
BHT, 1%
sodium aluminium silicate, max. 1%
dioctyl sodium sulfosuccinate, 0.04%
glucose sirup, ad 100%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: MUS Rattus, Brunnthal
- Age at study initiation: 42 days
- Weight at study initiation: 179 (150 - 205) g for males and 143 (114 - 172) g for females
- Acclimation period: 7 days (unsupplemented diet and water ad libitum)
- Fasting period before study: no
- Housing: Cage Typ D3, BECKER & CO ., Castrop-Rauxel, 3 or 2 animals per cage
- Diet: ad libitum: Ssniff-R-Mehl; SSNIFF Versuchstierdiäten GmbH, Soest
- Water ad libitum: tap water
The test article was mixed into the diet. The normal, unsupplemented diet already contained 8200 and 11400 IE Vitamin A/kg diet.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: food
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Experimental diets were prepared once weekly. - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 3 months
- Frequency of treatment:
- continuously in the diet
Doses / concentrations
- Remarks:
- Doses / Concentrations:
28, 112, 318 ppm in the diet; see freetext
Basis:
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- The experimental diets contained the basal level of Vitamin A plus the test substance at 15000 IE/kg feed (28 ppm), 60000 IE/kg feed (112 ppm), and 170000 IE/kg feed (318 ppm). Control rats were fed the basal diet. One hundred and sixty rats were assigned to 4 groups of 20 male and 20 female rats each. Three groups of rats were fed the experimental diets supplemented with Vitamin A at 28, 112 and 318 ppm. The fourth group served as control; these animals were fed the basal diet, which already contained Vitamin A at average levels of 8200 and 11400 IU.
Post-exposure period: none - Positive control:
- not applicable
Examinations
- Observations and examinations performed and frequency:
- Food consumption was recorded daily.
Body weights were determined weekly;
Substance intake has been calculated from mean daily food intake and body weight change within one study week.
Animals were observed for clinical signs and mortality daily.
Clinical-chemical examinations were performed prior to dosing and two times during the course of the study:
total bilirubin
creatinine
urea
sodium
potassium
total protein
glucose
anorganic phosphate
calcium
chloride
triglyceride
cholesterol
albumin
globulines
lactate-dehydrogenase
glutamate-pyruvate-transaminase
alkaline phosphatase
glutamate-oxalacetate-transaminase
Hematological examinations were performed prior to dosing and two times during the course of the study:
erythrocytes
mean cell volume
thrombocytes
leukocytes
hematocrit
hemoglobin content of erythrocytes
mean corpuscular hemoglobin concentration
differential blood count
Urinalyses were made two times during the course of the study.
pH
protein
glucose
ketones
bilirubin
blood
nitrite
urobilinogen
sediment
An ophthalmoscopic examination was made on half of the animal of each group at the end of the study. - Sacrifice and pathology:
- After 3 months of treatment, all surviving animals were sacrificed and evaluated grossly. Organs were removed, weighed and prepared for histological examination. An X-ray examination of the cranium, the left front limb and the right hind limb was made on each animal.
Organ weights:
heart
liver
spleen
kidney
adrenal glands
testes/ovaries
brain
Histophathology:
heart, trachea, lung with bronchae, tongue, esophagus, fore/stomach, duodenum, colon, glandula submandibularis, liver, pancreas, spleen, thymus, sternum, kidney, urinary bladder, testes, epididymides, ovaries, prostata, uterus, pituitary gland, adrenal glands, thyroid gland, brain, eye, skeletal muscle, bone, all macroscopic lesions - Other examinations:
- Liver samples have been taken from 10 males and 10 female animals per dose group for determination of vitamin A content.
Results and discussion
Results of examinations
- Details on results:
- Dose levels:
The uptake of the test substance varied during the course of the study. Generally, the average dose level decreased from the 1st to the 13th study week. Average weekly uptake of the test substance, males:
318-ppm group: 15.98 - 36.74 mg/kg bw/d
112 ppm group: 5.77 - 12.97 mg/kg bw/d
28-ppm group: 1.43 - 3.32 mg/kg bw/d
Average weekly uptake of the test substance, females:
318-ppm group: 18.55 - 35.79 mg/kg bw/d
112 ppm group: 6.40 - 12.57 mg/kg bw/d
28-ppm group: 1.62 - 3.07 mg/kg bw/d
Body weights:
Body weight and body weight gain was similar in all groups.
Food consumption:
Food consumption was similar in all groups.
Mortality:
No deaths occurred.
Clinical symptoms:
Clinical symptoms, if any, were unspecific in nature. The test substance was well tolerated without any effects on behaviour.
Ophthalmoscopy.
Ophthalmoscopy revealed no substance-related changes.
Toxicologically relevant findings:
The following findings were considered to be statistically significant and substance-related:
318 ppm group: - increased plasma triglyceride levels (both sexes) - slightly increased activity of glutamate pyruvate transaminase and glutamate oxalacetate transaminase in the plasma (males) - proteinuria (first urinalysis, one male) - increased absolute and relative liver weights (females) - brightened livers (both sexes) - lipid accumulation in Kupffer cells and decrease of the intrahepatocellular lipid droplets in the peripheral areas of the liver lobules (both sexes) - lipid accumulation in individual cells of the duodenal lamina propria
112 ppm group: - slightly increased activity of glutamate pyruvate transaminase and glutamate oxalacetate transaminase in the plasma (males) - brightened livers (2/20 females) - lipid accumulation in the Kupffer cells of the liver (both sexes)
28 ppm group: No substance-related changes were observed.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 28 ppm
- Sex:
- male/female
- Basis for effect level:
- other: corresponding to 1.43-3.32 mg/kg bw/d (males) and 1.62-3.07 mg/kg bw/d (females).
- Dose descriptor:
- LOAEL
- Effect level:
- 112 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Hypervitaminosis A
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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