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EC number: 205-126-1 | CAS number: 134-03-2
- 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
Endpoint summary
Administrative data
Description of key information
The NOAEL of the substance was determined to be 4500 mg sodium ascorbate /kg bw and day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- For justification please refer to read across statement in IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 6 524 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- target substance
- Sex:
- male
- Basis for effect level:
- other: no adverse effects seen
- Remarks on result:
- other: results of the source substance (5800 mg/kg bw/day) are converted to the target substance taking into account the molecular weights (factor 1.125)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 4 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- target substance
- Sex:
- female
- Basis for effect level:
- other: minimal reticulum-cell hyperplasia
- Remarks on result:
- other: results of the source substance (4000 mg/kg bw/day) are converted to the target substance taking into account the molecular weights (factor 1.125)
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 9 560 mg/kg bw/day (actual dose received)
- System:
- haematopoietic
- Organ:
- bone marrow
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- no
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- ophthalmology, clinical biochemistry, FOB not specified in the final report, TR 247
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- CAS number 50-81-7
Purity: 97.6 to 101.1% - Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Industries, Greenfield, IN
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 weeks
- Weight at study initiation: approx. 115 g (males) and 95 g (females)
- Housing: housed in groups of 5 per cage
- Diet; ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks - Route of administration:
- oral: feed
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 7/week
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- controls
- Dose / conc.:
- 25 000 mg/kg diet
- Remarks:
- dose approx. 1350 (m) and 1900 (f) mg/kg bw and day
- Dose / conc.:
- 50 000 mg/kg diet
- Remarks:
- dose approx. 2800 (m) and 3950 (f) mg/kg bw and day
- Dose / conc.:
- 100 000 mg/kg diet
- Remarks:
- dose approx. 5800 (m) and 8500 (f) mg/kg bw and day
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Positive control:
- not needed
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Compound intake calculated as time-weighted averages from the consumption data: Yes
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: No
OPHTHALMOSCOPIC EXAMINATION: Not specified
HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 0, 7, 30, and 90
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: all
- Parameters examined: at least: mean corpuscular volume; mean corpuscular haemoglobin; platelets; reticulocytes; haemoglobin; packed cell volume; red blood cell counts
CLINICAL CHEMISTRY: Not specified
URINALYSIS: Not specified
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified
OTHER:
data only shown for the second 90-day study that was conducted to gather additional data on the myelofibrosis observed in female rats in the first 13-week study. Groups of 20 female F344/N rats were fed diets containing 0, 25,000, or 50,000 ppm L-ascorbic acid for 91 days. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Necropsies were performed on animals that survived to the end of the study and on all animals found dead, unless precluded in whole or in part by autolysis or cannibalization. The following specimens were examined from control and the 100,000 ppm groups: gross lesions, tissue masses, abnormal lymph nodes, skin, mandibular lymph nodes, mammary gland, salivary gland, bone marrow, thymus, larynx, trachea, lungs and bronchi, heart, thyroid, parathyroid, esophagus, stomach, duodenum, jejunum, ileum, colon, mesenteric lymph nodes, liver, gallbladder (mice), pancreas, spleen, kidneys, adrenals, urinary bladder, seminal vesicles/ prostate/ testes or ovaries/ uterus, brain, pituitary, and spinal cord. Tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with haematoxylin and eosin. Femoral bone marrow sections were examined from female rats in the controls, 25,000-, 50,000-, and 100,000-ppm groups.
HISTOPATHOLOGY: Not specified - Statistics:
- yes, but not specified
- 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):
- no effects observed
- 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):
- In the first study, alterations of teh femur bone marrow (reticulum-cell hyperplasia) was observed in 2/ 10 female rats receiving 25,000 ppm, 1/ 10 female rats receiving 50,000 ppm, and 4/10 receiving 100,000 ppm.
This was not seen in the 2-year study. - Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 5 800 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: no adverse effects seen
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 4 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: minimal reticulum-cell hyperplasia
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 8 500 mg/kg bw/day (actual dose received)
- System:
- haematopoietic
- Organ:
- bone marrow
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- no
- Conclusions:
- Ascorbic acid was well tolerated in oral feed studies even at extreme dose levels. Classification criteria are not met.
- Executive summary:
In a pre-test to the 2-year carcinogenicity study, the repeated dose toxicity of ascorbic acid was investigated in 14-day studies (rats and mice, 5 animals per dose and sex; data not reported in this dossier) and in 90-day studies using rats and mice. The first of two 90-day rat studies is reported in this dossier. Ascorbic acid was administered to young Wistar rats (10 per sex and dose) in the feed at concentrations of 0, 25,000, 50,000, and 100,000 ppm. No adverse effects were seen apart from alterations of the femur bone marrow (reticulum cell hyperplasia) in females in a non-dose related manner (2/10 at the low dose; 1/10 at the mid dose; 4/10 at the high dose). These findings were not confirmed in a second 90-day rat study (only females) or in the two-year carcinogenicity study, both with 25,000 and 50,000 ppm ascorbic acid in the diet. This effect appears to be of minor importance.
In summary, ascorbic acid was not toxic to rats in a 90-day study (oral gavage) at doses up to 5800 mg/kg bw and day (male rats) and 4000 mg/kg bw and day (female rats). Based on these results, the maximum dose level for the carcinogenicity studies was defined to be 50,000 ppm in the feed (NTP, 1983).
Referenceopen allclose all
Changes in the femur bone marrow were seen in the first 90 -day study, but not in the 2 -year study. The reason is not known.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 4 500 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- excellent and sufficient for assessment
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In a pre-test to the 2-year carcinogenicity study, the repeated dose toxicity of ascorbic acid was investigated in 14-day studies (rats and mice, 5 animals per dose and sex; data not reported in this dossier) and in 90-day studies using rats and mice. The first of two 90-day rat studies is reported in this dossier.
Ascorbic acid was administered to young Wistar rats (10 per sex and dose) in the feed at concentrations of 0, 25,000, 50,000, and 100,000 ppm. No adverse effects were seen apart from alterations of the femur bone marrow (reticulum cell hyperplasia) in females in a non-dose related manner (2/10 at the low dose; 1/10 at the mid dose; 4/10 at the high dose). These findings were not confirmed in a second 90-day rat study (only females) or in the two-year carcinogenicity study, both with 25,000 and 50,000 ppm ascorbic acid in the diet. This effect appears to be of minor importance.
In summary, ascorbic acid was not toxic to rats in a 90-day study (oral gavage) at doses up to 5800 mg/kg bw and day (male rats) and 4000 mg/kg bw and day (female rats). Based on these results, the maximum dose level for the carcinogenicity studies was defined to be 50,000 ppm in the feed (NTP, 1983).
This result can be adopted for sodium ascorbate. Considering the molecular weights of ascorbic acid (176.13) and sodium ascorbate (198.11) results in a conversion factor of 1.125, Therefore, the NOAEL is 4500 mg sodium ascorbate /kg bw and day.
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on repeated dose toxicity, the test item is not classified specific organ toxicity (repeated dose) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.
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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