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Diss Factsheets
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EC number: 202-599-6 | CAS number: 97-65-4
- 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)
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 1 993
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- yes
Test material
- Reference substance name:
- Itaconic acid
- EC Number:
- 202-599-6
- EC Name:
- Itaconic acid
- Cas Number:
- 97-65-4
- Molecular formula:
- C5H6O4
- IUPAC Name:
- 2-methylidenebutanedioic acid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- every day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Basis:
nominal in diet
- No. of animals per sex per dose:
- 10 males and 10 females rats
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Three groups of 10 males and 10 females rats were given the test substance at 1500, 4700 or 14000 ppm, daily by oral route (dietary admixture) for 13 weeks. A group of 10 males and 10 females received the untreated died and acted as a control group.
The stability and the homogeneity of itaconic acid in the feed were checked. The achieved administered doses to the animals are established as follows (in mg/kg/day) :
males females
1500 ppm 106 119
4700 ppm 341 358
14000 ppm 1001 1088
Results and discussion
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 1 001 mg/kg bw (total dose)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
No clinical signs attributable to the treatment were noted in any group. No deaths were observed in any group during the study. The mean food consumption and the mean bodyweight gain of the treated males and females were similar to that of the respective controls. No treatment related findings were observed in any group.
At week 13, slight, but statistically significant differences from the control were noted :
Among the haematological parameters : increase of the erythrocyte count (males, 14 000 ppm), decrease of the mean cell haemoglobin quantity (males, 14 000 ppm), increase of the mean cell volume (females,14 000 ppm) and decrease of activated partial thromboplastin time (males, 14 000 ppm). They were minor and the individual values within the normal range of laboratory background data. Therefore they were considered to be of no toxicological significance.
In the blood biochemistry : decrease of Ca++ (females,14 000 ppm), decrease of inorganic phosphorus (males , all treated groups), decrease of glucose (females, 1500 and 14 000 ppm), decrease of alanine aminotransferase (males, 15 000 ppm),
Increase of bilirubin (males, 14 000 ppm), increase of total proteins (males, 4 700 and 14 000 ppm and ,females 14 000 ppm), increase of albumin (males, 4 700 ppm).
There were minor, not clearly dose ‑ related and the individual values within the normal range of laboratory background data. Therefore they were considered to be of no toxicological significance.
In urinalysis : a slightly higher specific gravity was noted in the males given 4 700 and 14 000 ppm together with a lower pH in males given 14 000 ppm when compared to the controls. A slight decrease of the pH was noted in the females given 4 700 ppm. No further qualitative or quantitative treatment ‑ related abnormalities were noted. Again these findings were considered to be of no toxicological significance.
A statistically significant increase of ovary weight was found in females given 1 500 ppm. Such a variation was not found in the animals given higher doses. No relevant morphological changes were observed. This observation was considered to be of no toxicological significance. Moreover no microscopic findings were observed in that organs in the highest dosed animals. No variations in testes weight nor macro- and microscopic findings were observed in the highest dosed animals compared to the controls.
Macroscopic and microscopic changes observed were those which are commonly observed as spontaneous in the strain used and were not related to the treatment.
Based on these results, no toxicologically significant observations were noted whenitaconic acidwas administered daily by oral route at 1 500, 4 700 and 14 000 ppm to Sprague‑Dawley rats for 13 weeks. Under this experimental conditions, a No Observed Effect Level (NOEL) of 14 000 ppm is established (i.e. a mean dose level of 1 001 mg/kg/day in the males and 1 088 mg/kg/day in the females).
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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