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Diss Factsheets
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EC number: 944-549-2 | CAS number: -
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- unscheduled DNA synthesis
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Justification for type of information:
- The present study, NDA report No. T-26, study nr. 940374, is described in a summary study report on Insulin aspart is based on GLP guideline studies prepared by Novo Nordisk. The summarised studies were performed as part of the non-clinical toxicity test regime for authorisation of Insulin aspart as human medicine and the studies are therefore in compliance with the guidelines for authorisation of human medicine.
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
- GLP compliance:
- yes
- Type of assay:
- unscheduled DNA synthesis
Test material
- Reference substance name:
- Insulin aspart
- Molecular formula:
- C256H381N65O79S6
- IUPAC Name:
- Insulin aspart
- Test material form:
- solid: particulate/powder
- Details on test material:
- Molecular weight: 5793.6 Da
Constituent 1
- Specific details on test material used for the study:
- Study performed using the active pharmaceutical ingredient Insulin aspart as test substance
Test animals
- Species:
- rat
- Strain:
- other: CD rats
- Details on species / strain selection:
- Not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not specified
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- Not specified
- Details on exposure:
- Insulin aspart was administered subcutaneously on two occasions approximately 10 hours apart at a dose volume of 5 ml/kg
- Duration of treatment / exposure:
- Two injectiions subcutaneusly, approximately 10 hours apart at a dose volume of 5 ml/kg
- Frequency of treatment:
- Two injections
- Post exposure period:
- 2-4 hours after the second injection (12-14 hours after initial dosing), animals were killed and their liver perfused with collagenase to provide a primary culture of hepatocytes.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 000 other: U/kg/day
- Remarks:
- Administered over two doses of 1000 U/kg
- Dose / conc.:
- 800 other: U/kg/day
- Remarks:
- Administered over two doses
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- yes
Examinations
- Tissues and cell types examined:
- hepatocytes from perfused livers
- Details of tissue and slide preparation:
- Livers were perfused with collagenase to provide primary cultures of hepatocytes. Cultures were made from three animals in each dose group and were treated with [3H] thymidine. Six slides from each animal were prepared with fixed hepatocytes and of these, three were dipped in photographic emulsion to prepare autoradiograms. The net grain count (NNG), the number of grains present in the nucleus minus the mean number of grains in three equivalent areas of cytoplasm, was determined for each of two of the three slides, for each animal and dose group.
- Evaluation criteria:
- Not specified
- Statistics:
- Not specified
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- N/A
Any other information on results incl. tables
Negative (vehicle) control animals gave a group mean NNG ( net grain count) value of less than zero with only 0.7 -1.7% cells in repair. Group mean NNG values were increased by positive control treatment to at least 7.5%, with more than 50% cells found to be in repair. The vehicle control NNG value was consistent with both published and historical control data, and the system was shown to be sensitive to a known DNA damaging agent requiring metabolism for its action. The assay was therefore accepted as valid.
Treatment of male and female rats with 800 or 2000 U/kg/day insulin aspart subcutaneously, did not produce a group mean NNG value greater than -1.2, nor were any more than 1% cells found in repair at either dose level.
Applicant's summary and conclusion
- Conclusions:
- Insulin aspart did not to induce unscheduled DNA synsthesis at doses up to 2000 U/kg/day
- Executive summary:
Treatment of male and female CD rats with 800 or 2000 U/kg/day insulin aspart subcutaneously, did not produce a group mean NNG value greater than -1.2, nor were any more than 1% cells found in repair at either dose level.
It was therefore concluded that insulin aspart failed to induce unscheduled DNA synsthesis detectable under the experimental conditions employed
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