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Diss Factsheets
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EC number: 944-551-3 | 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 somatic cell study: cytogenicity / erythrocyte micronucleus
- 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, Novo Nordisk preclinical expert report No. T-13, study nr. LSR 85/NLP005/508, is described in a tabular summary study report on Human Insulin 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 Human Insulin 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
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- other: micronuclei
Test material
- Reference substance name:
- Human Insulin
- Molecular formula:
- C257H383N65O77S6
- IUPAC Name:
- Human Insulin
- Test material form:
- solid: particulate/powder
- Remarks:
- White powder
- Details on test material:
- Molecular formula: C257H383N65O77S6
Molecular weight: 5807.66 g/mol
Constituent 1
- Specific details on test material used for the study:
- Study performed using the active pharmaceutical ingredient Human Insulin as test substance
Test animals
- Species:
- mouse
- Strain:
- not specified
- Details on species / strain selection:
- CD-1 Charles River BR Lab (UK)
- 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:
- S.C. administration of 4000, 800, 160 U/kg as single dose in the morning.
Sampling time 24, 48 and 72 hours after treatment.
Number of animals analyzed per group: 5 males and 5 females (160-800 U/kg) and 15 males and 15 females (4000 U/kg)
Positive control: Chlorabucil (60mg/kg, single oral administration) analyzed 24 post exposure.
Negative control: Acrapid Medium.
- Duration of treatment / exposure:
- One subcutaneous injection in the morning.
- Frequency of treatment:
- Onces (one subcutaneous injection in the morning)
- Post exposure period:
- Animals were sacrificed 24, 48 and 72 hours after exposure.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 160 other: U/kg
- Dose / conc.:
- 800 other: U/kg
- Dose / conc.:
- 4 000 other: U/kg
- No. of animals per sex per dose:
- above 15 animals/group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Yes
Examinations
- Tissues and cell types examined:
- Polychromatic erythrocytes (PCE) from bone marrow
- Details of tissue and slide preparation:
- Not specified
- Evaluation criteria:
- Micronucleus frequency was estimate din 2000 PCE per animal
- Statistics:
- Not specified
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Slides from all dose groups were analysed and micronucleus frequency estimated in 2000 PCE per animal. All positive control animals exhibited increased numbers of micronucleated PCE.
There were no instances of statistically significant increases in micornucleus frequency for any of the groups receiving the test article at either sampling time.
Applicant's summary and conclusion
- Conclusions:
- Human Insulin did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of mice treated with subcutaneous injection using dose levels up to 4000 U/kg of Human inuslin.
- Executive summary:
Human insulin was teset for its ability to induce micronuclei in the bone marrow of subcutaneously dosed male and female mice. Administration of 4000, 800 or 160 U/kg (one s.c. injection) were administered to the mice. Postive and negative (vehicle) control animals were also included. All animals were sacrificed 24, 48 or 72 hours after administration.
Slides from all dose groups were analysed and micronucleus frequency estimated in 2000 PCE per animal. All positive control animals exhibited increased numbers of micronucleated PCE.
There were no instances of statistically significant increases in micornucleus frequency for any of the groups receiving the test article at either sampling time.
It was concluded that insulin aspart did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of mice treated up to 4000 U/kg.
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