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EC number: 944-548-7 | 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 vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not specified
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Justification for type of information:
- The present study, NDA report No. T-24, study nr. 940373, 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
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- other: chromosome aberration
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:
- The study was conducted with the active pharmaceutical ingredient Insulin Aspart
Method
- Target gene:
- not specified
Species / strain
- Species / strain / cell type:
- lymphocytes: human periferal blood lymphocytes
- Details on mammalian cell type (if applicable):
- human lymphocyte cell cultures from a male and female donor
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver post-mitochondrial fraction (S9) from aroclor 1254 induced animals
- Test concentrations with justification for top dose:
- up to 5000 ug/ml.
- Vehicle / solvent:
- Not specified
Controls
- Untreated negative controls:
- yes
- Remarks:
- Histroical negative controls
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- not specified
- Details on test system and experimental conditions:
- Eksperiment 1:
Treatment in the absence of S9 was continuous for 20 hours.
Treatment in the presence of S9 was for 3 hours, followed by 17 hours recovery period prior to harvest.
The test item concentrations for chromosome analysis were selected by evalutating the effect of insulin aspart on mitotic index. Chromosome aberrtions were analysed at three consecutive treatments concentrations up to 5000 ug/ml.
Eksperiment 2:
Treatment in the absence of S9 was continuous for 20 hours.
Treatment in the presence of S9 was for 3 hours, followed by 17 hours recovery period prior to harvest.
A delayed sampling time compared to experiment one of 44 hours and pulse treatment in the absesence of S9 was included in this experiment.
Chromosome aberrations were analysed in celss receiving 20 hour continuous treatments in the absence of S9 and 3 hour pulse treatment in its presence at three consecutive treatment concentrations up to 5000 ug/ml.
The effect of a singe concentration only (without S9) were also investigated at the delayed (44 hour) sampling time after pulse and continuous treatment and following the 3 hour treatment in the absence of S9, at the 20 hour sampling time.
NUMBER OF REPLICATIONS:
2 - Rationale for test conditions:
- The test item concentrations for chromosome analysis were selected by evalutating the effect of insulin aspart on mitotic index. Chromosome aberrtions were analysed at three consecutive treatments concentrations up to 5000 ug/ml.
- Evaluation criteria:
- Comparison to historical negative controls and solvent controls.
- Statistics:
- N/A
Results and discussion
Test results
- Key result
- Species / strain:
- lymphocytes: Human periferal blood lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- No data
Applicant's summary and conclusion
- Conclusions:
- Insulin aspart did not induce chromosome aberrations in the cultured human periferal blood lymphocytes when tested up to a concentration of 5000 ug/ml in either the absece or presence of S9
- Executive summary:
The in vitro clastogenic potential of Insulin aspart was investigated in cultured human peripheral blood lymphocytes. Induction of chromosomal aberrations was investigated in two experiments at concentrations up to 5000 ug/ml with and without metabolic activation by S9. The treated lymphocytes had frequiencies of cells with aberrations which were similar to and not significantly different from those in concurrent solvent controls. Numbers of aberrant cells in all treated cultures fell within historical negative control ranges.
It was therefore concluded that Insulin aspart does not induce chromosome aberrations in cultured human periferal blood lymphocytes when tested up to a concentration of 5000 ug/ml in either the absece or presence of S9.
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