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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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Data on fertility and development is only available on the active pharmaceutical ingredient insulin aspart in connection with subcutaneous injections. The effects seen in relation to maternal toxicity, fertility and development are overall considered as a consequence of the hypoglycaemic mode of action of the substance and as secondary effects of the maternal toxicity.
In a study examining fertility and embryofoetal development in rats dosed with 0, 5, 25, 100U/kg dosed twice daily by s.c. administration (corresponding to 0; 0.38; 1.90; 7.60 mg/kg/day) the males were dosed from 4 weeks before mating and females from 2 weeks before mating until day 15 of pregnancy. Reduced blood glucose levels were observed in relation to the dosing and one male rat died presumably due to severe hypoglycaemia. No effects on mating performance or pregnancy rate was observed, but slightly increased pre-and post -implantation losses was seen at the highest dose level and a slight dose-related increase of foetuses with small orbital sockets was noted . Slightly histopathological changes in testes were found in males at the two highest dose levels. The findings in the study was considered most likely to be induced by hypoglycaemia.
The findings from these studies are considered relevant for Insulin aspart ethyl ester as well as this substance also bind 100% to the insulin receptor and thus has the potential to induce a hypoglycaemic response. The data does not indicate any need for CLP-classification for fertility or development as the effects seen is primarily considered secondary to maternal toxicity. Also, the dosing has been performed with s.c. administration which make interpretation for more relevant exposure routes in terms of classification questionalbe.
Effects on developmental toxicity
Description of key information
Data on fertility and development is only available on the active pharmaceutical ingredient insulin aspart in connection with subcutaneous injections. The effects seen in relation to maternal toxicity, fertility and development are overall considered as a consequence of the hypoglycaemic mode of action of the substance and as secondary effects of the maternal toxicity.
A two-generation reproductive toxicity study was conducted with insulin apart in rats using dose levels of 0, 5, 25, 100U/kg dosed twice daily by s.c. administration (corresponding to 0; 0.38; 1.90; 7.60 mg/kg/day). The administration of insulin apart did not result in any effects on fertility or development. Hypoglycaemia was observed at all dose levels in adult animals. Maternal toxicity was observed at the two highest dose levels that was considered to be linked to the induction of hypoglycaemia. Six of 28 females died at highest dose levels on day 20 to 23 of gestation. The lowest dose level of 0.38 mg/kg/d was concluded as NOAEL for maternal toxicity.
A developmental toxicity study in rabbits dosed with 0; 0.5; 1.5; 5 U/kg/ twice daily from day 6 to day 18 of pregnancy by s.c. injection (corresponding to 0; 0.04; 0.11; 0.38 mg/kg/d) resulted in an increase in early embryonic death and reduction of litter size at highest dose level and in a higher proportion of skeletal abnormalities. Blood glucose levels were affected in a dose-related manner and effects in relation to fertility and development were suggested to be secondary effects of lowered maternal blood glucose levels.
The findings from these studies are considered relevant for Insulin aspart ethyl ester as well as this substance also bind 100% to the insulin receptor and thus has the potential to induce a hypoglycaemic response. The data does not indicate any need for CLP-classification for fertility or development as the effects seen is primarily considered secondary to maternal toxicity. Also, the dosing has been performed with s.c. administration which make interpretation for more relevant exposure routes in terms of classification very difficult.
Justification for classification or non-classification
Based on weight of evidence Insulin aspart precusor is not to be classified for reproductive toxicity according to the CLP-criteria.
Additional information
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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