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EC number: 404-520-2 | CAS number: 139893-43-9 SIMVASTATIN AMMONIUM SALT
- 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
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Adequacy of study:
- other information
- Objective of study:
- other: Explanatory disposition study of substance in female rabbits
- Qualifier:
- according to guideline
- Guideline:
- other: Internal company method in accordance with company standard operating procedure.
- GLP compliance:
- yes
- Specific details on test material used for the study:
- Composition:
99.2% L-654,969, 0.2% lovastatin ammonium salt, 0.2% triol - Radiolabelling:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- female
- Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Remarks:
- 0.5% aqueous methylcellulose
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- No. of animals per sex per dose / concentration:
- Female: 1 animals at 0 mg/kg
Female: 3 animals at 50 mg/kg - Control animals:
- yes
- Conclusions:
- This study, carried out with the prodrug MK-733, shows rapid conversion to the notified substance. In a multiple dose study in 12 female rabbits, dosed with 50mg/kg/day for 10 days, plasma levels 30 minutes after dosing were 24.6 ug/ml on day 1, 37.2ug/ml on day 5 and 30.2 ug/ml on day 10. Faecal excretion of either the prodrug or the active metabolite was less than 10% of total dose, urinary excretion was not measured.
Reference
Blood and urine samples were taken at intervals for 48 hours after dosing, and analysed for the parent drug and its metabolites by HPLC, and also by enzyme assay of HMG-CoA reductase inhibitory activity.
HPLC results showed maximum plasma levels of the open acid form of MK-733 (the active metabolite- also the notified substance) at 30 minutes after dosing (mean 11.4ug/ml).At 6 hours levels had dropped to 1.1ug/ml and by 24 and 48 hours after dosing were beyond the limits of detection. The 'area under curve (AUC)' O-4 hr was 12850 mg/ml.hr, which is approximately 8 times that found in dogs receiving the same dose (AUC 1673 mg/ml.hr).The active metabolite was not detected in urine during the 48hr period after dosing, indicating extensive metabolism to other products.
Similar studies have been carried out in monkeys, dogs, rats.
Description of key information
This study, carried out with the prodrug MK-733, shows rapid conversion to the notified substance. In a multiple dose study in 12 female rabbits, dosed with 50mg/kg/day for 10 days, plasma levels 30 minutes after dosing were 24.6 ug/ml on day 1, 37.2ug/ml on day 5 and 30.2 ug/ml on day 10. Faecal excretion of either the prodrug or the active metabolite was less than 10% of total dose, urinary excretion was not measured.
Blood and urine samples were taken at intervals for 48 hours after dosing and analysed for the parent drug and its metabolites by HPLC, and also by enzyme assay of HMG-CoA reductase inhibitory activity.
HPLC results showed maximum plasma levels of the open acid form of MK-733 (the active metabolite- also the notified substance) at 30 minutes after dosing (mean 11.4ug/ml).At 6 hours levels had dropped to 1.1ug/ml and by 24 and 48 hours after dosing were beyond the limits of detection. The 'area under curve (AUC)' O-4 hr was 12850 mg/ml.hr, which is approximately 8 times that found in dogs receiving the same dose (AUC 1673 mg/ml.hr).The active metabolite was not detected in urine during the 48hr period after dosing, indicating extensive metabolism to other products.
Similar studies have been carried out in monkeys, dogs, rats.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
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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