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EC number: 239-784-6 | CAS number: 15687-27-1
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Limited information on analytical methods
Data source
Reference
- Reference Type:
- publication
- Title:
- Metabolic Chiral Inversion of 2-Arylpropionates in Rat H4IIE and Human Hep G2 Hepatoma cells - Relationship to in Vivo Metabolism
- Author:
- Menzel-Soglowek, S.; Geisslinger, G.; Mollenhauer, J.; Brune, K.
- Year:
- 1 992
- Bibliographic source:
- Biochemical Pharmacology, Vol. 43, No 7, pp. 1487-1492
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Human and rat hepatoma cell lines were used to determine capability and suitability for inversion experiments of the test substance, in which the R-form of the test substance was used as model compound. The test substance was exposed in varying conditions to determine any effects on the formation of the S-form of the test substance and on the elimination rate. Additionally, the enantiomer of the test substance was used to determine the elimination rate and the fraction inverted of the enantiomer.
- GLP compliance:
- no
Test material
- Reference substance name:
- Ibuprofen
- EC Number:
- 239-784-6
- EC Name:
- Ibuprofen
- Cas Number:
- 15687-27-1
- Molecular formula:
- C13H18O2
- IUPAC Name:
- 2-(4-isobutylphenyl)propanoic acid
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in publication): R-ibuprofen (model compound, enantiomer of ibuprofen
- Supplier: Pharma Trans Sanaq AG (Basel, Switzerland)
- Purity: >98.5% - Radiolabelling:
- no
Test animals
- Species:
- other: Rat H4IIE and Human Hep G2 Hepatoma cells
- Details on species / strain selection:
- The experiments were performed with existing rat- and human hepatoma cell lines.
Administration / exposure
- Route of administration:
- other: in solution
- Vehicle:
- unchanged (no vehicle)
- Duration and frequency of treatment / exposure:
- - Duration: 5 days
- Frequency: continuously
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15 other: µg/mL
- Remarks:
- Main substance
- Dose / conc.:
- 30 other: µg/mL
- Remarks:
- Main substance
- Dose / conc.:
- 75 other: µg/mL
- Remarks:
- Main substance
- Dose / conc.:
- 150 other: µg/mL
- Remarks:
- Main substance
- Dose / conc.:
- 20 other: µg/mL
- Remarks:
- Enantiomer
- Details on dosing and sampling:
- PASSAGING
- Enantiomer: the period of passaging the cell cultures was 2 days. After, they were incubated with (the enantiomers of) the test substance.
METABOLITE CHARACTERISATION STUDIES
- Time and frequency of sampling: at ± 24, 48, 72, 96 and 120 hours
- Method type for identification: enantionmeres were identified with stereoselective HPLC method using a chiral α1 acid glycoprotein column. Metabolites were quantified by a non-stereoselective HPLC assay. - Statistics:
- - Areas under data points were calculated by the linear trapezoidal rule.
- A regression equation was used to estimate the elimination rate constants of the concentration-time curves.
Results and discussion
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The S-form of the test substance was formed by the H4IIE rat hepatoma cell line. Also hydroxylated and carboxylated forms of the test substance were observed. For additional information, see 'Any other information on results incl. tables'.
Any other information on results incl. tables
- An increase of the R-form of test substance (main substance) caused an almost linear increase (r = 0.95) in the S-form of the test substance. The elimination rate constant of the R-form of test substance was not affected.
- The number of cells and varying glucose concentrations did not influence the S-form concentrations of the test substance, whereas a reduction in serum concentration did increase its concentration. Additionally, the elimination rate constant of the R-enantiomer increased with a decreasing serum concentration.
- In addition to elimination, hydroxylation and carboxylation of the test substance was observed. The concentrations of these metabolites were low however in comparison to formation of the S-form of the test substance.
- Both the human- and rat hepatoma cell line were able to invert the R-form of the test substance.
Table: elimination rates of the R-form/S-form of the test substance after incubation with the enantiomer.
|
Rat H4IIE hepatoma cells |
Human Hep G2 hepatoma cells |
||
Elimination rate (hr-1) |
Fraction inverted |
Elimination rate (hr-1) |
Fraction inverted |
|
R-form test substance |
0.0311 ± 0.0008 |
0.49 |
0.0035 ± 0.0001 |
0.26 |
S-form test substance |
0.0015 ± 0.0001 |
- |
0.0013 ± 0.0001 |
- |
Applicant's summary and conclusion
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.