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EC number: 276-743-1 | CAS number: 72624-02-3
- 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 vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Peer reviewed literature
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Quinone methode formation from para isomers of methylphenol (cresol), ethylphenol and isopropylphenol: Relationship to toxicity
- Author:
- Thompson DC, Perera K and London R
- Year:
- 1 995
- Bibliographic source:
- Chem. Res. Toxicol. 8: 55-60
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Test compounds (2 mM each) were dissolved in DMSO and added to pre-incubated rat liver slices (30 min at 37°C in 20 mL glass scintillation vials containing 2.5 mL Krebs-Hepes buffer (pH 7.4)) at a volume of 25 µL (1% v/v) and incubated for up to 6 h. Toxicity was measured as loss of intracellular potassium using a flame photometer ( liver slices removed at appropriate time intervals dried, washed and acidified before centrigugation for 10 minutes and dilution with water).
Microsoms for metabolite formation were prepared from similar rat livers to those used from the slice assays. Incubation at 37°C was performed for various time periods and stopped by acidification. Metabolism was analysed using HPLC, MS and Proton NMR. - GLP compliance:
- not specified
Test material
- Reference substance name:
- 4- methylphenol, 4-ethylphenol, 4-isopropylphenol
- IUPAC Name:
- 4- methylphenol, 4-ethylphenol, 4-isopropylphenol
- Details on test material:
- The test substances are structural analogs of the reference substance. Readacross of data is therefore applicable.
Purity: not specified but indicated to be of highest quality available.
[3H] Glutathione: 44 Ci/mmol
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories, Indianapolis, IN, USA
- Weight at study initiation: 200 - 225 g
Administration / exposure
- Route of administration:
- other: rats were not dosed, only liver and liver extracts used
- Vehicle:
- DMSO
- Details on exposure:
- Rat liver slices or rat liver micrsommes incubated with test material for up to 6 hours
- Duration and frequency of treatment / exposure:
- Up to 6 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
rat liver slices: 1% v/v
Microsomes: 1 mM
- No. of animals per sex per dose / concentration:
- Not stated.
- Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- Not applicable
- Details on study design:
- Test compounds (2 mM each) were dissolved in DMSO and added to pre-incubated rat liver slices (30 min at 37°C in 20 mL glass scintillation vials containing 2.5 mL Krebs-Hepes buffer (pH 7.4)) at a volume of 25 µL (1% v/v) and incubated for up to 6 h. Toxicity was measured as loss of intracellular potassium using a flame photometer ( liver slices removed at appropriate time intervals dried, washed and acidified before centrigugation for 10 minutes and dilution with water).
Microsoms for metabolite formation were prepared from similar rat livers to those used from the slice assays. Incubation at 37°C was performed for various time periods and stopped by acidification. Metabolism was analysed using HPLC, MS and Proton NMR. - Details on dosing and sampling:
- No data
- Statistics:
- No data
Results and discussion
- Preliminary studies:
- No data
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- No data
- Details on distribution in tissues:
- No data
- Details on excretion:
- No data
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- A single glutathione conjugate peak detected for each compound. Peaks were not observed in absence of glutathione. The rate of formation of the glutathione peak mirrors the toxicity of the parent material. Splitting of the conjugate peak shows two distinct forms suggesting diastereomeric conjugates. MS confirmed that the conjugates are monoglutathione conjugates where the glutathione is attached to the benzylic carbon. This is consistent with the formation of reactive quinone methide intermediates
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other: possible metabolic pathway in liver identified
Rat liver microsomes initiated the metabolisation of simple alkyl phenols to quinone methides. - Executive summary:
Test Guidance
No Guideline followed
Method and material
Test compounds (2 mM each) were dissolved in DMSO and added to pre-incubated rat liver slices (30 min at 37°C in 20 mL glass scintillation vials containing 2.5 mL Krebs-Hepes buffer (pH 7.4)) at a volume of 25 µL (1% v/v) and incubated for up to 6 h. Toxicity was measured as loss of intracellular potassium using a flame photometer ( liver slices removed at appropriate time intervals dried, washed and acidified before centrigugation for 10 minutes and dilution with water). Microsoms for metabolite formation were prepared from similar rat livers to those used from the slice assays. Incubation at 37°C was performed for various time periods and stopped by acidification. Metabolism was analysed using HPLC, MS and Proton NMR.
Results
A single glutathione conjugate peak was detected for each compound. Peaks were not observed in absence of glutathione. The rate of formation of the glutathione peak mirrors the toxicity of the parent material. Splitting of the conjugate peak shows two distinct forms suggesting diastereomeric conjugates. MS confirmed that the conjugates are monoglutathione conjugates where the glutathione is attached to the benzylic carbon. This is consistent with the formation of reactive quinone methide intermediates
Conclusions
Rat liver microsomes initiated the metabolisation of simple alkyl phenols to quinone methides.
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