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EC number: 223-773-8 | CAS number: 4066-02-8
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-10-22 - 2015-12-15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well-documented OECD GLP guideline study without deviations on the registered substance itself.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Version / remarks:
- OECD Guideline for Testing of Chemicals 437: Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage (July, 2013).
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Mainzer Straße 80, D65189 Wiesbaden
Test material
- Reference substance name:
- 2,2'-methylenebis[6-cyclohexyl-p-cresol]
- EC Number:
- 223-773-8
- EC Name:
- 2,2'-methylenebis[6-cyclohexyl-p-cresol]
- Cas Number:
- 4066-02-8
- Molecular formula:
- C27H36O2
- IUPAC Name:
- 2-cyclohexyl-6-[(3-cyclohexyl-2-hydroxy-5-methylphenyl)methyl]-4-methylphenol
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Substance type: pure substance
- Storage condition of test material: At room temperature, protected from light
Constituent 1
Test animals / tissue source
- Species:
- other: Freshly isolated bovine cornea (at least 9 month old donor cattle)
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Schlachthof Aschaffenburg, 63739 Aschaffenburg, Germany
- Age at study initiation: at least 9 month
Test system
- Vehicle:
- physiological saline
- Controls:
- yes, concurrent vehicle
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 ml (corresponds to approx. 150 mg)
- Concentration (if solution): 20% suspension
VEHICLE
- Amount(s) applied (volume or weight with unit): 0.75 ml suspension (corresponds to approx. 0.6 ml)
- Concentration (if solution): 0.9% (w/v) NaCl (saline) - Duration of treatment / exposure:
- 240 min
- Observation period (in vivo):
- no post-observation
- Number of animals or in vitro replicates:
- each 3 corneae for test group, positive and negative control
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with saline
- Time after start of exposure: 240 min
SCORING SYSTEM: IVIS = opacity value + (15 x OD490 value), In vitro Irritancy Score (according to OECD 437)
≤ 3 : No Category (according to GHS)
> 3; ≤ 55 : No prediction can be made
> 55 : Serious eye damage according to CLP/EPA/GHS (Cat 1)
TOOL USED TO ASSESS SCORE: opacitometer (OP_KiT opacitometer (Electro Design, 63-Riom, France)) / fluorescein + spectrophotometer (Versamax® Molecular Devices)
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- in vitro irritation score
- Remarks:
- test item
- Run / experiment:
- mean, 240 min
- Value:
- 5.31
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Remarks:
- yes, vehicle
- Positive controls validity:
- valid
- Remarks on result:
- other: test item
- Irritation parameter:
- in vitro irritation score
- Remarks:
- negative control
- Run / experiment:
- mean, 240 min
- Value:
- 1.14
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Remarks:
- negative control, not categorized
- Irritation parameter:
- in vitro irritation score
- Remarks:
- positive control
- Run / experiment:
- mean, 240 min
- Value:
- 127.14
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Remarks:
- positive control, Category 1
In vivo
- Irritant / corrosive response data:
- With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS = 1.14).
The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity of the corneae (mean IVIS = 127.14) corresponding to a classification as serious eye damaging (CLP/EPA/GHS (Cat 1)).
Relative to the negative control, the test item caused a slight increase of the corneal opacity. Permeability did not occur. The calculated mean IVIS was 5.31 (threshold for serious eye damage: IVIS ≥ 55). According to OECD 437 no prediction for the damage hazard of the test item to the eye can be made.
Applicant's summary and conclusion
- Interpretation of results:
- other: not serious eye damaging (CLP/EPA/GHS (Cat 1) but a prediction for the damage hazard cannot be made (GHS)
- Remarks:
- Criteria used for interpretation of results: OECD GHS
- Conclusions:
- Testing was performed via a GLP OECD 437 guideline study on the registered substance itself. The present in vitro method is recommended in a tiered testing approach and the validity criteria are met, making the results sufficiently reliable to assess the corrosivity of 2,2'-Methylen-bis-(4-methyl-6-cyclohexylphenol) to the eye. The present in vitro method allows the identification of corrosive chemical substances and mixtures or of substances which do not require classification.
According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage.
Hence, no conclusion can be drawn whether the substance needs to be classified as eye irritant, for a clear distinction an in vivo study would be required based on the current state of the art.
According to the OECD 437guideline, “Test chemicals inducing serious eye damage are classified as UN GHS Category 1. Chemicals not classified for eye irritation or serious eye damage are defined as those that do not meet the requirements for classification as UN GHS Category 1 or 2 (2A or 2B), i.e. they are referred to as UN GHS No Category“.
Based on the tonnage-driven data requirements under REACH (Annex VIII), the present result “inconclusive” may not serve as a stand-alone result. As, according to the present results, no prediction can be made with regard to the classification of 2,2'-Methylen-bis-(4-methyl-6-cyclohexylphenol), but it is evident that the substance does not need to be classified as UN GHS Category 1, it will be classified in a precautionary approach as UN GHS Category 2, as no additional testing is intended due to animal welfare. - Executive summary:
This in vitro study according to OECD guideline 437 under GLP was performed to assess the corneal damage potential of 2,2'-Methylen-bis-(4-methyl-6-cyclohexylphenol) by means of the BCOP assay using fresh bovine corneae.
After a first opacity measurement of the fresh bovine corneae (t0), the 20% (w/v) suspension in saline (0.9% (w/v) NaCl in deionised water) of the test item, the positive, and the negative controls were applied to corneae fixed in an incubation chamber in horizontal position and incubated for 240 minutes at 32 ± 1 °C. The posterior chamber contained incubation medium. After the incubation phase the test item, the positive, and the negative controls were each rinsed from the corneae and opacity was measured again (t240).
After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 ± 1 °C.
With the negative control (physiological saline) neither an increase of opacity nor permeability of the corneae could be observed.
The positive control (10% (w/v) Benzalkonium chloride in saline) showed distinct opacity of the corneae corresponding to a classification as serious eye damage (CLP/EPA/GHS (Cat 1)).
Relative to the negative control, 2,2'-Methylen-bis-(4-methyl-6-cyclohexylphenol) caused a slight increase of the corneal opacity, permeability effects were not observed compared with the values caused by the negative control. The calculated mean in vitro irritancy score was 5.31. According to OECD 437, the test item is not classified as serious eye damaging (CLP/EPA/GHS (Cat 1) but the test item’s hazard for eye damaging cannot be predicted. So, due to animal welfare, the substance will be classified as UN GHS Category 2.
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