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EC number: 700-232-9 | CAS number: 68489-09-8
- 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:
- 2011-10-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP guideline study with minor deviations to the OECD 437 (adopted July, 26th 2013) without effects on results: - IVIS cut-off values used for identifying test chemical were different, but no influence to the classification of the test item. - information on corneal diameter and time interval prior to initiating testing with the eyes were missing
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Version / remarks:
- adopted 2009-09-07
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Version / remarks:
- , 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Bovine Corneal Opacity and Permeability (BCOP) Assay, SOP of Microbiological Associates Ltd., UK, Procedure Details, April 1997
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2009-03-30
Test material
- Reference substance name:
- (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(propan-2-yl)cyclohexane-1-carboxamide
- EC Number:
- 700-232-9
- Cas Number:
- 68489-09-8
- Molecular formula:
- C18H27NO2
- IUPAC Name:
- (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(propan-2-yl)cyclohexane-1-carboxamide
- Test material form:
- solid: crystalline
- Details on test material:
- - Physical state: solid, whitish to white crystals
- Storage condition of test material: ambient temperature, dark, dry, in original container
Constituent 1
Test animals / tissue source
- Details on test animals or tissues and environmental conditions:
- Not applicable - Since this is an in vitro study there is no information on test animals.
Test system
- Vehicle:
- other: 0.9% (w/v) NaCl in deionised water
- Controls:
- other: Control (saline) bovine corneae were used.
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration: 10 % (w/v) suspension in vehicle - Duration of treatment / exposure:
- 10 minutes (± 30 seconds)
- Observation period (in vivo):
- not applicable
- Number of animals or in vitro replicates:
- Number of bovine corneae per dose:
Test item: triplicates
Negative control: triplicates
Positive control: triplicates - Details on study design:
- COLLECTION OF BOVINE EYES
- isolated bovine eyes of at least 9 month old donor cattle were collected from the abattoir and were transported in Hank's buffered salt solution (HBSS) supplemented with streptomycin / penicillin at ambient temperature.
PREPARATION OF CORNEAE
- all eyes were carefully examined macroscopically for defects.
- the cornea was carefully removed from the eye.
- each cornea was mounted in a specially designed cornea holder according to the description given in OEDC guideline 437, annex III, that consists of anterior and posterior compartments, which interface with the epithelial and endothelial sides of the cornea, respectively. Both compartments of the holder were filled with complete medium.
- for equilibration, the corneae in the holder were incubated in a vertical position for one hour at 32 ± 1 °C in a water-bath.
- at the end of the incubation period, the basal opacity was determined (t0) of all cornea.
- each corneae with a value of the basal opacity > 7 was discarded.
EXPOSURE OF THE TEST GROUPS TO THE CORNEAE
- the anterior compartment received the test item or negative control or positive control (2-Ethoxyethanol; tested neat) at a volume of 0.75 mL on the surface of the corneae.
- the corneae were incubated in a horizontal position at 32 ± 1 °C in the water-bath.
- the test item, positive control and negative control were tested in triplicate.
- the test item or control items were rinsed off with cMEM (complete medium).
- the corneae were then incubated at 32 ± 1 °C for further two hours in a vertical position, followed by a second opacity reading (t130).
- permeability of the corneae was determined.
PERMEABILITY MEASUREMENT
- after the final opacity measurement, the complete medium was removed from the anterior compartment and replaced by 0.5 % (w/v) fluorescein solution in HBSS.
- corneae were incubated in a horizontal position for 90 minutes in a water-bath at 32 ± 1 °C.
- complete medium from the posterior compartment was removed, well mixed and the optical density at 490 nm was determined with a spectrophotometer.
EVALUATION OF RESULTS
- Opacity: the change of opacity value of each treated cornea or positive and negative control corneae was calculated by subtracting the initial basal opacity from the post treatment opacity reading (t130 – t0), for each individual cornea.
The average change in opacity of the negative control corneae was calculated and this value is subtracted from the change in opacity of each treated cornea or positive control to obtain a corrected opacity.
- Permeability: the corrected OD490 value of each cornea treated with positive control and test item was calculated by subtracting the average negative control cornea value from the original permeability value for each cornea.
IN VITRO IRRITATION SCORE CALCULATION
The following formula was used to determine the in vitro irritation score (IVIS) of the negative control:
In vitro Irritation Score = opacity value + (15 x OD490 value)
The following formula was used to determine the in vitro irritation score of the positive control and the test item:
In vitro Irritation Score = (opacity value – opacity value mean negative control) + (15 x corrected OD490 value)
The mean IVIS value of each treated group was calculated from the individual IVIS values.
CRITERIA FOR DETERMINATION OF A VALID TEST
The test was acceptable if:
- in vitro irritation score of the positive control was ≥ 30
- in vitro irritation score of the negative control was ≤ 3
Results and discussion
In vivo
Results
- Irritation parameter:
- other: in vitro irritancy score
- Basis:
- mean
- Time point:
- other: 10 minutes
- Score:
- 0.55
- Irritant / corrosive response data:
- Relative to the negative control, the test item did not cause any increase of the corneal opacity or permeability.
Any other information on results incl. tables
Table 1: Results after 10 minutes incubation time
Test group |
Opacity value = Difference (t130 – t0) of opacity |
Permeability at 490 nm (OD490) |
In vitro score |
Mean in vitro irritation score |
||
|
|
Mean |
|
Mean |
|
|
Negative control |
-1 |
-0.67 |
0.064 |
0.058 |
-0.04 |
0.21 |
-1 |
0.055 |
-0.18 |
||||
0 |
0.056 |
0.84 |
||||
Positive control |
63.67* |
0.319* |
68.45 |
76.72 |
||
62.67* |
1.071* |
78.73 |
||||
60.67* |
1.489* |
83.00 |
||||
Test item |
0.67* |
-0.003* |
0.62 |
0.55 |
||
-0.33* |
-0.012* |
-0.52 |
||||
1.67* |
-0.008* |
1.54 |
* corrected values
- With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS= 0.21).
- The positive control (2-Ethoxyethanol) showed clear opacity and distinctive permeability of the corneae (mean IVIS =76.72).
Table 2: Historical data
|
Positive control |
Negative control |
Mean in vitro irritation score |
78.94 |
1.09 |
Standard deviation |
22.76 |
0.97 |
Values of 104 studies with liquid test items performed from 2007 until 2011
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Relative to the negative control, the substance did not cause any increase of the corneal opacity or permeability. Thus, the substance is not irritating to the eye (IVIS = 0.55) under the experimental conditions. A substance with an in vitro irritation score ≤ 3 does not require classification for eye irritation and serious eye damage according to OECD 437 (2013). According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not irritating to the eye.
- Executive summary:
The eye irritation potential was examined according to the OECD guideline 437 (2009) . Three fresh bovine corneae were exposed to the substance for 10 minutes, rinsed and incubated for another 120 minutes. Corneal opacity and permeability were measured and the irritancy score was calculated. Relative to the negative control, the substance did not cause any increase of the corneal opacity or permeability. The mean irritance score amounts to 0.55. According to OECD 437 (2013), a substance with an in vitro irritance score ≤ 3 does not require classification for eye irritation and serious eye damage. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not irritating to the eye.
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