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EC number: 213-796-1 | CAS number: 1013-75-8
- 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:
- weight of evidence
- Study period:
- November 7, 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Ethyl ethyl(phenyl)carbamate
- EC Number:
- 213-796-1
- EC Name:
- Ethyl ethyl(phenyl)carbamate
- Cas Number:
- 1013-75-8
- Molecular formula:
- C11H15NO2
- IUPAC Name:
- ethyl ethyl(phenyl)carbamate
- Test material form:
- liquid
- Details on test material:
- Colorless
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:room temperature
- Stability under test conditions:yes
Test animals / tissue source
- Species:
- chicken
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source:Slaughterhouse (Etablissement Brun, 33820 Etauliers, France)
- Characteristics of donor animals (e.g. age, sex, weight): 7 weeks old, 1.5-2.5 kg.
Animals were killed for human consumption.
- Storage, temperature and transport conditions of ocular tissue:
Heads have been removed immediately after sedation of the chickens by electric shock, and incision of the neck for bleeding. The heads have been collected on 07 November 2016 at 8:20 am.Because eyes were dissected in the laboratory, the intact heads were transported from the slaughterhouse at ambient temperature in plastic boxes humidified with towels moistened with physiological saline. The eyes were enucleated at Phycher on 07 November 2016 at 9:45 am.
- Time interval prior to initiating testing: November 7,2016 (8:20-9:45)
- indication of any existing defects or lesions in ocular tissue samples: NO
- Indication of any antibiotics used: NO
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 μL of the test item was applied, as supplied. - Duration of treatment / exposure:
- 10 seconds
- Duration of post- treatment incubation (in vitro):
- 240 minutes (± 5 minutes)
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- SELECTION AND PREPARATION OF ISOLATED EYES:
The eyelids were carefully excised, taking care not to damage the cornea. Then, the eye was further dissected from the skull, taking care not to damage the cornea. The eyeball was pulled from the orbit by holding the nictitating membrane firmly with surgical forceps, and the eye muscles were cut with a bent, blunt-tipped scissor. When the eye is removed from the orbit, a visible portion of the optic nerve should be left attached. Once removed from the orbit, the eye was placed on an absorbent pad and the nictitating membrane and other connective tissue were cut away. The enucleated eye was mounted in a stainless steel clamp with the cornea positioned vertically. The clamp was then transferred to a chamber of the superfusion apparatus. The clamps were positioned in the superfusion apparatus such that the entire cornea was supplied with the physiological saline drip (in the range 0.1 to 0.15 mL/min). The chambers of the superfusion apparatus was temperature controlled between 32.3°C and 32.6°C. After being placed in the superfusion apparatus, the eyes were examined with a slit-lamp microscope to ensure that they have not been damaged during the dissection procedure using sodium fluorescein. Corneal thickness was also measured at this time at the corneal apex using the depth measuring device on the slit-lamp microscope.Eyes with; (i), a fluorescein retention score of > 0.5; (ii) corneal opacity > 0.5; or, (iii), any additional signs of damage were replaced. For eyes that are not rejected based on any of these criteria, individual eyes with a corneal thickness deviating more than 10% from the mean value for all eyes are to be rejected.
EQUILIBRATION AND BASELINE RECORDINGS
Once all eyes had been examined and approved the eyes were incubated between 45 and 65 minutes to equilibrate them to the test system prior to dosing. Following the equilibration period, a zero reference measurement was recorded for corneal thickness and opacity to serve as a baseline (i.e., time = 0). The fluorescein score determined at dissection was used as the baseline measurement for that endpoint.
NUMBER OF REPLICATES:3
NEGATIVE CONTROL USED: physiological saline 30 μL (one eye)
SOLVENT CONTROL USED: not applicable
POSITIVE CONTROL USED: 5% Benzalkonium chloride 30 μL (three eyes)
APPLICATION DOSE AND EXPOSURE TIME: The test item was applied for 10 seconds
OBSERVATION PERIOD: Pretreatment and starting at 30, 75, 120, 180, and 240 minutes (± 5 minutes) after the post-treatment rinse.
REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period:20 mL of physiological saline at ambient temperature
- Indicate any deviation from test procedure in the Guideline: No
METHODS FOR MEASURED ENDPOINTS:
- CORNEAL OPACITY: It was calculated by using the area of the cornea that was most densely opacified for scoring. The mean corneal opacity value for all test eyes was calculated for all observation time points. Based on the highest mean score for corneal opacity, as observed at any time
- SWELLING: measured with Haag-Streit BP900 slit-lamp microscope with depth-measuring device no. I and slit-width setting at 9½, equaling 0.095 mm: was determined from corneal thickness measurements made with an optical pachymeter on a slit-lamp microscope. It was expressed as a percentage and was calculated from corneal thickness measurements according to the following formula:
((corneal thickness at time t - corneal thickness at gtime=0 )/ corneal thicnkness at time=0 )*100. The mean percentage of corneal swelling for all test eyes was calculated for all observation time points. Based on the highest mean score for corneal swelling, as observed at any time point, an overall category score was then given for each test item.
- Damage to epithelium based on fluorescein retention: The mean fluorescein retention value for all test eyes was calculated for the 30-minute observation time point only, which was used for the overall category score given for each test or control item.
- Macroscopic morphological damage to the surface: pitting of corneal epithelial cells, loosening of epithelium, rougheningof the corneal surface and sticking of the test item to the cornea. This findings can vary in severity and may occur simultaneously.
SCORING SYSTEM:
- Mean maximum opacity score:
0 - No opacity,
0.5 -Very faint opacity
1- Scattered or diffuse areas; details of the iris clearly visible
2- Easily discernible translucent area; details of the ris are slightly obscured,
3-Severe corneal opacity; no specific details of the iris are visible; size of the pupil is barely discernible
4-Complete corneal opacity; iris invisible
- Mean fluorescein retention score at 30 minutes post-treatment :
0-No fluorescein retention,
0.5-Very minor single cell staining,
1-Single cell staining scattered throughout the treated area of the cornea,
2-Focal or confluent dense single cell staining,
3-Confluent large areas of the cornea retaining fluorescein
DECISION CRITERIA:YES as indicated in the TG was used.
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- MEAN
- Value:
- ca. 0
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class I
- Irritation parameter:
- fluorescein retention score
- Run / experiment:
- MEAN
- Value:
- ca. 1.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class III
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- MEAN
- Value:
- ca. 0
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class I
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: No, no morphological effects were noted, whatever the examination time.
Three separated tests were conducted with this substance (performed on 05 January 2015, 02 March 2015 and 15 Apri l 2015), and all tests lead to the conclusion "No prediction can be made". This result is considered as not critical since all test items that come out "No prediction can be made" would be subsequently tested with other adequately validated in vitro test(s), or as a last option in rabbits, depending on regulatory requirements, using a sequential testing strategy.
DEMONSTRATION OF TECHNICAL PROFICIENCY: YES
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes, 3xI. The negative control is classified as “No Category”.
- Acceptance criteria met for positive control: Yes, 3xIV,The positive control is classified as “Corrosive/Severe Irritant.
In vivo
- Other effects:
- - Lesions and clinical observations: NO
- Ophthalmoscopic findings:NO
- Effects of rinsing or washing: NO
- Other observations: NO
Any other information on results incl. tables
Table No.1: Selected eyes for the performance of the ICE test
Acceptability criteria ensuring eyes quality:
Eyes with (i) a fluorescein retention score > 0.5; (ii) corneal opacity > 0.5; or, (iii) any additional signs
of damage were replaced.
For eyes that were not rejected based on any of these criteria, individual eyes with a corneal thickness
deviating more than 10% from the mean value for all eyes were rejected.
Chamber |
Fluorescein retention |
Corneal opacity |
Morphological effects |
Corneal thickness (e) |
1 |
0.5 |
0 |
N.t.R. |
0.54 |
2 |
0.5 |
0 |
N.t.R. |
0.60 |
3 |
0.5 |
0 |
N.t.R. |
0.56 |
4 |
0.5 |
0 |
N.t.R. |
0.57 |
5 |
0.5 |
0 |
N.t.R. |
0.54 |
6 |
0.5 |
0 |
N.t.R. |
0.57 |
7 |
0.5 |
0 |
N.t.R. |
0.54 |
8 |
0.5 |
0 |
N.t.R. |
0.62 |
9 |
0.5 |
0 |
N.t.R. |
0.60 |
10 |
0.5 |
0 |
N.t.R. |
0.61 |
11 |
0.5 |
0 |
N.t.R. |
0.62 |
12 |
0.5 |
0 |
N.t.R. |
0.60 |
13 |
0.5 |
0 |
N.t.R. |
0.62 |
14 |
0.5 |
0 |
N.t.R. |
0.59 |
15 |
0.5 |
0 |
N.t.R. |
0.60 |
16 |
0.5 |
0 |
N.t.R. |
0.54 |
Mean corneal thickness value = Range of accepted thickness : |
0.58 0.52≤e≤0.64 |
N.t.R.: Nothing to Report
Table No.2: Results for negative control, 30 μL of negative control, 07 November 2016
Endpoint measured |
Eye No. |
0 |
30 |
75 |
120 |
180 |
240 |
Corneal opacity |
16 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
ICE class |
|
|
|
|
I |
|
|
Fluorescein retention |
16 |
0.5 |
0.5 |
- |
- |
- |
- |
ICE class |
|
|
I |
- |
- |
- |
- |
Corneal thickness |
16 |
0.54 |
0.54 |
0.54 |
0.55 |
0.55 |
0.55 |
Corneal swelling (%) |
16 |
- |
0 |
0 |
2 |
2 |
2 |
ICE class |
|
|
|
|
I |
|
|
Combination of the 3 Endpoints |
3 x I |
||||||
CLASSIFICATION |
No Category |
No morphological effects were noted, whatever the examination time.
Table No.3:Results of positive control, 30 μL of positive control, 07 November 2016
Endpoint measured |
Eye No. |
0 |
30 |
75 |
120 |
180 |
240 |
Corneal opacity |
1 2 3 |
0 0 0 |
3 3 3 |
3 3 3 |
3 3 3 |
3 3 3 |
3 3 3 |
Mean |
|
0.0 |
3.0 |
3.0 |
3.0 |
3.0 |
3.0 |
ICE class |
|
|
|
|
IV |
|
|
Fluorescein retention |
1 2 3 |
0.5 0.5 0.5 |
3 3 3 |
- - - |
- - - |
- - - |
- - - |
Mean |
|
0.5 |
3.0 |
- |
- |
- |
- |
ICE class |
|
|
IV |
- |
- |
- |
- |
Corneal thickness |
1 2 3 |
0.54 0.6 0.56 |
0.63 0.78 0.72 |
0.98 0.89 0.72 |
1.06 0.99 0.88 |
1.20 0.99 0.88 |
1.20 0.99 0.90 |
Corneal swelling (%) |
1 2 3 |
- - - |
17 30 29 |
81 48 29 |
96 65 57 |
122 65 57 |
122 65 61 |
Mean |
|
- |
25 |
53 |
73 |
81 |
83 |
ICE class |
|
|
|
|
IV |
|
|
Combination of the 3 Endpoints |
3 x IV |
||||||
CLASSIFICATION |
Category 1 : Corrosive/Severe irritant |
Severe loosening of the corneal epithelium noted from 30 minutes post-dose in eyes No. 1, 2 & 3.
Table No.4:Results of test item, 30 μL of pure test item, 07 November 2016
Endpoint measured |
Eye No. |
0 |
30 |
75 |
120 |
180 |
240 |
Corneal opacity |
10 11 12 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
Mean |
|
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
ICE class |
|
|
|
|
I |
|
|
Fluorescein retention |
10 11 12 |
0.5 0.5 0.5 |
1 2 2 |
- - - |
- - - |
- - - |
- - - |
Mean |
|
0.5 |
1.7 |
- |
- |
- |
- |
ICE class |
|
|
III |
|
|
|
|
Corneal thickness |
10 11 12 |
0.6 0.62 0.60 |
0.61 0.62 0.60 |
0.61 0.62 0.60 |
0.61 0.62 0.60 |
0.61 0.62 0.60 |
0.61 0.62 0.60 |
Corneal swelling (%) |
10 11 12 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
0 0 0 |
Mean |
|
- |
0 |
0 |
0 |
0 |
0 |
ICE class |
|
|
|
|
I |
|
|
Combination of the 3 Endpoints |
1 x III, 2 x I |
||||||
CLASSIFICATION |
No prediction can be made |
No morphological effects were noted, whatever the examination time.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The combination of the three endpoints for the test item was 1 x III, 2 x I, therefore the test item is not predicted as causing serious eye damage or not classified for eye irritation/serious eye damage.
- Executive summary:
In accordance with OECD TG 438 and GLP study, the test item was tested for evaluation the possible ocular corrosive or severe irritating effects. Eyes were collected from the chicken killed for human consumption and transported in plastic boxes humified with towels moistened with physiological saline at ambient temperature in 1 hour 25 minutes to the laboratory at the same day. Thes test item was applied as supplied in amount 30 μL to 3 enucleated chicken eyes during 10 seconds. Then the eyes were rinsed twice with 20 mL of physiological saline at ambient temperature. Three eyes were treated in the same manner with a positive control and one eye with a negative control. Damages by the test item were assessed by determination of corneal swelling, opacity, and fluorescein retention at 30, 75, 120, 180 and 240 minutes post-dose. Then the results of each endpoint were assigned to ICE classes according the OECD guideline 438. Their combination - 1xIII and 2xI leads to the category : no prediction can be made.Therefore, the test item is not predicted as causing serious eye damage (Category 1) or as not classified for eye irritation/serious eye damage (No category) with ICE method.
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