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EC number: 603-303-1 | CAS number: 128819-84-1
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 19 Jul - 01 Sept 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- / No demonstration of technical proficiency
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 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)
- Version / remarks:
- 26 July 2013
- Deviations:
- yes
- Remarks:
- / no demonstration of technical proficiency
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Secrétariat général du GIPC - DGE - SI, Ivry-sur-Seine, France
Test material
- Reference substance name:
- Reaction products of trimethylolpropane triglycidyl ether and acrylic acid
- EC Number:
- 603-303-1
- Cas Number:
- 128819-84-1
- Molecular formula:
- C18 H30 O9, C21 H35 Cl O10, C24 H38 O12 and C27 H43 Cl O13 (mainly)
- IUPAC Name:
- Reaction products of trimethylolpropane triglycidyl ether and acrylic acid
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, protected from light
Handling: under inactinic light
Test animals / tissue source
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: abattoir EVA, Saint-Pierre-sur-Dives, France
- Characteristics of donor animals: maximum 12 month old donor cattle (typically 5 to 8 months)
- Storage, temperature and transport conditions of ocular tissue: The isolated eyes were transported in HBSS (with streptomycin / penicillin) in a cooling box.
- Time interval prior to initiating testing: Test was initiated as soon as possible after delivery of the eyes.
- indication of any existing defects or lesions in ocular tissue samples: no
- Indication of any antibiotics used: streptomycin / penicillin
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): 750 (± 8) µL
- Concentration (if solution): undiluted - Duration of treatment / exposure:
- 10 min ± 30 sec (at 32 ± 1 °C)
- Duration of post- treatment incubation (in vitro):
- 2 h ± 10 min (at 32 ± 1 °C)
- Number of animals or in vitro replicates:
- Number of eyes for the test item/ negative control/ positive control: 3
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS: A careful macroscopic examination was performed on all eyes to detect the presence of any defects (opacity, scratches, pigmentation, etc). Any eyes with defects were discarded. The tissues surrounding the eyeball were carefully pulled away and the cornea, surrounded by approximately 2 to 3 mm of sclera, was dissected out. The isolated corneas were stored in HBSS until all corneas had been prepared.
QUALITY CHECK OF THE ISOLATED CORNEAS: yes, eyes were free of defects
NUMBER OF REPLICATES: 3
NEGATIVE CONTROL USED: yes
POSITIVE CONTROL USED: yes
APPLICATION DOSE AND EXPOSURE TIME: 750 µl test item (100%), 10 min
TREATMENT METHOD: open chamber
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 6. The corneas were rinsed 5 times with pre-warmed cMEM containing phenol red. Then, they were finally rinsed with pre-warmed cMEM without phenol red.
- POST-EXPOSURE INCUBATION: yes, 2 h
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: determined by the amount of light transmission through the cornea via an opacitometer
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of spectrophotometry (OD490).
- Others: After permeability determination, the corneas were removed from the holders and observed for opaque spots, other irregularities and any separation of the epithelium (macroscopic examination).
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA: The decision criteria as indicated in OECD 437 was used.
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- positive control - mean out of all 3 eyes
- Value:
- 20.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- test item - mean out of all 3 eyes
- Value:
- 1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- fluorescein leakage
- Remarks:
- permeability
- Run / experiment:
- positive control - mean out of all 3 eyes
- Value:
- 1.151
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- fluorescein leakage
- Remarks:
- permeability
- Run / experiment:
- test item - mean out of all 3 eyes
- Value:
- 0
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- positive control - mean out of all 3 eyes
- Value:
- 38
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- test item - mean out of all 3 eyes
- Value:
- 1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: Application of the test item did not induce corneal opacity or altered permeability. Based on the estimated scores, an IVIS of 1 was determined. Fluorescein fixation was observed on the corneas treated with the test item. Opacity, fluorescein fixation and thickening of the corneas were observed on those treated with the positive control.
DEMONSTRATION OF TECHNICAL PROFICIENCY: no
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
Acceptance criteria
For the validation of an experiment, the following criteria had to be fulfilled:
- the mean IVIS of the positive control corneas should fall within two standard deviations of the historical mean
- the mean opacity of the negative control corneas should be < 1.8
- the mean OD490 nm of the negative control corneas should be < 0.0269
Any other information on results incl. tables
Table 1: Opacity values
Parameter |
Initial opacity (OPT0) |
Final opacity (OPT2) |
Opacity change (OPT2-OPT0) |
Mean opacity change of NC (after negative correction) |
Corrected opacity change (cOPT) |
Mean opacity value |
Negative control |
0 |
-1 |
-1 |
0 |
- |
- |
0 |
0 |
0 |
||||
0 |
0 |
0 |
||||
Test substance |
-2 |
0 |
2 |
- |
2 |
1.0 |
1 |
1 |
0 |
0 |
|||
1 |
2 |
1 |
1 |
|||
Positive control |
-1 |
21 |
22 |
- |
22 |
20.2 |
0 |
22 |
22 |
22 |
|||
2 |
19 |
17 |
17 |
Table 2: Permeability values (optical density (OD) at 490 nm)
Parameter |
OD490 change |
Mean OD490 change of NC |
Corrected OD490 change |
Mean OD490 value |
Negative control |
0.008 |
0.009 |
- |
- |
0.009 |
||||
0.009 |
||||
Test substance |
0.000 |
- |
0.000 |
0.000 |
0.000 |
0.000 |
|||
0.000 |
0.000 |
|||
Positive control |
1.392 |
- |
1.383 |
1.151 |
1.312 |
1.303 |
|||
0.774 |
0.765 |
Table 3: In-Vitro Irritancy Score (IVIS) values
|
IVIS |
Mean IVIS |
Test substance |
2 |
1 |
0 |
||
1 |
||
Positive control |
43 |
38 |
42 |
||
28 |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
- Conclusions:
- CLP: not classified
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