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EC number: 244-435-6 | CAS number: 21544-03-6
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1977
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: The procedure used was the test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not applicable
- GLP compliance:
- no
Test material
- Reference substance name:
- Bis(2,3-epoxypropyl) cyclohex-4-ene-1,2-dicarboxylate
- EC Number:
- 244-435-6
- EC Name:
- Bis(2,3-epoxypropyl) cyclohex-4-ene-1,2-dicarboxylate
- Cas Number:
- 21544-03-6
- Molecular formula:
- C14H18O6
- IUPAC Name:
- 1,2-bis[(oxiran-2-yl)methyl] cyclohex-4-ene-1,2-dicarboxylate
- Test material form:
- liquid
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or tissues and environmental conditions:
- The test was performed on 3 male and 3 female rabbits of the Himalayan breed weighing 1.5 to 2 kg. The animals were housed individually in metal cages, were kept at a constant room temperature of 22 + 1° C, at a relative humidity of 55 + 5 % and on a 10 hour light cycle day.
The animals had ad libitum access to Standard rabbit food - NAFAG, Gossau SG - and water. Prior to treatment they were adapted to our laboratories for a minimum of 4 days. Only rabbits with normal ophthalmip findings were used for these tests.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- 0.1 mL was inserted into the conjunctival sac of the left eye.
- Duration of treatment / exposure:
- One single application
- Observation period (in vivo):
- 7 days
- Duration of post- treatment incubation (in vitro):
- Not applicable
- Number of animals or in vitro replicates:
- 6 rabbits
- Details on study design:
- The test material in an amount of 0.1 ml was inserted into the conjunctival sac of the left eye of the 6 rabbits and the lids were gently closed for one second.
The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of lukewarm water. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit as outlined in table 1.
The primary eye irritation index represents the sum of the mean values for cornea, iris and conjunctivae. This procedure was carried out separately for unrinsed and rinsed eyes respectively.
SCORING SYSTEM: Table 1
Score for eye irritation i n rabbits (Table 1)
CORNEA:
A) Opacity and degree of density (most dense area scored)
- No opacity: 0
- Scattered or diffuse area, details of iris clearly visible: 1
- Easily discernible translucent areas, details of iris slightly obscured: 2
- Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
- Opaque, iris invisible: 4
B) Area of cornea involved
- One quarter (or less) but not zero: 1
- Greater than one quarter, but less than half: 2
- Greater than half, but less than three quarters: 3
- Greater than three quarters, up to whole area: 4
A x B x 5 Maximum possible score = 80
IRIS;
A) Values
- Normal: 0
- Folds above normal, congestion, swelling, circumcornea injection (any or all of. these or combination of any thereof) iris still reacting to light (sluggish reaction is positive: 1
- No reaction to light, hemorrhage, gross destruction (any or all of these): 2
A x 5 Maximum possible score = 10
CONJUNCTIVAE;
A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- Vessels normal: 0
- Vessels definitely injected above normal: 1
- More diffuse, deeper crimson red, individual vessels not easily discernible: 2
- Diffuse beefy red: 3
B) Chemosis
- No swelling: 0
- Any swelling above normal (includes nictitating membrane): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half closed: 3
- Swelling with lids about half closed to completely closed: 4
C) Discharge
- No discharge: 0
- Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
- Discharge with moistening of the lids and hairs just adj acent to lids: 2
- Discharge with moistening of the lids and hairs, and cohsiderable area around the eye: 3
(A + B + C) x 2 Maximum possible score = 20
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Remarks:
- eyes not rinsed after treatment.
- Basis:
- mean
- Remarks:
- Rabbit 1, 2 and 3
- Time point:
- other: 1-7 days
- Score:
- 15.7
- Max. score:
- 80
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Remarks:
- Eyes rinsed 30 sec. after treatment
- Basis:
- mean
- Remarks:
- Rabbit 4, 5 and 6
- Time point:
- other: 1-7 days
- Score:
- 2.7
- Max. score:
- 80
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- iris score
- Remarks:
- eyes not rinsed after treatment
- Basis:
- mean
- Remarks:
- Rabbit 1, 2 and 3
- Time point:
- other: 1-7 days
- Score:
- 0
- Max. score:
- 10
- Irritation parameter:
- iris score
- Remarks:
- Eyes rinsed 30 sec. after treatment.
- Basis:
- mean
- Remarks:
- Rabbit 4,5 and 6
- Time point:
- other: 1- 7 days
- Score:
- 0
- Max. score:
- 10
- Irritation parameter:
- conjunctivae score
- Remarks:
- Eyes not rinsed after treatment
- Basis:
- mean
- Remarks:
- Rabbit 1, 2 and 3
- Time point:
- other: 1-7 days
- Score:
- 9.5
- Max. score:
- 20
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Remarks:
- Eyes rinsed 30 sec. after treatment
- Basis:
- mean
- Remarks:
- Rabbit 4, 5 and 6
- Time point:
- other: 1-7 days
- Score:
- 1.7
- Max. score:
- 20
- Reversibility:
- fully reversible within: 2 days
- Irritant / corrosive response data:
- In the present experiment the iritaion index was established as 9.2 for cornea, 0 for Iris and 5.6 for the conjunctivae in not rinsed eyes after treatment.
Rinsing the eyes following instillation was of very good effect.
R=6 (R: 4.1-10) very good effect
Effect of rinsing:
R = unrinsed eyes / rinsed eyes = 8.4 / 1.4 = 6
Unrinsed eyes: (15.7 + 0 + 9.5) / 3 = 8.4
Rinsed eyes: (2.7 + 0 + 1.7) / 3 = 1.4
Any other information on results incl. tables
Eye irritation in individual rabbits with eyes not rinsed after treatment.
| Rabbit 1 (male) | Rabbit 2 (male) | Rabbit 3 (male) | |||||||
| Days after Application | Cornea | Iris | Conjunctivae | Cornea | Iris | Conjuctivae | Cornea | Iris | Conjunctivae |
| 1 | 20 | 0 | 12 | 20 | 0 | 12 | 10 | 0 | 8 |
| 2 | 20 | 0 | 14 | 20 | 0 | 12 | 10 | 0 | 6 |
| 3 | 20 | 0 | 14 | 20 | 0 | 12 | 10 | 0 | 6 |
| 4 | 20 | 0 | 12 | 20 | 0 | 10 | 10 | 0 | 6 |
| 7 | 20 | 0 | 10 | 10 | 0 | 8 | 5 | 0 | 0 |
- Cornea: 15.7
- Iris: 0
- Conjunctivae: 9.5
| Rabbit 4 (female) | Rabbit 5 (female) | Rabbit 6 (female) | |||||||
| Days after Application | Cornea | Iris | Conjunctivae | Cornea | Iris | Conjuctivae | Cornea | Iris | Conjunctivae |
| 1 | 5 | 0 | 8 | 5 | 0 | 6 | 5 | 0 | 6 |
| 2 | 5 | 0 | 0 | 5 | 0 | 0 | 5 | 0 | 6 |
| 3 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 |
| 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
- Cornea: 2.7
- Iris: 0
- Conjunctivae: 1.7
Applicant's summary and conclusion
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- Under the conditions of this experiment the test material was found to be classified as Category 2A (irrittaing to eyes) based on GHS criteria.
Rinsing the eyes following instillation was of very good effect. - Executive summary:
The test was performed to assess the irritation potential of the test item on in vivo rabbit eyes.
The test was done on 3 male and 3 female rabbits of the Himalayan breed.
The test material in an amount of 0.1 ML was inserted into the conjunctival sac of the left eye of the 6 rabbits and the lids were gently closed for one second.
The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatemnt the treated eyes was flushed with 10 mL of lukewarm water.
In the present experiment the iritaion index was established as 9.2 for cornea, 0 for Iris and 5.6 for the conjunctivae in not rinsed eyes after treatment.
Rinsing the eyes following instillation was of very good effect.
R=6 (R: 4.1-10) very good effect
Effect of rinsing:
R = unrinsed eyes / rinsed eyes = 8.4 / 1.4 = 6
Under the conditions of this experiment the test material was found to be classified as Category 2A (irrittating to eyes) based on GHS criteria.
Rinsing the eyes following instillation was of very good effect.
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