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EC number: 448-050-6 | CAS number: 444065-11-6
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 Aug - 04 Sep 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000, inciuding the most recent partial revisions
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 448-050-6
- EC Name:
- -
- Cas Number:
- 444065-11-6
- Molecular formula:
- C41 H57 N5 O8
- IUPAC Name:
- 2,6-di-tert-butyl-4-methylcyclohexyl 5-{[bis(2-ethoxy-2-oxoethyl)carbamoyl]oxy}-2-(4-tert-butylphenyl)-6-cyano-1H-pyrrolo[1,2-b][1,2,4]triazole-7-carboxylate
- Details on test material:
- - Name of test material (as cited in study report): UC-141
- Physical state: White powder
- Analytical purity: 99.7% (area %), 98.2% (mass %)
- Lot/batch No.: CE-203
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: At room temperature in the dark
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 1686-2017 g
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm)
- Diet: Approximately 100 g/d standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany). In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 18.0-23.2 °C)
- Humidity (%): 30-70 (actual range: 39-79%)
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as the control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit):49.3 mg (range: 48.8 — 49.7 mg), a volume of approximately 0.1 mL - Duration of treatment / exposure:
- Single application without washing
- Observation period (in vivo):
- 72 h
Reading time points: approximately 1, 24, 48 and 72 hours - Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eye remained unwashed
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: Fluorescein. Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of all 3 animals
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of all 3 animals
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- other: mean of 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritant / corrosive response data:
- Remnants of the test substance were observed in the treated eye of 3/3 animals on day 1. lridial irritation grade 1 was observed in 1/3 animals at the 1-hour reading time point, but had cleared completely within 24 hours. 1 hour after instillation, the conjunctival irritation consisted of mild-moderate redness and chemosis in 3/3 rabbits. The severity was reduced in all rabbits within 24 hours, with 1/3 animals free of conjunctivae and 1/3 free of chemosis. All effects were completely reversible within 48 hours for two animals and within 72 hours for the third animal. A slight dulling of the normal lustre of the cornea was noted in 1/3 animals. The corneal injury had resolved within 24 hours.
- Other effects:
- There was no mortality, and no signs of systemic toxicity were observed. The body weight was not affected by the treatment.
Any other information on results incl. tables
Table 1: individual eye irritation scores
Rabbit #
|
Time [h]
|
conjunctivae
|
iris
|
cornea
|
|
conjunctivae
|
iris
|
cornea
|
||
redness |
swelling |
redness |
swelling |
|||||||
1
|
1 |
2 |
2 |
1 |
1 |
|
||||
24 |
1 |
1 |
0 |
0 |
||||||
48 |
1 |
0 |
0 |
0 |
||||||
72 |
0 |
0 |
0 |
0 |
||||||
average |
0.67 |
0.33 |
0.0 |
0.0 |
Time to reversion |
72.0 |
48.0 |
0.0 |
24.0 |
|
2
|
1 |
1 |
2 |
0 |
0 |
|
|
|||
24 |
0 |
1 |
0 |
0 |
||||||
48 |
0 |
0 |
0 |
0 |
||||||
72 |
0 |
0 |
0 |
0 |
||||||
average |
0.0 |
0.33 |
0.0 |
0.0 |
Time to reversion |
24.0 |
48.0 |
0.0 |
0.0 |
|
3
|
1 |
1 |
1 |
0 |
0 |
|
|
|||
24 |
1 |
0 |
0 |
0 |
||||||
48 |
0 |
0 |
0 |
0 |
||||||
72 |
0 |
0 |
0 |
0 |
||||||
average |
0.33 |
0.0 |
0.0 |
0.0 |
Time to reversion |
48.0 |
24.0 |
0.0 |
0.0 |
|
|
Time [h] |
conjunctivae
|
iris |
cornea |
||||||
|
redness |
swelling |
|
|
avg. time to reversion |
48.0 |
40.0 |
0.0 |
8.0 |
|
average score |
1 |
1.33 |
1.67 |
0.00 |
0.33 |
|
||||
24 |
0.67 |
0.67 |
0.00 |
0.00 |
||||||
48 |
0.33 |
0.00 |
0.00 |
0.00 |
||||||
72 |
0.00 |
0.00 |
0.00 |
0.00 |
||||||
24+48+72 |
0.78 |
0.78 |
0.00 |
0.00 |
||||||
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
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