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EC number: 920-205-7 | CAS number: 1035204-85-3
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 02 to 09 February 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study run to a method comparable with current guidelines and to GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- tert-butyl 2-[(7R,9R)-9-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-6,10-dioxaspiro[4.5]decan-7-yl]acetate
- EC Number:
- 920-205-7
- Cas Number:
- 1035204-85-3
- Molecular formula:
- C42H49FN2O5
- IUPAC Name:
- tert-butyl 2-[(7R,9R)-9-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-6,10-dioxaspiro[4.5]decan-7-yl]acetate
- Details on test material:
- Batch No.: TCA-153-74
Purity: 98%
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 10-20 weeks old
- Weight at study initiation: 2-4 kg
- Housing: Animals were individually housed in labeled cages with perforated floors and shelters.
- Diet (e.g. ad libitum): Pelleted diet for rabbits was approximately 100 grams per day. Hay was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 ℃ (actual range: 21.1-22.7 ℃)
- Humidity (%): 30-70% (actual range: 42-65%)
- Air changes (per hr): Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day
No additional data
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): on average 37.0 mg (range 36.9-37.0 mg) of the test substance (a volume of approximately 0.1 mL)
No additional data - Duration of treatment / exposure:
- 72 h
- Observation period (in vivo):
- 72 h
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 1 week later, after considering the degree of eye irritation observed in the first animal.
Animals were treated by instillation of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after 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.
After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20%.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- other: mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0.3
- Max. score:
- 1
- Reversibility:
- fully reversible within: 48 hours
- Remarks on result:
- other: Redness were observed at 1 hour and 24 hour in all of three animals.
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 1
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: Chemosis were observed at 1 hour in all of three animals.
- Irritant / corrosive response data:
- Irritation
Instillation of approximately 37 mg of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 48 hours.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
Corrosion
There was no evidence of ocular corrosion. - Other effects:
- Coloration/Remnants
No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the eye on day 1.
Toxicity/Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Any other information on results incl. tables
Individual eye irritation scores
Animal |
Time after dosing |
Cornea |
Iris |
Conjunctivae |
||||
Opacity (0-4) |
Area (0-4) |
Fluor area (%)* |
(0-2) |
Redness (0-3) |
Chemosis (0-4) |
Discharge (0-3) |
||
121# |
1 h |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
24 h |
0 |
0 |
0 |
1 |
0 |
0 |
||
48 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
72 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
116 |
1 h |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
24 h |
0 |
0 |
0 |
1 |
0 |
0 |
||
48 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
72 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
128 |
1 h |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
24 h |
0 |
0 |
0 |
1 |
0 |
0 |
||
48 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
72 h |
0 |
0 |
0 |
0 |
0 |
0 |
||
# Sentinel
* Green staining after fluorescein treatment (percentage of total corneal area)
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Treatment with the test substance caused reversible effects on the conjunctivae of three (3/3) rabbits.
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