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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.1.2005 - 7.2.2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 2002
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(3S,5S)-5-[(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl]-3-(propan-2-yl)oxolan-2-one
EC Number:
608-748-5
Cas Number:
324763-46-4
Molecular formula:
C25 H39 N3 O5
IUPAC Name:
(3S,5S)-5-[(1S,3S)-1-azido-3-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-4-methylpentyl]-3-(propan-2-yl)oxolan-2-one

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Age at study initiation: at least 8 wks
- Weight at study initiation: 1780 - 2535 g
- Housing: Animals were housed individually in labelled cages with perforated floors.
- Diet: Charles River Breeding and Maintenance Diet for Rabbits, approximately 100 g/d
- Water: tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 21.6
- Humidity (%): 30 - 58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 17.01.2005
To: 07.02.2005

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Not required, the untreated eye of each animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 42.7 - 44.5 mg (average of 43.6 mg; equivalent to a volume of approximately 0.1 mL)
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 d
Reading time points: 1, 24, 48, 72 h and 7 d
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Immediately after the 24 h observation, a solution of 2% fluorescein in water (adjusted to pH 7) was instilled in both eyes of each animal to quantitatively determine corneal epithelial damage.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 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 over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h

Any other information on results incl. tables

Irritation:

Instillation of approximately 44 mg of the test substance (a volume of approximately 0.1 ml) into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 25% of the corneal area) in one animal. The corneal injury had resolved within 72 hours. lridial irritation grade 1 was observed in two animals and had resolved within 24 or 48 hours. The irritation of the conjunctivae consisted of redness (maximum grade 3), chemosis (maximum grade 1) and discharge and had completely resolved within 7 days.

Corrosion:

There was no evidence of ocular corrosion.

Colouration I Remnants

No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the treated eyes of all animals on day 1.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to REGULATION (EC) No 1272/2008 (CLP) the test substance does not require classification for eye irritation.