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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From March 23, 2009 to October 5, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

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: JMAFF, No 12 Nosan No 8147
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Cas Number:
915972-17-7
Molecular formula:
C33H39NO9
IUPAC Name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Test material form:
solid
Details on test material:
- Analytical purity: >94 %
Specific details on test material used for the study:
Batch no. 080722
Description: Pale yellow green powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Minowa Breeding Center (Nagano, Japan) of Kitayama Labes Co., Ltd.
- Age at study initiation: At least 10 weeks
- Weight at study initiation: 2168 to 2438 g
- Housing: Housed individually in aluminum cages with wire mesh floors.
- Diet: Certified pellet diet LRC4 (Lot No. 081113, Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (07.00 – 19.00 GMT) in each 24-hour period

IN-LIFE DATES: From 07-Apr-2009 to 10-Apr-2009

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g bulk volume


Duration of treatment / exposure:
24 hours
Observation period (in vivo):
maximum up to 28 days
Number of animals or in vitro replicates:
3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The main group’s eyes were not washed.

SCORING SYSTEM: See below

Cornea: degree of opacity (determined according to the most opaque area)
No ulceration or opacity: 0
Scattered or diffused opacity (different from the degree of cloudiness having ordinary luster); the details of the iris are clearly translucent: 1
There are some clear areas left, but nearly all of the iris is obscured: 2
Nacreous areas, no details of iris visible, size of pupil barely discernible: 3
Corneal opacity; iris not discernible through opaque areas: 4

Iris
Normal: 0
Clear and deep rugae, congestion, swelling, moderate hyperemia in the corneal periphery; any of these singly or in combination; the iris still reacts to light (reaction is slow and dull): 1
No reaction to light, haemorrhage, gross destruction (any or all of these): 2

Conjunctiva: Redness (refers to palpebral and bulbar conjunctiva)
Blood vessels normal: 0
Clear hyperemia in some blood vessels: 1
Diffuse crimson; individual blood vessels cannot be readily discerned: 2
Diffuse beefy red: 3

Edema (palpebral conjunctiva and/or nictitating membrane)
No swelling: 0
Greater than normal swelling (including nictitating membranes): 1
Obvious swelling accompanying ectropion of the eyelid: 2
Swelling such that the eyelid is less than half closed: 3
Swelling such that the eyelid is half or more closed: 4

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 adjacent to lids: 2
Discharge with moistening of the lids and hairs, and considerable area around the eye: 3

In addition, other signs of eye irritation except for scoring reaction were recorded.
The typical eye irritation observed in animals was photographed.

TOOL USED TO ASSESS SCORE: Hand-slit lamp and fluorescein staining

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour redness of score 1 was observed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour redness of score 1 was observed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour chemosis of score 1 was observed
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: after 1 hour chemosis of score 1 was observed
Other effects:
No other effects were observed in this study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met