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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin 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 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF in Japan, 12-Nousan-No. 8147, 2-1-4
Version / remarks:
2000
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

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Minowa Breeding Center (Nagano, Japan) of Kitayama Labes Co., Ltd.
- Age at study initiation: 11 weeks
- Weight at study initiation: 2202 to 2494g
- Housing: Housed individually in an aluminum cage with wire-mesh floors (485 mm in width x 570 mm in depth x 360 mm in height). Cages were fixed into a stainless steel rack.
- 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 (0700 – 1900 GMT) in each 24-hour period

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

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g moistened with 0.5 mL de-ionized water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 female animals
Details on study design:
TEST SITE
- Area of exposure: Dorsolateral skin area
- Type of wrap: Cotton lint patches were held in place and wrapped with non-irritating adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing: De-ionized water
- Time after start of exposure: Yes, after the exposure for 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours

SCORING SYSTEM:
All animals were observed daily for signs of ill health or toxicity.

- Method of calculation:
Erythema / Eschar Formation Score
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema: 4

Edema Formation Score
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (raised approximately l mm): 3
Severe edema (raised more than 1 mm and extending beyond area of exposure): 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Other effects:
Not specified

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met