Dodecahydro-3,8,8,11a-tetramethyl-5H-3,5a-epoxynaphth[2,1-c]oxepin

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 25, 2001 to November 14, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

rel-(3S,5aR,7aR,11aR,11bS)-3,8,8,11a-tetramethyldodecahydro-5H-3,5aepoxynaphtho[2,1-c]oxepine

Molecular formula:

C18H30O2

IUPAC Name:

rel-(3S,5aR,7aR,11aR,11bS)-3,8,8,11a-tetramethyldodecahydro-5H-3,5aepoxynaphtho[2,1-c]oxepine

Constituent 2

Reference substance name:

rel-(3R,5aS,7aR,11aR,11bS)-3,8,8,11a-tetramethyldodecahydro-5H-3,5aepoxynaphtho[2,1-c]oxepine

Cas Number:

220432-47-3

Molecular formula:

C18H30O2

IUPAC Name:

rel-(3R,5aS,7aR,11aR,11bS)-3,8,8,11a-tetramethyldodecahydro-5H-3,5aepoxynaphtho[2,1-c]oxepine

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
Lot No.: 9000412085
Purity: 99.6% (major peak)
Expiry date : 16-JAN-2003

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

New Zealand White Rabbit, SPF

Details on test animals or test system and environmental conditions:

- Test system : New Zealand White
- Source : Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Number of animals per test: 3 (Animals of both sexes were used)
- Age at start of treatment: 14-15 weeks (male) and 15-16 weeks (females)
- Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
- Conditions: Standard Laboratory Conditions Air-conditioned with target ranges for room temperature 17-23 °c, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the light period.
- Accommodation : Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ltd, Fullinsdorf) and haysticks for gnawing.
- Diet : Pelleted standard Kliba 3418 rabbit maintenance diet ad libitum
- Water : Community tap water from Fullinsdorf, ad libitum

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g per animal (no dilution)

Duration of treatment / exposure:

The duration of treatment was 4 hours.

Observation period:

1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item

Number of animals:

3

Details on study design:

Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.5 g of AMBERKETAL was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to approximately 6 cm2 of the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: NA

Results 4

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Results 5

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Results 6

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Irritant / corrosive response data:

Very slight erythema was observed in two animals from 1 to 24 hours after treatment and persisted in one animal up to the 48-hour reading .
Very slight swelling was noted at the test site of one animal at the 1-hour reading. No abnormal findings were observed at the test site of any animal 72 hours after treatment

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

AMBERKETAL does not met the criteria for skin irritation classication according the CLP Regulation (EC) No. 1272/2008. Therefore it can be considered as non irritant to skin.

Executive summary:

The primary skin irritation potential of AMBERKETAL was investigated by topical semi­ occlusive application of 0.5 g to 6 cm2 intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 0.33, 0.67 and 0.00, respectively and the mean oedema score was 0.00 for all three animals.

The application of AMBERKETAL resulted in mild, early-onset and transient signs of irritation, such as very slight erythema and very slight swelling. These findings were reversible and were no longer evident at the 72-hour reading, the end of the observation period for all animals. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

AMBERKETAL does not met the criteria for skin irritation classication according the CLP Regulation (EC) No. 1272/2008. Therefore it can be considered as non irritant to skin.