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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16-0CT-2001 to 05-DEC-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:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

New Zealand White Rabbit, SPF

Details on test animals or tissues and environmental conditions:

- Source: Elevage Scientifique des Dombes, F-01400 Chatmon sur Chalaronne / France
- Number of animals per test : 3 (Animals of both sexes were used)
- Age at start of treatment: 10-11 weeks (male) and 12-13 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 ACC. 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 Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water : Community tap water from Fullinsdorf, ad libitum

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g (per animal) undiluted

Duration of treatment / exposure:

instillatoin

Observation period (in vivo):

approximately 1, 24, 48 and 72 hours after application

Number of animals or in vitro replicates:

3

Details on study design:

The eyes of the animals were examined one day prior to test item administration.
Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, AMBERKETAL was placed in the conjunctiva! sac of the left eye of each animal 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 test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 25, 26 and 27

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: NA

Results 2

Irritation parameter:

iris score

Basis:

animal: 25, 26 and 27

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: NA

Results 3

Irritation parameter:

chemosis score

Basis:

animal: 25, 26 and 27

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: NA

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: 25, 26 and 27

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: NA

Irritant / corrosive response data:

No abnormal findings were observed in the cornea or iris of any animal during the observation period.
Moderate reddening of the conjunctivae and slight swelling was observed in all animals 1 hour after treatment.
A slight to moderate watery discharge was evident in all animals at the 1-hour reading
Moderate reddening of the sclera was present in all animals 1 hour after treatment and slight reddening persisted in one animal up to the 24-hour reading.
With the exception of the scleral reddening in one animal, the test item did not elicit any reactions in the treated eye of any animal at the 24-, 48- or 72-hour readings (all scores 0).

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 is considered to be "not irritating" to the rabbit eye,it does not met the criteria for skin irritation classication according the CLP Regulation (EC) No. 1272/2008.

Executive summary:

The primary eye irritation potential of AMBERKETAL was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

With the exception of the scleral reddening in one animal, the test item did not elicit any reactions in the treated eye of any animal at the 24-, 48- or 72-hour readings (all scores 0). The eye reactions (mean values from 24 to 72 hours) were therefore of grade 0.00 corneal opacity, grade 0.00irislesions, grade 0.00 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae.

The instillation of the test item into the eye resulted in mild, early onset and transient ocular changes, such as watery discharge, swelling and reddening of the conjunctivae and sclera of the animals. These effects were reversible and were no longer evident at the 48-hour reading. No abnormal findings were observed in the cornea or iris of any animal durin.9 the observation period. No staining of the treated eyes by the test item was observed. No corrosion was observed at any of the measuring intervals.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

AMBERKETAL is considered to be "not irritating" to the rabbit eye,it does not met the criteria for skin irritation classication according the CLP Regulation (EC) No. 1272/2008.