Reaction mass of (3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulen-6-yl rel-acetate and rel-(1aR,4aR,8aR)-2,4a,8,8-tetramethyl-1,1a,4,4a,5,6,7,8-octahydrocyclopropa[d]naphthalene and rel-(3R,3aS,7S,8aS)-3,6,8,8-tetramethyl-2,3,4,7,8,8a-hexahydro-1H-3a,7-methanoazulene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 April 2000 - 17 April 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

In accordance with GLP conditions

Justification for type of information:

This information is used for read across to Cedryl Acetate EOA

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate

EC Number:

201-036-1

EC Name:

[3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate

Cas Number:

77-54-3

Molecular formula:

C17H28O2

IUPAC Name:

(3R,3aS,6R,7R,8aS)-3,6,8,8-tetramethyloctahydro-1H-3a,7-methanoazulen-6-yl acetate

Test animals / tissue source

Species:

rabbit

Strain:

other: Albino Chbb:HM(SPF) - Littlerussian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: BI Pharma KG, 88397 Biberach
- Age at study initiation: no information available
- Weight at study initiation: Body weights were 1.9 - 2.0 kg
- Housing: Individually
- Diet: ad libitum pelleted complete rabbit diet (Altromin 2123)
- Water: free access to domestic water (acidified with hydrochloric acid)
- Acclimation period: no information available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 55+/-15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye served as negative control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

4 (female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
-Washing: No

SCORING SYSTEM: Irritation was assessed in accordance with the scoring system as included in OECD TG 405 (1981).

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 7

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 8

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Results 10

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible

Results 11

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Results 12

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 13

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 14

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 15

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 16

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No or only very mild (at 1 hour after instillation) cornea and iris effects were noted in the study. Redness and chemosis of the conjunctiva was more apparent but disappeared in the first few days. All irritation effects were reversible within the observation period. For animal 3 this was seen after 72 hours, for the other 3 animals this was seen on day 7.

Other effects:

- Lesions and clinical observations: No lesions of the cornea were observed in any of the animals after 7 days.

Any other information on results incl. tables

Individual scores for the treated animals:

	Time after administration
	1 hour				24 hours				48 hours				72 hours
Animal:	1	2	3	4	1	2	3	4	1	2	3	4	1	2	3	4
Cornea score (opacity)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris score	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae score (redness)	2	2	2	3	1	2	2	2	2	2	1	1	1	1	1	0
Chemosis score	2	2	2	3	2	2	1	2	1	1	1	1	0	0	1	0

Applicant's summary and conclusion

Interpretation of results:

other: Not an eye irritant

Remarks:

according to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In this eye irritation study, no effects were observed on the cornea and iris. Some effects were noted on the conjunctiva in the first days. All effects were reversible. Based on the individual mean scores for the four animals at 24, 48 and 72 hours, it was established that none meet the classification criteria as outlined in Annex I of the CLP Regulation (1272/2008/EC). Therefore, the substance is considered not to be an eye irritant.

Executive summary:

Undiluted Cedryl acetate was tested in an eye irritation test in four female rabbits, in accordance with OECD TG 405 (1981) and under GLP conditions. A 21 day observation period was used to score ocular lesions to the cornea, iris and conjunctiva in accordance with the scoring system in the OECD guideline. No effects were observed on the cornea and iris. Some effects were noted on the conjunctiva in the first days. All effects were reversible. Based on the individual mean scores for the four animals at 24, 48 and 72 hours, it was established that none meet the classification criteria as outlined in Annex I of CLP (1272/2008/EC). Therefore, Cedryl acetate is considered not to be an eye irritant.