2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 06 February and 05 March 2012.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD Guideline No. 405 without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2010-12-07 / Signed on 2011-03-07.

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol

Cas Number:

1401065-88-0

Molecular formula:

C16 H26 O

IUPAC Name:

2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol

Test material form:

other: See specific details on each Endpoint Study Records

Details on test material:

- Storage condition of test material: Room temperature

Specific details on test material used for the study:

- Physical state: Colourless gel
- Date received: 13 January 2012

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe).
- Weight at study initiation: 2.73 - 3.19 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SDS - C15), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: from 06 February to 05 March 2012

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

- Concentration (if solution): Test item was instilled, as supplied

Duration of treatment / exposure:

No washing was done

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1, 24, 48 and 72 h & Days 7, 14 and 21 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
- 0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
- Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: According to OECD guideline 405

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 2 days.

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 2 days.

Remarks on result:

probability of weak irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days.

Remarks on result:

probability of weak irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to important and totally reversible:
- at the conjunctivae level: a slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 21;
- at the iris level: a congestion, noted 1 or 24 hours after the test item instillation in all animals, and totally reversible between days 2 and 7;
- at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation in all animals and totally reversible between days 3 and 7.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A1789 Male	1 h	0	0	1	1
	24 h	2	1	1	1
	48 h	2	0	1	1
	72 h	2	0	1	1
	Day 7	0	0	1	0
	Day 14	0	0	0	0
	Total (24, 48 and 72 h)	6	1	3	3
	Mean (24, 48 and 72 h)	2	0.3	1	1

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A1820 Male	1 h	0	1	2	2
	24 h	2	1	2	2
	48 h	2	0	1	1
	72 h	0	0	1	1
	Day 7	0	0	1	0
	Day 14	0	0	0	0
	Total (24, 48 and 72 h)	4	1	4	4
	Mean (24, 48 and 72 h)	1.3	0.3	1.3	1.3

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A1821 Male	1 h	0	1	2	2
	24 h	2	0	2	2
	48 h	2	0	1	1
	72 h	2	1	1	1
	Day 7	0	0	0	1
	Day 14	0	0	0	1
	Day 21	0	0	0	0
	Total (24, 48 and 72 h)	6	1	4	4
	Mean (24, 48 and 72 h)	2	0.3	1.3	1.3

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions, test material is classified as irritating to eyes in category 2 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and in category 2A according to the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 3 New Zealand White male rabbits were exposed to 0.1 mL of test item in one eye while the contralateral eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and from 4 to 21 days following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

A slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 21. At the iris level, a congestion was noted 1 or 24 hours after the test item instillation in all animals, and totally reversible between days 2 and 7. A moderate corneal opacity, noted 24 hours after the test item instillation in all animals and totally reversible between days 3 and 7.

 

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 1.3, 2.0 for cornea score; 0.3, 0.3, 0.3 for iris score; 1.0, 1.3, 1.3 for conjunctivae score and 1.0, 1.3, 1.3 for chemosis score. These effects are reversible between days 2 and 21.

 

Under the test conditions, test material is classified as irritating to eyes in category 2 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and in category 2A according to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.