2-(3,3-dimethylcyclohex-1-enyl)-2,5,5-trimethyl-1,3-dioxane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 27 July and 06 August, 2015.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 405 without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 October 2012.

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 2015-04-23&24 / Signed on 2015-10-23

Test material

Test material information

Constituent 1

Reference substance name:

2-(3,3-dimethylcyclohex-1-en-1-yl)-2,5,5-trimethyl-1,3-dioxane

EC Number:

815-500-1

Cas Number:

1853175-99-1

Molecular formula:

C15 H26 O2

IUPAC Name:

2-(3,3-dimethylcyclohex-1-en-1-yl)-2,5,5-trimethyl-1,3-dioxane

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: room temperature, darkness.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: EUROLAP (F-35140 GOSNE)
- Weight at study initiation: no data.
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SAFE - 112), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: from 27 July to 06 August, 2015.

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 females

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:

0.7

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of 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: 7 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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days.

Remarks on result:

probability of weak irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable.

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 2 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:

0.7

Max. score:

4

Reversibility:

fully reversible within: 2 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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to moderate 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 2 and 7, associated with a slight to moderate chemosis noted 1 or 24 hours after the test item instillation and totally reversible between days 2 and 7;
- at the iris level: a congestion, noted 1 hour after the test item instillation in one animal, and totally reversible on day 1.
- at the corneal level: a slight to moderate corneal opacity, noted 24 hours after the test item instillation and totally reversible on day 2.

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
A5235 Female	1 h	0	1	1	1
	24 h	2	0	1	1
	48 h	0	0	1	1
	72 h	0	0	1	1
	Day 7	0	0	0	0
	Total (24, 48 and 72 h)	2	0	3	3
	Mean (24, 48 and 72 h)	0.7	0.0	1	1

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A5266 Female	1 h	0	0	2	1
	24 h	1	0	2	2
	48 h	0	0	0	0
	72 h	0	0	0	0
	Day 7	0	0	0	0
	Total (24, 48 and 72 h)	1	0	2	2
	Mean (24, 48 and 72 h)	0.3	0.0	0.7	0.7

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A5270 Female	1 h	0	0	1	1
	24 h	1	0	1	1
	48 h	0	0	0	0
	72 h	0	0	0	0
	Day 7	0	0	0	0
	Total (24, 48 and 72 h)	1	0	1	1
	Mean (24, 48 and 72 h)	0.3	0	0.3	0.3

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified as irritating to eyes according to the annex I of the Regulation (EC) No. 1272/2008 (CLP) and 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 female 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, 72 h and day 7 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 2 and 7, associated with a slight to moderate chemosis noted 1 or 24 hours after the test item instillation and totally reversible between days 2 and 7. At the iris level, a congestion was noted 1 hour after the test item instillation in one animal, and totally reversible on day 1. A slight to moderate corneal opacity, noted 24 hours after the test item instillation and totally reversible on day 2.

 

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.7, 0.3, 0.3 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 0.7, 0.3 for conjunctivae score and 1.0, 0.7, 0.3 for chemosis score. These effects are reversible between days 2 and 7.

 

Under the test conditions, the test material is not classified as irritating to eyes according to the annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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