Reaction mass of (3R)-3-[(1R)-4-methyl-3-cyclohexen-1-yl]-1-butanol and (3S)-3-[(1R)-4-methyl-3-cyclohexen-1-yl]-1-butanol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3R)-3-[(1R)-4-methylcyclohex-3-en-1-yl]butan-1-ol; (3S)-3-[(1R)-4-methylcyclohex-3-en-1-yl]butan-1-ol

EC Number:

940-702-2

Molecular formula:

C11H20O

IUPAC Name:

(3R)-3-[(1R)-4-methylcyclohex-3-en-1-yl]butan-1-ol; (3S)-3-[(1R)-4-methylcyclohex-3-en-1-yl]butan-1-ol

Test material form:

other: liquid

Details on test material:

- Physical state: liquid
- Storage condition of test material: approximately 4oC in the dark under nitrogen

Test animals / tissue source

Species:

other: bovine

Strain:

not specified

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: negative (0.9% w/v sodium chloride solution) and positive (ethanol) controls were used in this study.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

10 minutes at 32 ± 1ºC

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 10 minutes exposure, test material was removed from the chambers of the BCOP chamber and the epithelium was washed with MEM containing phenol red (Eagle’s Minimum Essential Medium) and thereafter with complete MEM
- Time after start of exposure: 10 minutes

SCORING SYSTEM: The mean opacity and mean permeability values (OD492) were used for each treatment group to calculate an in vitro score:
In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD492 value). A test item that induces an In Vitro Irritancy Score >/=55.1 is defined as an ocular corrosive or severe irritant.

Results and discussion

In vivo

Results

Irritation parameter:

other: In vitro irritancy score

Basis:

mean

Score:

23.5

Reversibility:

not specified

Irritant / corrosive response data:

The corneas treated with the test item were clear post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation.

Any other information on results incl. tables

Table 1. Individual and Mean Corneal Opacity and Permeability Measurements

Treatment	Cornea number	Opacity					Permeability		In vitro irritancy score
		Pre-treatment	Post-treatment	Post-incubation	Post incubation - Pre-treatment	Corrected value	-	Corrected value	-
Negative control	1	1	1	4	3	-	0.032	-	3.4
	2	2	1	5	3	-	0.034	-
	3	3	3	6	3	-	0.017	-
	Mean	-	-	-	3	-	0.028	-
Positive control	1	2	29	27	25	22	0.821	0.793	36.2
	2	1	24	24	23	20	0.966	0.938
	3	1	28	29	28	25	1.07	1.042
	Mean	-	-	-	-	22.3	-	0.925
Test material	1	1	5	14	13	10	0.364	0.336	23.5
	2	1	8	28	27	24	0.841	0.813
	3	2	9	21	19	16	0.247	0.219
	Mean	-	-	-	-	16.7	-	0.456

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test material is not considered to be a severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test.

Executive summary:

The study was performed to assess the eye irritancy potential of the test material in isolated bovine corneas. The study was performed under GLP and followed a method equivalent to OECD guideline 437. The ocular irritancy of the test substance was tested through topical application for 10 ± 1 minutes.

The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (ethanol), was 36.2 and was within the historical positive control data range (22.5 to 60.9). The test substance did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 23.5 after 10 minutes of treatment. Under the conditions of this study the test material is not considered to be a severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test.