(Z)-hex-3-enyl acetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 30 April 2012 and 11 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-hex-3-enyl acetate

EC Number:

222-960-1

EC Name:

(Z)-hex-3-enyl acetate

Cas Number:

3681-71-8

Molecular formula:

C8H14O2

IUPAC Name:

(Z)-hex-3-enyl acetate

Details on test material:

- Name of test material (as cited in study report): (z)-hex-3-enyl acetate (LEAC)
- Physical state: clear colourless liquid
- Analytical purity: 98.45 %
- Lot/batch No.: 1Z00151
- Expiration date of the lot/batch: 13 June 2015
- Stability under test conditions: room temperature in the dark under nitrogen
- Storage condition of test material:
- Other:

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Leicestershire, UK
- Age at study initiation: 12-20 weeks old
- Weight at study initiation: 2.45 or 2.94 kg
- Housing: the animals were individually housed in suspended cages. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a lvel that might have affected the purpose or integrity of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

Immediately and 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

2

Details on study design:

PROCEDURE
Initially, a single rabbit was treated. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about 1 sec immediately after treatment, to prevent loss of the test item, and then released. Immediately after administration of the test item, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, a second animal was treated.

Any other ocular effects were also noted. Any clinical signs of toxicity, if present, were also recorded. Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.


SCORING SYSTEM: Draize scale (see Appendix 2 attached). If evidence of irreversible ocular damage is noted, the test item will be classified as corrosive to the eye.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: mean score for all animals

Time point:

other: 24, 48, 72 h

Score:

0

Results 2

Irritation parameter:

iris score

Basis:

other: mean score for all animals

Time point:

other: 24, 48, 72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

other: mean score for animal 1

Time point:

other: 24, 48, 72 h

Score:

1

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

other: mean score for animal 2

Time point:

other: 24, 48, 72 h

Score:

0.67

Results 5

Irritation parameter:

chemosis score

Basis:

other: mean score for animal 1

Time point:

other: 24, 48, 72 h

Score:

0.67

Results 6

Irritation parameter:

chemosis score

Basis:

other: mean score for animal 2

Time point:

other: 24, 48, 72 h

Score:

0.33

Irritant / corrosive response data:

No corneal effects were noted during the study.

Iridial inflammation was noted in 1 treated eye 1 h after treatment.

Moderate conjunctival irritation was noted in both treated eyes 1 h after treatment. Moderate conjunctival irritation persisted in 1 treated eye with minimal conjunctival irritation noted in the other treated eye at the 24-Hour observation. Minimal conjunctival irritation was noted in both treated eyes at the 48-Hour observation.

Both treated eyes appeared normal at the 72-Hour observation.

Other effects:

Bodyweight: both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Individual scores and individual total scores for ocular irritation

Rabbit number and sex	71969 Male				71992 Male
	IPR= 2				IPR= 2
Time after treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E= Degree of opacity	0	0	0	0	0	0	0	0
F= Area of cornea involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	1	0	0	0	0	0	0	0
Score (D x 5)	5	0	0	0	0	0	0	0
CONJUNCTIVAE
A= Redness	2	2	1	0	2	1	1	0
B= Chemosis	2	1	1	0	1	1	0	0
C= Discharge	2	1	0	0	1	0	0	0
Score (A + B + C) x 2	12	8	4	0	8	4	2	0
Total score	17	8	4	0	8	4	2	0

 IPR= initial pain reaction

Individual total scores and group mean scores for ocular irritation

Rabbit number and sex	Individual total scores at:
	1 Hour	24 Hours	48 Hours	72 Hours
71969 Male	17	8	4	0
71992 Male	8	4	2	0
Group total	25	12	6	0
Group mean score	12.5	6.0	3.0	0.0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was assessed for acute eye irritation according to OECD guideline 405. The test item is classified as not irritating although it was found to be a mild irritant under the conditions of this study according to a modified Kay and Calandra classification system.