2-Propenoic acid, 2-[2-(ethenyloxy)ethoxy]ethyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 19th September 2003 and 30th October 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: November 2002 Date of signature: March 2003

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-690-9

EC Name:

-

Cas Number:

86273-46-3

Molecular formula:

C9H14O4

IUPAC Name:

2-[2-(ethenyloxy)ethoxy]ethyl prop-2-enoate

Constituent 2

Reference substance name:

2-(2-Vinyloxyethoxy) ethyl acrylate

IUPAC Name:

2-(2-Vinyloxyethoxy) ethyl acrylate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-(2'-vinyloxyethoxyl)ethyl acrylate and VEEA
- Substance type: Liquid
- Physical state: Transparent liquid
- Analytical purity: 99%
- Lot/batch No.: FX02T15
- Storage condition of test material: Store in a dark, cool place.
other: Wear suitable protective clothing,

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Charlaronne, France
Harlan UK Limited, Bicester, Oxon, UK

- Age at study initiation:
11 weeks male
12 - 13 weeks females

- Weight at study initiation:
2259g to 2292g

- Housing:
The animals were individually housed in stainless steel cages.

- Diet (e.g. ad libitum):
ad libitum - pelleted standard Provimi Kliba 3418 rabbit maintenance diet.

- Water (e.g. ad libitum):
ad libitum, community tap water.

- Acclimation period:
Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS

- Temperature (°C):
17 to 23°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
10 - 15 changes per hour

- Photoperiod (hrs dark / hrs light):
Twelve hours continuous light followed by twelve hours darkness

IN-LIFE DATES:
From: day 1 To:day 3

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as a reference control.

Amount / concentration applied:

TEST MATERIAL

- Amount(s) applied (volume or weight with unit):
A volume of 0.1 ml of the test material was placed into the conjunctival sac of the left eye, formed by gently pulling the lower lid away from the eyeball.

- Concentration (if solution):
Undiluted and used as supplied

VEHICLE

- Amount(s) applied (volume or weight with unit):
Not applicable

- Concentration (if solution):
Not applicable

- Lot/batch no. (if required):
Not applicable

- Purity:
Not reported
EXAMPLE

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

Approximately 1, 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 1 and 24-hour examinations, the test was completed using the two remaining animals.

Details on study design:

REMOVAL OF TEST SUBSTANCE

- Washing (if done):
Not applicable

- Time after start of exposure:
Not applicable


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment, according to the numerical evaluation given in attachment 1. The classification system used in this study was the EU classification and labelling guide.

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of a Varta Cliptrix diagnostic-lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

Male 76

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect observed

Results 2

Irritation parameter:

cornea opacity score

Remarks:

Female 77

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 3

Irritation parameter:

cornea opacity score

Remarks:

Female 78

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 4

Irritation parameter:

iris score

Remarks:

Female 78

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Results 5

Irritation parameter:

iris score

Remarks:

Female 77

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Results 6

Irritation parameter:

iris score

Remarks:

Male 76

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Male 76

Basis:

mean

Remarks:

redness

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Female 77

Basis:

mean

Remarks:

redness

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

conjunctivae score

Remarks:

Female 78

Basis:

mean

Remarks:

redness

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Remarks:

Male 76

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks:

24 hours

Results 11

Irritation parameter:

chemosis score

Remarks:

Female 77

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 12

Irritation parameter:

chemosis score

Remarks:

Female 78

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Ocular Reactions
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (attached background material)
No corneal effects were noted during the study.
Iridial inflammation was not noted during the study.
Moderate conjunctival irritation was noted in all treated eyes at one, 24 and 48 hours after treatment with minimal conjunctival irritation noted at the 72 hour observation mark in 2 out of the 3 animals.

Other effects:

Body weight
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Irritation:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis od the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0 for all 3 animals. The individual mean scores for the conjunctivae were 1.33, t 72 hours treatment.

Slight to moderate occular discharge was observed in all animals at the 1 -hour reading.

No abnormal findings were observed in the treated eye of any animals 7 days after treatment, the end of the observation period for all animals.

Coloration:

No staining of the treated eyes produced by the test item was observed

Corrosion:

No corrosion of the cornea was observed at any of the reading times.

Body weights:

The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification (Commission Directive 2001/59/EC of August 06, 2001), 2-(2'Vinyloxy ethoxy) ethyl acrylate is considered to be "not irritating" to the rabbit eye.

Executive summary:

Eye irritation:

The Primary eye irritation potential of 2 -(2'-Vinyloxy ethosy) ethyl acrylate was investigated according to OECD guideline test no. 405. The test item was applied by instillation of 0.1mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation.

The mean score was calculated across 3 scoring items (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjuctivae, separately. The individual mean scores for corneal opacity and iris were 0 for all three animals. The individual mean scores for the conjuctivae were 1.33, 1.33 and 1.00 for reddening and 0, 0 and 0.33 for chemosis respectively.

The instillation of 2 -(2'-Vinyloxyethoxy) ethyl acrylate into the eye resulted in mild, early onset and transient occular changes, such as reddening of the conjuctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no other clinical signs of test item related effects were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), 2 -(2'-Vinyloxy ethoxy) ethyl acrylate is considered to be "not irritating" to the rabbit eye.