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

Endpoint summary

Description of key information

Skin irritation:

The substance has been determined as not irritating to the skin using the CLP classification criteria.

Eye irritation:

The substance has been determined as not irritating to the eye using the CLP classification criteia.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 16, 2002 to December 18, 2002

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of signature 18/12/2002

Species:

rabbit

Strain:

other: Japanese white rabbits

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hokusetsu Sangyo Co. (20-4 Beppu 1-chome, Settsu, Osaka 5660046)
-Age at study initiation: 9 to 10 weeks of age
- Weight at study initiation: Their body weights were 2.58 to 2.69kg
- Housing: Rabbits were housed individually in aluminum bracket cages (320W x 550D x 350Hmm)
- Diet (e.g. ad libitum): Animals had free access to standard laboratory chow (RC 4, Oriental
Yeast Co., Ltd.) in feed baskets.
- Water (e.g. ad libitum): Animals had free access to tap water from the automatic water supply system.
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature of 21 to 25°C
- Humidity (%): relative humidity of 43 to 58%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 8 hour light cycle (0900 to 1700 hours).


IN-LIFE DATES: From: Day 0 To: End of study

Type of coverage:

open

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
A dose of 0.5mL ofthe test substance was loaded on the cloth disc (2.5cm in diameter) of adhesive plaster for patch test and applied to the two sites
(abraded skin and intact skin) of each animal by closed patch for 4 hours.

- Concentration (if solution):
The test material was used as supplied.

VEHICLE
No vehicle used

Duration of treatment / exposure:

4 hours

Observation period:

Skin reactions including erythemaleschar formation and
edema formation were examined at 4, 24, 48 and 72 hours after application, and thereafter every other day until the skin irritation disappeared (till 14 days after application).

Number of animals:

Three rabbits were used for the study.

Details on study design:

TEST SITE
- Area of exposure:
The test material was applied to the epidermal surface of four skin discs for a contact period of 4 hours. ( each 2.5cm
in diameter)

- % coverage:
Not recorded

- Type of wrap if used:
None used

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
The test material was removed by washing the skin disc with a jet of warm tap water for approximately 10 seconds until no further test material could be removed.

- Time after start of exposure:
Not recorded.

SCORING SYSTEM:

The evaluation criteria of skin reactions were scored according to the Draize method (please see below)

Evaluation of skin reactions:
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema formation
Noedema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (area raised approximately 1mm) 3
Severe edema (raised more than 1mm and extending beyond area of exposure) 4

The classification system used was the EU classification and labelling guide.

Irritation parameter:

erythema score

Remarks:

M 1

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Remarks:

M 2

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Remarks:

M 3

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Remarks:

M 1

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Remarks:

M 2

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Remarks:

M 3

Basis:

mean

Remarks:

Abraded skin

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 9 days

Results

1) General conditions and body weights

No abnormal findings were observed in general conditions of all three rabbits except the skin reactions during the observation period.

The body weights on 0 (the day of application), 3 (72 hours) and 14 days after application of the test substance are shown in Table 1. The body weights were increased smoothly during the observation period.

2) Skin reactions:

The scores of skin reactions at the applied sites of the test substance in each rabbit during the observation period are shown in the tables below.

VEEA, loaded on the cloth disc of adhesive plaster for patch test, was applied to the intact and abraded skin of three rabbits by closed patch for 4 hours and the primary skin irritation such as erythema and edema was still observed at 72 hours after application. Nothing was loaded on the cloth disc of adhesive plaster as control. Since the skin irritation was still observed at 72 hours after application of the test substance, the observation was continued for 14 days after application (until the skin irritation disappeared).

No abnormal changes in general conditions and body weight gains were found in all three animals through the observation period, By closed patch for 4 hours, the application of VEEA to the intact skin caused very slight erythema and edema in all three animals at 4 hours after application, but these irritant effects disappeared at 24 hours. On the other hand, the application of VEEA to the abraded skin produced slight to moderate erythema and edema in all animals at 4 hours after application, but these irritant effects were reduced with time. These adverse effects disappeared in two animals on 5 days after application and in the remaining one till 14 days. The application of adhesive plaster only as control to the intact skin caused no skin irritation in all three animals. On the other hand, the application of adhesive plaster only to the abraded skin produced very slight erythema in all animals at 4 hours after application. These signs were reduced with time, and disappeared in two animals at 72 hours after application and in the remaining one till 5 days. No edema was observed in all animals through the observation period. The primary irritation index (P.I,I.) was 2,00 for VEEA and 0.39 for adhesive plaster only as control. From these results, according to the criteria of Draize, VEEA was considered to be mildly irritating for rabbit skin under our experimental conditions.

Application site 1 (intact skin): Erythema

Animal No.	Score for Erythema
	4h	24h	48h	72h
M 1	1	0	0	0
M 2	1	0	0	0
M 3	1	0	0	0
Total	3	0	0	0

Application site 1 (intact skin): Edema

 

Animal No.	Score for edema
	4h	24h	48h	72h
M 1	1	0	0	0
M 2	1	0	0	0
M 3	1	0	0	0
Total	3	0	0	0

 

Application site 2 (abraded skin): Erythema

 

Animal No.	Score for Erythema
	4h	24h	48h	72h
M 1	2	1	1	1
M 2	2	1	1	1
M 3	3	2	2	2
Total	7	4	4	4

Animal M1 fully reversible after 5 days.

Animal M2 fully reversible after 5 days.

Animal M3 fully reversible after 14 days.

 

Application site 2 (abraded skin): Edema

 

Animal No.	Score for edema
	4h	24h	48h	72h
M 1	2	1	1	1
M 2	2	1	1	1
M 3	3	2	2	2
Total	7	4	4	4

Animal M1 fully reversible after 5 days.

Animal M2 fully reversible after 5 days.

Animal M3 fully reversible after 9 days.

Application site 3 (adhesive plaster only, intact skin): Erythema

 

Animal No.	Score for Erythema
	4h	24h	48h	72h
M 1	0	0	0	0
M 2	0	0	0	0
M 3	0	0	0	0
Total	0	0	0	0

 

 Application site 3 (adhesive plaster only, intact skin): Edema

 

Animal No.	Score for edema
	4h	24h	48h	72h
M 1	0	0	0	0
M 2	0	0	0	0
M 3	0	0	0	0
Total	0	0	0	0

  

Application site 4 (adhesive plaster only, abraded skin): Erythema

 

Animal No.	Score for Erythema
	4h	24h	48h	72h
M 1	1	1	1	0
M 2	1	1	1	0
M 3	1	1	1	1
Total	3	3	3	1

 

 Application site 4 (ashesive plaster only, abraded skin): Edema

 

Animal No.	Score for edema
	4h	24h	48h	72h
M 1	0	0	0	0
M 2	0	0	0	0
M 3	0	0	0	0
Total	0	0	0	0

Primary skin irritation index (P.I.I.) ofVEEA when applied to the rabbit skin by closed patch for 4 hours

Animal No.	VEEA	Adhesive plaster (control)
M 1	1.67	0.33
M 2	1.67	0.33
M 3	2.67	0.5
Mean	2.00	0.39

Interpretation of results:

GHS criteria not met

Conclusions:

The skin irritation has been determined as not irritating to the skin according to CLP classification criteria.

Executive summary:

Skin Irritation:

VEEA, loaded on the cloth disc of adhesive plaster for patch test, was applied to the intact and abraded skin of three rabbits by closed patch for 4 hours. Nothing was loaded on the cloth disc as control. The application of the test substance to the intact skin caused very slight erythema and edema in all three animals after 4 hours, but these irritant effects disappeared till 24 hours. On the other hand, the application of the test substance to the abraded skin produced slight to moderate erythema and edema in all animals after 4 hours. These adverse effects were reduced with time, but remained still after 72 hours. Therefore, the observation was continued for 14 days (until the skin irritation disappeared). The skin irritation disappeared in two animals on 5 days after application and in the remaining one till 14 days. There were no abnormal findings in general condition and body weight gain in all animals during the observation period. The primary irritation index (P. I.I) was 2.00 for VEEA and 0.39 for control. According to the criteria by Draize, VEEA was evaluated to be mildly irritating for rabbit skin under our experimental conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

VEEA, loaded on the cloth disc of adhesive plaster for patch test, was applied to the intact and abraded skin of three rabbits by closed patch for 4 hours. Nothing was loaded on the cloth disc as control. The application of the test substance to the intact skin caused very slight erythema and edema in all three animals after 4 hours, but these irritant effects disappeared till 24 hours. On the other hand, the application of the test substance to the abraded skin produced slight to moderate erythema and edema in all animals after 4 hours. These adverse effects were reduced with time, but remained still after 72 hours. Therefore, the observation was continued for 14 days (until the skin irritation disappeared). The skin irritation disappeared in two animals on 5 days after application and in the remaining one till 14 days. There were no abnormal findings in general condition and body weight gain in all animals during the observation period. The primary irritation index (P. I.I) was 2.00 for VEEA and 0.39 for control. According to the criteria by Draize, VEEA was evaluated to be mildly irritating for rabbit skin under our experimental conditions.

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.

Justification for classification or non-classification

Skin irritation:

Based on the Draize method the study found the substance to be mildly irritating to rabbit skin.

However, based on the CLP classification criteria the substance does not meet the criteria for classification as a skin irritant (based on results of both intact skin and abraded skin).

Eye irritation:

Based on the CLP classification criteria the substance does not meet the criteria for classification as an eye irritant.