2-Propenoic acid, 1,1'-[7,13-dimethyl-10-(3-methyl-11-oxo-2,4,7,10-tetraoxatridec-12-en-1-yl)-10-[[2-[(9-oxo-9H-thioxanthen-2-yl)oxy]acetyl]amino]-3,6,8,12,14,17-hexaoxanonadecane-1,19-diyl] ester

Skin irritation / corrosion

Administrative data

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

86273-46-3

Cas Number:

86273-46-3

IUPAC Name:

86273-46-3

Constituent 2

Reference substance name:

-

EC Number:

451-690-9

EC Name:

-

Constituent 3

Reference substance name:

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

IUPAC Name:

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

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

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

M 1

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: max score seen after 4 hours

Results 2

Irritation parameter:

erythema score

Remarks:

M 2

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: max score seen after 4 hours

Results 3

Irritation parameter:

erythema score

Remarks:

M 3

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: max score seen after 4 hours

Results 4

Irritation parameter:

edema score

Remarks:

M 1

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks:

24 hours

Remarks on result:

other: max score seen after 4 hours

Results 5

Irritation parameter:

edema score

Remarks:

M 2

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: max score seen after 4 hours

Results 6

Irritation parameter:

edema score

Remarks:

M 3

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: max score seen after 4 hours

Any other information on results incl. tables

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 and photos at the applied sites of the test substance in each rabbit during the observation period are shown in Tables 2 to 5 and Photos 1 to 4, respectively. (1) The application site No. 1: VEEA (intact skin) (Table 2, Photo 1)

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: 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: 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: 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

 

Application site 2: 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

 

Application site 3: 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: 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: 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: 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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The skin irritation has been determined as not irritating to the skin based on the OECD 404 study.

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.