2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate; 2,2-bis(acryloyloxymethyl)butyl acrylate; trimethylolpropane triacrylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 July 1996 to 22 July 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD guideline 404 with minor deviations: no certificate of analysis, no data on the purity of the test substance, observation period of 7 days instead of 14 days.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline No. 404 adopted in July 1992

Deviations:

yes

Remarks:

: no certificate of analysis, no data on the purity of the test substance, observation period of reversibility for 7 days instead of 14 days.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

EC Number:

239-701-3

EC Name:

2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

Cas Number:

15625-89-5

Molecular formula:

C15H20O6

IUPAC Name:

2,2-bis(prop-2-enoyloxymethyl)butyl prop-2-enoate

Constituent 2

Reference substance name:

Trimethylolpropane Triacrylate (TMPTA)

IUPAC Name:

Trimethylolpropane Triacrylate (TMPTA)

Details on test material:

- Physical state: clear liquid
- Analytical purity: no data
- Lot/batch No.: #HBE0946
- Expiration date of the lot/batch: no data
- Storage condition of test material: at room temperature and humidity

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Aace animals, Boyertown, PA, USA
- Age at study initiation: about 3 months
- Weight at study initiation: 2.2-2.5 kg
- Housing: individually in wire cages
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321), provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 1996-03-31 to 1996-04-14

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 hours and on day 7 after the removal of the dressing.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25 x 25 mm on the dorso area of the trunk
- Type of wrap if used: 25 mm x 25 mm gauze pad covered with a non-irritating tape. The torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle washing with distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM:

Erythema & Eschar
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
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1.0 mm) 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

ca. 1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

ca. 0.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

Erythema scores ranged from very slight to well defined through 72 hours after patch removal, and from absent to very slight on day 7.
Edema scores ranged from absent to slight through 48 hours after patch removal, and from absent to very slight through day 7.
See details in Table 7.3.1/1

Other effects:

For one animal, 48 hours after the removal of the dressing, diarrhea and wetness of the anogenital area were observed. Seven days after the removal of the dressing all animals presented skin flaking.

Any other information on results incl. tables

Table 7.3.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema and Eschar formation	Edema
	Max. score: 4	Max. score: 4
1h	1/1/2	0/0/2
24 h	1/2/2	0/1/1
48 h	2/2/2	1/1/2
72 h	1/1/2	0/0/1
Average 24h, 48h, 72h	1.3/1.7/2	0.3/0.7/1.3
Reversibility (within 7 days)^a	n.c.^b	n.c.
Average time (unit) for reversion	?	?

aReversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

bFlaking skin

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, SR 351 is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a dermal irritation GLP study performed according to the OECD guideline No. 404 (approved in July 1992), three young adult male White New-Zealand rabbits were dermally exposed to 0.5 mL of test article for 4 hours to 6.25 cm² of clipped skin in semi-occlusive conditions. Animals then were observed for 7 days. Reactions were scored again at 24, 48 and 72 hours and on day 7. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods.

Under the test conditions, there were slightly irritant effects, with mean individual scores within 24, 48 and 72 hrs of 1.3/1.7/2.0 for erythema and 0.3/0.7/1.3 for edema. These effects were not fully reversible within 7 days for one animal only. Considering these scores the test substance is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

Primary Irritation Index is 2.00

The author concludes: The test article is a dermal irritant but not corrosive.