Reaction mass of 2-(phosphonooxy)ethyl acrylate and bis[2-(acryloyloxy)ethyl] hydrogen phosphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

the in vivo study was already available before it became mandatory to first run in vitro studies for this endpoint

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 16, 2004 to March 26, 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted with read across substance according to OECD Guideline 404, EU Method B.4, US EPA OPPTS 870.2500 and JMAFF Japanese test Guidelines, 2000, in compliance with GLP.

Justification for type of information:

The target substance for which a read across has been proposed is '2-propenoic acid, 2-hydroxyethyl ester, phosphate'. The hypothesis is that ‘2-propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)’ (source substance), on which tests have been conducted, is suitable as read-across for this target substance. See attached document in section 13 for full justification.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)

IUPAC Name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)

Constituent 2

Reference substance name:

1187441-10-6

Cas Number:

1187441-10-6

IUPAC Name:

1187441-10-6

Constituent 3

Reference substance name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

EC Number:

258-053-2

EC Name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

Cas Number:

52628-03-2

IUPAC Name:

2-(methacryloyloxy)ethyl phosphate

Test material form:

other: Liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Kisslegg, Germany
- Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1 kg.
- Identification: Earmark
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per h, a temperature of 21.0±3.0°C (actual range: 17.0 – 24.1°C), a relative humidity of 30-70% (actual range: 33 - 67%) and 12 h artificial fluorescent light and 12 h darkness per day.
- Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approximately 100 g per d. In addition, hay (BMI, Helmond, the Netherlands) was provided at least three times a week.
- Water: ad libitum
- Acclimatisation period: At least 5 d before start of treatment under laboratory conditions.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3 males

Details on study design:

A single rabbit was tested at the initial step. Two other rabbits were treated in a similar manner one week later, after considering the degree of skin irritation observed in the first rabbit.

Approximately 24 h before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm²). Whenever considered necessary the treated skin areas were re-clipped at least 3 h before the observations, to facilitate scoring.

A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities. Each animal was treated by dermal application of 0.5 mL of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

Observations:
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 h and / or 7 d after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Numerical scoring system:
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) *.................................................................. 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema ........................................................................................................ 0
Very slight oedema (barely perceptible) ....................................................... 1
Slight oedema (edges of area well-defined by definite raising) ................ 2
Moderate oedema (raised approximately 1 mm) ......................................... 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: The skin irritation had resolved within 72 h after exposure in two animals and within 7 d after exposure in the remaining animal.

Results 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: The skin irritation had resolved within 72 h after exposure in two animals and within 7 d after exposure in the remaining animal

Irritant / corrosive response data:

Irritation:
Four hours exposure to 0.5 mL of test substance resulted in well-defined erythema and in slight or moderate oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 72 h after exposure in two animals and within 7 d after exposure the remaining animal. Scaliness was noted in one animal at 72 h after exposure.

Corrosion:
There was no evidence of a corrosive effect on the skin.

Colouration / remnants:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Other effects:

Toxicity / mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Mean value irritation scores (24, 48 and 72 h)

 

Animal number	Mean 24 - 72 h
	Erythema	Oedema
1	1.3	0.3
2	1.0	1.0
3	0.7	0.3
Primary irritation index: 1.6

 

Table 2: Mean value irritation scores (24 and 72 h)

 

Animal number	Mean 24 - 72 h
	Erythema	Oedema
1	1.5	0.5
2	1.0	1.0
3	0.5	0.5
Primary irritation index: 1.7

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was considered to be not irritating to the skin.

Executive summary:

A study was conducted to assess the skin irritation potential of the read across substance (2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)) in rabbits according to OECD Guideline 404, EU Method B.4, US EPA 870.2500 and JMAFF Japanese test Guidelines, 2000, in compliance with GLP. A total of 0.5 mL of the test substance was applied onto the clipped skin of three animals for 4 h using a semi-occlusive dressing. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. After exposure for 4 h, the dressing was removed and residues of substance were carefully rinsed off with distilled water. Observations were made 1, 24, 48 and 72 h and / or 7 d after exposure. Exposure to test substance resulted in well-defined erythema and in slight or moderate oedema in the treated skin areas of the three rabbits. The skin irritation had resolved within 72 h after exposure in two animals and within 7 d after exposure in the remaining animal. Scaliness was noted in one animal at 72 h after exposure only. Based on the 24 and 72 h readings, the primary irritation index was calculated to be 1.7. Under the study conditions, the substance was considered to be not irritating to the skin (van Huygevoort AHBM, 2004).