Urea

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

OECD 404

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 May to 7 June 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes

Remarks:

OECD

Test material

Test material information

Constituent 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

Details on test material:

The test substance, urea, was given identification number AD1006 and batch number A71611R, and was described as a white powder. Purity provided by the sponsor was ≥ 99.8% (impurities were listed as Cl ≤0.001%, SO4 ≤0.001%, Cu ≤2 ppm, Pb ≤2 ppm. Fe ≤5 ppm and NH4 ≤0.02%); for the purpose of the study the purity was 100%. The test substance was stored at room temperature in the dark, and was confirmed to be stable under the storage conditions.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were male SPF New Zealand White rabbits, obtained from Charles River Deutschland, Germany. The rabbits were 7-9 weeks old with body weights of 1388 - 1622 g at the start of the study. The rabbits were acclimatised for at least 5 days prior to treatment.The temperature of the animal room was 17.5-22.0°C, and relative humidity was 48-77%. Fluorescent lighting was provided on a 12 hour light/dark cycle, and there were approximately 15 air changes per hour.The rabbits were housed individually in cages with perforated floors (Scanbur, Denmark). Approximately 100 g standard laboratory diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) was provided to each rabbit per day. Pressed hay (BMI, the Netherlands) was provided twice weekly. The rabbits were given free access to tap water.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g test substance was applied, moistened with 0.2 ml water (Milli-U).

Duration of treatment / exposure:

Four hours

Observation period:

72 hours after dressing removal

Number of animals:

3 rabbits

Details on study design:

Initially, a single rabbit was treated with the test substance as follows: approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 cm². If necessary, treated areas were re-clipped at least 3 hours prior to the observations to facilitate scoring. 0.5 g moistened test substance was applied to the skin of one flank, using a 2x3 cm metalline patch (Lohmann GmbH, Germany). The patch was mounted in micropore tape (3M, USA), which was wrapped around the abdomen and secured with Coban elastic bandage (3M, USA). Four hours after the application, the dressing was removed and the skin cleaned of residual test material using water. The above procedure was repeated in the other 2 rabbits 8 days later, after considering the degree of skin irritation observed in the first animal.The rabbits were observed for mortality/vitality twice daily, and for signs of toxicity at least once daily. Body weights were recorded on the day of treatment (prior to application) and at termination.The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores (erythema & eschar formation 0-4, oedema formation 0-4) and a description of all other local effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No skin irritation was caused by 4 hours exposure to the test substance. There was no evidence of a corrosive effect on the skin. The test substance did not stain the treated skin. No symptoms of systemic toxicity were observed, and no mortality was observed. All 3 rabbits gained weight during the observation period.

Other effects:

No other effects reported.

Any other information on results incl. tables

All rabbits were assigned an irritant score of 0 at all time points.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The test substance was found to be non-irritating to the skin of rabbits, and therefore according to Council Directive 67/548/EEC does not require classification or labelling.

Executive summary:

The primary skin irritation potential of urea (AD1006) was assessed in three rabbits. 0.5 g moistened test substance was applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made at 1, 24, 48 and 72 hours after exposure.

No skin irritation was caused by 4 hours exposure to the test substance. There was no evidence of a corrosive effect on the skin. The test substance did not stain the treated skin. No symptoms of systemic toxicity were observed, and no mortality was observed. All 3 rabbits gained weight during the observation period. The test substance was found to be non-irritating to the skin of rabbits, and therefore according to Council Directive 67/548/EEC does not require classification or labelling.