Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in accordance with OPPTS 870.2500 and OECD TG 404

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
yes
Remarks:
The test duration was 24 hours instead of 4 hours
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
version 1998
Deviations:
yes
Remarks:
The test duration was 24 hours instead of 4 hours
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): EXP 3982 N-2-hydroxyethylurea
- Physical state: clear yellow liquid
- Analytical purity: aqueous solution containing 57.58 % hydroxyethyl urea
- Impurities (identity and concentrations): not reported
- Composition: aequeous solution containing 57.58 % hydroxyethyl urea
- Purity test date: not reported
- Lot/batch No.: 84714
- Expiration date of the lot/batch: 15 July 2001
- Storage condition of test material: at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, USA
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 2.4-2.7 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Chow #5322 (Purina Mills) ad libitum
- Water (e.g. ad libitum): municipal tap water treated by reverse osmosis ad libitum
- Acclimation period: acclimated to the laboratory conditions for a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 26-56
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours darkness

Test system

Type of coverage:
occlusive
Preparation of test site:
other: clipped by avoiding abrasion and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of pure substance and of dilution
- Concentration (if solution): 100% and 52% of test substance in aqueous dilution (57.58% and 30% of hydroxyethyl urea)
Duration of treatment / exposure:
24 hours
Observation period:
Up to 10 days after patch removal
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: about 6.4 square centimetres per test site, in total 4 test sites per animal (two tested with undiluted and two with diluted test material)
- % coverage: about 1% of total body surface
- Type of wrap if used: plastic wrap plus additional elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): remaining test material was removed with moistened gauze
- Time after start of exposure: 24 hours

SCORING SYSTEM:
Effects were scored according to Draize JH (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Association of Food and Drug Officials of the United States, 49-51, 1959).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
0.63
Max. score:
8
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Result for the pure test substance on intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
0.5
Max. score:
8
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Result for the dilution on intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
1.13
Max. score:
8
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Test result with pure substance on abraded skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
0.33
Max. score:
8
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Result for the dilution on abraded skin
Other effects:
No other effects related to treatment were noted

Any other information on results incl. tables

Table 1: Individual scoring for 100% test material (containing 57.58% hydroxyethyl urea) tested on intact skin

Animal

Scoring interval after patch removal

 

ERYTHEMA

R4467

0

0

0

0

-

-

R4472

1

1

1

0

-

-

R4471

1

1

1

0

-

-

R4430

1

1

1

0

-

-

R4426

1

1

1

1

0

-

R4461

1

0

0

0

-

-

 

Oedema

R4467

0

0

0

0

-

-

R4472

0

0

0

0

-

-

R4471

1

0

0

0

-

-

R4430

0

0

0

0

-

-

R4426

0

0

0

0

0

-

R4461

0

0

0

0

-

-

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance EXP 3982 N-2-hydroxyethylurea is an aqueous solution containing 57.58% hydroxyethyl urea. The substance is not irritating to the intact rabbit skin when tested as pure substance and does not need to be classified.
Executive summary:

The skin irritation potential of the test substance EXP 3982 N-2-hydroxyethylurea containing 57.58% of the active ingredient hydroxyethyl urea was studied under GLP in accordance with OECD TG 404. Six healthy male rabbits of the New Zealand White strain (11 to 12 weeks old, weighing 2.4 to 2.7 kg) were used in the study. The treatment area was clipped 24 hours prior to the start of the experiment. The pure test substance (57.58% hydroxyethyl urea) and a 52% aqueous solution (30% hydroxyethyl urea) were applied topically on areas of intact and abraded skin under occlusion for a duration of 24 hours, which is longer than the normal exposure duration of 4 hours given in the guideline. Each animal was treated on four sites. The skin surface area treated per site was approximately 6.5 cm2. The patches were removed after 24 hours and remaining test material was wiped off. Scoring of the skin reaction according to Draize (1959) was performed 1, 24, 48 and 72 hours and up to 10 days after removal of the patches. The scores of individual animals for erythema/eschar and oedema were up to 1 at individual ratings 24, 48 and 72 hours after patch removal. All skin reactions were fully reversible within 10 days. The test substance was non-corrosive. No other effects related to treatment were observed. Hydroxyethyl urea is not classified as a skin irritant based on GHS criteria.