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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May - June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1-dimethylurea
EC Number:
209-957-0
EC Name:
1,1-dimethylurea
Cas Number:
598-94-7
Molecular formula:
C3H8N2O
IUPAC Name:
1,1-dimethylurea
impurity 1
Chemical structure
Reference substance name:
Urea
EC Number:
200-315-5
EC Name:
Urea
Cas Number:
57-13-6
Molecular formula:
CH4N2O
IUPAC Name:
urea
impurity 2
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
dihydrogen oxide
Test material form:
solid: crystalline
Specific details on test material used for the study:
- Analytical purity: at least 98 %
- Impurities (identity and concentrations): max. 2 % Urea, max. 0.2 % Isopropanol, max. 0.5 % diethyleneglycolmonoethylether
- Lot/batch No.: KG 03-13

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany.
- Weight at study initiation: 2.0, 2.0 and 1.7 kg
- Housing: Individual caging in metal wire cages, Ehret GmbH, Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 cm height, with a wooden rest shelf, 15 cm x 59 cm. Exception: rest shelves are withdrawn during the exposure
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitu. Hay-briquettes (supplied by SSNIFF, 59494 Soest, Germany) was offered additionally as a dietry supplement.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 19.5 °C (continuous control and recording)
- Humidity (%): Average of 67.5 % (continuous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Samples with approximately 0.5 g of the test substance (the weighed amount of the individual doses were 500, 498 and 500 mg) were moistened with 1.0 mL deionised water and were placed on cellulose patches.
Duration of treatment / exposure:
The duration of the exposure was 4 hours.
Observation period:
The skins of the animals were examined for local alterations one day before the administration of the test substance (after clipping of the hair) and immediately before the administration. The treated areas and the surrounding untreated skin (control area) of the animals were examined for erythema/eschar and oedema as well as for other local alterations approximately 1, 24, 48 and 72 hours after patch removal.
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: Test sites were median on the dorsal thoracal region

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period the dressings, the taps with the patches and th collars were removed, residual test substance was wiped off with wet Kleenex-tissues, if necessary.

SCORING SYSTEM:
Erythema / Eschar formation:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) or eschar formation (injuries in depth)

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
Eschar
Basis:
animal #1
Remarks:
11
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
Eschar
Basis:
animal #2
Remarks:
12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
Eschar
Basis:
animal #3
Remarks:
13
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
11
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
13
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured. All exposed skin sites were normal at each examination term and 1,1 -Dimethylurea was classified as "non-irritant" to skin.
Executive summary:

Possible irritation or corrosion by the test substance 1,1 -Dimethylurea was investigated by a single application to the intact skin of rabbits. The study was performed in accordance with method B.4 of Directive 92/69/EEC.

0.5 g 1,1 -Dimethylurea, moistened with deionised water, was applied via a patch to a site of 2.5 cm x 2.5 cm of the intact skin of each 3 rabbits and covered by a semi-occlusive dressing. The duration of the exposure was 4 hours.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured. All exposed skin sites were normal at each examination term and 1,1 -Dimethylurea was classified as "non-irritant" to skin.