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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - 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:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

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

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelman GmbH, 33176 Borchen, Germany
- Age at study initiation: about 8 weeks at the first administration
- Weight at study initiation: 16.9 g - 20.8 g
- Housing: Single caging. Makrolon cages type II, (22 cm x 16.5 cm ground area, 15 cm high)
- Diet (e.g. ad libitum): Altromin maintenance diet for rats and mice, item No. 1324forte, ad libitum
- Water (e.g. ad libitum): Tap water offered in Makrlon-bottles with stainless steel canules, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 21.8 °C (continuous monitoring and recording)
- Humidity (%): Average of 55.7 % (continuous monitoring and recording)
- Photoperiod (hrs dark / hrs light): only artifical light from 6.00 a.m. to 6 p.m.

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
Group A (low dose): 2.5 % solution of 1,1-Dimethylurea in Propyleneglycol.
Group B (mid dose): 5 % solution of 1,1-Dimethylurea in Propyleneglycol.
Group C (high dose): 7.2 % (w/w) solution of 1,1-Dimethylurea in Propyleneglycol.
No. of animals per dose:
five females per group
Details on study design:
see "any other information on material and methods incl. tables"
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
Application of 25 % Hexyl Cinnamic Aldehyde in Acetone:olive oil (4:1, v/v) resulted in an SI (Stimulation Index) of 35.8. This result proves the sensitivity of the strain of animals used and the reliability of the experimental technique.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
1
Test group / Remarks:
negative control
Key result
Parameter:
SI
Value:
2.8
Test group / Remarks:
low dose
Key result
Parameter:
SI
Value:
1.1
Test group / Remarks:
mid dose
Key result
Parameter:
SI
Value:
0.7
Test group / Remarks:
high dose
Parameter:
SI
Value:
35.8
Test group / Remarks:
positive control

Any other information on results incl. tables

Mortality:

All animals survived till the end of the study.

General observations:

One animal of the positive control group had reduced motor activities on Day 2, which is not of relevance for the results. No adverse effects were noted in this animal on the other days and in all other animals throughout the whole study.

Skin reactions:

No local irritations were observed at the application sites of all animals of the test substance groups and both control groups throughout the whole study.

Body mass:

Body masses and body mass gains of all animals were in the range of to be expected from animals of the same strain, sex and age. Body weight loss was noted in 1/5 animals in the negative control group.

Calculation of the stimulation indices (SIs)

The SIs of the substance groups were between 0.7 and 2.8. There was no concentration related response.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Although one SI value is very near the limit of 3, 1,1 -Dimethylurea is regarded as a non sentiser in the LLNA, since the SIs of all examines test substance concentrations were smaller than 3 and no concentration related response was observed.
Executive summary:

A Local Lymph Node Assay was performed according to OECD Guideline 429 to evalute a possible skin sensitising potential of 1,1 -Dimethylurea.

Three test substance concentrations (2.5, 5 and 7.2 % solution of 1,1 -Dimethylurea in 1,2 -Propanediol) were administered to three groups of 5 female CBA/Ca mice. All animals survived till the end of the study. One animal of the positive control group had reduced motor activities on Day 2, which is not of relevance for the results. No adverse effects were noted in this animal on the other days and in all other animals throughout the whole study. No local irritations were observed at the application sited of all animals of all test substance groups and both control groups throughout the whole study. Body masses and body mass gains of all animals were in the range to be expected from animals of the same strain, sex and age.

The SIs of the tested test substance concentrations were 2.8 (low dose), 1.1 (mid dose) and 0.7 (high dose). Although one SI value is very near the limit of 3, 1,1 -Dimethylurea is regarded as a non sentiser in the LLNA, since the SIs of all examines test substance concentrations were smaller than 3 and no concentration related response was observed.