Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no skin sensitisation studies available for methylurea. Therefore, a weight of evidence approach using two independent QSAR systems and a reliable animal study with the structural analogon N,N'-Dimethylurea (CAS 96-31-1) was used to assess the skin sensitizing potential of methylurea.

 

The skin sensitizing potential of the N,N'-Dimethylurea was assessed using the non-radioactive variant of the Murine Local Lymph Node Assay in a GLP conform study according to OECD guideline 429 (BASF 2006). Groups of 6 female CBA/Ca mice were treated each with 10%, 30% and 70% w/w preparations of the test substance in 1% aqueous Pluronic® or with the vehicle alone. Each test animal was applied with 2 x 12.5 µl per ear of the respective test-substance preparation to the dorsum of both ears for three consecutive days. The control group was treated with 2 x 12.5 µl per ear of the vehicle alone. The total volume of 25 µl per ear and application was split into two portions in order to prevent run off of the test-substance preparations due to high volume. The second daily application was performed immediately after the first daily application was finished in all animals of the study collective. Three days after the last application the mice were sacrificed and the auricular lymph nodes were removed. Lymph node response was evaluated by measuring the cellular content (indicator of cell proliferation) and weight of each animals' pooled lymph nodes. Moreover, a defined area with a diameter of 0.8 cm was punched out of the apical part of each ear and for each animal the weight of the pooled punches was determined in order to obtain an indication of possible skin irritation. No signs of systemic toxicity were noticed. The test substance did not induce a statistically significant or biologically relevant response of the auricular lymph nodes when applied as 10%, 30% or 70% preparations in 1% aqueous Pluronic®. The statistically significant increase in ear weight at the concentration of 70% demonstrates the achievement of a skin irritation effect concentration. Thus, it is concluded that N,N'-Dimethylurea, a structural analogon of methylurea, does not have a skin sensitizing effect in the Murine Local Lymph Node Assay under the test conditions chosen.

Using the OECD Toolbox (version 3.3.0.152; database version: 3.8.3/3.1.2) the skin sensitization potential of methylurea was predicted from category members using read-across based on 5 values from 5 nearest neighbours compared by prediction descriptors. The category members are single chemicals selected based on the profile of the target chemical while only chemicals having experimental data are listed in the category: 2-imidazolidinone (CAS 120-93-4), N,N'-Dimethylurea (CAS 96-31-1), 6-methyl-2-oxoperhydropyrimidin-4-ylurea1 (CAS 129-42-6) and 1,3-dimethyl-2-imidazolidinone (CAS 80-73-9). Methylurea was predicted not to be a skin sensitizer.

Methylurea was also predicted to be a non-sensitizer using OASIS TIMES (version 2.27.16.8). The TIMES-SS model aims to encode structure toxicity and structure metabolism relationships through a number of transformations simulating skin metabolism and interaction of the generated reactive metabolites with skin proteins. The skin metabolism simulator mimics metabolism using 2D structural information. The autoxidation (abiotic oxidation) of chemicals is also accounted for. Neither the parent compound methylurea nor its simulated metabolites for skin metabolism and autoxidation were predicted to be skin sensitizers.

In conclusion, methylurea is not considered to be a skin sensitizer according to the results of a Murine Local Lymph Node Assay with the structural analogon N,N'-Dimethylurea as well as the results of two independent QSAR predictions accounting for methylurea and its metabolites (OASIS TIMES) and data from animal tests for five category members (OECD Toolbox).


Migrated from Short description of key information:
QSAR OECD Toolbox (BASF 2015): not sensitizing
QSAR OASIS TIMES (BASF 2015): not sensitizing
LLNA (test substance: N,N-Dimethylurea; BASF 2006): not sensitizing

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

On the basis of the available data, the classification of methylurea for skin sensitization is not warranted according to directive 67/548/EEC and regulation (EC) No. 1272/2008.

Due to missing data, the classification of methylurea for skin sensitization is not possible according to directive 67/548/EEC and regulation (EC) No. 1272/2008.