2-cyano-N-methylacetamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: in-silico

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OASIS TIMES v2.27.19.13

2. MODEL
Skin sensitization with autoxidation, v. 21.26

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CNC(=O)CC#N

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The QMRF is attached.
- Defined endpoint: Predicts Skin sensitizer versus non-Sensitizer
- Unambiguous algorithm: yes
- Defined domain of applicability: yes
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Statistics for goodness-of-fit:
For 875 chemicals, the TIMES-SS model was able to predict correctly 90% of the strong sensitizers,
55% of the weak sensitizers and 77% of the non-sensitizers, i.e., an overall performance of 78 %.
Sensitivity: 78 %
Specificity: 77 %

An external validation with substances not in the model training set was published by Teubner et al., Regulatory Toxicology and Pharmacology 67 (2013) 468–485 showing perfect predictivity for substances 100% in the model domain.
- Mechanistic interpretation: Alerts for protein binding

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: The substance is in the descriptor domain.
- Structural and mechanistic domains: The following atom-centered fragments are identified:
Fragments in correctly predicted training chemicals – 85.71%
Fragments in non-correctly predicted training chemicals – 0.00%
Fragments not present in the training chemicals – 14.29%
In the absence of a mechanistic alert, the mechanistic domain is not applicable.
- Similarity with analogues in the training set: No similar substances were found in the training set using the following search criteria:
Target: CNC(=O)CC#N
Threshold=60%,
Tanimoto (Jaccard)(Atom centered fragments)
Atom type; Count H attached; Hybridization
- Other considerations (as appropriate): Similar substances (Tanimoto, 80%) were identified via ChemIDplus advanced. CAS 107-91-5 and CAS 621-03-4 were identified as similar substances. No skin sensitization hazard data could be retrieved in the registrant`s internal database nor in Toxnet or in eChemPortal. Secondary information on a Buehler test (OECD 406) with a more remote analogue substance CAS 105-34-0 indicates absence of a skin sensitizing potential. In CAS 105-34-0 , the nitrogen of the amide function is an oxygen (=ester function).

6. ADEQUACY OF THE RESULT
No structural alert for protein binding was identified for the parent or predicted metabolites. The substance is well represented by the training set since 85.7% of the atom-centered fragments are found in substances in the model training set, and off of these fragments belong to substances that are currectly predicted by the training set. There are no fragments that give conflicting predictings. 14.3% of the atom-centered fragments are not represented in the model training set.

Materials and methods

Principles of method if other than guideline:

The chemical structure is processed against a database containing structural alerts for protein binding (OASIS protein binding module of the OECD QSAR toolbox, v.2.0). The module for skin metabolism prediction was included.

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-N-methylacetamide

EC Number:

228-705-0

EC Name:

2-cyano-N-methylacetamide

Cas Number:

6330-25-2

Molecular formula:

C4H6N2O

IUPAC Name:

2-cyano-N-methylacetamide

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is predicted as being non-skin sensitzing by QSAR (TIMES-SS).