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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Allergic Contact Dermatitis Guinea pig and human
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
22 June 2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
Danish QSAR database, OECD QSAR Toolbox v4.4

2. MODEL (incl. version number)
SciQSAR v3.1.00
CASEUltra v1.4.6.6
Leadscope v3.1.1‐10

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
please refer to attached QMRFs

5. APPLICABILITY DOMAIN
Please refer to attached QPRF

Data source

Referenceopen allclose all

Reference Type:
other: QSAR
Title:
MultiCASE CASE Ultra commercial model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.
Author:
MultiCASE Inc.; 23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA;
Year:
2014
Bibliographic source:
A categorical (Q)SAR model based on structural fragments and calculated molecular descriptors
Reference Type:
other: QSAR
Title:
Leadscope Enterprise version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.
Author:
MultiCASE Inc.; 23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA;
Year:
2014
Bibliographic source:
A categorical (Q)SAR model based on structural features and numeric molecular descriptors.
Reference Type:
other: QSAR tool
Title:
SciMatics SciQSAR version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.
Author:
MultiCASE Inc.23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA
Year:
2014
Bibliographic source:
This is a categorical (Q)SAR model based on calculated molecular descriptors, and if available the modeller’s own or third party descriptors or measured endpoints can be imported and used as descriptors.
Reference Type:
other: QSAR software
Title:
Unnamed
Year:
2020

Materials and methods

Test guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Danish QSAR database, OECD QSAR Toolbox v4.4
- Model(s) used: SciQSAR, Leadscope, CaseUltra
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification'
Justification for non-LLNA method:
Data for these models include results from human epidemiological studies on ACD and results from the Guinea Pig Maximization Test (GPMT). The experimental protocol for GPMT is described in OECD guideline 406.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Remarks on result:
positive indication of skin sensitisation
Remarks:
Leadscope model (in applicability domain)
Remarks on result:
positive indication of skin sensitisation
Remarks:
SciQSAR model (in applicability domain)
Remarks on result:
not determinable
Remarks:
CASEUltra model
Key result
Remarks on result:
positive indication of skin sensitisation
Remarks:
battery approach (2 out of three models give positive prediction in applicability domain)

Any other information on results incl. tables

The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain).

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain).
Executive summary:
Skin sensitisation was predicted by the statistical QSAR models SciQSAR, Leadscope and CaseUltra implemented in the Danish QSAR database. The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain). Thus, the prediction is considered to be reliable.