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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in chemico
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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Software tool(s) used including version: OASIS TIMES v2.27.19.13
- Model(s) used: Skin sensitization with autoxidation, v. 21.26 (Algorithm)
- Reporting Format: The QPRF (QSAR Prediction Reporting Format) v.1.4 is a harmonised template for summarising and reporting substance-specific predictions generated by (Q)SAR models. The present QPRF is generated by LMC software, University "Prof. As. Zlatarov", Bourgas, Bulgaria
- Appropriate measures of goodness-of–fit, robustness and predictivity:
External Validation: Not performend
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 %.
- Model predictions are based on simulation of skin metabolism and covalent interactions with proteins.
GLP compliance:
no
Justification for non-LLNA method:
1-Methylimidazole is corrosive to the skin, therefore, an skin sensitisation study is not required according to REACH regulation (1907/2006) Annex VII, 8.3, column 2.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vitro / in chemico

Results
Parameter:
other: The chemical is out of the interpolation structural space.
Other effects / acceptance of results:
Applicability domain:
I: Parameter domain: log Kow (calulcated): 0.61 (in domain), MW (calculdated): 82.1Da (in domain)
II. strucural fragment domain: The following ACF are identified: Fragments in correctly predicted training chemicals – 66.67%. Fragments in non-correctly predicted training chemicals – 0.00%. Fragments not present in the training chemicals – 33.33%. CONCLUSION: The chemical is out of the interpolation structural space
III. Mechanistic domain: Interpolation space. Domain result: N/A

Any other information on results incl. tables

List of metabolites of the parental chemicals with their predicted value (although out of domain):

- Methylimidazole: Non sensitiser

- Imidazole: Non sensitiser

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
(out of domain)