Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
skin sensitisation
in vivo
Type of information:
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation. This study is used to provide a weight of evidence for the hazard endpoint that is sufficient for the purpose of classification and labelling and/or risk assessment. An additional study on this endpoint is available.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
OECD Toolbox v3.1
Estimation by TIMES: Skin sensitization v. 16.19 with autoxidation
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of study:
other: QSAR

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising.

Interpretation of results:
not sensitising
Migrated information negative Criteria used for interpretation of results: expert judgment
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising.
Executive summary:

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising. The target substance falls within applicability domain of the prediction. Supporting documentation is provided in the attached prediction report.


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

There are a number of steps that a chemical is required to overcome in order for it to induce skin sensitisation. The steps include gaining access to the viable epidermis, protein binding, metabolic activation (if required), internalisation and processing by Langerhans cells (LC), transport of antigen by LC to draining lymph nodes, and presentation to and recognition by T lymphocytes. Of these steps, the rate determining one is the ability to bind with proteins to form a stable adduct. The binding is assumed to be covalent whereby the chemical behaves as an electrophile and the skin protein as a nucleophile. Efforts to predict skin sensitisers have thus focused on identifying the electrophilic features in chemicals and relating these back to skin sensitisation potential. Such mechanistic information has been encoded as protein binding alerts within the OECD Toolbox (Enoch et al, 2010). Alerting groups underpinned by 3D QSAR have been incorporated into expert systems such as TIMES-SS (Patlewicz et al, 2007). A qualitative read-across was attempted in the OECD Toolbox. Substances were categorised on the basis of common MOA - i.e. absence of alerting groups as flagged by the protein binding alert schemes. Data were taken from all protocols to maximise the number of analogues and thus the ability to investigate a read-across. The test substance was predicted to be non-sensitising. A prediction was also made using the TIMES-expert system. The test substance was found to be non-sensitising by TIMES.


Literature references

Enoch SJ, Ellison CM, Schultz TW, Cronin MTD. 2010. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity. Crit Rev Toxicol 41(9):783-802.

Patlewicz G, Dimitrov S, Low LK, Kern PS, Dimitrova GD, Comber MI, Aptula AO, Phillips RD, Niemelä J, Madsen C, Wedebye EB, Roberts DW, Bailey PT, Mekenyan OG. 2007. TIMES-SS - A promising tool for the assessment of skin sensitization hazard. A characterization with respect to the OECD validation principles for (Q)SARs and an external evaluation for predictivity. Reg. Toxicol. Pharmacol. 48(2): 225-239.


Migrated from Short description of key information:
QSARs indicate that the test substance is not sensitising to the skin.

Justification for selection of skin sensitisation endpoint:
Multiple QSARs are provided as part of a weight of evidence

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substance is not expected to be a skin sensitiser based on QSAR evaluation. Therefore, no classification is required for skin sensitisation according to EU Directive 67/548/EEC and EU Classification and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.