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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
QSAR result
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
Title:
Skin CAESAR Model version 2.1.6
Year:
2010
Bibliographic source:
Chaudhry, Q., Piclin, N., Cotterill, J., Pintore, M., Price, N. R., Chrétien, J. R. and Roncaglioni, A. (2010). Global QSAR models of skin sensitisers for regulatory purposes., Chem Cent J 4 Suppl 1, S5.

Materials and methods

Test guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Model developer(s) and contact details:
[1] Qasim Chaudhry Food & Environment Research Agency, Sand Hutton, York
qasim.chaundhry@fera.qsi.gov.uk
[2] Nadège Piclin BioChemics Consulting, 111 Bld. Duhamel du Monceau
nadege.piclin@biochemics-consulting.com
[3] Jane Cotterill Food & Environment Research Agency, Sand Hutton, York
jane.cotterill@fera.qsi.gov.uk
[4] Marco Pintore BioChemics Consulting, 111 Bld. Duhamel du Monceau
marco.pintore@biochemics-consulting.com
[5] Nick R Price Food & Environment Research Agency, Sand Hutton, York
nick@technologyforgrowth.co.uk
[6] Jacques R Chrétien BioChemics Consulting, 111 Bld. Duhamel du Monceau
jacues.chretien@biochemics-consulting.com
[7] Alessandra Roncaglioni IRCCS - Istituto di Ricerche Farmacologiche Mario Negri
alessandra.roncaglioni@marionegri.it

Reference(s) to main scientific papers and/or software package:
Chaudhry, Q., Piclin, N., Cotterill, J., Pintore, M., Price, N. R., Chrétien, J. R. and Roncaglioni, A. (2010). Global QSAR models of skin sensitisers for regulatory purposes., Chem Cent J 4 Suppl 1, S5.

Availability of information about the model:
Available through the VEGA software, free download of software is possible on VEGA website. The training, test and validation sets are also available

Endpoint:
QMRF 4.6. Skin sensitisation. Skin sensitisation on mouse (local lymph node assay model) OECD 429.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
C(=C\F)\C(F)(F)F

Results and discussion

In vivo (LLNA)

Results
Parameter:
other: QSAR
Test group / Remarks:
QSAR
Remarks on result:
no indication of skin sensitisation based on QSAR/QSPR prediction

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Skin CAESAR Model version 2.1.6 predicts the substance is a NON-SENSITISER.
Executive summary:

The present software provides the result indicating lack of effect for skin sensitization. However, this result is only based on the descriptors and cannot be supported by the evidence from the presence of structurally similar compounds. Thus, there is a high level of uncertainty.

To reduce this uncertainty, the results of this model have to be supported by other lines of evidence. In our case we also a second model present in VEGA, to increase reliability, and we also verified if on a mechanistic basis there were reasons indicating possible sensitization. For the mechanistic basis we used the OECD QSAR Toolbox. The OECD QSAR Toolbox reports that there is no alert found for Protein bonding by OASIS. In a previous study done by JRC (Mr David Asturiol) in collaboration with Istituto Mario Negri (Mrs Serena Manganelli) this profiler was the best one, compared with other profilers for skin sensitization present within the OECD QSAR Toolbox ( Internal data). To support the results of the QSAR model, the OECD QSAR Toolbox identifies for the target substance the possibility of SN2 according to the Protein binding by OECD. However, the energy of the binding between C and F is quite high, and the plausibility that this reaction occurs at the body temperature is quite limited.

Overall, considering that there are two QSAR models indicating lack of effect, and that the OECD QSAR Toolbox is aligned with the same conclusion on a mechanistic basis, as indicated by the OASIS profiler, these joined lines of evidence support the call for lack of skin sensitization.