Registration Dossier

Administrative data

Endpoint:
eye irritation
Remarks:
other: QSAR
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable with restrictions because it is an acceptable and reliable study carried out by Toxtree (Estimation of Hazard - A Decision Tree Approach) v.2.5.0. Meets generally accepted scientific principles, acceptable for assessment.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Referenceopen allclose all

Reference Type:
other: Software
Title:
TOXTREE (Estimation of Toxic Hazard - A Decision Tree Approach) v.2.5.0
Author:
Nina Jeliazkova
Year:
2011
Bibliographic source:
http://www.opentox.org/dev/documentation/components/toxtree and http://toxtree.sourceforge.net/
Report Date:
2011
Reference Type:
publication
Title:
Unnamed
Year:
2005
Reference Type:
publication
Title:
Assessment of the eye irritating properties of chemicals by applying alternatives to the Draize rabbit eye test: the use of QSARs and in vitro tests for the classification of eye irritation.
Author:
Gerner, I.; Liebsch, M.; Spielmann, H.
Year:
2005
Bibliographic source:
Gerner, I.; Liebsch, M.; Spielmann, H. Alternatives to Laboratory Animals 2005, 33, 215-237.
Reference Type:
publication
Title:
The Skin Irritation Corrosion Rules Estimation Tool (SICRET).
Author:
Walker, J.D.; Gerner, I.; Hulzebos, E.; Schlegel, K.
Year:
2005
Bibliographic source:
Walker, J.D.; Gerner, I.; Hulzebos, E.; Schlegel, K. QSAR & Combinatorial Science 2005, 24, 378-384.
Report Date:
2005
Reference Type:
secondary source
Title:
Use of physico-chemical property limits to develop rules for identifying chemical substances with no skin irritation or corrosion potential.
Author:
Gerner, I.; Schlegel, K..; Walker, J.D.; Hulzebos, E.
Year:
2004
Bibliographic source:
Gerner, I.; Schlegel, K.; Walker, J.D.; Hulzebos, E. QSAR and Combinatorial Science, 2004, 23, 726-733.
Report Date:
2004
Reference Type:
secondary source
Title:
(Q)SARs for Predicting Skin Irritation and Corrosion: Mechanisms, Transparency and Applicability of Predictions.
Author:
Walker, J.D.; Gerner, I.; Hulzebos, E.; Schlegel, K.
Year:
2004
Bibliographic source:
Walker, J.D.; Gerner, I.; Hulzebos, E.; Schlegel, K. QSAR & Combinatorial Science 2004, 23, 721-725.
Report Date:
2004

Materials and methods

Test guideline
Guideline:
other: REACH guidance on QSARs, R.6 May/July 2008
Principles of method if other than guideline:
General model for eye irritation/corrosion based on the QSAR evaluation of the BfR carried out by TOXTREE.

A decision support system (DSS) developed by the German Federal Institute for Risk Assessment (BfR) uses physico-chemical exclusion rules to predict the absence of skin irritation/corrosion potential in combination with structural inclusion rules (SARs) to predict the presence of such potential (Gerner et al., 2004; Walker et al., 2004). The exclusion rules are based on physicochemical properties such as molecular weight, aqueous solubility, and log Kow, whereas the inclusion rules are based on substructural molecular features. The physico-chemical rules implicitly take into account bioavailability (skin penetration) whereas the structural rules take reactivity into account. The physico-chemical and structural rulebases are designed to predict the EU risk phrases for skin irritation (R38) and skin corrosion (R34 and R35).

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Smiles notation (if other than submission substance): C[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)CO

Results and discussion

In vivo

Results
Irritation parameter:
other: QSAR result
Basis:
other: Exclusion rule
Remarks on result:
other: The prediction is based on the exclusion rule: Melting Point[°C] > 200 -Yes- Class. NOT skin corrosion R34 or R35. Thus is not evaluated for eye irritation.

Any other information on results incl. tables

From "Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance" © European Chemicals Agency, 2008.

Page 245 and 249 - The performance of the BfR physico-chemical rulebase for predicting the absence of skin effects has been validated by the RIVM (Rorije & Hulzebos, 2005), whereas the structural rulebase for predicting the occurrence of skin effects has been validated by the ECB (Gallegos Saliner et al., 2007). The endpoint is EU classification, the algorithms and domain of applicability are transparent, the rules and alerts are independently validated by ECB and RIVM (Gallegos Saliner et al., 2007, Rorije & Hulzebos, 2005). Though the rules are empirically derived, a mechanism of action can be deduced. For chemicals in the applicability domain of the rulebase, the rules may be used on their own to predict the presence or absence of hazard. Thus, the resulting predictions can be used as the basis for classification. It should be determined, on a case-by-case basis, whether the predictions for a given chemical provide a sufficient basis for classification, or whether additional information is needed in a weight-of-evidence approach.

To predict the eye rritation these rules are used analogously to those described in the skinirritation and corrosion section above. The physico-chemical and structural rulebases are designed to predict the EU risk phrases for eye irritation (R36) and severe eye irritation/corrosion (R41). Independent validation exercises by the ECB support the performance of the physico-chemical rulebase for predicting the absence of eye effects (Tsakovska et al., 2005), as well as the performance of the structural rulebase for predicting the occurrence of eye effects (Tsakovska et al., 2007).

Applicant's summary and conclusion

Interpretation of results:
other: Not evaluated for eye irritation.
Remarks:
Criteria used for interpretation of results: other: Exlusion rule was applied.
Conclusions:
Betamethasone is not considered to have characteristics responsible for skin irritation. Thus, based on the exclusion rule of TOXTREE, no classification is needed for this Endpoint.