Registration Dossier

Administrative data

Endpoint:
skin sensitisation
Remarks:
other: in silico prediction
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Principles of method if other than guideline:
Several computational tools are nowadays available for applying in silico approaches. Among them, for QSAR predictions the following was selected and used:
-Toxtree for the prediction of skin and eye irritation, skin sensitization, gene mutation (Ames test), micronucleus in vivo (rodent) and biodegradation (ready)
-Vega for the prediction of skin sensitization
GLP compliance:
no
Type of study:
other: Toxtree and Vega tools

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified

Results and discussion

In vivo (non-LLNA)

Results
Reading:
other: prediction
Clinical observations:
Not sensitizer
Remarks on result:
other: Reading: other: prediction. Clinical observations: Not sensitizer.

Any other information on results incl. tables

 In silico tool  Prediction  Structural alert  Reliability assessment
 Toxtree  NOT SENSITIZER  No skin sensitisation reactivity domains alert  
 Vega  SENSITIZER    NOT RELIABLE
 CONSENSUS  NOT SENSITIZER    

Toxtree

Toxtree decision rule system identifies alerts for skin sensitization using a SMARTS pattern based approach (Enoch SJ, Madden JC, Cronin MT. SAR&QSAR Environ Res. 2008,19(5-6),555-78). Toxtree did not identify any structural alert for skin sensitization for 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol, concluding that it is not skin sensitizer.

Vega

Vega assess the reliability of the gene mutation prediction according to many parameters, e.g. descriptor ranges, chemical similarity index, fragments similarity, ...Vega predicted 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol as skin sensitizer. The prediction is to be considered not reliable, since, only moderately similar compounds with known experimental value in the training set were found and a prominent number of atom centered fragments of the compound were not found in the compounds of the training set or are rare fragments.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The skin sensitization of 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol was predicted employing two different in silico approaches: the decision rule system provided by Toxtree and the QSAR model as provided by Vega. The two predictors were employed in order to apply a consensus approach to enhance the reliability of the prediction. In the consensus assessment only reliable predictions were taken into account. Therefore, based on Toxtree prediction, it was concluded that 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol is NOT SKIN SENSITIZER.