Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion
Remarks:
other: in silico predictions
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
2015

Materials and methods

Principles of method if other than guideline:
Estimated by using ACD/Percepta QSAR model and Toxtree decision rule system.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

The prediction results of skin irritation are illustrated in the following Table .

 ACD/Percepta prediction  Toxtree prediction  Consensus prediction
 SKIN IRRITANT Little Reliable  NOT SKIN CORROSIVE  SKIN IRRITANT Little Reliable

ACD/Percepta model for skin irritation estimates the potential of a chemical to cause skin irritation in a standard rabbit Draize test. It calculates the probability for a chemical to cause moderate or above irritation to skin of rabbit at a standard dose of 100 and 500 mg, respectively. It lists all the rules that are applicable and are used in the calculation, it highlights the structural fragments corresponding to the listed rules on the molecule of interest and it provides a list of up to five most similar structures from the training set with the experimental values of their standard Draize test result and references.

 ACD/Percepta Probability to cause moderate or stronger rabbit skin irritation  ACD/Percepta prediction  Reliability assessment
0.74   SKIN IRRITANT   LITTLE RELIABLE

ACD/Percepta predicted 2-phenyl-2-piperidin-2-ylacetamide as skin irritant, with a probability to cause skin irritation equal to 0.74. However, this prediction is considered of little reliability since the target compound is not represented in the model training set (no training compounds with similarity greater than 0.5 with respect to the target were found).

Toxtree predicts the skin irritation caused by a chemical according to the EU risk phrases (R34: Causes burns; R35: Causes severe burns; R38: Irritating to skin). Toxtree predicts the skin irritation caused by a chemical based on physicochemical property exclusion rules and structural inclusion rules. Physicochemical exclusion rules depend on: molecular weight, LogP, melting point, water solubility, lipid solubility and surface tension. Toxtree prediction for the target compound is illustrated in the Table .

 Toxtree exclusion rules  Toxtree inclusion rules  Toxtree prediction
Group CN Vapour pressure (Pa) < 0.0001  No  NOT SKIN CORROSIVE

Toxtree predicted 2-phenyl-2-piperidin-2-ylacetamide as not skin irritant, since it fulfils one exclusion rule since the target belongs to the structural class made of chemicals containing Carbon (C), Hydrogen (H), Oxygen (O) and Nitrogen (N)atomswith a vapour pressure < 0.0001 Pa (EPISuite/MPBPVP estimated vapour pressure = 0.0000593 Pa). In addition, no structural inclusion rule were met.

Therefore Toxtree predicted the target 2-phenyl-2-piperidin-2-ylacetamide as not skin corrosive. A detailed assessment of the reliability of the prediction is not provided.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information with little reliability
Conclusions:
The skin irritation potential of the target chemical was predicted employing two different in silico approaches: the QSAR statistical model as provided by ACD/Percepta and the decision rule system provided by Toxtree. The two predictors were employed in order to apply a consensus approach to enhance the reliability of the prediction. The two predictors were not in agreement since ACD/Percepta provided a positive prediction while Toxtree a negative prediction. Although ACD/Percepta prediction resulted to be of little reliability, since Toxtree didn’t provide a detailed assessment of its reliability, and according to a precautionary approach it was concluded with a little level of confidence that the target 2-phenyl-2-piperidin-2-ylacetamide is SKIN IRRITANT.