5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Type of information:

(Q)SAR

Adequacy of study:

key 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:

2014

Materials and methods

Principles of method if other than guideline:

Carcinogenicity on rat (male, female and composite) was estimated by using two predictors: Leadscope
Model Applier and ACD/Percepta.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(1-methylpiperidin-4-yl)tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaen-2-ol

EC Number:

609-737-8

Cas Number:

3967-32-6

Molecular formula:

C21H23NO

IUPAC Name:

2-(1-methylpiperidin-4-yl)tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaen-2-ol

Test animals

Species:

rat

Sex:

male/female

Results and discussion

Any other information on results incl. tables

Model	Leadscope	ACD/Percepta	Consensus prediction
Rat male	NEGATIVELittle reliable	-	NEGATIVELittle reliable
Rat female	NEGATIVELittle reliable	-	NEGATIVELittle reliable
Rat composite	NEGATIVELittle reliable	-	NEGATIVELittle reliable

Leadscope Model Applier

Model	Leadscope	LeadscopePositivePrediction probability	Model FeaturesCount	30% Sim. Training Neighbors Count
Rat male	NEGATIVELittle reliable	0.49	6	3
Rat female	NEGATIVELittle reliable	0.19	11	3
Rat composite	NEGATIVELittle reliable	0.21	8	3

Model Features Count. Parameter used to verify that the target compound, i.e. 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol, contains a significant number of features that are present in the prediction model. The structural features used to make the prediction provide information on the reliability of the prediction: a prediction provided by a low number of features means that the model is not able to fully describe the test compound, while a prediction supported by a high number of features reveals that the test compound is well described by the model. Since 6, 11 and 8 features were found for carcinogenicity on rat male, female and composite, respectively, it was concluded that 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol is well represented by the models.

30% Similarity Training Neighbours Count. Number of compounds structurally similar to the target, i.e. 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol, in the model's training set of compounds. Another way to assess the reliability of the prediction is looking at the analogues, i.e. the compounds structurally similar to the target in the model's training set of compounds. While this information does not take part to the prediction, it provides the user a complementary means to see how similar compounds were predicted and what the experimental values of similar compounds are. Look at analogues is also an initial, less-sophisticated easy way to understand estimate of toxicity.

Three compounds were identified in the training set off the three models as analogues to the test substance characterized by little similarity with respect to the target 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol. Therefore, the prediction was considered of little reliability.

ACD/Percepta did not provide any prediction for the target 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol since it resulted to be out of the applicability domain of the models.

Applicant's summary and conclusion

Conclusions:

Carcinogenicity on rat male, female and composite of the target was estimated by using two predictors:
Leadscope Model Applier and ACD/Percepta. 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 are to be taken into account.
In the cases of the carcinogenicity on rat male and female, the target 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol resulted to be out of the applicability domain of ACD/Percepta.
Leadscope predictor concluded that the target 5-(1-methylpiperidin-4-yl)-5Hdibenzo[a,d][7]annulen-5-ol is NEGATIVE for carcinogenicity on rat male and female, although the predictions are of little reliability.