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Administrative data

Type of information:
Adequacy of study:
supporting study
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference Type:
study report
Report date:

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:

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetamide and (2S)-2-phenyl-2-[(2S)-piperidin-2-yl]acetamide
EC Number:
Molecular formula:
Reaction mass of (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetamide and (2S)-2-phenyl-2-[(2S)-piperidin-2-yl]acetamide

Test animals


Results and discussion

Effect levels

Dose descriptor:
other: alert
Basis for effect level:
other: Negative prediction, little reliable
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Any other information on results incl. tables

The prediction results are illustrated in Table:

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

Leadscope Model Applier

The table shows the result of Leadscope model which includes a prediction (positive, negative or not in domain), a positive prediction probability and two parameters which assess the reliability of the prediction.

 Model  LeadscopePredictioncall  LeadscopePositivePrediction probability  Model FeaturesCount  30% Sim. Training Neighbors Count  Reliabilityassessment
 Rat male  NEGATIVE  0.41  18  2  LITTLE RELIABLE
 Rat female  NEGATIVE  0.13  20  2  LITTLE RELIABLE
 Rat composite  NEGATIVE  0.14 19  2  LITTLE RELIABLE

Model Features Count. Parameter used to verify that the target compound, i.e.c-racemate, 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 18, 20 and 19 features were found for carcinogenicity on rat male, female and composite, respectively, it was concluded thatc-racemateis well represented by the models.

30% Similarity Training Neighbours Count. Number of compounds structurally similar to the target, i.e. 2c-racemate, 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. Two compounds (in common in the rat male, female and composite models) were identified in the training set as analogues toc-racemate, illustrated in Table 30.It has to be noted that the identified analogues exhibit little similarity with respect to the targetc-racemate, and inconsistent experimental data, being Methylphenidate negative while Atenolol is positive. Therefore, the predictions were considered of little reliability.

 Methylphenidate Result: NEGATIVESimilarity: 0.58
 Atenolol Result: POSITIVE Similarity: 0.32


The ACD/Perceptacarcinogenicity on ratpredictions reliability is estimated with the reliability index (RI), whichtakes into account the similarity of the tested compound with the training set compounds and the consistency of experimental values for similar compounds. Itranges from0 to 1: if the RI is less than 0.3 the prediction has to be considered not reliable while if RI is more than 0.5 the prediction is considered reliable.

ACD/Percepta did not provide any prediction of carcinogenicity on rat male and female since the target c-racemate resulted to be out of the models domain. ACD/Percepta prediction of carcinogenicity on rat compositeresulted to be undefined, meaning that it cannot be can be reliably classified on the basis of the positive probability (0.26) and the reliability index value (0.39).

Together with the prediction, ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results for the corresponding compounds. The structural similarity is evaluated by a fragmental approach. The information on the structurally similar compounds in the training set is used to further assess the reliability of the prediction, since it illustrates how the test compound, i.e. c-racemate, is represented in the training set. The five mostly similar compounds from the training set of the carcinogenicity onrat composite, illustrated in the Table, exhibit moderate similarity with respect to c-racematemeaning that the target compound is moderately represented in the training set of the model. It has also to be noted that the five training set chemicals mostly similar toc-racemateexhibit consistent experimental test results, being all of them negative. Thus, taking into account the little positive probability value and the negative experimental test results of the training chemicals mostly similar to the target, it was concluded thatc-racemateis likely to be negative for carcinogenicity on ratcomposite.

 METHYLPHENIDATE Result: negative Similarity: 0.64
 FROVATRIPTAN Result: negative Similarity: 0.59
 CAPROLACTAM Result: negative Similarity: 0.58
PHENFORMINR esult: negative Similarity: 0.57
 DISOPYRAMIDE Result: negativeSimilarity: 0.57

Applicant's summary and conclusion

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. Concerning carcinogenicity on rat male and female, based on Leadscope predictions it was concluded that the target c-racemate is NEGATIVE, although the predictions were assessed as little reliable. Concerning carcinogenicity on rat composite, based on both ACD/Percepta and Leadscope predictions it was concluded that the target c-racemate is NEGATIVE, although the prediction was assessed as little reliable.