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Key value for chemical safety assessment

Additional information

 ACD/Percepta  Leadscope Vega   Toxtree  Weight of evidence
 UNDEFINED (na*)  NEGATIVE (Borderline reliable)  NEGATIVE (Borderline reliable)  NEGATIVE (High reliable)  NEGATIVE (High reliable)

ACD/Percepta prediction resulted to be undefined, meaning that the target 2-phenyl-2-(pyridin-2- yl)acetamide could not be reliably classified on the basis of p and RI values. ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results. The information on the structurally similar compounds in the training set was used to further assess the reliability of the prediction. Five compounds were identified as analogues of 2-phenyl-2- (pyridin-2-yl)acetamide. These training compounds exhibit moderate similarity with respect to 2-phenyl-2- (pyridin-2-yl)acetamide (similarity index ranging from 0.77 to 0.86), meaning that the target compound is moderately represented in the training set of the model, but not consistent experimental Ames test results, being two positive and three negative.

Leadscope FDA Model Applier prediction for microbial in vitro Salmonella resulted to be negative, since the positive prediction probability was equal to 0.18. Eleven model features and four analogues were identified leading to the conclusion that the target is in the model domain. Additionally, the majority of the identified features are mainly represented in negative training compounds. The robustness of the prediction was further evaluated by examining compounds similar to the target from the training set. While this information don’t take part to the prediction, it provides complementary means to see how similar compou nds are predicted and what the experimental values of similar compounds are. Four structures were identified in the training set as analogues to 2-phenyl-2-(pyridin-2-yl)acetamide (similarity > 30%), two of them are characterized by similarity indices greater than 0.5. These training compounds exhibit moderate similarity with respect to 2-phenyl-2-(pyridin-2-yl)acetamide but experimental not consistent negative Ames test results. Based on these considerations, Leadscope prediction was assessed as borderline reliable.

Vega predicted 2-phenyl-2-(pyridin-2-yl)acetamide as negative, and the prediction was assessed as borderline reliable based on the applicability domain index equal to 0.74 and the following considerations: i) only moderately similar compounds with known experimental value in the training set have been found; ii) accuracy of prediction for similar molecules found in the training set is not optimal; iii) similar molecules found in the training set have experimental values that disagree with the predicted value.

Toxtree predicted the 2-phenyl-2-(pyridin-2-yl)acetamide as non mutagen and the prediction was assessed as high reliable since the ADI (global Applicability Domain Index) was equal to 0.91. In fact, strongly similar compounds with known experimental value in the training set have been found; the accuracy of prediction for similar molecules found in the training set is good, similar molecules found in the training set have experimental values that agree with the predicted value and all atom centered fragment of the compound have been found in the compounds of the training set.


Justification for selection of genetic toxicity endpoint
In silico prediction by using ACD/Percepta, Leadscope, Vega and Toxtree decision rule system

Short description of key information:
Gene mutation as microbial in vitro Salmonella was estimated by using four predictors: ACD/Percepta, Leadscope, Vega and Toxtree decision rule system.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In the weight of evidence assessment only reliable predictions are to be taken into account. In the case of 2-phenyl-2-(pyridin-2-yl)acetamide, ACD/Percepta prediction resulted to be undefined, while the other three predictors were all in agreement providing negative predictions of different level of confidence, i.e. Leadscope and Vega borderline reliable, high reliable Toxtree. Thus, it was concluded that the target 2- phenyl-2-(pyridin-2-yl)acetamide is predicted as NEGATIVE for microbial in vitro Salmonella.