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Ames test

Gene mutation as microbialin vitroSalmonella of the target Pipamperone was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system.

The four predictors were employed in order to apply a weight of evidence (WoE) approach to enhance the reliability of the prediction. In the weight of evidence assessment only reliable predictions are to be taken into account. In the case of Pipamperone, ACD/Percepta and Toxtree predictions were not taken into account in the weight of evidence prediction, being undefined and not reliable, respectively. The other two predictors, i.e. Leadscope and Vega, were in agreement providing a negative prediction although with a different level of confidence (borderline Leadscope; high Vega). Therefore, it was concluded that Pipamperone was predicted with a high level of confidence as negative formicrobial in vitroSalmonella.

Chromosome aberrationin vitrocomposite

ACD/Percepta model for chromosome aberrationin vitro(composite) estimates probability (“p-value”) that a compound will result positive in the chromosome aberrationin vivoassay.

ACD/Percepta prediction resulted to be negative, and the prediction was assessed as moderate reliable being the reliability index equal to 0.53. 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 Pipamperone. These training compounds exhibit moderate to high similarity with respect to Pipamperone (similarity index ranging from 0.64 to 1) and four out of the five analogues exhibit experimental negative chromosome aberrationin vitrotest results. It has to be noted that among the analogues, the target itself was identified in the training set of the model with an experimental negative test result.These considerations further supported the reliability of the prediction.

Micronucleus in vivorodent

Genotoxicity asmicronucleusin vivoon rodent predictions were generated employing three predictors: ACD/Percepta, Leadscope Model Applier and Toxtree decision rule system.

In the weight of evidence assessment only reliable predictions are to be taken into account. In the case of Pipamperone, the weight of evidence assessment was based only on Toxtree prediction and lead to a positive borderline reliable prediction for genotoxicity asmicronucleusin vivoon rodent.


Justification for selection of genetic toxicity endpoint
In silco prediction

Short description of key information:
Four predictors were used: ACD/Percepta, Leadscope, Vega and Toxtree decision rule system.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the weight of evidence assessments Pipamperone was predicted as negative for microbial in vitroSalmonella (Ames test) (high reliable), negative for chromosome aberration in vitro composite (moderate reliable), and positive for micronucleus in vivo on rodent (borderline reliable). Taking into account the higher reliability of microbial in vitroSalmonella and chromosome aberration in vitro composite predictions and the fact that the toxic micronucleus potential of the H-acceptor-path3-H-acceptor structural alert is only limited translated into actual toxicity in the experimental system, it was concluded that Pipamperone was predicted as negative for genotoxicity and the prediction was assessed as moderate reliable.