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Key value for chemical safety assessment

Effects on fertility

Description of key information
Reproductive  toxicity  on  rat  (male  and  female)  of  the  target  Phenyl(pyridin-2-yl)acetonitrile  was estimated by Leadscope QSAR probabilistic model.

Toxicity to reproduction: other studies

Additional information

Leadscope model for reproductive toxicity on rat estimates probability that a compound will result positive in a reproductive toxicitytes test on rats (males and females). Leadscope results include a reproductive toxicity prediction (positive,negative or not in domain), a positive prediction probability and two parameters which assess the reliability of the prediction: 1)ModelFeaturesCount,i.e.,containing structural model features that are present in the prediction model; 2)30%SimilarityTrainingNeighboursCount,i.e.number of training compounds with at least 30% similarity. It is to note that two separate models formale (ReproRatMale) and female (ReproRatFemale) mice are available. Additionally, for the endpoint reproductive toxicity on rat female, four QSAR models are generated with a balance of positive and negative compounds and the results are calculated as an average of the four models (weigh of evidence model).

Leadscope FDA Model Applier prediction for reproductive toxicity on rat (both males and females) resulted to be NEGATIVE, since the positive prediction probability is equal to 0.22 (male) and 0.21 (female). Since at least four features were found, it was concluded that Phenyl(pyridin-2-yl)acetonitrile is represented by the models. 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 does not take part to the prediction, it provides the complementary means to see how similar compounds are predicted and what the experimental values of similar compounds are. One structure from the training set of Repro Rat Male model and two structures from the training set of Repro Rat Female model were identified as analogues to Phenyl(pyridin-2-yl)acetonitrile (similarity > 30%). However, these compounds exhibit little similarity with respect to the target Phenyl(pyridin-2-yl)acetonitrile (similarity index lower than 0.5). Based on these considerations, Leadscope predictions were assessed as borderline reliable.

Justification for classification or non-classification

Leadscope FDA Model Applier prediction for reproductive toxicity on rat (both males and females) resulted to be NEGATIVE, but

the predictions were assessed as borderline reliable.