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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
(Q)SAR
Adequacy of study:
supporting 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:
2015

Materials and methods

Principles of method if other than guideline:
Gene mutation as microbial in vitro Salmonella was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

Name

ACD/Percepta

Leadscope

Vega

Toxtree

Consensus prediction

2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile

OUT OF THE DOMAIN

NEGATIVE

(borderline reliable)

POSITIVE

(borderline reliable)

NEGATIVE

(not reliable)

POSITIVE

(borderline reliable)

Leadscope FDA Model Applier prediction formicrobialin vitroSalmonellaresulted to be NEGATIVE, since the positive prediction probability was equal to 0.18. Since 4 features were found, it was concluded that 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile is well represented by the model.Additionally, all the identified features are mainly represented in negative training compounds.The robustness of the prediction was further evaluated by examining compounds similar to the 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile from the training set.While this information don’t take part to the prediction, it provides complementary means to see how similar compounds are predicted and what the experimental values of similar compounds are. Two structures were identified in the training set as analogues to 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile (similarity > 30%) but none of them is characterized by similarity indices greater than 0.5.Thus, Leadscopeprediction was assessed as borderline reliable.

Vega predicted 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile as positive, and the prediction was assessed as borderline reliable since the applicability domain index was equal to 0.78. In factonly moderately similar compounds with known experimental value in the training set have been found and some similar molecules found in the training set have experimental values that disagree with the predicted value. Thus, the prediction was considered borderline reliable.

Toxtree predicted the 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile as NOT-mutagen since it didn’t identify any structural alert for genotoxicity. The prediction was assessed as not reliablesince theADI (global Applicability Domain Index) was equal to 0.44. In fact, only moderately similar compounds with known experimental value in the training set have been found and a prominent number of atom centered fragments of the compound have not been found in the compounds of the training set or are rare fragments.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive borderline reliability

ACD/Percepta did not provide any prediction since the target was out of the model domain, while Toxtree prediction resulted to be not reliable. Leadscope and Vega predictions resulted to be both of borderline reliability but providing conflicting results. Thus, according to a precautionary approach it was concluded that the target 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile is predicted with a borderline level of confidence as POSITIVE for microbial in vitro Salmonella.