Benzonitrile, 2-chloro-4-(1H-pyrazol-3-yl)-

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

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:

Micronucleus in vivo on rodent predictions were generated employing three predictors: Leadscope Model Applier, ACD/Percepta and Toxtree decision rule system.

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-4-(1H-pyrazol-3-yl)benzonitrile

EC Number:

941-761-7

Cas Number:

1297537-37-1

Molecular formula:

C10H6N3Cl

IUPAC Name:

2-chloro-4-(1H-pyrazol-3-yl)benzonitrile

Test animals

Species:

other: rodent

Results and discussion

Any other information on results incl. tables

Leadscope	ACD/Percepta	Toxtree	Consensus prediction
NEGATIVE (borderline reliable)	Undefined (borderline reliable)	NEGATIVE	NEGATIVE (Borderline reliable)

   

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-chloro-4-(1H-pyrazol-5-yl)benzonitrile. These training compounds exhibit moderate similarity with respect to 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile (similarity index ranging from 0.57 to 0.73), meaning that 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile compound is moderately represented in the training set of the model, and experimental not consistent Ames test results. These considerations explained the borderline undefined prediction.

             

Leadscope Model Applier

Leadscope FDA Model Applier prediction for micronucleusin vivoon rodentresulted to be NEGATIVE, since the positive prediction probability was equal to 0.17. Since two features were found, it was concluded that 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile is represented by the model.Additionally, 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-(1H-pyrazol-5-yl)benzonitrile 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. Six structures were identified in the training set as analogues to 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile (similarity > 30%), but none of them with similarity greater than 0.5.Based on that, Leadscopeprediction was assessed as borderline reliable.

Toxtree predicts the positive or negative micronucleus activity according to decision rules based on the identification of Structural Alerts (SA)[1]. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential micronucleus activity of the chemical. Toxtree did not identify any structural alert in the target 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile compound 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile leading to a negative prediction. A detailed assessment of the reliability of the prediction is not provided.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
In the consensus assessment only reliable predictions are to be taken into account. In the case of 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile, ACD/Percepta prediction resulted to be undefined, thus based on Leadscope and Toxtree predictions it was concluded that the target 2-chloro-4-(1H-pyrazol-5-yl)benzonitrile is predicted NEGATIVE for genotoxicity as micronucleus in vivo on rodent and the prediction was assessed as borderline.