Benzonitrile, 2-chloro-4-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

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:

Carcinogenicity on mouse and rat (male, female) was estimated by using two predictors: Leadscope Model Applier and ACD/Percepta.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-4-[1-(oxan-2-yl)-1H-pyrazol-5-yl]benzonitrile

EC Number:

941-996-5

Cas Number:

1297537-35-9

Molecular formula:

C15H14N3ClO

IUPAC Name:

2-chloro-4-[1-(oxan-2-yl)-1H-pyrazol-5-yl]benzonitrile

Test animals

Species:

other: rat and mouse

Sex:

male/female

Results and discussion

Any other information on results incl. tables

Name	Model	ACD/Percepta	Leadscope	Consensus prediction
2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile	Rat male	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)
	Rat female	NOT IN THE DOMAIN	POSITIVE (borderline reliable)	POSITIVE (borderline reliable)

Name	Model	ACD/Percepta	Leadscope	Consensus prediction
2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile	Mouse male	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)
	Mouse female	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)

 

ACD/Percepta did not provide any prediction since the 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile compound resulted out of the applicability domain of the two models.

Leadscope Model Applier

Leadscope prediction for carcinogenicity on rat:

Name	Model	Prediction call	Positive Prediction probability	Prediction reliability parameters
				Model Features Count	30% Sim. Training Neighbors Count	Reliability assessment
2-chloro-4-(1H-pyrazol-5-yl)benzonitrile	Carc Rat Male	NEGATIVE	0.41	5	1	BORDERLINE RELIABLE
	Car Rat Female	POSITIVE	0.71	7	1	BORDERLINE RELIABLE

Leadscope FDA Model Applier prediction forcarcinogenicity on rat male and femaleresulted to be NEGATIVE and POSITIVE, respectively since the positive prediction probability was equal to 0.41 (male) and 0.71 (female). Since at least 5 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 models.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 does not take part to the prediction, it provides the complementary means to see how similar compounds were predicted and what the experimental values of similar compounds are. Only one structure (Chlorothalonil) from the training set ofCar Rat Malemodel andCar Rat Femalemodel was identified as analogues to 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile (similarity > 30%), although with similarity lower than 0.5.Based on that, Leadscopepredictions were assessed as borderline reliable.

Leadscope prediction for carcinogenicity on mouse:

Name	Model	Prediction call	Positive Prediction probability	Prediction reliability parameters
				Model Features Count	30% Sim. Training Neighbors Count	Reliability assessment
2-chloro-4-(1H-pyrazol-5-yl)benzonitrile	Carc Mouse Male	NEGATIVE	0.31	6	1	BORDERLINE RELIABLE
	Carc Mouse Female	NEGATIVE	0.45	6	1	BORDERLINE RELIABLE

Leadscope FDA Model Applier prediction forcarcinogenicity on mouse (both males and females)resulted to be NEGATIVE, since the positive prediction probability was equal to 0.31 (male) and 0.45 (female). Since at least 6 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 models.Additionally, the majority of/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 does not take part to the prediction, it provides the complementary means to see how similar compounds were predicted and what the experimental values of similar compounds are. Only one structure (Chlorothalonil) from the training set ofCar Mouse Malemodel andCar Mouse Femalemodel was identified as analogues to 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile (similarity > 30%), although with similarity lower than 0.5.Based on that, Leadscopepredictions were assessed as borderline reliable.

Applicant's summary and conclusion

Conclusions:

Based on the consensus assessments, the 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile was predicted as NEGATIVE for carcinogenicity on mouse (borderline reliable) and SUSPECT POSITIVE for carcinogenicity on rat. Since equally reliable but not consistent predictions were obtained for carcinogenicity in the two considered species, priority was given to the outcome relating to the most sensitive species (in this specific case rat). Thus, based on the precautionary approach, 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile was predicted as SUSPECT POSITIVE for carcinogenicity and the prediction was assessed as borderline reliable.