Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent

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.