1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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:

1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

EC Number:

640-188-7

Cas Number:

903550-26-5

Molecular formula:

C14H23BN2O3

IUPAC Name:

1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Test animals

Species:

other: rat and mouse

Sex:

male/female

Results and discussion

Any other information on results incl. tables

Model	Leadscope	ACD/Percepta	Consensus prediction
Rat male	POSITIVE (borderline reliable)	NOT IN THE DOMAIN	POSITIVE (borderline reliable)
Rat female	NEGATIVE (borderline reliable)	NOT IN THE DOMAIN	NEGATIVE  (borderline reliable)

Name	Model	ACD/Percepta	Leadscope	Consensus prediction
1-(tetrahydro-2H-pyran- 2-yl)-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-pyrazole	Mouse male	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)
	Mouse female	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)

 

Leadscope Model Applier

Leadscope FDA Model Applier prediction forcarcinogenicity on rat male and female resulted to be POSITIVE and NEGATIVE, respectively since the positive prediction probability was equal to 0.50 (male) and 0.40 (female). Since one feature was found, it was concluded that 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole is poorly represented by the models.The robustness of the prediction was further evaluated by examining compounds similar to the 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 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. Two structures (Tetrahydrofuran and Dioxane, 1,4-) from the training set ofCar Rat Malemodel andCar Rat Femalemodel were identified as analogues to 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (similarity > 30%), but none with similarity greater than 0.5.Based on that, Leadscopepredictions were assessed as 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 0.40 (male) and 0.43 (female). Since two features were found, it was concluded that 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole is represented by the models.Additionally, the two identified features are mainly represented in negative training compounds.The robustness of the prediction was further evaluated by examining compounds similar to the 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 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. Two structures (Tetrahydrofuran and Dioxane, 1,4-) from the training set ofCar Mouse Malemodel andCar Mouse Femalemodel were identified as analogues to 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (similarity > 30%), but none with similarity greater than 0.5.Based on that, Leadscopepredictions were assessed as borderline reliable.

Applicant's summary and conclusion

Conclusions:

Based on the consensus assessments, the 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 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, 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole was predicted as SUSPECT POSITIVE for carcinogenicity and the prediction was assessed as borderline reliable.