1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S)-

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:

1,2-di-tert-butyl (2S)-4-oxopyrrolidine-1,2-dicarboxylate

EC Number:

807-593-2

Cas Number:

166410-05-5

Molecular formula:

C14H23NO5

IUPAC Name:

1,2-di-tert-butyl (2S)-4-oxopyrrolidine-1,2-dicarboxylate

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
1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S)	Mouse male	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)
	Mouse female	NOT IN THE DOMAIN	NEGATIVE (borderline reliable)	NEGATIVE (borderline reliable)

Name	Model	ACD/Percepta	Leadscope	Consensus prediction
1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S)	Rat male	OUT OF THE DOMAIN)	NEGATIVE (Borderline reliable)	NEGATIVE (Borderline reliable)
	Rat female	OUT OF THE DOMAIN	NEGATIVE (Borderline reliable)	NEGATIVE (Borderline reliable)

 

Leadscope Model Applier

Leadscope FDA Model Applier prediction forcarcinogenicity on mouse (both males and females)resulted to be NEGATIVE, since the positive prediction probability was equal to 0.06 (male) and 0.21 (female). Since at least 15 features were found, it was concluded that 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) is well represented by the models.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 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) 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 from the training set ofCar Mouse Malemodel andCar Mouse Femalemodel were identified as analogues to 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) (similarity > 30%), although both characterized by little similarity (similarity < 0.5).Based on that, Leadscopepredictions were assessed as borderline reliable.

Leadscope FDA Model Applier prediction for carcinogenicity on rat (both males and females) resulted to be NEGATIVE, since the positive prediction probability was equal to 0.26 (male) and 0.28 (female). Since at least 12 features were found, it was concluded that 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) is well represented by the models. 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 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) 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 from the training set ofCar Rat Malemodel andCar Rat Femalemodel were identified as analogues to 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) (similarity > 30%), although both characterized by little similarity (similarity < 0.5).Based on that, Leadscopepredictions were assessed as borderline reliable.

Applicant's summary and conclusion

Conclusions:

Since ACD/Percepta predictions resulted to be out of the model domains, based on Leadscope predictions of carcinogenicity on mouse and rat (male and female) the target 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) was predicted as NEGATIVE for mouse and rat carcinogenicity, and the predictions were assessed as borderline reliable.