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

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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:

Gene mutation as microbial in vitro Salmonella was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

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

Results and discussion

Any other information on results incl. tables

ACD/Percepta	Leadscope	Vega	Toxtree	Consensus prediction
NEGATIVE (Borderline reliable)	NEGATIVE (Borderline reliable)	POSITIVE (Borderline reliable	POSITIVE (not reliable)	POSITIVE (borderline reliable)

ACD/Percepta prediction resulted to be negative, and the prediction was assessed as borderline reliable being the reliability index equal to 0.40. 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 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S). These training compounds exhibit moderate similarity with respect to 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) (similarity index ranging from 0.62 to 0.64), meaning that the target compound is moderetly represented in the training set of the model, and experimental not consistent Ames test results, being two negative and three positive. These considerations explained the borderline reliability of the prediction.

Leadscope FDA Model Applier prediction formicrobialin vitroSalmonellaresulted to be NEGATIVE, since the positive prediction probability was equal to 0.11. Since 10 features were found, it was concluded that 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) 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 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) from the training set. While this information don’t take part to the prediction, it provides complementary means to see how similar compounds are predicted and what the experimental values of similar compounds are. Only one training compound was were identified in the training set as analogue to 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) (similarity > 30%), which however, is characterized by little similarity (similarity = 0.37).Thus, Leadscopeprediction was assessed as borderline reliable.

Vega predicted 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) as positive, and the prediction was assessed as borderline reliable since the applicability domain index was equal to 0.73. In factonly moderately similar compounds with known experimental value in the training set have been found, some similar molecules found in the training set have experimental values that disagree with the predicted value and the accuracy of prediction for similar molecules found in the training set is not optimal. Thus, the prediction was considered borderline reliable.

Toxtree predicted the 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) as -mutagen since it identified the alkyl carbamate and thiocarbamate structural alert for genotoxicity (Benigni/Bossa structural alert no. 16). The prediction was assessed as not reliablesince theADI (global Applicability Domain Index) was equal to 0.0. In fact, only moderately similar compounds with known experimental value in the training set have been found and similar molecules found in the training set have experimental values that disagree with the predicted value.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive Borderline reliable

Based on ACD/Percepta, Leadscope and Vega and following a precautionary approach, it was concluded that the target 1,2-Pyrrolidinedicarboxylic acid, 4-oxo-, 1,2-bis(1,1-dimethylethyl) ester, (2S) is predicted with a borderline level of confidence as POSITIVE for microbial in vitro Salmonella.