di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

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:

di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

EC Number:

942-146-6

Cas Number:

166410-06-6

Molecular formula:

C17H28N2O5

IUPAC Name:

di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

Results and discussion

Any other information on results incl. tables

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

Leadscope FDA Model Applier prediction for microbial in vitro Salmonella resulted to be NEGATIVE, since the positive prediction probability was equal to 0.09. Since 13 features were found, it was concluded that di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate is represented by the model. Additionally, the identified features are represented only in negative training compounds. The robustness of the prediction was further evaluated by examining compounds similar to the di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate 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 identified in the training set as analogue to di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate (similarity > 30%), which however, is characterized by little similarity (similarity = 0.32). Thus, Leadscope prediction was assessed as borderline reliable.

Vega predicted di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate as positive, but the prediction was assessed as not reliable since the applicability domain index was equal to 0.51. In fact only 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 not reliable.

Toxtree predicted the di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2 -dicarboxylate as positive since it identified the alfa, beta unsaturated carbonyls structural alert for genotoxicity (Benigni/Bossa structural alert no. 10). The prediction was assessed as not reliable since the ADI (global Applicability Domain Index) was equal to 0.62. In fact, only moderately similar compounds with known experimental value in the training set have been found, the accuracy of prediction for similar molecules found in the training set is not optimal and some similar molecules found in the training set have experimental values that disagree with the predicted value.

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):
negative Borderline reliable

In the consensus assessment only reliable predictions are to be taken into account. In the case of di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate, ACD/Percepta did not provide any prediction, Vega and Toxtree predictions resulted to be not reliable. Thus, based on Leadscope prediction, it was concluded that the target di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate is predicted with a borderline level of confidence as NEGATIVE for microbial in vitro Salmonella.