2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester

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:

2014

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:

methyl 3-[(2-methoxy-2-oxoethyl)sulfamoyl]thiophene-2-carboxylate

EC Number:

600-780-8

Cas Number:

106820-63-7

Molecular formula:

C9H11NO6S2

IUPAC Name:

methyl 3-[(2-methoxy-2-oxoethyl)sulfamoyl]thiophene-2-carboxylate

Results and discussion

Any other information on results incl. tables

Leadscope	ACD/Percepta	Vega	Toxtree	Consensus prediction
-	NEGATIVE Borderline reliable	POSITIVE Not reliable	NEGATIVE Not reliable	NEGATIVE Borderline reliable

Leadscope did not provide any prediction for the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester since it resulted to be out of the model applicability domain.

ACD/Percepta genotoxicity prediction

The prediction is provided together with a reliability index, which assesses the degree of confidence of the prediction. The reliability index (RI) takes into account the similarity of the target with the training set compounds and the consistency of experimental values for similar compounds. It ranges from 0 to 1: if the RI is less than 0.3 the prediction has to be considered not reliable while if RI is more than 0.5 the prediction is considered reliable. ACD/Percepta prediction resulted to be negative, and the prediction is of borderline reliability being the reliability index equal to 0.47.

ACD/Percepta prediction call	ACD/Percepta positive probability	ACD/Percepta RI	Reliability assessment
NEGATIVE	0.09	0.47	BORDERLINE

No hazardous fragment was identified.

Together with the prediction, ACD/Percepta displays up to 5 most structurally similar structures from the training set along with experimental Ames test results for the corresponding compounds. The structural similarity is evaluated by a fragmental approach. The information on the structurally similar compounds in the training set is used to further assess the reliability of the prediction, since it illustrates how the test compound, i.e. 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester, is represented in the training set. The five mostly similar compounds from the training set, illustrated in Table 11, exhibit moderate similarity with respect to 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester (similarity index ranging from 0.51 to 0.53), meaning that the target compound is only moderately represented in the training set of the model. Despite the five training set chemicals mostly similar to 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester exhibit consistent experimental test results, their moderate similarity with respect to 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester is the main reason of the borderline reliability of the prediction.

N-Ethyl-4 -methylbenzenesulfonamide Result: NEGATIVE Similarity: 0.53

Name: Benzenesulfonamide,N-ethyl-2(or 4)-methyl- Result: NEGATIVE Similarity: 0.53

Name: o-toluensulfonamide Result: NEGATIVE Similarity: 0.52

Name: 4-Methylbenzenesulfonamide Result: NEGATIVE Similarity: 0.52

Name: Benzenesulfonamide, 4-amino-N-methyl- Result: NEGATIVE Similarity: 0.51

CAESAR QSAR model for mutagenicity implemented in Vega is an integrated model arranged cascading

two models, a trained Support Vector Machine (SVM) classifier, and an additional for false negatives (FNs)

removal based on Structural Alerts (SAs) matching. It assesses the reliability of the mutagenicity prediction

according to a global applicability domain index, which ranges from 0 (not reliable) to 1 (fully reliable)

taking into account many parameters, e.g. descriptor ranges, chemical similarity index, fragments similarity,

etc… An ADI value greater than 0.9 means that the predicted substance is into the applicability domain of

the model; ADI value lower than 0.7 means that the predicted substance is out of the applicability domain of

the model, while an ADI value between 0.7 and 0.9, means that the predicted substance could be out of the

Applicability Domain of the model.

Vega Prediction call	Vega prediction reliability	Reliability assessment
POSITIVE	AD Index = 0.66	NOT RELIABLE

Vega predicted the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl

ester as positive but the prediction is not reliable, being the ADI equal to 0.66, since only moderately similar

compounds with known experimental value in the training set have been found and some of the analogues

have experimental values that disagree with the predicted value (i.e., they have negative experimental

results). The five compounds most similar to 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-

oxoethyl)amino]sulfonyl]-, methyl ester are:

CAS: 59804-37-4 Result: negative Similarity: 0.77

CAS: 92 -55 -7 Result: positive Similarity: 0.75

CAS: 57-66-9 Result: negative Similarity: 0.74

CAS: 23256-30-6 Result: positive Similarity: 0.73

CAS: 68162-37-8 Result: positive Similarity: 0.72

Toxtree predicts the positive or negative mutagenicity according to decision rules based on the identification

of Structural Alerts (SA) for mutagenicity, i.e. molecular functional groups or substructures known to be

linked to the mutagenicity activity of chemicals. As one or more SAs embedded in a molecular structure are

recognised, the system flags the potential mutagenicity of the chemical. The reliability of Toxtree

mutagenicity prediction was evaluated by the Applicability Domain Index (ADI) implemented in VEGA

platform (ADI > 0.9: into the domain; 0.9 > ADI ≥ 0.7: could be out of the domain; ADI < 0.7: out of the

domain). Toxtree did not identify any structural alert in the target 2-Thiophenecarboxylic acid, 3-[[(2-

methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester leading to the conclusion that 2-Thiophenecarboxylic

acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester is negative for genotoxic activity. However,

the prediction is not reliable being the ADI (global Applicability Domain Index) equal to 0.43. In fact, the

following issues were addressed: only moderately similar compounds with known experimental value in the

training set have been found and these molecules have experimental values that disagree with the predicted

value and a prominent number of atom centered fragments of the compound have not been found in the

compounds of the training set or are rare fragments. The five training compounds mostly similar to 2-

Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester are:

CAS: 92-55-7 Result: positive Similarity: 0.75

CAS: 57-66-9 Result: negative Similarity: 0.74

CAS: 5036-03-3 Result: positive Similarity: 0.72

CAS: 58-93-15 Result: negative Similarity: 0.72

CAS: 54-31-9 Result: negative Similarity: 0.71

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative Borderline reliability

Based on ACD/Percepta prediction, it was concluded that the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester is NEGATIVE for microbial in vitro Salmonella, and the prediction is of borderline reliability.

Executive summary:

Gene mutation of the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system. The four predictors were employed in order to apply a consensus approach to enhance the reliability of the prediction. In the consensus assessment only reliable predictions are to be taken into account. Thus, in the case of 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester, based on ACD/Percepta prediction, it was concluded that the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester is NEGATIVE for microbial in vitro Salmonella, and the prediction is of borderline reliability.