Benzonitrile, 4-bromo-2-chloro-

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:

4-bromo-2-chlorobenzonitrile

EC Number:

679-039-6

Cas Number:

154607-01-9

Molecular formula:

C7H3BrClN

IUPAC Name:

4-bromo-2-chlorobenzonitrile

Results and discussion

Any other information on results incl. tables

Leadscope	ACD/Percepta	Vega	Toxtree	Consensus prediction
NEGATIVE (high reliable)	NEGATIVE Moderate reliable	NEGATIVE (high reliable)	NEGATIVE Not reliable	NEGATIVE High reliable

Leadscope FDA Model Applier prediction formicrobialin vitroSalmonellaresulted to be NEGATIVE, since the positive prediction probability was equal to 0.07. Since 7 features were found, it was concluded that 4-bromo-2-chlorobenzonitrile is well represented by the model.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 4-bromo-2-chlorobenzonitrile 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. Twenty-nine structures were identified in the training set as analogues to 4-bromo-2-chlorobenzonitrile (similarity > 30%) two of them characterized by similarity indices greater than 0.5 and consistent experimental negative Ames test results.Thus, Leadscopeprediction was assessed as high reliable.

ACD/Percepta genotoxicity prediction

ACD/Percepta prediction resulted to be negative, and the prediction was assessed as moderate reliable being the reliability index equal to 0.71. 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 4-bromo-2-chlorobenzonitrile. These training compounds exhibit moderate to high similarity with respect to 4-bromo-2-chlorobenzonitrile (similarity index ranging from 0.76 to 0.94), meaning that the target compound is well represented in the training set of the model, and experimental consistent negative Ames test results. These considerations explained the moderate reliability of the prediction.

ACD/Percepta prediction call	ACD/Percepta positive probability	ACD/Percepta RI	Reliability assessment
NEGATIVE	0.08	0.71	Moderate

Vega predicted 4-bromo-2-chlorobenzonitrile as negative, and the prediction was assessed as high reliable since the applicability domain index was equal to 0.94. In factstrongly similar compounds with known experimental value in the training set have been found, the molecules found in the training set have experimental values that agree with the predicted value, the accuracy of prediction for similar molecules found in the training set is good, all atom centered fragment of the compound have been found in the compounds of the training set and descriptors for the target have values inside the descriptor range of the compounds of the training set. Thus, the prediction was considered high reliable.

Vega Prediction call	Vega prediction reliability	Reliability assessment
NEGATIVE	AD Index = 0.94	HIGH RELIABLE

Toxtree predicts the positive or negative mutagenicity according to decision rules based on the identification of Structural Alerts (SA) for mutagenicity. 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 theApplicability Domain Index (ADI)implemented in VEGA platform.

Toxtree predicted the 4-bromo-2-chlorobenzonitrile as NOT-mutagen since it didn’t identify any structural alert for genotoxicity. The prediction was assessed as not reliablesince theADI (global Applicability Domain Index) was equal to 0.53. 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 adequate, and some atom centered fragments of the compound have not been found in the compounds of the training set.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative High reliability

Gene mutation of the 4-bromo-2-chlorobenzonitrile 4-bromo-2-chlorobenzonitrile was estimated by using four predictors: ACD/Percepta, Leadscope, 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. In the case of 4-bromo-2-chlorobenzonitrile, Toxtree prediction resulted to be not reliable. Thus, based on ACD/Percepta, Leadscope and Vega it was concluded that the target 4-bromo-2-chlorobenzonitrile is predicted with a high level of confidence as NEGATIVE for microbial in vitro Salmonella.

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.