3-amino-4-chlorobenzamide

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD QSAR Toolbox prediction for single chemical based on read-across. The target chemical FALLS within applicability domain.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: company data

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: based on: Guidance on information requirements and chemical safety assessment, Chapter R.6: QSARs and grouping of chemicals (ECHA, May 2008)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: based on: Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship Models (OECD, September 2007)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: based on: GUIDANCE DOCUMENT FOR USING THE OECD (Q)SAR APPLICATION TOOLBOX TO DEVELOP CHEMICAL CATEGORIES ACCORDING TO THE OECD GUIDANCE ON GROUPING OF CHEMICALS (OECD Feb. 2009)

Principles of method if other than guideline:

QSAR Toolbox prediction of Gene mutation potential based on read-across

GLP compliance:

no

Type of assay:

other: QSAR in vitro Genetic Toxicity

Test material

Test material information

Constituent 1

Reference substance name:

3-amino-4-chlorobenzamide

EC Number:

243-231-4

EC Name:

3-amino-4-chlorobenzamide

Cas Number:

19694-10-1

Molecular formula:

C7H7ClN2O

IUPAC Name:

3-amino-4-chlorobenzamide

Details on test material:

Target substance:
3-amino-4-chlorobenzamide, CAS 19694-10-1
SMILES: C(N)(=O)c1cc(N)c(Cl)cc1

Category members used for read-across:
4-aminobenzamide, CAS 2835-68-9
2,4-difluoroaniline, CAS 367-25-9
2-chloroaniline, CAS 95-51-2
3-chloroaniline, CAS 108-42-9
2,4-dimethylaniline, CAS 95-68-1
2,5-dimethylaniline, CAS 95-78-3

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium

Metabolic activation:

not specified

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium

Metabolic activation:

not specified

Genotoxicity:

negative

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"

Estimation method: Takes highest mode value from the 5 nearest neighbours

Domain logical expression: Result: In Domain

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The predicted value using the QSAR toolbox is "negative". The substance is therefore considered to be not mutagenic (in vitro).

Executive summary:

Category justification

Specific mechanisms or modes of action are identified for the target chemical, which are relevant for the investigated endpoint genetic toxicity. Therefore, the grouping was conducted by the DNA binding alerts and in vitro mutagenicity alerts, and then refined by subcategory of structure similarity and organic functional groups.

Estimation method: Taking highest mode value from the 5 nearest neighbours, based on 95 data points from 6 neighbour chemicals.

Domain logical expression: Result: In Domain

(((("a" and("b" and(not "c")) ) and "d") and("e" and(not "f")) ) and("g" and "h") )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic halogens OR Alkyl (C<5) or benzyl ester of sulphonic or phosphonic acid OR Alkyl carbamate and thiocarbamate OR alpha,beta-unsaturated carbonyls OR Aromatic diazo OR Aromatic mono-and dialkylamine OR Aromatic N-acyl amine OR Aromatic nitroso group OR Aromatic ring N-oxide OR Coumarins and Furocoumarins OR Epoxides and aziridines OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Hydrazine OR Nitro-aromatic OR No alert found OR Polycyclic Aromatic Hydrocarbons OR Quinones OR Simple aldehyde by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "d"

Similarity boundary: Target: C(N)(=O)c1cc(N)c(Cl)cc1; Threshold=50%; Dice(Atom centered fragments)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Benzamide by Organic functional groups

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Alkyl halide OR Aminoaniline, meta OR Aminoaniline, ortho OR Aminoaniline, para OR Benzopyran OR Benzyl OR Biphenyl OR Carboxylic acid OR Cycloketone OR Dianilines OR Ether OR Fused carbocyclic aromatic OR No functional group found OR Phenol OR Precursors quinoid compounds OR Unsaturated heterocyclic fragment by Organic functional groups

Domain logical expression index: "g"

Parametric boundary: The target chemical should have a value of log Kow which is >= -0.181

Domain logical expression index: "h"

Parametric boundary: The target chemical should have a value of log Kow which is <= 2.17

Prediction approach:

Read-across among category members:

4-aminobenzamide, CAS 2835-68-9 (Negative 17x)

2,4-difluoroaniline, CAS 367-25-9 (Negative 9x, Positive 4x)

2-chloroaniline, CAS 95-51-2 (Negative 21x)

3-chloroaniline, CAS 108-42-9 (Negative 10x, Positive 2x)

2,4-dimethylaniline, CAS 95-68-1 (Negative 8x, Positive 7x, Equivocal 1x)

2,5-dimethylaniline, CAS 95-78-3 (Negative 7x, Positive 7x, Equivocal 2x)

Summary

Toxicity of the target chemical (Negative) is predicted from category members using read-across based on 95 values (Positive x20, Equivocal x3, Negative x72) from 6 nearest neighbours compared by prediction descriptors. Category members are single chemicals or mixtures and are selected based on the profile of the target chemical. Only chemicals having experimental data are listed in the category.

Predicted target value: Negative (75.8%)