5-amino-2-chlorobenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 5-amino-2-chlorobenzenesulfonic acid (88-43-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 5-amino-2-chlorobenzenesulfonic acid was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4, 2017.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material: 5-amino-2-chlorobenzenesulfonic acid
- Molecular formula: C6H6ClNO3S
- Molecular weight: 207.636 g/mol
- Smiles notation: S(c1c(ccc(c1)N)Cl)(O)(=O)=O
- InChl: 1S/C6H6ClNO3S/c7-5-2-1-4(8)3-6(5)12(9,10)11/h1-3H,8H2,(H,9,10,11)
- Substance type: Organic
- Physical state: Solid

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

Prediction was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

not specified

Remarks on result:

other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 9 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and "n" )  and "o" )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 17 - Halogens Br OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "m"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B by Repeated dose (HESS)

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.85

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.889

Conclusions:

5-amino-2-chlorobenzenesulfonic acid (88-43-7) was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for5-amino-2-chlorobenzenesulfonic acid (88-43-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 5-amino-2-chlorobenzenesulfonic acid was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Genetic Toxicity in vitro

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 5-amino-2-chlorobenzenesulfonic acid (88-43-7). The studies are as mentioned below

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for5-amino-2-chlorobenzenesulfonic acid (88-43-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 5-amino-2-chlorobenzenesulfonic acid was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Gene mutation toxicity was predicted for 5-amino-2-chlorobenzenesulfonic acid (88-43-7) using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain.

Gene mutation toxicity study as predicted by 5-amino-2-chlorobenzenesulfonic acid is negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by H. E. Seifried et al. (Chem. Res. Toxicol, 2006) to determine the mutagenic nature of2-amino-5-methylbenzene sulfonic acid (88-44-8; 2). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. 2-amino-5-methylbenzolsulfonsäure (88-44-8) was assessed for its possible mutagenic potential .For this purpose Ames test was performed on Salmonella typhimurium strain TA 98, TA 100, TA1535, TA 1537and TA 1538. The test material was exposed at the concentration of 0, 33-1000 µg/plate in the absence of S9. While in the presence of S( the test material concentration was 0,667-10000 µg/plate. No mutagenic effects were observed in all strailin the presence and absence of metabolic activation. Therefore 2-amino-5-methylbenzolsulfonsäure was considered to be non mutagenic in Salmonella typhimurium strain  TA 98,TA 100,TA1535,TA 1537and TA 1538 by AMES test. Hence the test chemical cannot be classified as gene mutant in vitro.

 

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by H. E. Seifried et al. (Chem. Res. Toxicol, 2006) to determine the mutagenic nature of 4-amino-3-methylbenzenesulfonic acid (98-33-9 ).The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Ames mutagenicity test was conducted for chemical 4-amino-m-toluenesulfonic acid to evaluate the mutagenic effects. The test chemical exposed to S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 10-10000 µg/plate by plate incorporation method. Negative mutagenic effects were observed in Ames Salmonella test when exposed to strains TA98, TA100, TA1535, TA1537, and TA1538 in the presence and absence of S9 metabolic activation Therefore 4-amino-m-toluenesulfonic acid was considered to be non mutagenic in S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 by Ames test. Hence the test chemical cannot be classified as gene mutant in vitro.

Based on the data available for the target chemical and its read across substance and applying weight of evidence 5-amino-2-chlorobenzenesulfonic acid (88-43-7)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for the target chemical. 5-amino-2-chlorobenzenesulfonic acid (88-43-7)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.