5-amino-2-methoxybenzenesulphonic acid

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) was predicted based on OECD QSAR toolbox 2374 mg/kg bw and different studies available on structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) 5000 mg/kg bw and 2,4-diaminobenzenesulfonic acid (CAS no: 88-63-1) 3480 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 5-amino-2-methoxybenzenesulphonic acid can be classified as category V of acute oral toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) was predicted based on OECD QSAR toolbox 3518 mg/kg bw and differentstudies available for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) >2000 mg/kg bw and functionally similar read across substance 4,4'-Diamino diphenyl sulfone (80-08-0) >4000 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 5-amino-2-methoxybenzenesulphonic acid can be classified as category V of acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: 5-amino-2-methoxybenzenesulphonic acid
SMILES:O=S(=O)(O)c1c(OC)ccc(N)c1
InChI:1S/C7H9NO4S/c1-12-6-3-2-5(8)4-7(6)13(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
Molecular Weight: 203.217 g/mole
Mol. formula: C7H9NO4S

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

2374 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

2 374 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed.

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 >> Hydroquinones OR SN1 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 by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Ether AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic Functional groups

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.508

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2374 mg/kg bw, when Sprague-Dawley female rats were treated with 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) via oral gavage route.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3). The LD50 was estimated to be 2374 mg/kg bw, when Sprague-Dawley female rats were treated with 5-amino-2-methoxybenzenesulphonic acid via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 374 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: 5-amino-2-methoxybenzenesulphonic acid
SMILES:O=S(=O)(O)c1c(OC)ccc(N)c1
InChI:1S/C7H9NO4S/c1-12-6-3-2-5(8)4-7(6)13(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
Molecular Weight: 203.217 g/mole
Mol. formula: C7H9NO4S

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

3518 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 518 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed.

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aromatic amines AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

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 v1.1

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 93 Da

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 248 Da

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 3518 mg/kg bw, when New Zealand White male and female rabbit was treated with 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3). The LD50 was estimated to be 3518 mg/kg bw, when New Zealand White male and female rabbit was treated with 5-amino-2-methoxybenzenesulphonic acid for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 518 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute oral toxicity:

In different studies, 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 5-amino-2-methoxybenzenesulphonic acid along with the study available on structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) and 2,4-diaminobenzenesulfonic acid (CAS no: 88-63-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3). The LD50 was estimated to be 2374 mg/kg bw, when Sprague-Dawley female rats were treated with 5-amino-2-methoxybenzenesulphonic acid via oral gavage route.

The above study is supported by Sustainability Support Services (Europe) AB (study no.19166, 2017) was designed and conducted for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 (Cut-off value) of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) was 5000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.

This study is further supported by Richard J Lewis, Sr. (Sax’s Dangerous Properties of Industrial Materials, 12th Edition, 2012), for the structurally similar read across substance 2,4-diaminobenzenesulfonic acid (CAS no: 88-63-1). Acute oral toxicity was conducted in rat at the concentration of 3480 mg/kg bw orally. 50 % mortality was observed in treated rat. Therefore, LD50 was considered to be 3480 mg/kg when rats were treated with 2,4-diaminobenzenesulphonic acid orally.

 Thus, based on the above studies on 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 5-amino-2-methoxybenzenesulphonic acid can be classified as category V of acute oral toxicity.

Acute Dermal toxicity:

In different studies, 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for 5-amino-2-methoxybenzenesulphonic acid along with the study available on the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) and functionally similar read across substance 4,4'-Diamino diphenyl sulfone (80-08-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3). The LD50 was estimated to be 3518 mg/kg bw, when New Zealand White male and female rabbit was treated with 5-amino-2-methoxybenzenesulphonic acid for 24 hours by dermal application occlusively.

This study is supported by Sustainability Support Services (Europe) AB (study no.19167, 2017) was designed and conducted for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) in Sprague Dawley rats.The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.  It was concluded that the acute dermal median lethal dose (LD50) of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight.Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.

The above study is further supported by Carpenteret al. (Toxicology and Applied Pharmacology Volume 28, Issue 2, May 1974, Pages 313–319) and IFA GESTIS (GESTIS SUBSTANCE Database, 2017), for the functionally similar read across substance 4,4'-Diamino diphenyl sulfone (80-08-0).Acute Dermal toxicity study was conducted in rabbits at the concentration of 4000 mg/kg bw. No Mortality observed at 4000 mg/kg. Therefore, LD50 was considered to be >4000 mg/kg bw, when rabbits were treated with 4,4'-Diamino diphenyl sulfone by dermal application to the skin.

Thus, based on the above studies on 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 5-amino-2-methoxybenzenesulphonic acid can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 5-amino-2-methoxybenzenesulphonic acid (CAS no: 6470-17-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, 5-amino-2-methoxybenzenesulphonic acid can be classified as category V for acute oral and dermal toxicity.