2-aminotoluene-4-sulphonic acid

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance 2-aminotoluene-4-sulphonic acid (618-03-7) was estimated to be 2307.95 mg/kg bw,and the QSAR prediction done using the Danish (Q)SAR Databasefor target substance 2-aminotoluene-4-sulphonic acid (618-03-7) was estimated to be 3100 mg/kg bw, and for differentstudies available on the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5) was considered to be 5000 mg/kg bw, for 4-aminotoluene-3-sulphonic acid(88-44-8) was considered to be 12000 mg/kg bw and for 1,3-Phenylenediamine-4-sulfonic acid(88-63-1) was considered to be 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,2-aminotoluene-4-sulphonic acid (618-03-7) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

2-aminotoluene-4-sulphonic acid (618-03-7) has very low vapor pressure (9.43E-006 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance 2-aminotoluene-4-sulphonic acid (618-03-7) was estimated to be 2152.55 mg/kg bw ,and for differentstudies available on structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5) was considered to be >2000 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, 2-aminotoluene-4-sulphonic acid (618-03-7) cannot be classified for 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:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from Danish QSAR

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done by using Danish QSAR database

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-aminotoluene-4-sulphonic acid
- Molecular formula: C7H9NO3S
- Molecular weight: 187.218 g/mol
- Smiles notation: O=S(=O)(O)c1ccc(c(N)c1)C
- InChl: 1S/C7H9NO3S/c1-5-2-3-6(4-7(5)8)12(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
- Substance type: Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

3100 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

other: not classified

Conclusions:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3100 mg/kg bw on rats for test substance 2-aminotoluene-4-sulphonic acid (618-03-1) orally.

Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3100 mg/kg bw on rats for 2-aminotoluene-4-sulphonic acid  (618-03-1) having Reliability Index: 0.65 (moderate prediction quality)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 307.95 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

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 QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-aminotoluene-4-sulphonic acid
- Molecular formula: C7H9NO3S
- Molecular weight: 187.218 g/mol
- Smiles notation: O=S(=O)(O)c1ccc(c(N)c1)C
- InChl: 1S/C7H9NO3S/c1-5-2-3-6(4-7(5)8)12(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
- Substance type: Organic
- Physical state: Solid powder (white to pinkish white)

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

2152.55 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

female

Dose descriptor:

LD50

Effect level:

2 152.55 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Moderate binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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 binding by OASIS v.1.3 ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 1 to 10 days by Ultimate biodeg

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 107 Da

Domain logical expression index: "n"

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

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 2152.55 mg/kg bw,when female wistar rats were occlusively exposed with 2-aminotoluene-4-sulphonic acid (618-03-1) by dermal application for 24 hours.

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 2-aminotoluene-4-sulphonic acid (618-03-1).The LD50 was estimated to be 2152.55 mg/kg bw,when female wistar rats were occlusively exposed with 2-aminotoluene-4-sulphonic acid (618-03-1)by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

LD50

Value:

2 152.55 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, 2-aminotoluene-4-sulphonic acid (618-03-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 2-aminotoluene-4-sulphonic acid (618-03-7) along with the study available on the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5), 4-aminotoluene-3-sulphonic acid(88-44-8) and 1,3-Phenylenediamine-4-sulfonic acid(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 2-aminotoluene-4-sulphonic acid(618-03-7).The LD50 was estimated to be 2307.95 mg/kg bw,when male and female Sprague-Dawley rats were orally exposed with 2-aminotoluene-4-sulphonic acid(618-03-7).

The above study was further supported bythe QSAR prediction done using the Danish (Q)SAR Databasefor target substance 2-aminotoluene-4-sulphonic acid (618-03-7). Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 3100 mg/kg bw on rats for 2-aminotoluene-4-sulphonic acid  (618-03-1) having Reliability Index: 0.65 (moderate prediction quality).

This is further supported by Sustainability Support Services (Europe) AB (study number: 19166, 2017-08-10) for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5). The acute oral toxicity profile of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)in Sprague Dawley rats.1% aqueous Tween 80 was used as vehicle. 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. Hence,The lethal concentration (LD50) valuefor acute oral toxicity testwas considered to be 5000mg/kg bw,when female Sprague Dawley rats were treated with 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Also these results are further supported by Ministry of Health & Welfare, Japan (Ministry of Health & Welfare, Japan (1996a): Toxicity Testing Reports of Environmental Chemicals, vol.4 p99-106) and OECD SIDS (SIDS Initial Assessment Report For SIAM 16 Paris, 27-30 May 2003) for the structurally similar read across substance 4-aminotoluene-3-sulphonic acid(88-44-8).In acute oral toxicity study,male and female Sprague-Dawley rats were treated with 2-Amino-5-Methylbenzenesulfonic Acid (88-44-8) in the concentration of 12000 mg/kg bw orally. Sesame oil was used as vehicle.50% mortality observed at 12000 mg/kg bw in treated rats. Therefore, LD50 was considered to be 12000 mg/kg bw when rats were orally exposed with 2-Amino-5-Methylbenzenesulfonic Acid (88-44-8).

This is supported by Richard J Lewis(Sax’s Dangerous Properties of Industrial Materials, 12th Edition); IFA GESTIS (Gestis Substance Database ,2017) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance 1,3-Phenylenediamine-4-sulfonic acid(88-63-1). Acute oral toxicity test of 1,3-Phenylenediamine-4-sulfonic acid (88-63-1) was conducted with rat in 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 (88-63 -1) orally.

Thus, based on the above studies on 2-aminotoluene-4-sulphonic acid (618-03-7) and it’s structurally similar 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, 2-aminotoluene-4-sulphonic acid (618-03-7) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

2-aminotoluene-4-sulphonic acid (618-03-7) has very low vapor pressure (9.43E-006 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In different studies, 2-aminotoluene-4-sulphonic acid (618-03-7) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for 2-aminotoluene-4-sulphonic acid (618-03-7) along with the study available on structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5).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 2-aminotoluene-4-sulphonic acid (618-03-1).The LD50 was estimated to be 2152.55 mg/kg bw,when female wistar rats were occlusively exposed with 2-aminotoluene-4-sulphonic acid (618-03-1)by dermal application for 24 hours.

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 19167, 2017-08-10) for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5). The acute dermal toxicity profile of 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. Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above studies on 2-aminotoluene-4-sulphonic acid (618-03-1) and it’s structurally similar 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, 2-aminotoluene-4-sulphonic acid (618-03-1) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 2-aminotoluene-4-sulphonic acid (618-03-7) and it’s structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (93-00-5), 4-aminotoluene-3-sulphonic acid(88-44-8) and 1,3-Phenylenediamine-4-sulfonic acid(88-63-1), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-aminotoluene-4-sulphonic acid (618-03-7) cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.