3-methylsulphanilic acid

Endpoint summary

Description of key information

 LD50 was estimated to be 2441 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 4-amino-3-methylbenzenesulfonic acid.

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: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-amino-3-methylbenzenesulfonic acid
- Molecular formula (if other than submission substance): C7H9NO3S
- Molecular weight (if other than submission substance): 187.218 g/mole
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

2441 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

No data

Statistics:

No data No data

Preliminary study:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 441 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data

Clinical signs:

No data

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

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

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 Alkyl arenes AND Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aniline AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

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 >> 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 OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Not categorized OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic diazo by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.789

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2441 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 4-amino-3-methylbenzenesulfonic acid.

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 4-amino-3-methylbenzenesulfonic acid. The LD50 was estimated to be 2441 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 4-amino-3-methylbenzenesulfonic acid.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 441 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 4-amino-3-methylbenzenesulfonic acid has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-amino-3-methylbenzenesulfonic acid along with the study available on structurally similar read across substance -aminotoluene-3-sulphonic acid (CAS: 98-33-9) and3-Aminobenzenesulfonic acid (CAS: 121-47-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

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 4-amino-3-methylbenzenesulfonic acid. The LD50 was estimated to be 2441 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 4-amino-3-methylbenzenesulfonic acid.

In another prediction done by SSS (2016) using Danish (Q) SAR Database, the acute oral toxicity was estimated for 4-amino-3-methylbenzenesulfonic acid, the acute oral toxicity was estimated for 4-amino-3-methylbenzenesulfonic acid. The LD50 was estimated to be 5600 mg/kg bw when rats were orally exposed with 4-amino-3-methylbenzenesulfonic acid.

Also it is further supported experimental data given by J-CHECK (1996) and OECD SIDS (2003) on structurally similar read across substance 4-aminotoluene-3-sulphonic acid (CAS: 98-33-9), Sprague-Dawley rats were treated with 4-aminotoluene-3-sulphonic acid in the concentration of 12000 mg /kg bw orally by gavage . 50 % mortality obsserved at 12000 mg / kg in treated rats. Therefore, LD50 was considered to be 12000 mg/kg bw when rats were orally exposed with 4-aminotoluene-3-sulphonic acid.

This is further supported by experimental data given by J-CHECK (Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation, 2010)on another structurally similar read across substance 3-Aminobenzenesulfonic acid (CAS: 121-47-1), Crj: CD (SD) male and female rat were treated with 3-Aminobenzenesulfonic acid in the concentration of 500, 1000, 2000 mg/kg orally by gavage. No mortality was observed in treated rats at 500, 1000, 2000 mg/kg. Diarrhea with soft feces on the administration day and the following day, and yellow-discolored urine on the administration day were observed in treated rats at 500 and 1000 mg/kg. In addition, No change in body weight, gross pathological and histopathology were observed in treated male and female rats at 500, 1000, 2000 mg/kg. Therefore, LD50 was considered to be > 2000 mg/kg bw when rat were treated with 3-Aminobenzenesulfonic acid orally.

Thus, based on the above predictions and studies on 4-amino-3-methylbenzenesulfonic acid and its 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, 4-amino-3-methylbenzenesulfonic acid can be “Not-classified” for acute oral toxicity.

Justification for classification or non-classification

Based on the above predictions and studies on 4-amino-3-methylbenzenesulfonic acid and its 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, 4-amino-3-methylbenzenesulfonic acid can be “Not-classified” for acute oral toxicity.