2-aminotoluene-4-sulphonic acid

Endpoint summary

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 2-aminotoluene-4-sulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 18 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-aminotoluene-4-sulphonic acid is predicted to be 948.0 mg/Kg bw/day.

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

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose 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 from OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4, 2018

GLP compliance:

not specified

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:

Sprague-Dawley

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: unspecified

Details on route of administration:

No data

Vehicle:

not specified

Details on oral exposure:

No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

18 days

Frequency of treatment:

Daily

Remarks:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Positive control:

No data

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

No data

Other examinations:

No data

Statistics:

No data

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No data

Dose descriptor:

NOAEL

Effect level:

948 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
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" )  or "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

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 Moderate binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Aminoaniline, meta OR Aminoaniline, ortho by Organic Functional groups

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Surfactants - Anionic by Organic Functional groups

Domain logical expression index: "o"

Similarity boundary:Target: Cc1ccc(S(O)(=O)=O)cc1N
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.28

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.244

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for 2-aminotoluene-4-sulphonic acid is predicted to be 948.0 mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 2-aminotoluene-4-sulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 18 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-aminotoluene-4-sulphonic acid is predicted to be 948.0 mg/Kg bw/day.

Based on this value 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

Dose descriptor:

NOAEL

948 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from K2 QSAR prediiction database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Prediction model based estimation and data from read across chemicals have been reviewed to determine the mutagenic nature of

2-aminotoluene-4-sulphonic acid. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 2-aminotoluene-4-sulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 18 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-aminotoluene-4-sulphonic acid is predicted to be 948.0 mg/Kg bw/day.

The predicted data for the target chemical is further supported by the data from read across chemicals as mentoined below:

Repeated dose toxicity study was performed to evaluate the toxic nature of 80 -90% structurally similar read across chemical 2-amino-5-methyl benzene sulfonic acid (RA CAS no 88 -44 -8) (J-check, 2018) using male and female Crj: CD (SD) rats. The test chemical was dissolved in sesame oil and used at dose levels of 0, 30, 300 or 1000 mg/Kg/day. The treated animals were observed for clinical signs, mortality, changes in body weight and food consumption, and the animals were subjected to gross and histopathology. In both males and females, there was no effect of administration of test substance on change in general condition and body weight.In males, the mean daily food intake for the 8 to 15 days in the 1000 mg / kg group showed a statistically significant high value, and the cumulative food consumption from 1 to 15 days of administration showed a high value. In females, there was no difference between the control group and each test substance-administered group over the administration period. In males, no difference was observed between the control group and each test substance-administered group throughout the administration period. In females, at 100 and 1000 mg / kg group, the statistically significant low values were observed only on the 4th day of nursing compared to the control group. However, since there was no obvious difference on the other measurement day and it was a change only for 1 day, and since there was no obvious change in body weight gain during the nursing period, the influence of administration of the test substance It was not thought to be an accidental change. In the 300 mg / kg group, the actual weight of the epididymis showed a statistically significant lower value than the control group, but there was no difference in the relative weight, and a similar change was observed in the 1000 mg / kg group. There was no difference between the control group and each test substance administered group for testicular weight. No findings that could be attributed to the administration of the test substance were observed in any of the animals. In males, black lesions of the lungs were observed in the control group and 1 group in the 300 mg / kg group in the male, 1 red subject in the liver and white spots in the 300 mg / kg group, 1 in the same individual, testis and epididymal atrophy was observed in one group of the same individual in the 300 mg / kg group, and one in each group in the 300 and 1000 mg / kg group of thinning of the coat. No abnormal findings were observed in one female in the 100 mg / kg group that did not mate. Tissue findings showed seminiferous tubular atrophy in male. However, although it is suggested that it may be a factor of mating failure, it was judged that there is no relation with the administration of the test substance from the frequency of occurrence. Based on the observations made, the No observed adverse effect level (NOAEL) was considered to be 1000mg/kg/day for 2-amino-5-methyl benzene sulfonic acid in male and female Crj: CD (SD) rats during subchronic repeated dose toxicity study.

50 -60% structurally and functionally similar read across chemical 2-phenyl-1H-benzimidazole-5-sulphonic acid (RA CAS no 27503 -81 -7) was administered orally to male and female Wistar rats 7 days/week for 13 weeks (SCCP, 2006). The study was conducted according to OECD guideline 408. The dosage was 0, 100, 330 and 1000 mg/kg bw, and the vehicle (5% aqueous tylose) administration group was provided as a control. Animals were examined with respect to in-life-observations (viz. mortalities and clinical signs of toxicity, body weight and food-/water consumption were recorded.), clinical pathology (viz. haematology, clinical chemistry and urinalysis) and anatomic pathology (viz. organ weights, necropsy, histopathology.). Three mortalities (1♂, week 5, control group; 1♀, week 13, 330 mg/kg-group; 1♀, week 6, 1000 mg/kg-group) occurred intercurrently but were not substance related. No clinical signs of toxicity were seen in any group. Food- and water consumption were the same in test- and control groups. Haematology results (total and differential blood count) of test animals did not differ from controls throughout the experiment. The same holds for clinico-chemical parameters, except for protein content in serum in females of the 1000 mg/kg-group, which was increased as compared to controls. However, the level found was within the biological variability range on record for female rats of this age and was therefore not considered substance related. Necropsy-findings in the animals which had died intercurrently, revealed no pathological changes attributable to the test substance. Neither did the animals which were sacrificed pursuant to protocol at the end of the study exhibit any such changes. Differences in organ weights, if observable at all (e.g. spleen in♀'s), were small and not dose dependent. Histopathology did not reveal any organ change or –damage in any one of the dose groups. Based on the above study, the toxicologically no adverse effect amount by repetitive oral administration of 2-phenyl-1H-benzimidazole-5-sulphonic acid ( Novantisol saure) (CAS No. 27503 -81 -7) for 13 weeks was observed and hence under this test condition NOAEL was considered to be 1000 mg/kg bw/day.

Based on the data available for the target chemical and its read across, 2-aminotoluene-4-sulphonic acid is not likely to be toxic upon repeated exposure by oral route as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 2-aminotoluene-4-sulphonic acid (CAS no 618 -03 -1) is not likely to be toxic upon repeated exposure by oral route as per the criteria mentioned in CLP regulation.