5-amino-2-anilinobenzenesulphonic acid

Endpoint summary

Description of key information

The chemical 5-Amino-2-anilinobenzenesulfonic acid is not likely to classify as a toxicant upon repeated exposure by oral route of administration

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term 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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.3

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

Specific details on test material used for the study:

- Name of test material: 5-amino-2-anilinobenzenesulphonic acid
- Molecular formula: C12H12N2O3S
- Molecular weight: 264.304 g/mol
- Smiles notation: O=S(=O)(O)c1c(Nc2ccccc2)ccc(N)c1
- Substance type: Organic

Species:

rat

Strain:

Crj: CD(SD)

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Details on route of administration:

not specified

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

not specified

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

Description (incidence and severity):

not specified

Details on results:

not specified

Dose descriptor:

NOEL

Effect level:

1 295.603 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

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

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

no

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL
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("g" and(not "h")) ) and("i" and(not "j")) ) and("k" and "l") )

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 Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aniline AND Aryl 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 Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] 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 Secondary amine AND Secondary 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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

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 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Methyldopa (Hepatotoxicity) Alert OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Not categorized OR o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B OR p-Aminophenols (Renal toxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.909

Conclusions:

5-amino-2-anilinobenzenesulphonic acid has a predicted No Observed Effect Level (NOEL) of 1295.602783203 mg/Kg/day.

Executive summary:

Repeated dose oral toxicity was predicted for the test compound 5-amino-2-anilinobenzenesulphonic acid using SSS QSAR prediction database, 2016. The study assumed the use of male and female Sprague Dawley rats in subacute study period. The animals were dosed by oral gavage route of exposure. 5-amino-2-anilinobenzenesulphonic acid has a predicted No Observed Effect Level (NOEL) of 1295.602783203 mg/Kg/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 295.603 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from K2 prediction 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 chemical have been reviewed and summarised below to determine the mutagenic nature of 5-Amino-2-anilinobenzenesulfonic acid:

Repeated dose oral toxicity was predicted for the test compound 5-amino-2-anilinobenzenesulphonic acid (CAS no 91 -30 -5) using SSS QSAR prediction database, 2016. The study assumed the use of male and female Sprague Dawley rats in subacute study period. The animals were dosed by oral gavage route of exposure. 5-amino-2-anilinobenzenesulphonic acid has a No Observed Effect Level (NOEL) of 1295.602783203 mg/Kg/day.

Repeated dose oral toxicity study was performed (Japan Chemicals Collaborative Knowledge Database, 2016) to evaluate the toxic nature of 4-amino-1-sodium naphthalene sulfonic acid (RA CAS no 130 -13 -2) upon repeated application by oral route of administration. The test chemical was dosed at levels of 0, 100, 300 or 1000 mg/Kg once daily for 28 days. Recovery test was set up in the study designed. During the administration period and during the recovery test period, no deaths were observed in any of the treatment groups, and the results of general condition, body weight, food intake and urinalysis, hematology examination, pathological examination were also used for administration of the test substance There was no change thought to be caused. On the other hand, in the blood biochemical test at the end of the administration period, high GPT activity was observed in the group administered 1000 mg / kg of male and female, and it was judged that it is highly likely that it is a finding attributable to administration of the test substance. Hence, The No observed adverse effect level (NOAEL) in male and female SPF strain Sprague Dawley rats is found to be 300 mg/Kg bw/day.

In another study by Japan Chemicals Collaborative Knowledge Database, 2016, Combined repeated dose repro-devp. Screen was performed for 2-Amino-1-naphthalenesulfonic acid (RA CAS no 81 -16 -3) to evaluate its toxic nature upon repeated application by the oral route of exposure. The test compound was administered to Crj: CD (SD), (SPF) male and female rats at dose levels of 0, 8, 40, 200 or 1000 mg/Kg bw. The animals were observed for clinical signs, mortality, hematological and blood chemistry parameters, changes in body weight and alteration in gross and histopathology if any. Salivation was observed in males and females during the administration period in the 1000 mg/Kg group. However, it diasaapered after 10 minutes of administration. In the organ weight, the liver absolute weight and the relative weight were both significantly low in the 1000 mg / kg treated males. No other significant changes were noted at 200 mg/Kg bw in male and female animals. Therefore, the No Observed Adverse Effect Level (NOAEL) in Crj: CD (SD), (SPF) rats is found to be 200 mg/Kg bw.

Based on the weight of evidence data summarized, 5-Amino-2-anilinobenzenesulfonic acid (CAS no 91 -30 -5) not likely to classify as a toxicant upon repeated exposure by oral route of exposure.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Data is from prediction database; 5-amino-2-anilinobenzenesulphonic acid has a No Observed Effect Level (NOEL) of 1295.602783203 mg/Kg/day.

Justification for classification or non-classification

Based on the weight of evidence data summarized, 5-Amino-2-anilinobenzenesulfonic acid (CAS no 91 -30 -5) not likely to classify as a toxicant upon repeated exposure by oral route of exposure.