Sodium 2-(p-aminoanilino)-5-nitrobenzenesulphonate

Endpoint summary

Description of key information

LD50 was estimated to be 5072 mg/kg bw, when female wistar rat were exposed with sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3) orally.

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 from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name of the test chemical: sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate
Molecular Formula: C12H10N3NaO5S
Molecular Weight: 331.283 g/mol
Smiles Notation: c1cc(ccc1N)Nc2ccc(cc2S(=O)(=O)[O-])[N+](=O)[O-].[Na+]
Substance type: Organic
Physical State:

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No data available

Doses:

5072mg/kg bw

No. of animals per sex per dose:

10

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

female

Dose descriptor:

LD50

Effect level:

5 072 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

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 7 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 ( not "i") )  )  and "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 Amine OR Anion OR Aromatic compound OR Cation OR Nitro compound OR Primary amine OR Primary aromatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitro, aromatic attach [-NO2] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Nitrobenzene OR Overlapping groups OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline OR Aryl OR Nitrobenzene OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides 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 Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes 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 Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroalkanes 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) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> DNA bases alkylation by carbenium ion formed OR SN1 >> DNA bases alkylation by carbenium ion formed >> Diazoalkanes 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 >> Fused-Ring Nitroaromatics 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Nucleophilic substitution after nitrite formation OR SN2 >> Nucleophilic substitution after nitrite formation >> Nitroalkanes 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: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.43

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 5072 mg/kg bw, when female wistar rat were exposed with sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3) orally.

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 estimatedsodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3).The LD50 was estimated to be 5072 mg/kg bw. When female wistar rats were exposed with sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3)orally

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 072 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

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, sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3) 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 sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3). 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 sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3).The LD50 was estimated to be 5072 mg/kg bw. When female wistar rats were exposed with sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3)orally.

 In another experimental study given by IFA GESTIS (GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn).2017)on structurally similar read across substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid. An acute toxicity study of 4-nitro-4’ aminodiphenylamine-2-sulfonic acid was carried out in 5 male and 5 female Wistar rats The test substance, formulated in starch gruel and administered by gavage at a dose of 5000 mg/kg body weight. The observation period was 14 days. The clinical signs of toxicity observed on the day of administration included motor hyperactivity, ruffled fur, crouch position, retracted flanks and widening of the palpebral fissure. In all animals the urine showed an orange colour up to 3 days after administration of the substance. Autopsy at the end of the observation period did not yield any pathological findings.  During the observation period of 14 days no animals died. Thus, the acute oral toxicity LD 50 value for 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) in Wistar rat was considered to be > 5000 mg/kg.When rats were treated with 4-nitro-4’-aminodiphenylamine-2-sulfonic acid orally.

Also it is further supported by experimental study given byU. S. Environmental Protection Agency (EPA)(U. S. Environmental Protection Agency (EPA) Office of Pollution Prevention and Toxic Substances (OPPTS), 2012) on structurally similar read across substance Disodium 4,4’-diaminostilbene-2,2’-disulphonate(7336-20-1), Acute oral toxicity study was done in male wistar rat using Disodium 4,4’-diaminostilbene-2,2’-disulphonate.Test material was dissolved in water and administered by oral gavage route. All the animals were observed for 14 days .No mortality was observed in rats at dose 5000mg/kg bw .Hence LD50 was considered to be>5000mg/kg body weight. When rats were treated with Disodium 4,4’-diaminostilbene-2,2’-disulphonate (7336-20-1) orally.

 

Thus, based on the above studies and predictions on sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3) and its read across substances, it can be concluded that LD50 value is 5072 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3) can be “Not classified” for acute oral toxicity.

 

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation sodium 2-[(4-aminophenyl) amino]-5-nitrobenzene-1-sulfonate (14846-08-3) can be “Not classified” for acute oral toxicity.