4-acetamido-5-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]anthranilic acid, sodium salt

Endpoint summary

Description of key information

Acute oral toxicity

LD50 was estimated to be 26453.31mg/kg bw ,when  female wistar rats were exposed with 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4) 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 material: 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium
- IUPAC name: 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium
- Molecular weight: 566.4984 g/mol
- Molecular formula: C16H18N4O10S3.xNa
- Substance type: Organic
- Smiles: S(=O)(=O)(c1cc(c(cc1N)NC(=O)C)/N=N/c1ccc(S(=O)(=O)CCOS(=O)(=O)[O-])cc1)[O-].[Na+].[Na+]

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:

26453.31mg/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:

26 453.31 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 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 ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Not categorized AND Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND No alert found by Protein binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Quinones OR Radical 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) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 >> N-Hydroxylamines 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 >> Nitroarenes with Other Active Groups OR SN2 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: "i"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR 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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 13 - Metalloids B OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Mixture by Substance Type ONLY

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.92

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.232

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 26453.31mg/kg bw ,when female wistar rats were exposed with 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4) 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 estimated for 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4),LD50 was estimated to be 26453.31mg/kg bw ,when female wistar ratswereexposed with 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4)orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

26 453.31 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, 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4)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 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4).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 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4),LD50 was estimated to be 26453.31mg/kg bw ,when female wistar rats were exposed with 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4)orally.

 Also these results are further supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substance,Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(CAS No.3734-67-6).The acute oral toxicity profile of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo) naphthalene-2,7-disulphonate in 12 female Sprague Dawley rats.The test material dissolved in distilled water and given by oral gavage route. 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, hence 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. No mortality was observed at dose concentration 2000mg/kg bw. Hence The LD50 value was considered to be >2000 mg/kg body weight. When Sprague Dawley rats were treated with Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate orally.

In another experimental study given by U.S. National Library of Medicine (ChemIDplusA TOXNET Database, 2017) on structurally similar read across substance2-amino-5-[(4-sulfophenyl)diazenyl]benzene sulfonic acid(101-50-8). Acute oral toxicity study was done in rat using 2-amino-5-[(4-sulfophenyl)diazenyl]benzene sulfonic acid(101-50-8).50%mortality was observed at dose 14800mg/kg bw. Hence, LD50 was considered to be 14800mg/kg body weight. When rat was treated with 2-amino-5-[(4-sulfophenyl)diazenyl]benzene sulfonic acid(101-50-8)orally.

Thus, based on the above studies and predictions on 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4) and its read across substances, it can be concluded that LD50 value is 26453.31mg/kg bw. Thus, comparing this value with the criteria of CLP 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4) can be “Not classified” for acute oral toxicity.

 

 

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP 2-amino-4-acetamido-5-[(E)-2-(4-{[2-(sulfooxy)ethane]sulfonyl}phenyl)diazen-1-yl]benzoic acid sodium (94158-82-4) can be “Not classified” for acute oral toxicity.