7-anilino-4-hydroxynaphthalene-2-sulphonic acid

Endpoint summary

Description of key information

7-anilino-4-hydroxynaphthalene-2-sulphonic acid  is likely to be non hazardous by oral route of exposure.

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)

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 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Test type:

other: Estimated data

Specific details on test material used for the study:

Name: 7-anilino-4-hydroxynaphthalene-2-sulphonic acidMolecular Formula: C16H13NO4SMolecular Weight: 315.3477 g/mole SMILES:Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccccc3)ccc12

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 513.8 mg/kg bw

Based on:

test mat.

Mortality:

50 % mortality observed in treated rats.

Clinical signs:

No data available

Body weight:

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") ) and("e" and(not "f")) ) and("g" and(not "h")) ) and "i") and("j" and(not "k")) ) and "l") and("m" and(not "n")) ) and("o" and(not "p")) ) and("q" and(not "r")) ) and("s" and(not "t")) ) and("u" and(not "v")) ) and("w" and "x") )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Strong binder, OH 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  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

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 and Trihydroxybenzenes OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane 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) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after 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 >> Conjugated Nitro Compounds 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards 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 >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives 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.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

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 >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes 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 SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as 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: "k"

Referential boundary:The target chemical should be classified as Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccccc3)ccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift OR Keto form (5-membered heteroarenes) - 1,3-H shift by Tautomers unstable

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Amiodarone (Hepatotoxicity) Alert OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Oxyphenistain (Hepatotoxicity) Alert OR Pirprofen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on quinone type chemicals OR Michael Addition >> Michael addition on quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "t"

Referential boundary:The target chemical should be classified as Arylethanamine-like derivatives (11a) OR Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Prostaglandin receptor agonists (3c) OR Steroid nucleus derived ER and AR binders OR Steroid nucleus derived ER and AR binders >> Androgens, anti-androgens (2a-4) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "u"

Referential boundary:The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "v"

Referential boundary:The target chemical should be classified as 1,3-Benzodioxoles (Nongenotox) OR Heterocyclic Polycyclic Aromatic Hydrocarbons (Genotox) OR Structural alert for nongenotoxic carcinogenicity OR Structural alerts for both genotoxic and nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.58

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.96

Interpretation of results:

other: not classified

Conclusions:

Estimated LD50 was considered to be 3513.8 mg/kg bw when rats were treated with 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally.

Executive summary:

Acute oral toxicity was estimated QSAR Toolbox 3.4. (2016) in rats by using 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally. 50 % mortality were observed in treated rats at 3513.8 mg/kg bw. Therefore, estimated LD50 was considered to be 3513.8 mg/kg bw when rats were treated with 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 513.8 mg/kg bw

Quality of whole database:

Data is Klimish 2 and from QSAR Toolbox 3.4. (2016)

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:

Based on Based on the data available for target 7-anilino-4-hydroxynaphthalene-2-sulphonic acid (CAS no 119-40-4) and its read across 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid (CAS no 6099-57-6), C.I. Acid Orange 10 (CAS no 1936-15-8) and 1-Naphthol-4-sulfonic acid sodium salt (CAS no 6099-57-6) are summarized below

Based on prediction done by using QSAR Toolbox 3.4. (2016), acute oral toxicity was estimated in rats by using 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally. 50 % mortality were observed in treated rats at 3513.8 mg/kg bw. Therefore, estimated LD50 was considered to be 3513.8 mg/kg bw when rats were treated with 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally. 

In a study conducted by Sustainability Support Services (Europe) AB (2013) for read across, acute oral toxicity was evaluated in Wistar female rats by using 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid in the concentration of 2000 mg/kg bw orally by gavage in distilled water and observed for 14 days. No effect on survival, clinical sign and body weight of treated female rats at 2000 mg/kg bw. No gross pathological changes were observed in treated female rata at 2000 mg/kg bw. Therefore, LD50 was considered to be > 2000 mg/kg bw when Wistar female rats were treated with 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid orally by gavage.

In a study conducted by National Toxicology Program (1987) for read across, acute oral toxicity was evaluated in group of five F344/N male and female rats and B6C3F1 male and female mice by using C.I. Acid Orange 10 in the concentration of 600, 1250, 2500, 5000, 10000 and 20000 mg/kg bw orally in feed for 24 hours and observed for 14 days. No mortality at 600, 1250, 2500, 5000, 10000 and 20000 mg/kg bw and no gross pathological changes were observed in treated male and female rats at 20000 mg/kg bw. Therefore, LD50 was considered to be >20000 mg/kg bw when F344/N male and female rats and B6C3F1 male and female mice were treated with C.I. Acid Orange 10 orally by feed for 24 hours.

In a study given by Japan chemical collaborative knowledge database (2016) for read across, acute oral toxicity was evaluated in Crj:CD(SD)IGS group of 5 male and 5 female rats by using 1-Naphthol-4-sulfonic acid sodium salt in the concentration 2000 mg/kg bw orally. No mortality and change in clinical signs, body weight and gross pathology were observed in treated male and female rats at 2000 mg/kg bw. Therefore, LD50 was considered to be >2000 mg/kg bw when Crj:CD(SD)IGS male and female rats were treated with 1-Naphthol-4-sulfonic acid sodium salt orally.

Thus, based on weight of evidence for target 7-anilino-4-hydroxynaphthalene-2-sulphonic acid (CAS no 119-40-4) and its read across 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid (CAS no 6099-57-6), C.I. Acid Orange 10 (CAS no 1936-15-8) and 1-Naphthol-4-sulfonic acid sodium salt (CAS no 6099-57-6) is likely to be non hazardous by oral route of exposure.

Justification for selection of acute toxicity – oral endpoint

estimated LD50 was considered to be 3513.8 mg/kg bw when rats were treated with 7-anilino-4-hydroxynaphthalene-2-sulphonic acid orally.  

Justification for classification or non-classification

Based on weight of evidence for target 7-anilino-4-hydroxynaphthalene-2-sulphonic acid (CAS no 119-40-4) and its read across 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid (CAS no 6099-57-6), C.I. Acid Orange 10 (CAS no 1936-15-8) and 1-Naphthol-4-sulfonic acid sodium salt (CAS no 6099-57-6) is likely to be non hazardous by oral route of exposure.