4,4'-dihydroxy-7,7'-iminodi(naphthalene-2-sulphonic acid)

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 value was estimated to be 3755 mg/kg bw for rats when treated with

4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid orally.

Acute dermal toxicity:

LD50 value was estimated to be 7026 mg/kg bw for rabbits. when treated with 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid by dermal application.

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C20H15NO8S2
- Molecular weight: 461.47 g/mol
- Smiles notation: O=S(=O)(O)c1cc(O)c2c(cc(Nc3ccc4c(cc(S(=O)(=O)O)cc4O)c3)cc2)c1
- InChl: 1S/C20H15NO8S2/c22-19-9-15(30(24,25)26)7-11-5-13(1-3-17(11)19)21-14-2-4-18-12(6-14)8-16(10-20(18)23)31(27,28)29/h1-10,21-23H,(H,24,25,26)(H,27,28,29)
- Substance type: Organic
- Physical state: Solid

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:

3755 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 755 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 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 ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very 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 Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 to Quinones and Quinone-type Chemicals 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 SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 >> Aromatic phenylureas 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 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides 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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation 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 Radical OR Radical >> Radical mechanism via ROS formation (indirect) 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) >> Nitrobiphenyls and Bridged Nitrobiphenyls OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 >> Acetates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Hydroxy compound AND Phenol 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: "q"

Referential boundary: The target chemical should be classified as Alcohol OR Aldehyde OR Alkylarylether OR Carbonic acid derivative OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid derivative OR Ether OR Ketone OR Nitrile OR Primary aliphatic amine OR Primary amine OR Secondary alcohol OR Sulfone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert OR Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.228

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.9

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 3755 mg/kg bw when rats were orally exposed with 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid.

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 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (87 -03 -6). The LD50 was estimated to be 3755 mg/kg bw when rats were orally exposed with 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 755 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox 3.4

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

other information

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C20H15NO8S2
- Molecular weight: 461.47 g/mol
- Smiles notation: O=S(=O)(O)c1cc(O)c2c(cc(Nc3ccc4c(cc(S(=O)(=O)O)cc4O)c3)cc2)c1
- InChl: 1S/C20H15NO8S2/c22-19-9-15(30(24,25)26)7-11-5-13(1-3-17(11)19)21-14-2-4-18-12(6-14)8-16(10-20(18)23)31(27,28)29/h1-10,21-23H,(H,24,25,26)(H,27,28,29)
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

7026 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

7 026 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % motality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

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 ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very 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 Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly by Aquatic toxicity classification by ECOSAR

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 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain 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 via ROS formation (indirect) 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) >> Nitrobiphenyls and Bridged Nitrobiphenyls 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 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 >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 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, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane 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 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 >> 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 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 nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as 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 Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> Other non-steroidal estrogen receptor (ER) binding compounds (2b-2) OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) OR Toluene and small alkyl toluene derivatives (8a) OR Triarylmethane dyes (12c) by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups

Domain logical expression index: "s"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.339

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.19

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 value was estimated to be 7026 mg/kg bw for rabbits.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, Based on the prediction done using the OECD QSAR toolbox version 3.4 and considering the five closest read across substances, the acute dermal toxicity in rats was predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid. LD50 value was estimated to be 7026 mg/kg bw for rabbits. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 026 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox 3.4

Additional information

Acute oral toxicity:

In different studies, 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experimental and estimations in rodents, i.e. most commonly in mice and rats for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid along with the study available on structurally similar read across substance Tetrasodium 3,3'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonate] (CAS no 72-57-1) and 2,7-Naphthalenedisulfonic acid, 4-(4,6-dichloro-s-triazin-2-ylamino)-5-hydroxy-6-(2-hydroxy-5-nitrophenylazo)- (CAS no 73826-58-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, Based on the prediction done using the OECD QSAR toolbox version 3.4 and considering the five closest read across substances, the acute oral toxicity in rats was predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid. LD50 value was estimated to be 3755 mg/kg bw for rats. 

In another experimental study summarized by Lewis et al (Sax's Dangerous Properties of Industrial Materials. 11th Edition, p. 935, 2004.), Hazardous Substances Data Bank (HSDB (Hazardous Substances Data Bank), US national Library of Medicine, 2017) and National Technical Reports Library (NTRL, Acute oral toxicity study prepared by food and Drug Research Laboratories Incorporated, OTS0215154, 1972) on structurally similar read across substance Tetrasodium 3,3'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonate] (CAS no 72-57-1), 4 groups of albino rats, consisting of 3 males and 2 females of the Sherman-Wistar rat were treated with Tetrasodium 3,3'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonate] at the concentration of 4000, 5000, 6250 and 7900 mg/kg orally by gavage. The test substance was in the form of Dark Blue Powder which dissolved at 25% W/V Suspension in Water (Vehicle). The animals were observed initially for a Acclimation period of 1 week to assure normalcy. The animals were allowed food and waterad libitumduring a 14 day observation period. The mortality data were evaluated according to the Thompson Moving Average Method. At 6250 gm/kg, 3 animals were died and at 7900 mg/kg all animals died. No mortality was observed at 4000, 5000 mg/kg. Therefore, LD50 was considered to be 6200 mg/kg at 19/20 Confidence Limits of 5500 - 6900 mg/kg bw, when Sherman-Wistar rat was treated with Tetrasodium 3,3'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonate] orally by gavage.

Further supported by experimental study given by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE, Lite Browse Advanced, 2017) and RTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017) on structurally similar read across substance 2,7-Naphthalenedisulfonic acid, 4-(4,6-dichloro-s-triazin-2-ylamino)-5-hydroxy-6-(2-hydroxy-5-nitrophenylazo)- (CAS no 73826-58-1), rats were treated with 2,7-Naphthalenedisulfonic acid, 4-(4,6-dichloro-s-triazin-2-ylamino)-5-hydroxy-6-(2-hydroxy-5-nitrophenylazo)- in the concentration of 9120 mg/kg bw. 50% mortality was observed at 9120 mg/kg bw in treated rats. Therefore, LD50 was considered to be 9120 mg/kg bw, when rat was treated with 2,7-Naphthalenedisulfonic acid, 4-(4,6-dichloro-s-triazin-2-ylamino)-5-hydroxy-6-(2-hydroxy-5-nitrophenylazo)- orally.

Thus, based on the above studies and predictions on 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid and its read across substances, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-Hydroxy-4-methylbenzoic acid can be classified as category IV of acute oral toxicity.

Acute dermal toxicity:

In different studies, 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experimental and estimations in rodents, i.e. most commonly in mice and rabbits for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid along with the study available on structurally similar read across substanceResorcinol (CAS no 108-46-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, Based on the prediction done using the OECD QSAR toolbox version 3.4 and considering the five closest read across substances, the acute dermal toxicity in rats was predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid. LD50 value was estimated to be 7026 mg/kg bw for rabbits. 

In another experimental study summarized by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE, Lite Browse Advanced, 2017), U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank), US national Library of Medicine, 2017), World Health Organization (World Health Organization, International Programme on Chemical Safety (IPCS), United Nations Environment Programme (UNEP), 2006) and European Commission (EC) - Scientific Committee on Cosmetology (SCC) (Opinion of the Scientific Committee on Cosmetology (11/86 - 10/90), European Commission (EC) - Scientific Committee on Cosmetology (SCC), 1993) on structurally similar read across substanceResorcinol (CAS no 108-46-3), male rabbits were treated with Resorcinol at the concentration of 1000, 2000 and 3360 mg/kg bw for 24 h applied by topically. Animals were observed for clinical signs, body weight and Gross pathology. 50% morality was observed in rabbits at 3360 mg/kg along with clinical signs such as - At 1000 mg/kg body weight – Animals were experienced slight hyperkeratosis and moderate to severe irritation after 24 h of exposure. At ≥2000 mg/kg body weight - skin necrosis was seen in treated rabbits.Body weight loss was observed at 1000 mg/kg. No gross lesions were observed at 1000 mg/kg body weight. Therefore, LD50 was considered to be 3360 mg/kg bw, when male rabbits were treated with Resorcinol by topically application for 24 hours.

Further experimental study summarized by World Health Organization (World Health Organization, International Programme on Chemical Safety (IPCS), United Nations Environment Programme (UNEP), 2006) on structurally similar read across substanceResorcinol (CAS no 108-46-3), rabbits were treated with Resorcinol at the concentration of 3830 mg/kg. Clinical signs and Gross pathology were examination in treated rabbits.50% morality was observed with the signs of intoxication included salivation, tremors, and convulsions and the treated skin areas showed slight erythema and extreme dryness. After necropsy, the survivors gave no significant findings, whereas haemorrhages of the gastrointestinal tract were noted in the dead animals. Therefore, LD50 was considered to be 3830 mg/kg bw, when rabbits were treated with Resorcinol by dermal application.

Again this is supported by experimental study given by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE, Lite Browse Advanced, 2017) on structurally similar read across substance Bisphenol S (CAS no 80-09-1), rabbits were treated with Bisphenol S in the concentration of 10250 mg/kg by dermal application. No morality was observed at 10250 mg/kg bw in treated rabbits. Therefore, LD50 was considered to be > 10250 mg/kg, when rabbits were treated with Bisphenol S by dermal application.

Thus, based on the above studies and predictions on 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid and its read across substances, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-Hydroxy-4-methylbenzoic acid can be classified as category IV of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-Hydroxy-4-methylbenzoic acid can be classified as category V of acute oral and dermal toxicity.