7-acetamido-4-hydroxy-3-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2-sulphonic acid

Endpoint summary

Description of key information

Acute Oral Toxicity:

The LD50 was estimated to be 7025.71 mg/kg bw,when Sprague-Dawley female rats were orally exposed with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) via gavage.

Acute Dermal Toxicity:

The LD50 value was estimated to be 20812.42 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) by dermal application for 24 hours.

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 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid
- IUPAC name: 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid
- Molecular formula: C20H19N3O11S3
- Molecular weight: 573.578 g/mol
- Smiles: c1c(c(c(c2ccc(cc12)NC(=O)C)O)\N=N\c1ccc(cc1)S(=O)(=O)CCOS(=O)(=O)O)S(=O)(=O)O
-InChI:1S/C20H19N3O11S3/c1-12(24)21-15-4-7-17-13(10-15)11-18(36(28,29)30)19(20(17)25)23-22-14-2-5-16(6-3-14)35(26,27)9-8-34-37(31,32)33/h2-7,10-11,25H,8-9H2,1H3,(H,21,24)(H,28,29,30)(H,31,32,33)/b23-22+
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

7025.71 mg/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:

7 025.71 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 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

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 by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Phenol Amines AND Phenols 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.1.3

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 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Dicarbonyl compounds 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 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins 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) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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-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 >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives 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 >> 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 >> N-Hydroxylamines 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 >> Nitro Azoarenes 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 attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom 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 >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates 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 sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated 1,3,5-triazine derivatives OR Low reactive OR Low reactive >> Activated haloarenes OR Low reactive >> N-substituted aromatic amides OR Low reactive >> Saturated carboxylic acid anhydrides OR Moderate reactive OR Moderate reactive >> Unsaturated carboxylic acid anhydrides by DPRA Lysine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> N-Acylloxysuccinimides  OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  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 No alert found 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 SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  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 by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Moderate reactive OR Moderate reactive >> Five-membered heterocyclic urea by DPRA Cysteine peptide depletion

Domain logical expression index: "o"

Similarity boundary:Target: CC(=O)Nc1ccc2c(c1)cc(S(O)(=O)=O)c(N=Nc1ccc(S(=O)(=O)CCOS(O)(=O)=O)cc1)c2O
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR Perhexiline (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> N-Acylamides by Keratinocyte gene expression

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Pyrrolidones by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as > 100 days OR 1 to 10 days by Ultimate biodeg

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.46

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.93

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 7025.71 mg/kg bw,when Sprague-Dawley female rats were orally exposed with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) via gavage.

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 7-acetamido-4-hydroxy-3-[(E)-2-{4 -[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9).The LD50 was estimated to be 7025.71 mg/kg bw,when Sprague-Dawley female rats were orally exposed with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 025.71 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid
- IUPAC name: 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid
- Molecular formula: C20H19N3O11S3
- Molecular weight: 573.578 g/mol
- Smiles: c1c(c(c(c2ccc(cc12)NC(=O)C)O)\N=N\c1ccc(cc1)S(=O)(=O)CCOS(=O)(=O)O)S(=O)(=O)O
-InChI:1S/C20H19N3O11S3/c1-12(24)21-15-4-7-17-13(10-15)11-18(36(28,29)30)19(20(17)25)23-22-14-2-5-16(6-3-14)35(26,27)9-8-34-37(31,32)33/h2-7,10-11,25H,8-9H2,1H3,(H,21,24)(H,28,29,30)(H,31,32,33)/b23-22+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

20812.42 mg/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:

male/female

Dose descriptor:

LD50

Effect level:

20 812.42 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" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and ("s" and "t" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

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 by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Phenol Amines AND Phenols 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.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 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 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 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain 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 >> 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) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones 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 >> 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Unsaturated acid anhydrides OR Low reactive OR Low reactive >> N-substituted aromatic amides OR Low reactive >> Saturated acid anhydrides OR Moderate reactive OR Moderate reactive >> Five-membered heterocyclic urea by DPRA Cysteine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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 by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Has superfragment AND OS(=O)(=O)OCCS(=O)(=O)R{*} by Superfragments ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  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 v1.3

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Carboxamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfate AND Sulfone AND Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Carboxamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfate AND Sulfone AND Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.06

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.263

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 20812.42 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9).The LD50 was estimated to be 20812.42 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

20 812.42 mg/kg bw

Quality of whole database:

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

Additional information

Acute Oral Toxicity:

In different studies, 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid(68189-39-9).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 7-acetamido-4-hydroxy-3-[(E)-2-{4 -[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9).The LD50 was estimated to be 7025.71 mg/kg bw,when Sprague-Dawley female rats were orally exposed with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) via gavage.

In another experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance sodium 5-oxopyrrolidine-2-carboxylate (28874-51-3).Acute oral toxicity study was done in mice using test material sodium 5-oxopyrrolidine-2-carboxylate(28874-51-3).50% Mortality was observed at dose 10400 mg/kg bw. Hence,LD50 value was considered to be 10400 mg/kg bw,when mice were treated with sodium 5-oxopyrrolidine-2-carboxylate(28874-51-3) orally.

In another experimental study conducted by I. F. Gaunt et. al. (Fd Cosmet. Toxtcol. Vol. 5, pp. 171-177,1967) for the structurally similar read across substance Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4). Acute oral toxicity study was done in group of 10 ICI Alderley Park Strain 1 SPF male and female mice using test material Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4).No mortality was observed at dose 2000 mg/kg bw.In clinical signs examination, substantial amounts of coloured material was excreted in the faeces.Hence,LD50 value was considered to be >2000 mg/kg bw,when mice were treated with Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4) orally.

In another experimental study conducted by I. F. Gaunt et. al. (Fd Cosmet. Toxtcol. Vol. 5, pp. 171-177,1967) for the structurally similar read across substance Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4). Acute oral toxicity study was done in group of 5 male and female Carworth Farm Strain E SPF rats using test material Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4).No mortality was observed at dose 5000 mg/kg bw.In clinical signs examination, substantial amounts of coloured material was excreted in the faeces.Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4) orally.

In another experimental study conducted by Margaret Creasey and P. Grasso (Fd Cosmet. ToxicoL Vo]. 7, pp. 557-563,1969) for the structurally similar read across substance Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4). Acute oral toxicity study was done in mice using test material Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when mice were treated with Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4) orally.

Also these results are further supported by the experimental study conducted by Margaret Creasey and P. Grasso (Fd Cosmet. ToxicoL Vo]. 7, pp. 557-563,1969) for the structurally similar read across substance Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4). Acute oral toxicity study was done in rats using test material Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with Tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate(2519-30-4) orally.

Thus, based on the above studies and predictions on 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid(68189-39-9)and its read across substances, it can be concluded that LD50 value was 7025.71 mg/kg bw. Thus, comparing this value with the criteria of CLPregulation,7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid(68189-39-9)can be “Not classified” for Acute Oral Toxicity.

Acute Dermal Toxicity:

In different studies, 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9)has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid(68189-39-9). 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 dermal toxicity was estimated for 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9).The LD50 was estimated to be 20812.42 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9) by dermal application for 24 hours.

In another experimental study conducted by Charles P . Carpenter, et. al. (Toxicology and Applied Pharmacology 28,313-319 (1974)) for the structurally similar read across substance 4-morpholinecarbaldehyde (4394-85-8). In acute dermal toxicity study, rabbits were treated with 4-morpholinecarbaldehyde (4394-85-8) in the concentration of 16000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 16000 mg/kg bw. Therefore, LD50 value was considered to be >16000 mg/kg bw,when rabbits were treated with 4-morpholinecarbaldehyde (4394-85-8)by dermal application.

Also these results are further supported by the experimental study conducted by U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) for the structurally similar read across substance 5,5-dimethylhydantoin (77-71-4). In acute dermal toxicity study,four males and four females albino rabbits were treated with 5,5-dimethylhydantoin(77-71-4) in the concentration of 3000 mg/kg bw by dermal application for observation period of 14 days following the 24-hour exposure period. Rabbits were 10 to 13 weeks old and weighed 2.75 to 3.35 kg. Twenty-four hours prior to the application of the test substance the hair was clipped from the back and flanks of each rabbit. The exposure sites of two rabbits (one male and one female) were lightly abraded. No mortality was observed in treated rabbits at dose 3000 mg/kg bw. Slight erythema was noted in one female rabbit for the first two days following the 24-hours exposure period.No other irritation was noted throughout the study.During the first two or three days of the observation period, most of the rabbits exhibited a creamy nasal discharge, these signs reappeared intermittently throughout the remainder of the observation period. Watery eye discharge was noted daily in one female rabbit. A gross necropsy revealed no significant gross pathologicalfindings in any of the rabbits. Therefore, LD50 value was considered to be >3000 mg/kg bw,when rabbits were treated with 5,5-dimethylhydantoin(77-71-4) occlusively by dermal application.

Thus, based on the above studies and predictions on 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9)and its read across substances, it can be concluded that LD50 value was 20812.42 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9)can be “Not classified” for Acute Dermal Toxicity.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation, 7-acetamido-4-hydroxy-3-[(E)-2-{4-[2-(sulfooxy)ethanesulfonyl]phenyl}diazen-1-yl]naphthalene-2-sulfonic acid (68189-39-9)can be “Not classified” for Acute oral and Dermal Toxicity.