[μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) was predicted based on OECD QSAR toolbox, the value estimated to be 6892 mg/kg bw and different studies available on structurally similar read across substances Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo)) naphthalene-4,6-disulphonate (CAS No. 2519-30-4), the LD50 was considered to be >2000 mg/kg bw and Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (CAS no: 3567-69-9), the LD50 was considered to be 4166.66 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt cannot be classified for acute oral toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) was predicted based on OECD QSAR toolbox, the value estimated to be 9606 mg/kg bw and different studies available for the structurally similar read across substances Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) LD50 was considered to be >2000 mg/kg bw and Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (CAS no: 3567-69-9)LD50 was considered to be >2000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt cannot be classified for acute dermal toxicity.

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:

Data is predicted using OECD QSAR toolbox version 3.3 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 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name:[μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt
SMILES:Oc1cc(N=N(=O)c2ccc(N=Nc3c(S(=O)(=O)O{-}.[Na]{+})cc4cc(S(=O)(=O)O{-}.[Na]{+})ccc4c3O)c(O)c2)ccc1N=Nc1c(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc2c1O
InChI:1S/C32H22N6O17S4.2Cu.4Na/c39-25-13-17(1-7-23(25)33-35-29-27(58(50,51)52)11-15-9-19(56(44,45)46)3-5-21(15)31(29)41)37-38(43)18-2-8-24(26(40)14-18)34-36-30-28(59(53,54)55)12-16-10-20(57(47,48)49)4-6-22(16)32(30)42;;;;;;/h1-14,39-42H,(H,44,45,46)(H,47,48,49)(H,50,51,52)(H,53,54,55);;;;;;/q;2*+2;4*+1/p-8/b35-33+,36-34+,38-37+;;;;;;
Molecular Weight: 1101.8036 g/mole
Mol. formula: C32H14Cu2N6Na4O17S4

Species:

rat

Strain:

other: Wistar derived

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

6892 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 892 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and "ak" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Cation OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

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

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 >> Quinoneimines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> 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) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> 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 metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 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 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

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 Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo 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 Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Metals (1a) 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 Not covered by current version of the decision tree OR Organophosphorus compounds (1b) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

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 Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Carboxylic acids (Hepatotoxicity) No rank OR Chlorphentermine (Hepatotoxicity) Alert OR Oxyphenistain (Hepatotoxicity) Alert OR Phenols (Mucous membrane irritation) Rank C OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "q"

Similarity boundary:Target: Oc1cc(N=N(=O)c2ccc(N=Nc3c(S(=O)(=O)O{-}.[Na]{+})cc4cc(S(=O)(=O)O{-}.[Na]{+})ccc4c3O)c(O)c2)ccc1N=Nc1c(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc2c1O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as tert-Butyl by Organic Functional groups

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Pyrimidine OR Quinoline/ Isoquinoline OR Sulfonamide OR Sulfonate ester by Organic Functional groups

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Ketone OR Melamine OR Nitrile by Organic Functional groups

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Fused heterocyclic aromatic OR Fused saturated heterocycles OR Heterocyclic Phenol by Organic Functional groups

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Alcohol OR Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "ad"

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

Domain logical expression index: "ae"

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

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Azoxy AND Fused carbocyclic aromatic AND Overlapping groups AND Phenol AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Triazine by Organic Functional groups (nested)

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Azoxy AND Fused carbocyclic aromatic AND Overlapping groups AND Phenol AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Biphenyl OR Carboxylic acid by Organic Functional groups (nested)

Domain logical expression index: "aj"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.227

Domain logical expression index: "ak"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.89

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 6892 mg/kg bw, when 10 male and female Wistar derived rats were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) via oral gavage route.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1). The LD50 was estimated to be 6892 mg/kg bw, when 10 male and female Wistar derived rats were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 892 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

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 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 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name:[μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt
SMILES:Oc1cc(N=N(=O)c2ccc(N=Nc3c(S(=O)(=O)O{-}.[Na]{+})cc4cc(S(=O)(=O)O{-}.[Na]{+})ccc4c3O)c(O)c2)ccc1N=Nc1c(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc2c1O
InChI:1S/C32H22N6O17S4.2Cu.4Na/c39-25-13-17(1-7-23(25)33-35-29-27(58(50,51)52)11-15-9-19(56(44,45)46)3-5-21(15)31(29)41)37-38(43)18-2-8-24(26(40)14-18)34-36-30-28(59(53,54)55)12-16-10-20(57(47,48)49)4-6-22(16)32(30)42;;;;;;/h1-14,39-42H,(H,44,45,46)(H,47,48,49)(H,50,51,52)(H,53,54,55);;;;;;/q;2*+2;4*+1/p-8/b35-33+,36-34+,38-37+;;;;;;
Molecular Weight: 1101.8036 g/mole
Mol. formula: C32H14Cu2N6Na4O17S4

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

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:

9606 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

9 606 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 ( 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 ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and ( not "ah") )  )  and ("ai" and "aj" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Cation OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

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

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 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 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

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 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

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 Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 11 - Trans.Metals Cu,Ag,Au OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 13 - Metalloids B by Chemical elements

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [-CH3] by Organic functional groups (US EPA)

Domain logical expression index: "aa"

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

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Calcium [Ca] by Organic functional groups (US EPA)

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Hydroxy, nitrogen attach [-OH] by Organic functional groups (US EPA)

Domain logical expression index: "ae"

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

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as No functional group found by Organic functional groups (US EPA)

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Azo compound AND Cation AND Hydroxy compound AND Phenol AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Carbonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "ai"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.793

Domain logical expression index: "aj"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.23

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 9606 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1). The LD50 was estimated to be 9606 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

9 606 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Additional information

Acute oral toxicity:

In different studies, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt along with the study available on structurally similar read across substances Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) and Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (CAS no: 3567-69-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1). The LD50 was estimated to be 6892 mg/kg bw, when 10 male and female Wistar derived rats were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) via oral gavage route.

The above study is supported by Sustainability Support Services (Europe) AB (study no.18817, 2016) was designed and conducted for the structurally similar read across substance Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in diarrhoea (black colour stools) in all animals with onset at 2 hours and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in diarrhoea (black colour stools) in all animals with onset at 4 hours and no mortality after the dosing. All animals from 300 mg/kg and 2000 mg/kg dose groups survived through the study period of 14 days. Staining of the stool is attributed to the black colour of the test item. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo)) naphthalene-4,6-disulphonate (CAS No. 2519-30-4) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4), when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

This study is further supported by Lamiaet al.(International Journal of PharmTech Research, Vol.9, No.4, pp 364-367, 2016), for the structurally similar read across substance disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1- sulfonate (CAS no: 3567-69-9). The acute oral toxicity study was conducted in male Sprague-Dawley white mice at the concentrations of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg, 5000 mg/kg, 6250 mg/kg bw. 6 animals/dose were administered the given test chemical via oral gavage route and control animals were received distilled water. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. The LD50 of the substances was calculated using the arithmetic method of Karber. 50% mortality was observed at 4166.66 mg/kg bw. The clinical signs such as, loss of appetite, drowsiness, tachycardia, decrease in locomotion and anorexia were distinctive signs observed in the mice before dead. Therefore, LD50 was considered to be 4166.66 mg/kg bw, when male Sprague- Dawley white mice were treated with Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl] naphthalene-1-sulfonate for 3 days via oral gavage route.

Thus, based on the above studies on [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt cannot be classified for acute oral toxicity.

Acute Dermal toxicity:

In different studies, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt along with the study available on the structurally similar read across substances Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) and Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (CAS No. 3567-69-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1). The LD50 was estimated to be 9606 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) for 24 hours by dermal application occlusively.

This study is supported by Sustainability Support Services (Europe) AB (study no.18818, 2016) was designed and conducted for the structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

The above study is further supported by Sustainability Support Services (Europe) AB (study no.18824, 2016) was designed and conducted for the structurally similar read across substance Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (CAS No. 3567-69-9) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (3567-69-9) supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate does not exhibits acute toxicity by the dermal route.

Thus, based on the above studies on [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (CAS no: 75173-68-1) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt cannot be classified for acute oral and dermal toxicity.