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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) was predicted based on OECD QSAR toolbox 22107 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) >2000 mg/kg bw and Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) >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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) has very low vapour pressure (1.613E-17 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) was predicted based on OECD QSAR toolbox 13739 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) >2000 mg/kg bw and Disodium 4-hydroxy-3-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-1-sulfonate (3567-69-9) >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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium 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)
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:
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: 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt
SMILES:[Mg]_[Na]_Oc1c2ccc(Nc3ccccc3)cc2cc(S(O)(=O)=O)c1N=Nc1ccc(N=Nc2ccc(N=Nc3cc(S(O)(=O)=O)ccc3S(O)(=O)=O)c3ccc(S(O)(=O)=O)cc23)c2ccccc12
InChI:1S/C42H29N7O13S4.Mg.Na/c50-42-29-13-10-26(43-25-6-2-1-3-7-25)20-24(29)21-40(66(60,61)62)41(42)49-47-35-16-15-34(30-8-4-5-9-31(30)35)44-46-37-18-17-36(32-14-11-27(22-33(32)37)63(51,52)53)45-48-38-23-28(64(54,55)56)12-19-39(38)65(57,58)59;;/h1-23,43,50H,(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62);;/q;+2;+1/p-3/b46-44+,48-45+,49-47+;;
Molecular Formula: C42H29N7O13S4.xMg.xNa
Molecular Weight: 1012.2624 g/mole
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
not specified
Doses:
22107 mg/kg bw
No. of animals per sex per dose:
5
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:
22 107 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
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 ( not "t") )  )  and "u" )  and ("v" and ( not "w") )  )  and "x" )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Azo compound OR Hydroxy compound OR Phenol OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid 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 Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Hydroxy, aromatic attach [-OH] OR Hydroxy, sulfur attach [-OH] OR Magnesium [Mg] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR No functional group found OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] 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 Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR No functional group found 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 Aromatic amine OR Aryl OR Azo 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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> 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 >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione 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 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 >> Secondary 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 Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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 >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Exclusion rules not met AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Melting Point > 200 C AND Group All Molecular Weight > 650 g/mol AND Group CNS Aqueous Solubility < 0.006 g/l AND Group CNS log Kow > 1.5 AND Group CNS log Kow > 3.6 AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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 Exclusion rules not met AND Group All Melting Point > 200 C 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: "p"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Group CNS log Kow < 0.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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 AND Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra by Chemical elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Selennm Se by Chemical elements

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Hydroxy, sulfur attach [-OH] AND Magnesium [Mg] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND No functional group found AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Azo compound AND Hydroxy compound AND No functional group found AND Phenol AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Acidic [90,100] AND Basic [0,10) AND No pKa value AND No pKb value by Ionization at pH = 9

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Acidic [0,10) by Ionization at pH = 9

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.873

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.14

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 22107 mg/kg bw, when 5 male and female Wistar rats were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) via oral gavage route.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3). The LD50 was estimated to be 22107 mg/kg bw, when 5 male and female Wistar rats were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt via oral gavage route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
22 107 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.3.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

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:
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: 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt
SMILES:[Mg]_[Na]_Oc1c2ccc(Nc3ccccc3)cc2cc(S(O)(=O)=O)c1N=Nc1ccc(N=Nc2ccc(N=Nc3cc(S(O)(=O)=O)ccc3S(O)(=O)=O)c3ccc(S(O)(=O)=O)cc23)c2ccccc12
InChI:1S/C42H29N7O13S4.Mg.Na/c50-42-29-13-10-26(43-25-6-2-1-3-7-25)20-24(29)21-40(66(60,61)62)41(42)49-47-35-16-15-34(30-8-4-5-9-31(30)35)44-46-37-18-17-36(32-14-11-27(22-33(32)37)63(51,52)53)45-48-38-23-28(64(54,55)56)12-19-39(38)65(57,58)59;;/h1-23,43,50H,(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62);;/q;+2;+1/p-3/b46-44+,48-45+,49-47+;;
Molecular Formula: C42H29N7O13S4.xMg.xNa
Molecular Weight: 1012.2624 g/mole
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
not specified
Duration of exposure:
24 hour
Doses:
13739 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:
13 739 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
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 ("t" and ( not "u") )  )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Azo compound OR Hydroxy compound OR Phenol OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid 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 Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Hydroxy, aromatic attach [-OH] OR Hydroxy, sulfur attach [-OH] OR Magnesium [Mg] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR No functional group found OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] 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 Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR No functional group found 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 Aromatic amine OR Aryl OR Azo 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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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-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) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives 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 SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione 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 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 Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acyl halides (Genotox) OR Metals, oxidative stress (Nongenotox) OR o-phenylphenol (Nongenotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "m"

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 Exclusion rules not met AND Group All Melting Point > 200 C 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: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CN Melting Point > 180 C OR (!Undefined)Group CN Vapour Pressure < 0.001 Pa OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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 AND Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra by Chemical elements

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Similarity boundary:Target: [Mg]_[Na]_Oc1c2ccc(Nc3ccccc3)cc2cc(S(O)(=O)=O)c1N=Nc1ccc(N=Nc2ccc(N=Nc3cc(S(O)(=O)=O)ccc3S(O)(=O)=O)c3ccc(S(O)(=O)=O)cc23)c2ccccc12
Threshold=20%,
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 Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Azo compound AND Hydroxy compound AND No functional group found AND Phenol AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Hydroxy, sulfur attach [-OH] AND Magnesium [Mg] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND No functional group found AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.873

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.14

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 13739 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) for 24 hours by dermal application occlusively.
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 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3). The LD50 was estimated to be 13739 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt for 24 hours by dermal application occlusively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
13 739 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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) 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 for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium 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 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6). 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 (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3). The LD50 was estimated to be 22107 mg/kg bw, when 5 male and female Wistar rats were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt 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 Sustainability Support Services (Europe) AB (study no.18819, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) 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 (reddish 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 (reddish colour stools) in all animals with onset at 2 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 reddish 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 Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Thus, based on the above studies on 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) 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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) has very low vapour pressure (1.613E-17 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

In different studies, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) 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 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium 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 (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 (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3). The LD50 was estimated to be 13739 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt 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 (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 bySustainability 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 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) 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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (CAS no: 93941-74-3) 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, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt cannot be classified for acute oral and dermal toxicity.For Acute Inhalation toxicity wavier was added so, not possible to classify.