6-[(2,4-diaminophenyl)azo]-3-[[4-[[4-[[7-[(2,4-diaminophenyl)azo]-1-hydroxy-3-sulpho-2-naphthyl]azo]phenyl]amino]-3-sulphophenyl]azo]-4-hydroxynaphthalene-2-sulphonic acid

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7)was assessedin various experimental studies which were conducted on rabbits for target chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) and structurally similar read across substanceTetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4]andfunctionally similar read across substance aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) was assessedin various experimental studies which were conducted on rabbits for target chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) and functionally similar read across substancesaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) and D & C Red No. 6 (CAS no: 5858-81-1). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 from OECD QSAR toolbox version 3.3 and 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

Specific details on test material used for the study:

- Name of test material: 1,4-bis[(2-methylphenyl)amino]anthraquinone
- Molecular formula: C28H22N2O2
- Molecular weight: 418.494 g/mol
- Smiles notation : c1cc2C(=O)c3c(C(=O)c2cc1)c(Nc1ccccc1C)ccc3Nc1c(cccc1)C
- InChl : 1S/C28H22N2O2/c1-17-9-3-7-13-21(17)29-23-15-16-24(30-22-14-8-4-10-18(22)2)26-25(23)27(31)19-11-5-6-12-20(19)28(26)32/h3-16,29-30H,1-2H3
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

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 Primary amine OR Primary aromatic amine 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 Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] 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 Aminoaniline, meta OR Aromatic amine OR Aryl OR Azo 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 Aminoaniline, meta OR Aniline OR 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 >> 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) >> 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 >> 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 after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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, non cyclic structure 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, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg 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: "j"

Referential boundary: The target chemical should be classified as Group C Molecular Weight > 380 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Hydrazine by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "m"

Similarity boundary:Target: Nc1ccc(N=Nc2ccc3cc(S(O)(=O)=O)c(N=Nc4ccc(Nc5ccc(N=Nc6c(S(O)(=O)=O)cc7ccc(N=Nc8ccc(N)cc8N)cc7c6O)cc5S(O)(=O)=O)cc4)c(O)c3c2)c(N)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.13

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.4

Interpretation of results:

other: not irritating

Conclusions:

The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7)was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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 from OECD QSAR toolbox version 3.3 and 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

Specific details on test material used for the study:

- Name of test material: 6-[(2,4-diaminophenyl)azo]-3-[[4-[[4-[[7-[(2,4-diaminophenyl)azo]-1-hydroxy-3-sulpho-2-naphthyl]azo]phenyl]amino]-3-sulphophenyl]azo]-4-hydroxynaphthalene-2-sulphonic acid
- Molecular formula: C44H35N13O11S3
- Molecular weight: 1018.0385 g/mol
- Smiles notation : c1cc(ccc1Nc2ccc(cc2S(=O)(=O)O)/N=N/c3c(cc4ccc(cc4c3O)/N=N/c5ccc(cc5N)N)S(=O)(=O)O)/N=N/c6c(cc7ccc(cc7c6O)/N=N/c8ccc(cc8N)N)S(=O)(=O)O
- InChl : 1S/C44H35N13O11S3/c45-24-3-12-35(33(47)17-24)54-51-28-5-1-22-15-39(70(63,64)65)41(43(58)31(22)19-28)56-50-27-9-7-26(8-10-27)49-37-14-11-30(21-38(37)69(60,61)62)53-57-42-40(71(66,67)68)16-23-2-6-29(20-32(23)44(42)59)52-55-36-13-4-25(46)18-34(36)48/h1-21,49,58-59H,45-48H2,(H,60,61,62)(H,63,64,65)(H,66,67,68)/b54-51+,55-52+,56-50+,57-53+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and "h" )  and "i" )  and "j" )  and "k" )  and "l" )  and "m" )  and "n" )  and "o" )  and "p" )  and ("q" and "r" )  )

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 Primary amine OR Primary aromatic amine 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 Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] 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 Aminoaniline, meta OR Aromatic amine OR Aryl OR Azo 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 Aminoaniline, meta OR Aniline OR 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 Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra by Chemical elements

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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 Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] 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: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.27

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.11

Interpretation of results:

other: not irritating

Conclusions:

The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7)can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7)was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7)can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) and its structurally similar read across substanceTetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4]andfunctionally similar read across substance aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}.The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7). The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is estimated to be not irritating to skin of New Zealand White rabbits.

 

A study was designed and conducted by Sustainability Support Services (Europe) AB, 2017 to determine the dermal reaction profile of read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4] in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion study. The test item Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate 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.  The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal. Hence, it was concluded that Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested.

 

Another dermal irritation study was conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} that supported the above mentioned results. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) foraluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}after 14 days of observation was 0.0.Alsoaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}can be concluded to be not irritating to New Zealand White rabbit skin.

 

Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) andits functionally similar read across substancesaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) and D & C Red No. 6 (CAS no: 5858-81-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7). The chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is estimated to be not irritating to eye of New Zealand White rabbits.

 

An ocular irritation study was conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) was 0.0 after 72 hours. Also aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5)can be concluded  to be not irritating to New Zealand White rabbit eyes.

 

The above results were further supported by the experimental study reported by IFA GESTIS {GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017} for read across chemical D & C Red No. 6 (CAS no: 5858-81-1) in rabbits. Each rabbit received 2 installation of 0.2 ml of a 10% D & C Red No. 6 aqueous suspension into the conjunctival sac of rabbits 5 times per week for 4 weeks. The chemical produced only minimal irritative effects after 2 hours which could not confirmed the irritation potential. Hence, on the basis of findings the chemical D & C Red No. 6 (CAS no: 5858-81-1) can be considered as not irritating to the rabbits’ eye.

 

Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) is unlikely to cause skin and eye irritation. Hence 6 -[(2,4 -diaminophenyl)azo]-3 -[[4 -[[4 -[[7 -[(2,4 -diaminophenyl)azo]-1 -hydroxy-3 -sulpho-2 -naphthyl]azo]phenyl]amino]-3 -sulphophenyl]azo]-4 -hydroxynaphthalene-2 -sulphonic acid (CAS no. 76186 -07 -7) can be classified under the category “Not Classified” for skin and eye as per CLP.