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

Endpoint summary

Description of key information

The skin sensitization potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 3.4 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 3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

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

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

not specified

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR No alert found OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "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 Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0563

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.72

Interpretation of results:

other: Not sensitizing

Conclusions:

The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and mice for target chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substancesResorcinol (CAS No: 108-46-3) and 2-biphenylol (CAS no: 90-43-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

 

 

The D. A. BASKETTR, E. W. SCHOLES et al. { Food and Chemical Toxicology Vol. 32. No. 6. pp. 543-547. 1994} conducted the Local Lymph Node Assay (LLNA) on Female mice for read across substance Resorcinol (CAS No: 108-46-3). The LLNA was conducted on groups of CBA/Ca mice (8-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl of one of three concentrations (5%, 10% and 25%)of the test chemical. 5 days after the first topical application, all mice were injected iv with 250µl phosphate buffered saline (PBS) containing 20µCi of [³H]methyl thymidine (³HTdR) .The mice were killed 5 hr later and the draining auricular lymph nodes excised and pooled for each experimental group. A single cell suspension of lymph node cells (LNC) was prepared by gentle disaggregation through 200 mesh stainless steel gauze. Pooled LNC were pelleted by centrifugation at 190g for 10 min, washed twice with 10 ml PBS and resuspended in 3 ml 5% trichloroacetic acid (TCA). After incubation overnight at 4°C, the precipitate was recovered by centrifugation, resuspended in 1 ml 5% TCA and transferred to 10 ml scintillation fluid. Incorporation of³HTdR was measured by p-scintillation counting. The proliferative response of LNC was expressed as mean radioactive disintegrations per minute per lymph node (dpm/node for each experimental group and as the ratio of³HTdR incorporation into LNC of test nodes relative to control nodes [test: control (T:C) ratio]. A chemical was regarded as a sensitizer in the LLNA if at least one concentration resulted in a T:C ratio of 3 or greater and the data were not incompatible with a biological dose response. The test: control (T:C) ratios were 2.2, 2.2 and 2.7 at concentration of 5%, 10% and 25% respectively. Since the resulted test: control (T:C) ratio was less than 3 at each concentration, the chemical Resorcinol (CAS No: 108-46-3) was considered to be not sensitizing in Local Lymph Node Assay (LLNA).

 

The above results were further supported by the Buehler test reported by the European Commission (EC) - Scientific Committee on Consumer Safety (SCCS) { European Commission (EC) - Scientific Committee on Consumer Safety (SCCS); 25 June 2015} in ten Hartley Albino Guinea Pigs performed read across chemical 2-biphenylol (CAS no: 90-43-7) in accordance withOECD Guideline 406 (Skin Sensitisation).In induction, the 400mg (0.4 g) of2-biphenylolmoistened with 0.2 ml water was applied to a clipped area of the animals’ left side in Hill top chambers and left in place for 6 hr. The procedure was repeated once weekly for three consecutive weeks. After two weeks, animals were challenged a 7.5 % suspension of test material in distilled water was applied to the right side of the animals for 6 hr. Application sites were observed for sensitization response 24 and 48 hr after challenge application. Challenge application with the positive control caused slight to moderate erythema in 9 of 10 animals. The chemical did not induce any skin sensitization reaction in treated group. Therefore2-biphenylol (CAS no: 90-43-7)was considered to be not sensitizing to the skin ofHartley Albino Guinea Pigs.

 

 

Thus on the basis of available data for thetarget chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substances Resorcinol (CAS No: 108-46-3) and 2-biphenylol (CAS no: 90-43-7),it can be concluded thatchemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substances Resorcinol (CAS No: 108-46-3) and 2-biphenylol (CAS no: 90-43-7) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.