2-amino-5-hydroxynaphthalene-1,7-disulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) 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.

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: as mentioned below

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:

No data available

Specific details on test material used for the study:

- Name of test material: 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Smiles notation: c1cc(c(c2c1c(cc(c2)S(=O)(=O)O)O)S(=O)(=O)O)N
- InChl: 1S/C10H9NO7S2/c11-8-2-1-6-7(10(8)20(16,17)18)3-5(4-9(6)12)19(13,14)15/h1-4,12H,11H2,(H,13,14,15)(H,16,17,18)
- Physical state: Solid
- Substance type: Organic

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

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

No. of animals per dose:

No data available

Details on study design:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

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 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

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  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Alkyl vinyl sulfones (MA) by Protein binding potency

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "m"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.65

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.226

Interpretation of results:

other: Not sensitizing

Conclusions:

The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) 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:

Skin sensitization:

Various studies has been investigated for the test chemical2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and humans for target chemical2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)and Sulphanilic Acid(CAS no:121-57-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs

 

The Guin JD. (2003) conducted skin sensitization study forstructurally similar read across substanceD & C Red No. 6 (CAS no: 5858-81-1)to determine the allergic contact dermatitis caused by the chemical via performing patch test on human patients. The dye was applied on15patients in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories. None of the treated patients showedany signs ofallergic contact dermatitis. Hencethe chemical D & C Red No. 6 (CAS no: 5858-81-1) can be considered as non sensitizer to human skin.

 

The above results were further supported by the cumulative contact enhancement test (CCET) carried out by D. A. Basketter, E. W. Scholes, M. Cumberbatch, C. D. Evans, I. Kimber (1992) of structurally similar read across substance Sulphanilic Acid(CAS no:121-57-3). To induce sensitization a group of 10 guinea pig were albino Dunkin-Hartley strain and weighed approximately 350 g at the start of testing were treated twice weekly for 2 weeks using 24 hrs occluded patches containing 25% sulphanilic acid in vehicle 0.9% PEG 400 (50/50, w/w) over the shoulder region. Immediately before the third application, the test and 4 control guinea pigs were injected with Freund's complete adjuvant in the shoulder region at the site to be patched. Test and control animals were challenged after a 12 days rest period by open application at the maximum nonirritant concentration (25%). Challenge sites were scored for erythema (scale 0-3) at 24- h and 48 h. Sulphanilic Acid did not produce any positive reaction and failed to induce any evidence of sensitization at higher concentrations in the cumulative contact enhancement test (CCET). Therefore Sulphanilic Acid (CAS no: 121-57-3) was considered to be non sensitizing.

Thus on the basis of available data for thetarget chemical2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)and Sulphanilic Acid(CAS no:121-57-3),it can be concluded thatchemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) 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 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) and its structurally similar read across substances D & C Red No. 6 (CAS no: 5858-81-1)and Sulphanilic Acid(CAS no:121-57-3) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.