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Description of key information

The skin sensitization potential of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was predicted to be not sensitizing to the skin of male Dunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
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 v3.3 and the QMRF report has been attached.
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3, 2017
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
No data available
Specific details on test material used for the study:
- Name (IUPAC): 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C16H13NO7S2
- Molecular weight: 395.4107 g/mol
- Smiles notation: c1cc(cc(c1)S(=O)(=O)O)Nc2ccc3cc(cc(c3c2)O)S(=O)(=O)O
- InChl : 1S/C16H13NO7S2/c18-16-9-14(26(22,23)24)6-10-4-5-12(8-15(10)16)17-11-2-1-3-13(7-11)25(19,20)21/h1-9,17-18H,(H,19,20,21)(H,22,23,24)
- Substance type: Organic
-Physical state: light grey coloured crystalline solid
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
No data available
No. of animals per dose:
12
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Reading:
1st reading
Group:
test group
Dose level:
0.5g
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
No skin sensitization reaction was observed
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest 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" and "r" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] 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: "d"

Referential boundary: The target chemical should be classified as Amine OR Aromatic 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: "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-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) >> 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 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 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 >> 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 No alert found by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Exclusion rules not met 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 OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "p"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2ccc(Nc3cccc(S(O)(=O)=O)c3)cc12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.39

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.72

Interpretation of results:
other: not sensitizing
Conclusions:
The skin sensitization potential of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was predicted to be not sensitizing to the skin of male Dunkin-Hartley guinea pig.
Executive summary:

The skin sensitization potential of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was predicted to be not sensitizing to the skin of male Dunkin-Hartley guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitizaton

In different studies, 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical, 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) and its structurally similar read across substances Methanesulfonic Acid (75-75-2),toluene–4–sulphonic acid (104-15-4) and 2-Dodecylbenzenesulfonic acid (85536-14-7) ,the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7)was predicted to be not sensitizing to the skin of male Dunkin-Hartley guinea pig.

The experimental study conducted byUS EPA(High Production Volume Information System (HPVIS), 2003)to evaluate the skin sensitizing potential of read across substanceMethanesulfonic Acid (75-75-2).The skin sensitization study of Methanesulfonic Acid (75-75-2) was performed by Buehler test in 20Male and female Hartley guinea pigs.. An additional 10 animals served as the vehicle control group; a positive control group was not included in the study. Doses were selected on the bases of preliminary study. In induction phase, 3 induction given using concentration 0.3ml of 50 % test substance in water by epidermal open application for 6 hr at shoulder region on day 1,7 and 14.In challenge phase, 0.3 ml test substance of 25 % concentration in same vehicle used for challenge dose. Test material expose for 24hr on right flank.Evolution done 24hr after challenge application. 0: no reaction,±: slight, patch y erythema,1: slight but confluent or moderate, patchy erythema,2: moderate erythema,3: severe erythema with or without oedema as grading system used .No skin sensitizing reaction observed after challenge application. Hence it is considered that Methanesulfonic Acid (75-75-2) was performed by Buehler test was considered to be not skin sensitizing in guinea pig.

The experimental study conducted byEUROPEAN COMMISSION – European Chemicals Bureau (Iuclid dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 2000)to evaluate the skin sensitizing potential of read across substance toluene–4–sulphonic acid (104-15-4).The skin sensitization study toluene–4–sulphonic acid (104-15-4) was performed on guinea pigs. No indication of skin sensitization was observed. Hence toluene–4–sulphonic acid(104-15-4) was considered to be not sensitizing in guinea pig.

The experimental study conducted byEUROPEAN COMMISSION – European Chemicals Bureau (Iuclid dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 2000)to evaluate the skin sensitizing potential of read across substance 2-Dodecylbenzenesulfonic acid (85536-14-7).The skin sensitization study 2-Dodecylbenzenesulfonic acid (85536-14-7) was performed on guinea pigs. No indication of skin sensitization was observed. Hence 2-Dodecylbenzenesulfonic acid (85536-14-7) was considered to be not sensitizing on guinea pigs.

 Thus based on the above predictions on4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) as well as its read across and applying weight of evidence, it can be concluded that 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) can be considered as not classified for skin sensitization.

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 4-hydroxy-6-[(3-sulfophenyl)amino]naphthalene-2-sulfonic acid (25251-42-7) can be considered as not classified for skin sensitization.