4-hydroxy-6-(methylamino)naphthalene-2-sulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) was assessedin various experimental studies which were conducted on guinea pigs and mouse for target chemicalaluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9), Acid Red 18 (CAS No: 2611-82-7)and D & C Red no. 33 (CAS no: 3567-66-6). 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 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) is unable to cause skin sensitization and thus can be considered as not sensitizing. 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 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 (IUPAC name): 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
- Molecular formula: C11H11NO4S
- Molecular weight: 253.2769 g/mol
- Smiles notation: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- InChl: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

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

Concentration / amount:

No data available

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

No data available

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No contact sensitization was observed in treated group.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No contact sensitization was observed in treated group.

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" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "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 SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols 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 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene 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 Primary Aromatic Amines 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) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 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 >> Nitro Azoarenes 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High (Class III) AND Low (Class I) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group C Aqueous Solubility < 0.0005 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group CN log Kow > 4.5 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 Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group C Melting Point > 55 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.99

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.457

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley 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 studieshas been investigated for the test chemical4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) 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 mouse for target chemical4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)and its structurally similar read across substancesaluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9), Acid Red 18 (CAS No: 2611-82-7)and D & C Red no. 33 (CAS no: 3567-66-6).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 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

 

The IPCS INCHEM {Allura red AC (WHO Food Additives Series 15); IPCS INCHEM; 1981} conducted Draize-Shelanski repeated insult patch test was conducted on 200 human subjects to assess the skin sensitization potential of chemical aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9). In this study, the chemical applied to the subjects volvar forearms (200 subjects) as an aqueous solution for 10 alternate days, for 24-hour periods, followed by a 14-day rest period. Challenge batches were then applied under occlusion to fresh skin sites on the subjects scapular backs for 24 hours. The colour did not produce either irritation or allergic responses during the induction phase nor contact dermatitis in the challenge period. Therefore aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9) was considered to be not sensitizing in a Draize-Shelanski repeated insult patch test conducted on 200 human subjects.

 

The above results were supported by the Local Lymph Node Assay (LLNA) reported by the Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP) for read across chemical Acid Red 18 (CAS No: 2611-82-7) on 55 female (11 groups of 5 animals) mouse according to OECD Guideline 429.On days 0, 1 and 2 the animals received 25 μl of one of the test preparations or vehicle on the dorsal surface of each ear. On day 5 all mice received intravenous injection of tritium labelled thymidine in phosphate buffered saline, and 5 hours later they were killed humanely and the draining auricular lymph nodes were removed. Single cell suspensions were prepared for each animal, appropriately treated and measured by liquid scintillation counting. The stimulation indices were less than 3 at all tested concentrations, hence an EC3 value could not be calculated, and thus the test substanceAcid Red 18 (CAS No: 2611-82-7)was considered as non-sensitizing in the vehicles tested.

 

The above results were further supported by the Maximization test reported by Scientific Committee on Consumer Safety (SCCS){ Opinion on Acid Red 33 ,Scientific Committee on Consumer Safety (SCCS), SCCP/1102/07} in female 15 (10 test and 5 control)Guinea pig for read across chemical D & C Red no. 33 (CAS no: 3567-66-6). The intradermal induction of sensitization in the test group was performed in the nuchal region with a 5% dilution of the test item in 1% CMC and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted for 18 hours under occlusion with the test item at 25% in 1% CMC one week after the intradermal induction. The test areas are pretreated with 10 sodium-laureth-sulfates (SLS) 24 hours prior to application of the test item. The animals of the control group were intradermally induced with 1% CMC and FCA/physiological saline and epidermally induced with 1% CMC under occlusion following pre-treatment with 10% SLS. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing. No known skin sensitization reactions were observed in treated as well as control group. Hence the chemical D& C Red no. 33 (CAS no: 3567-66-6) was considered to be not sensitizing.

 

Thus on the basis of available data for thetarget chemical4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)and its structurally similar read across substancesaluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9), Acid Red 18 (CAS No: 2611-82-7)and D & C Red no. 33 (CAS no: 3567-66-6),it can be concluded thatchemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) 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-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6)and its structurally similar read across substancesaluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 68583-95-9), Acid Red 18 (CAS No: 2611-82-7)and D & C Red no. 33 (CAS no: 3567-66-6) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS No:6259-53-6) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.