6-aminonaphthalene-1,3-disulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) 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 (LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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

Type of study:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material: 6-aminonaphthalene-1,3-disulfonic acid
- Common name: 6-Amino-1,3-naphthalenedisulfonate
- Molecular formula: C10H9NO6S2
- Molecular weight: 303.314 g/mol
- Smiles notation: c12c(cc(S(O)(=O)=O)cc1S(O)(=O)=O)cc(N)cc2
- InChl: 1S/C10H9NO6S2/c11-7-1-2-9-6(3-7)4-8(18(12,13)14)5-10(9)19(15,16)17/h1-5H,11H2,(H,12,13,14)(H,15,16,17)
- 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:

other: not specified

Route:

other: not specified

No. of animals per dose:

not specified

Details on study design:

not specified

Challenge controls:

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

no sensitizing effects were observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitizing effects were 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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and "k" )  )

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) AND beta-Naphthylamines, Sulfonated 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.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 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: "h"

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: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All log Kow < -3.1 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 Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNS log Kow < -2 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.61

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.88

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) 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:

Various studies has been investigated for the test chemical6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) and its structurally similar read across substancesDapsone (CAS No: 80-08-0) and Ensulizole(CAS No: -27503 -81 -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 of 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) was estimated to be not sensitising to the skin of guinea pigs. Based on the estimated result 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

 

 

The National Technical Reports library (NTRL, 1991) conducted a preliminary dose-range finding study on structurally similar read across substancein which four animals (two males and two females) were exposed to one concentration (as received) of Dapsone (CAS No: 80-08-0) at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %. Dapsone was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration. An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4-dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge. No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in quinea piqs. Hence Dapsone (CAS No: 80-08-0) is not sensitizer to the skin of Guinea pig.

 

 

The above results were further supported by guinea pig maximization study carried out by the HEALTH AND CONSUMER PROTECTION DIRECTORATE GENERAL (2016)onstructurally similar read across substance Ensulizole(CAS No: -27503 -81 -7 ) in Dunkin Hartley guinea pigs. In induction phase 20 animals in test group and 10 animals in negative controls were used. Animals were induced with intradermal injections of 0.1ml Freund’s complete adjuvant in water, Phenylbenzimidazole Sulfonic Acid 1% w/v in arachis oil, and Freund’s and Phenylbenzimidazole Sulfonic Acid 1% w/v in arachis oil (1:1) into three separate sites.After 1 week, a single topical application of0.2 – 0.3 ml Phenylbenzimidazole Sulfonic Acid 50% w/w in arachis oilunder occlusion for 48 hours was applied.On day 21 animals were challenged with 0.l-0.2 ml Phenylbenzimidazole Sulfonic Acid 25 and 10% w/w in arachis oil.Since there was no evidence of any skin reaction, the test materialEnsulizole/Phenylbenzimidazole Sulfonic Acid (CAS No: -27503-81-7) can be concluded as not sensitizing to guinea pigs.

 

Thus on the basis of available data for thetarget chemical6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) and its structurally similar read across substancesDapsone (CAS No: 80-08-0) and Ensulizole(CAS No: -27503 -81 -7 ),it can be concluded thatchemical 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) 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 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) and its structurally similar read across substancesDapsone (CAS No: 80-08-0) and Ensulizole(CAS No: -27503 -81 -7 ) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 6-aminonaphthalene-1,3-disulfonic acid (CAS No: 118-33-2) is not likely to cause skin sensitization and hencecan be classified under the category “Not Classified”as CLP regulation.