Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate

Endpoint summary

Description of key information

The skin sensitization potential of target chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was assessedi n various experimental studies which were conducted on guinea pigs and humans for target chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) 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

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 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:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name: Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate
SMILES:Nc1ccc2cc(S(=O)(=O)O{-}.[Na]{+})cc(O)c2c1N=Nc1ccc(Cl)cc1C(F)(F)F
InChI:1S/C17H11ClF3N3O4S.Na/c18-9-2-4-13(11(6-9)17(19,20)21)23-24-16-12(22)3-1-8-5-10(29(26,27)28)7-14(25)15(8)16;/h1-7,25H,22H2,(H,26,27,28);/q;+1/p-1/b24-23-;
Mol. formula: C17H10ClF3N3NaO4S
Molecular Weight: 467.786 g/mole

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

Challenge controls:

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 skin sensitization reaction was observed in treated guinea pigs.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization reaction was observed in treated guinea pigs.

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" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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: "c"

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

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 Acid moiety AND Anilines (Unhindered) AND Phenol Amines AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure 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 No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Similarity boundary:Target: Nc1ccc2cc(S(=O)(=O)O{-}.[Na]{+})cc(O)c2c1N=Nc1ccc(Cl)cc1C(F)(F)F
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Amine AND Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Azo compound AND Cation AND Halogen derivative AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Diarylether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Amine AND Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Azo compound AND Cation AND Halogen derivative AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aryl fluoride by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0777

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.35

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) 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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) 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:

Various studies has been investigated for the test chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) 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 humans for target chemicalSodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance Sodium 6-amino-5 -[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs

 

The Guin JD. (Contact Dermatitis 2003: 49: 217–218) 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 showed any signs of allergic contact dermatitis. Hence the 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 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 chemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1) and D& C Red no. 33 (CAS no: 3567-66-6) ,it can be concluded thatchemical Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) 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”.

Justification for classification or non-classification

The skin sensitization potential of test substance Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1) 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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS No: 57741-47-6) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.