Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was predicted to be not sensitizing to the skin of female CBA mice.

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

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of test material: Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)
- IUPAC name: Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)
- Molecular formula: C33H22CoN9O11S2. 2 Na
- Molecular weight: 890 g/mole
- Smiles :Cc1cc(N(=O)=O)c2c(c1)N=N1c3c4ccc(S(O)(=O)=O)cc4ccc3N[Co]{2+}113(Nc4ccc5cc(S(=O)(=O)N C)ccc5c4N1=Nc1ccc(N(=O)=O) cc1O{-}.3).O{-}2Na
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

no data available

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

15% w/v

No. of animals per dose:

4

Details on study design:

no data available

Positive control substance(s):

not specified

Parameter:

SI

Test group / Remarks:

test group- no reactions observed

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

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" )  and ("c" and ( not "d") )  )  and "e" )  and ("f" and ( not "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" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

Similarity boundary:Target: CNS(=O)(=O)c1ccc2c(c1)ccc1c2N2=Nc3ccc(N(=O)=O)cc3O{-}.[Co]{2+}223(N1)Nc1ccc4cc(S(=O)(=O)O{-}.[Na]{+})ccc4c1N2=Nc1ccc(N(=O)=O)cc1O{-}.3
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Lactim form by Tautomers unstable

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Cyanamide form OR Enol form by Tautomers unstable

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aryl AND Cobalt, salt AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Naphtalene AND Nitrobenzene AND Phenol AND Sulfonamide AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Biphenyl by Organic Functional groups

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aryl AND Cobalt, salt AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Naphtalene AND Nitrobenzene AND Phenol AND Sulfonamide AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Urea derivatives by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aryl AND Cobalt, salt AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Naphtalene AND Nitrobenzene AND Phenol AND Sulfonamide AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 829 Da

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 931 Da

Interpretation of results:

other: Negative

Conclusions:

Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was predicted to be not sensitizing to the skin of female CBA mice.

Executive summary:

The skin sensitization potential of Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was predicted to be not sensitizing to the skin of female CBA mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated to ascertain the degree of dermal sensitization caused by Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) to a greater or lesser extent. The studies are based on in vivo experiments in humans along with predicted data for target chemical and its structurally similar read across chemicals, Disodium 6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate(Allura Red AC)[CAS: 25956-17-6] and disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) was predicted to be not sensitizing to the skin of female CBA mice.

Draize-Shelanski repeated insult patch test was conducted (487. Allura red AC (WHO Food Additives Series 15), 1981) on 200 human subjects to assess the skin sensitization potential of the structurally similar read across chemical,Disodium 6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate(Allura Red AC)[CAS: 25956-17-6]. The chemical applied to the subject’s 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 Allura Red AC dye was considered to be not sensitizing in a Draize-Shelanski repeated insult patch test conducted on 200 human subjects.

The above results are also supported by a series of patch tests performed by Guin JD. (Contact Dermatitis 2003: 49: 217–218) to determine the allergenic potential of the structurally similar read across chemical, disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1].The dye was applied on15 patients 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.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)was not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) indicates that it is not likely to cause any dermal sensitization to skin.

Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.