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Administrative data

Description of key information

Skin Sensitization:

The skin sensitization potential of C.I Direct Blue 218[CAS: 28407 -37 -6] was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. C.I Direct Blue 218[CAS: 28407 -37 -6] was predicted to be not sensitizing to the skin of female Dunkin- Hartley guinea pigs.

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
Reference:
Composition 0
Qualifier:
according to
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
Test material information:
Composition 1
Specific details on test material used for the study:
Name of the test chemical: Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI)
Common Name: C.I Direct Blue 218
Molecular Formula: C32H20Cu2N6Na4O16S4
Molecular Weight: 1087.84 g/mol
SMILES Notation: c12c3c(c(S(=O)(=O)[O-])cc1cc(S(=O)(=O)[O])cc2N)N=Nc1ccc(cc1O[Cu]O3)c1cc2c(N=Nc3c(cc4c(c3O[Cu]O2)c(cc(c4)S(=O)(=O)[O-])N)S(=O)(=O)[O-])cc1.[Na+].[Na+].[Na+].[Na+]
InChI: 1S/C32H24N6O16S4.2Cu.4Na/c33-19-11-17(55(43,44)45)5-15-9-25(57(49,50)51)29(31(41)27(15)19)37-35-21-3-1-13(7-23(21)39)14-2-4-22(24(40)8-14)36-38-30-26(58(52,53)54)10-16-6-18(56(46,47)48)12-20(34)28(16)32(30)42;;;;;;/h1-12,39-42H,33-34H2,(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54);;;;;;/q;2*+2;4*+1/p-8/b37-35-,38-36-;;;;;;
Substance Type: Organic
Physical State: Solid
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
no data available
Route:
intradermal and epicutaneous
Vehicle:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
20
Details on study design:
no data available
Challenge controls:
no data available
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
Clinical observations:
no signs of sensitization 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" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and "h" )  )

Domain logical expression index: "a"

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: "b"

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: "c"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "d"

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 (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met 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 < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Biphenyl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of Water Solubility which is >= -68.6 mg/L

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of Water Solubility which is <= 7.01E004 mg/L

Interpretation of results:
other: Negative
Conclusions:
C.I Direct Blue 218[CAS: 28407 -37 -6] was predicted to be not sensitizing to the skin of female Dunkin- Hartley guinea pigs.
Executive summary:

The skin sensitization potential of C.I Direct Blue 218 [CAS: 28407 -37 -6] was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. C.I Direct Blue 218[CAS: 28407 -37 -6] was predicted to be not sensitizing to the skin of female Dunkin- Hartley guinea pigs.

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

Skin Sensitization:

Various studies have been investigated for assessing the dermal sensitization potential of C.I Direct Blue 218 to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with predicted data for target chemical and its structurally similar read across substances,trisodium 5-amino-3-[(E)-2-(4-{4-[(E)-2-(7-amino-1-hydroxy-3-sulfonatonaphthalen-2-yl)diazen-1-yl]phenyl}phenyl)diazen-1-yl]-4-hydroxynaphthalene-2,7-disulfonate(Chlorazol Black BH)[CAS: 2429-73-4] and Disodium 6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate(ALLURA RED AC)[CAS: 25956-17-6]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

 

The skin sensitization potential of C.I Direct Blue 218[CAS: 28407 -37 -6] was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. C.I Direct Blue 218[CAS:28407 -37 -6] was predicted to be not sensitizing to the skin of female Dunkin- Hartley guinea pigs.

Modified Draize- Shelanski Repeat Insult Patch Test was performed (OTS0215154, NTRL report, last updated 1983) on human volunteers to ascertain the degree of sensitization caused bythe structurally similar read across substance, trisodium 5-amino-3-[(E)-2-(4-{4-[(E)-2-(7-amino-1-hydroxy-3-sulfonatonaphthalen-2-yl)diazen-1-yl]phenyl}phenyl)diazen-1 -yl]-4-hydroxynaphthalene-2,7-disulfonate(Chlorazol Black BH)[CAS: 2429-73-4].Undiluted Chlorazol Black BH [CAS:2429-73-4] was applied to the patch sites on the backs of 208 male volunteers for ten alternate-day 24-hour period under occlusion. Following a seven day rest period, challenge patches of Chlorazol Black BH [CAS:2429-73-4] were applied to the fresh sites on the backs of 208 male volunteers similar to the induction phase for 24 hours. The challenge sites were evaluated 24 hours after removal of the challenge patches.

No instances of contact sensitization were observed in any of the volunteers.

Hence, Chlorazol Black BH [CAS:2429-73-4] can be considered to be not sensitizing to skin.

Prophetic patch test was performed (487. Allura red AC (WHO Food Additives Series 15), 1981) on 200 human subjects for screening the skin sensitization potential caused bythe structurally similar read across substance, Disodium 6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate(ALLURA RED AC)[CAS: 25956-17-6].Allura Red AC was applied either as a neat or as a 25% aqueous solution to the skin of 200 human subjects. The initial exposure to the compound was for 72 hours, and this was followed by a 24-hour application 10 to 14 days later. None of the subjects exhibited compound induced contact sensitization. Hence the chemical Allura Red AC (CAS No: 25956-17-6) was considered to be not sensitizing to the skin of 200 human subjects in a prophetic patch test.

Based on the available data for the target as well as its structurally similar read across substances and applying the weight of evidence approach,C.I Direct Blue 218[CAS: 28407 -37 -6] can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,C.I Direct Blue 218[CAS: 28407 -37 -6] 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 C.I Direct Blue 218[CAS:28407 -37 -6] indicates that it is not likely to cause dermal sensitization to skin.

C.I Direct Blue 218[CAS:28407 -37 -6] can be considered to be not sensitizer to skin.