Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pigs.

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 v3.4 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 v3.4

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

Name of the test chemical: Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt
Molecular formula: C27H32N2O6S2.1/3Al
Molecular weight: 1658.0277 g/mol
Smiles Notation: CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+](CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+] (CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+](CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].[Al+3]
InChI: 1S/3C27H32N2O6S2.Al/c3*1-5-28(6-2)22-13-9-20(10-14-22)27(21-11-15-23(16-12-21)29(7-3)8-4)25-18-17-24(36(30,31)32)19-26(25)37(33,34) 35;/h3*9-19H,5-8H2,1-4H3,(H-,30,31,32,33,34,35);/q;;;+3/p-3
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:

epicutaneous, occlusive

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:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

no dermal reactions noted

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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(("a" or "b" or "c" or "d" or "e" )  and ("f" and "g" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Aryl AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Sulfonic acid AND Sulfonic acid derivative AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Similarity boundary:Target: CCN(CC)c1ccc(C(=C2C=CC(=N{+}(CC)CC)C=C2)c2ccc(S(=O)(=O)O{-})cc2S(O)(=O)=O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.413

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.55

Interpretation of results:

other: Negative

Conclusions:

[4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pigs

Executive summary:

The skin sensitization potential of Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies have been investigated for assessing the dermal sensitization potential of Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt to a greater or lesser extent. The studies are based on in vivo experiments along with predicted data for target chemical and its structurally similar read across substances, FD&C Red No. 4 [CAST: 4548-53-2]and disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate[CAS: 3567-66-6].

The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt was predicted to be non sensitizing to the skin of male and female Dunkin-Hartley guinea pigs

Kligman maximization test was conducted (REPORTS of the Scientific Committee on Cosmetology (seventh series), 1988) onto the skin of 25 human subjects to determine the sensitization potential of the structurally similar read across substances, FD&C Red No. 4 [CAS: 4548-53-2].

 FD and C red 4 0.3% (0.3 gm) in petrolatum was applied under occlusion to the skin of the volunteers for 48 hours and observed for dermal reactions.

Since, none of the subjects showed any signs of skin sensitizing effects, FD and C red 4(CAS No.4548-53-2)was considered to be not sensitizing to the skin of humans

These results are also supported by the experimental study summarized in Opinion on Acid Red 33 ,Scientific Committee on Consumer Safety (SCCS), SCCP/1102/07; for the structurally similar read across substance,disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate[CAS:3567-66-6].The study was conducted in accordance with OECD 406 Guidelines.15 female (10 test and 5 control) Ibm:GOHI; SPF quality guinea pigs were used for the study. 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 and following pre-treatment of the test areas with 10% sodium-laureth-sulfate (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. 2-Mercaptobenzothiazole was used as a positive control.

Even after 48 hours post challenge exposure, no dermal sensitization reactions were observed in the test and control groups. Hence, it was considered that disodium 5-amino-4 -hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(3567 -66 -6) was not a skin sensitizer.

Based on the available data for the target and read across substances and applying the weight of evidence approach, [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt can be considered to be not sensitizing to skin.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

Available data for Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt suggests that it is not likely to cause any dermal sensitization to skin.

Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.