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Description of key information

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)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Type of study:
Draize test
Species:
guinea pig
Strain:
Hartley
Sex:
female
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Route:
epicutaneous, open
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
No. of animals per dose:
10
Details on study design:
(Traditional tests):
A. INDUCTION EXPOSURE
Induction was performed by intradermal injection and topical application of 100 % acetone according to the protocol of Magnusson and Kligman (no further details available)

B. CHALLENGE EXPOSURE
Challenge was performed 21 days after the initial intradermal injection by topical open application of 0.1 ml 100 % acetone to the shaved area of the flank

C. EVALUATION
48 hrs after the challenge application skin reactions were avaluated according to a modified scale for scoring:
erythema formation: grades from 0 to 4
edema formation: grades from 0 to 3
possible total maximum: 7
sensitization rate: number of animals with positve reaction/number of tested animals
mean response: [sum from all animals of (erythema score + edema score)] : numer of tested animals
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Positive control results:
Positve responses were found with 2-mercaptobenzothiazole with a sensitization rate of 5/5 and mean responses uo to 5.0 (depending on induction and challlenge concentrations)
Reading:
1st reading
Group:
test chemical
Clinical observations:
Not sensitizing
Remarks on result:
other: Reading: 1st reading. Group: test group. Clinical observations: Not sensitizing.





The prediction was based on dataset comprised from the following descriptors: "S M W N"
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 ( 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 Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Diketone OR Fused carbocyclic aromatic OR Fused heterocyclic aromatic OR Indandione OR Pyridine OR Quinoline/ Isoquinoline OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Fused carbocyclic aromatic OR Indandione OR Overlapping groups OR Quinoline/ Isoquinoline OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonyl compound OR Ketone OR Sulfonic acid OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 2-Alken-1-als (MA) OR Highly reactive (GSH) >> Cinnamaldehydes (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Substituted 2-Alken-1-als (MA) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as C1 to C4 non-branched alkyl alcohols- sub category (25a) OR Known precedent reproductive and developmental toxic potential OR Multi-halogenated alkyl ethers (23b) by DART scheme v.1.0

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.27

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.89

Interpretation of results:
not sensitising
Remarks:
Migrated information Non sensitizer Criteria used for interpretation of results: EU
Conclusions:
The test chemical sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not a skin sensitizer.
Executive summary:

Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guines pigs. The test chemical sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not a skin sensitizer.

As per CLP classification, the test material is not likely to classify as a skin sensitizer.

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

Prediction model based estimation and data from read across chemical are used to predict the skin sensitization potential of the test chemical CAS no 84864 -68 -6. The summary is as follows:

Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guines pigs. The test chemical sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate (CAS no 84864 -68 -6) is not a skin sensitizer.

Maximization test was performed (Kita et al, 1984) to study the sensitizing potential of the test chemical D & C Yellow no.10 (CAS no 8004 -92 -0). 5% of the test chemical was used in the induction phase. Five 48 hrs exposure were given on the upper right arm using Duhring chambers (120 mm in diameter) on sites pretreated with sodium lauryl sulfate. None of the 15 subjects exposed to induction doses of 5% test chemical in water became sensitized. The test chemicalD & C yellow no 10 is thus not sensitizing to the skin of humans.

Repeat insult patch test was conducted (Weaver, 1983) to evaluate the sensitizing potential of the test compound D & C yellow no 10 (CAS no 8004 -92 -0) with groups of volunteers in the St. Petersburg, Florida area. The materials for these tests were varying concentrations of D & C Yellow No. 10 in an aqueous soap vehicle. The patches employed were occlusive Parke Davis clinical Readi-Band® patches (20 mm square non-woven cotton pads on 37 mm square Blenderm® Surgical Tape). 0.3 ml of the test liquids was measured onto each pad to achieve saturation. Patches were applied to the same test sites on the upper arm each Monday, Wednesday and Friday for 24 h exposures for 3 weeks during the induction phase of the tests. Following a 2-week rest period, challenge patches of the same test material were applied to the initial test sites as well as to naive sites on the contralateral arms for 24 h. Scoring of induction patches was performed immediately prior to application of succeeding patches and 48 h following removal of the 9th patch during induction.Scoring of challenge patches was performed 48 h and 96 h following patch application. Greater skin response at challenge compared with the response at the original exposure was considered suggestive of cutaneous sensitization. Positive ( +, + +, + + +) reactions occurring early in the induction phase of the tests were considered suggestive of preexistant hypersensitivity. No signs of pre-existant or induced delayed contact hypersensitivity were produced by any of these concentrations. In addition, a non-certified Acid Yellow 3 produced no signs of hypersensitivity in a repeat insult patch test of0.1% of the dye in the 0.5% w/v aqueous soap vehicle.

Modified Buehler Method was conducted (lamson, 1982) to evaluate the sensitizing potential of the test compound D & C yellow no 10 (CAS no 8004 -92 -0). Adult female albino guinea pigs (Hartley Strain), initially weighing 300-500 g, were housed 5 per cage. The induction phase was accomplished with a 24-h occluded patch in the nuchal area once weekly for 3 consecutive weeks. Test and vehicle control groups were run concurrently. Following a 2-week rest period, the guinea pigs were challenged with a 24 h occluded patch containing the appropriate dye. Each test group was initially challenged with the dye used during the induction phase. Challenge concentrations for each dye were 1.0, 3.0 and 10.0%. Animals induced with D & C Yellow No. 11 were challenged with commercial products containing the D & C Yellow No. 11 or D & C Yellow No. 10. After the patches were removed, the guinea pigs were rested for 24 h, depilated with a chemical depilatory (Neet), and evaluated for erythema and edema. Guinea pigs treated with D & C Yellow No. 10 and challenged with 1, 3 and 10% did not exhibit sensitization responses. The test material D & C yellow no 10 is not sensitizing to the skin of guinea pigs in the modified Buehler test performed.

As per CLP classification, the test material is not likely to classify as a skin sensitizer.


Migrated from Short description of key information:
Skin sensitization was estimated using SSS QSAR prediction model, 2016 using Guines pigs. The test chemical sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not a skin sensitizer.

Justification for selection of skin sensitisation endpoint:
The test chemical sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not a skin sensitizer.

Justification for classification or non-classification

Skin sensitization:

As per CLP classification, the test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not likely to classify as a skin sensitizer.