2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione

Endpoint summary

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:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

Buehler test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:CHARLES RIVER (F-69592 L’ARBRESLE)
- Age at study initiation:4 weeks old
- Weight at study initiation: 234g and 275g
- Housing: housed in groups of 2 in polycarbonate containers. The flooring of the cages was covered with dust-free wood shavings and the top fitted a stainless steel lid containing with a feeding device and drinking device of 500 mL
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum acclimatization period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° C ± 3° C
- Humidity (%):from 30 % to 70 %,
- Air changes (per hr):at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light):12 hrs day / 12 hrs darkness

Route:

epicutaneous, occlusive

Vehicle:

other: unchanged or diluted with liquid paraffin

Concentration / amount:

Induction phase: 100% test item
1st Challenge: 50% test item (maximal non irritant concentration)
2st Challenge: 10% test item

Route:

epicutaneous, occlusive

Vehicle:

other: unchanged or diluted with liquid paraffin

Concentration / amount:

Induction phase: 100% test item
1st Challenge: 50% test item (maximal non irritant concentration)
2st Challenge: 10% test item

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: Maximum Non Irritant Concentration (M.N.I.C.) determination, Three guinea pigs were treated with the test item placed onto the selected treatment sites and covered with an occlusive dressing (25mm x 25mm gauze patches hydrophilic Codex of 8-layer Gazin® from
Lohmann & Rauscher held in contact with the skin by means of 50 mm wide hypoallergenic micropore™ adhesive tape from 3M and Blenderm™ from 3M) for a period of 6 hours at 4 different concentrations: 100% diluted at 75% (v/v), 50% (v/v) and 25% (v/v) in liquid paraffin.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 local applications were performed at D0, D6 and D13 during 6 hours under occlusive dressing (25mm x 25mm gauze patches hydrophilic Codex of 8-layer Gazin
- Exposure period:6h
- Test groups: yes, treated group received 0.5 mL of the test item at 100%, third induction with 75% testitem diluted in liquid paraffin.
- Control group: liquid paraffin
- Frequency of applications:D0, D6 and D13
- Duration: 14d + 14d rest phase
- Concentrations: 100% and 75%

1st CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6h
- Test groups: 0.5 mL of the test item at 50% (v/v) (MNIC = maximal non irritant concentration) diluted in liquid paraffin
- Control group:liquid paraffin
- Concentrations: 50%
- Evaluation (hr after challenge): 24h, 48h, 72h

2st CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 6h
- Test groups: 0.5 mL of the test item at 10% diluted in liquid paraffin
- Control group: liquid paraffin
- Concentrations: 10%
- Evaluation (hr after challenge): 24h, 48h, 72h

Positive control substance(s):

yes

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Not sensitising

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Not sensitising.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Biphenyl AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Imide AND Naphtalene AND Quinolone/ Quinolinedione/ Isoquinolinedione AND Sulfide by Organic Functional groups

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 >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Organic disulfides OR High reactive >> Unsaturated acid anhydrides OR Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.66

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 14.5

Interpretation of results:

not sensitising

Conclusions:

The substance Solvent Yellow 98 is estimated to be not sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitizing potential for Solvent yellow98 is estimated using OECD QSAR toolbox version 3.3. The substance Solvent Yellow 98 is estimated to be not sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

The skin sensitizing potential for Solvent yellow98 is estimated using OECD QSAR toolbox version 3.3. The substance Solvent Yellow 98 is estimated to be not sensitizing to the skin of guinea pig.

 

In other study by (The rapporteur Member State the Netherlands, 2005) with similar substance (57960-19-7) skin sensitization was observed.The skin sensitization studyofAcequinocyl(CAS No: -57960-19-7)was performed in 20 guinea pigs to observed its sensitizing efficacy.During induction phase, animals were treated with test material at concentrations of50% v/v intradermally and 100% v/v topically under an occlusion of 48 hours.Following induction, the animals were challenged at concentration of100% and 30 % v/v for 24 hours (occlusion).Control animals were also used. Since no known sensitizing effects were observed, Acequinocyl(CAS No: -57960-19-7) can be concluded as non sensitizing.

In other study by (INVENTORY MULTI-TIERED ASSESSMENT AND PRIORITISATION (IMAP) – NICNAS , 2016 ) with similar substance (68814-95-9) skin sensitization was observed. The skin sensitization study ofAmines, tri-C8-10-alkyl (CAS No:-68814-95-9) was performed in guinea pigs to observed its sensitizing efficacy.The induction period included 3 topical applications with tri-C8-10-alkylamines at 100 % concentration (inductions 1 and 2) and 75 % concentration in liquid paraffin (induction No.3). Followed by induction phase, animals were challenged at concentration of 50% or 10% in liquid paraffin along with the control animals.In the treatment group (50 %concentration in liquid paraffin), slight to moderate oedema in 65, 55 and 50 % of the animals at 24, 48 and 72 hours respectively was reported after the challenge phase, on the treated area. In the control group, slight oedema in 70, 60 and 60 % of the animals at 24, 48 and 72 hours respectively was reported after the challenge phase, on the treated area. A new challenge was performed with the chemical diluted at 10% in liquid paraffin, after a rest period of 6 days. In the treatment group (10% concentration), moderate erythema in 20% and 30% of the animals at 48 and 72 hours respectively was reported. In the control group (for the 10% challenge), moderate erythema in 30% of the animals at 48 and 72 hours was reported. However, the reactions in the test groups did not exceed the most severe reactions reported in the control groups and, therefore, the effects were not attributed to skin sensitization. Therefore the test chemicalAmines, tri-C8-10-alkyl (CAS No:-68814-95-9) was found to be non sensitizing to the guinea pigs.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not sensitising to the skin

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance Solvent yellow98 was classified as non –sensitizer to skin.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.