3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one

Endpoint summary

Description of key information

The skin sensitizing potential for Solvent Red 49 (509-34-2) is estimated using OECD QSAR toolbox version 3.4.The test substance Solvent Red 49 is estimated to be not sensitizing in guinea pig.

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 QSAR toolbox version3.4.

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

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of the test material: Solvent Red 49
- Molecular formula: C28H30N2O3
- Molecular weight: 442.556 g/mol
- Substance type: Organic
- Smiles: C12(c3c(Oc4c1ccc(c4)N(CC)CC)cc(N(CC)CC)cc3)c1c(cccc1)C(O2)=O

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

Route:

other: No data

No. of animals per dose:

No data

Key result

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

No 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 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" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

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: "c"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group 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, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as Extremely reactive (GSH) OR Extremely reactive (GSH) >> Maleimides (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) OR Slightly reactive (GSH) OR Slightly reactive (GSH) >> Methacrylates (MA) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.0001 g/L AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 AND Group CN log Kow > 5.5 AND Group CN Melting Point > 180 C AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal Molecular Weight > 370 g/mol OR Group CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

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"

Similarity boundary:Target: CCN(CC)c1ccc2c(c1)Oc1cc(N(CC)CC)ccc1C21c2ccccc2C(=O)O1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.3

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.97

Interpretation of results:

other: No sensitization observed

Conclusions:

The substance Solvent Red 49 is estimated to be not sensitizing in guinea pig.

Executive summary:

The skin sensitizing potential for Solvent Red 49 is estimated using OECD QSAR toolbox version 3.4.The test substance Solvent Red 49 is estimated to be not sensiting in guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

Various studies for target (Solvent Red 49, CASno-509-34-2) and its read across were summarized as follows:

The skin sensitizing potential for Solvent Red 49 (509-34-2) is estimated using OECD QSAR toolbox version 3.4.The test substance Solvent Red 49 is estimated to be not sensitizing in guinea pig.

In other study by (Guin JD, 2003) with similar substance (509-47-8) was observed in human .The sensitization potential of D&C yellow 8 was determined by performing patch tests on humans. The dye was applied 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 16 patients were tested with the dye. As only 1 positive reaction was reported by a patient.  D&C yellow 8 can be considered as a non- sensitizer in humans. Therefore D&C yellow 8 can be considered as a non- sensitizer in humans.

In other study by (E. Nucera, D. Schiavino et al., 2003) with similar substance (509-47-8) was observed in human. Patch test was conducted on 1 human male patient to evaluate skin sensitising potency of chemical sodium Fluorescein. An allergological evaluation (patch tests) with 20% sodium Fluorescein was performed. Saline and histamine solutions were used, respectively, as negative and positive controls .The patch test result was negative. Hence, Non-sensitising effects were observed in patch test conducted on human male patient applied with 20% sodium Fluorescein .Therefore sodium Fluorescein was considered to be a non sensitizing in human.

In another study by (SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS (SCCP), 2006)with similar substance (302776-68-7) was observed in guinea pigs. The skin sanitization test of Diethylamino hydroxybenzoyl hexyl benzoate(CAS No: -302776-68-7)was conducted in 10 female guinea pigs to determine its sensitization potential. For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua test 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua test 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application.Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals.

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

Basis of available information for the target Solvent Red 49(CASno-509-34-2) as well as read across andapplying weight of evidence approach, the test substance can be classified as not sensitising to the skin.