Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor.Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was predicted to be non sensitizing to the skin of male 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

Qualifier:

according to guideline

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

Specific details on test material used for the study:

- Name of test material: C.I. Pigment Violet 1
- IUPAC name: Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
- Molecular formula: C112H127MoN8O23PW
- Molecular weight (if other than submission substance): 2264.729736 g/mol
- Smiles : CCN(CC)C1=CC2=C(C=C1)C(=C3C=CC(=[N+](CC)CC)C=C3O2)C4=CC=CC=C4C(=O)O.OP(=O)(O)[O-].OS(=O)(=O)O.O=[Mo]=O
- Inchi : 1S/C28H30N2O3.Mo.H3O4P.H2O4S.2O/c1-5-29(6-2)19-13-15-23-25(17-19)33-26-18-20(30(7-3)8-4)14-
16-24(26)27(23)21-11-9-10-12-22(21)28(31)32;;2*1-5(2,3)4;;/h9-18H,5-8H2,1-4H3;;(H3,1,2,3,4);(H2,1,2,3,4);;
- Substance type: Organic
- Physical state: Solid powder (purple)

Species:

guinea pig

Strain:

Hartley

Sex:

male

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:

10 guinea pigs

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions 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" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cation by Substance Type

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Phosphates, Inorganic by US-EPA New Chemical Categories

Domain logical expression index: "c"

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: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine 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 Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN1 OR SN1 >> Carbenium ion formation (enzymatic) OR SN1 >> Carbenium ion formation (enzymatic) >> Carbenium ion OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "l"

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 Exclusion rules not met AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 AND Group CN Molecular Weight > 290 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Molecular Weight > 650 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Metalloids OR Metals OR Rare Earth by Groups of elements

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 223 Da

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 519 Da

Interpretation of results:

other: Negative

Conclusions:

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was predicted to be non sensitizing to the skin of male Hartley guinea pigs

Executive summary:

The skin sensitization potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor.Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was predicted to be non sensitizing to the skin of male Hartley guinea pigs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated to ascertain degree of dermal sensitization caused by the target chemical, Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate. These include in vivo experiments in rabbits for the target chemical as well as its structurally similar read across chemicals, Sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate [CAS: 3520-42-1], Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester [CAS: 302776-68-7] and2'-anilino-6'-(diethylamino)-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one[CAS: 29512-49-0]..The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

The skin sensitization potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was predicted to be non sensitizing to the skin of male Hartley guinea pigs.

This is supported by the experimental study summarized in Opinion on Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester-COLIPA n° S83- SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS (SCCP)- 20 June 2006; for the structurally similar read across chemical, Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester [CAS: 302776-68-7]. The study was conducted according to OECD 406 Guidelines.

For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 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 dest 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. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed neither in control group nor in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed.

Therefore, it was concluded that the test substance Diethyl amino hydroxybenzoyl hexyl benzoate(CAS No: -302776-68-7)does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

These results are supported by the experimental study summarized in THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) /0803/ 23 April 2004; to assess the dermal sensitization potential of the structurally similar read across chemical, C.I. Acid Red 52(sodium 4-[3,6-bis(diethylamino)-2,7 -dimethylxanthenium-9-yl]benzene-1,3-disulfonate) [CAS: 3520-42-1].The study was performed as per OECD 406 Guidelines. 10 female were used for and 5 female Himalayan spotted guinea pigs were used in the test and control groups respectively. In induction treatment, 10 females in test group, 5 females in control group were used. Animals were induced with intradermal induction of Freund´s Complete Adjuvant (FCA) and physiological saline (1:1), test item at 5% in 1 % CMC and 5 % dilution of the test item in 1% CMC in a 1:1 mixture with FCA / physiological saline on day 1. After 7 days, epidermal induction of sensitization (day 8) was conducted under occlusion with the test item at 50 % in 1 % CMC for 48 hours.The challenge was performed at day 22 by application of the test item at 10 % in 1 % CMC under occlusive patch for 24 h at a different part of the skin. Observations were made at 24 and 48 hours removal of the dressing.

After challenge exposure, no skin reactions were observed. Hence, sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate was considered to be non sensitizing to the Himalayan spotted albino guinea pigs.

The above results are supported by the experimental study summarized in Robust Summary & Test Plans: Color Former Category: Robust Summary, EPA HPV Challenge Color Former Category,2 May 2003; for the structurally similar read across substance, 2'-anilino-6'-(diethylamino)-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one[CAS: 29512-49-0]. The study was performed according to the Maximization Technique (Magnusson and Kligman), which satisfies OECD Guidelines – 406.75 albino Hartley Guinea pigs (38 male, 37 female) were used for the study.

A preliminary Primary irritation study was conducted in guinea pigs with doses of 0.1ml of 0.25%, 0.5%, 1%, 2.5%, 5%, 10%,25%, 50% TEST CHEMICAL in acetone to determine the concentration for the induction and challenge exposure. 5% w/v of test chemical in acetone and 50% w/v of test chemical in acetone were chosen as the concentrations for intradermal induction and epicutaneous induction and challenge exposure respectively.

The guinea pigs were divided into the following groups:25 test , 10 vehicle control, 10 naïve control, 10 positive control (alpha-hexylcinnamaldehyde), 5 naïve positive control group.

In the intradermal induction exposure, 0.1 ml of 5% w/v TEST CHEMICAL in acetone was injected into the skin of 25 guinea pigs. The intradermal induction was followed by epicutaneous induction of0.8 ml of 50% w/v of test chemical in acetone. Following a suitable result period, 0.4 ml of 50% w/v of test chemical in acetonewas used in the primary challenge exposure. The dosage pattern was one dosage per 24 to 48 hour observation period. Assessment of damage/irritation was made 24 and 48 hours following treatment. Following primary challenge using alpha-hexylcinnamaldehyde, tech 85% as a 5% w/v formulation in acetone, the incidence of grade 1 responses or greater in the positive control group and the naive positive control group was 5 of 10 and 0 of 10 respectively.

0% incidence of grade 1 responses to test chemical as a 50% w/v formulation in acetone in the test group at challenge, relative to that of the appropriate controls, indicates a non-sensitizer nature of the test chemical.

Hence, 2'-anilino-6'-(diethylamino)-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one can be considered to be not sensitizing to skin.

Based on the available data for the target as well as the structurally similar read across substances and applying the weight of evidence approach,Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate  was not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical 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 Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate suggests that it is not likely to cause any dermal sensitization.

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.