Registration Dossier

Skin Irritation:

The dermal irritation potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to the skin of New Zealand White rabbits.

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

Eye Irritation:

The ocular irritation potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to eyes of New Zealand White rabbits.

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

Reference

Endpoint:

skin irritation: 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

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 5 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 ( not "r") ) ) and ("s" and ( not "t") ) ) and ("u" and ( not "v") ) ) and ("w" and "x" ) )

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) >> Hydrazine Derivatives 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 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 >> Secondary aromatic 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 No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "i"

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 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: "j"

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: "k"

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: "l"

Referential boundary: The target chemical should be classified as Aromatic mono- and dialkylamine AND H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

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 Alkaline Earth by Groups of elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 11 - Trans.Metals Cu,Ag,Au by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic acid [-C(=O)-OH] AND Aromatic-CH AND Aromatic-H AND -CH2- [linear] AND Methyl [-CH3] AND Not calculated AND Tertiary amine by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Quaternary amine by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic acid [-C(=O)-OH] AND Aromatic-CH AND Aromatic-H AND -CH2- [linear] AND Methyl [-CH3] AND Not calculated AND Tertiary amine by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aliphatic alcohol [-OH] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 393 Da

Domain logical expression index: "x"

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

Interpretation of results:

other: not irritating

Conclusions:

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to the skin of New Zealand White rabbits.

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

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: 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

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:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

4

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 7 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 ( not "o") ) ) and ("p" and ( not "q") ) ) and ("r" and ( not "s") ) ) and "t" ) and ("u" and ( not "v") ) ) and ("w" and ( not "x") ) ) and ("y" and ( not "z") ) ) and ("aa" and ( not "ab") ) ) and "ac" ) and ("ad" and ( not "ae") ) ) and ("af" and ( not "ag") ) ) and "ah" ) and ("ai" and "aj" ) )

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) >> Hydrazine Derivatives 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 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 >> Secondary aromatic 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 OR Weak 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 >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> alpha,beta-Unsaturated oximes 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 OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds 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 Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds AND Peroxide Type Compounds by Oncologic Primary Classification

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Organophosphorus Type Compounds by Oncologic Primary Classification

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic amines AND Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Quaternary organic ammonium compounds by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr by Chemical elements

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Group 3 - Lanthanoids by Chemical elements

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Group 15 - Metals Bi by Chemical elements

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Group 8 - Trans.Metals Fe,Ru,Os by Chemical elements

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND No functional group found by Organic Functional groups ONLY

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND 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 Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Hydroxy, phosphorus attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, oxygen attach [-O-] AND Phosphine oxide [O=P] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "ai"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 251 Da

Domain logical expression index: "aj"

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

Interpretation of results:

other: not irritating

Conclusions:

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to eyes of New Zealand White rabbits.

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

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Various studies have been investigated to ascertain the dermal irritation potential of 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, Rhodamine B[CAS: 81-88-9], Sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate [CAS: 3520-42-1] and Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester [CAS: 302776-68-7].The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.3 with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical Xanthylium, 9-(2 -carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate. Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to skin of New Zealand White rabbits.

This is supported by the experimental study performed by JAMES E. FULTON, JR(J. Soc. Cosmet. Chem., 40, 321-333 (November/December), 1989) indicate the Comedogenicity and irritancy of structurally similar read across chemical, Rhodamine B[CAS: 81-88-9]. Rhodamine B was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

Rhodamine B falls under Grade 0 (no irritation observed).Hence it can be concluded that Rhodamine B was not irritating to rabbit ears.

These results are ably supported by the experimental study summarized in THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) /0803/ 23 April 2004; for the structurally similar read across chemical, sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate [CAS: 3520-42-1]. The test sample was applied topically at concentration of 500mg to one intact and one additionally scarified flank of 6 Albino-Himalaya rabbits under occlusion for 24 hours exposure period. The scoring of skin reactions was performed immediately, 48 hours and 73 hours after removal of the occlusive patch.

Since the test chemical did not elicit any skin reactions at the application site of any rabbit and all scores were 0, therefore C.I. Acid Red 52 (CAS No: -3520-42-1) was considered to be not irritating on rabbits’ skin.

The above results are further 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 test was performed according to OECD 404 Guidelines. 500mg of the test material was applied topically to intact skin of 3 young adult White New Zealand rabbits for exposure period of 4 hours under semiocclusive conditions. The skin reactions were scored after 72 hours. Slight erythema was observed in 2 animals on the day of application. No oedema was observed. The third animal did not show any skin reactions. The cutaneous reactions were reversible in the animals within 48 hours after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.1 for erythema and 0.0 for oedema.

Considering the observed cutaneous reactions as well as the average score for irritation, the test substance, Diethylamino hydroxybenzoyl hexyl benzoate (CAS No: -302776-68-7) was not irritating to the skin of New Zealand White rabbits.

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

Various studies have been investigated to ascertain the ocular irritation potential of 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,C.I. Acid Red 52(sodium 4-[3,6-bis(diethylamino)-2,7 -dimethylxanthenium-9-yl]benzene-1,3-disulfonate) [CAS: 3520-42-1] and 2'-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.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.3 with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical, Xanthylium, 9-(2 -carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate. Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate was estimated to be not irritating to eyes of New Zealand White rabbits.

This result is 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 ocular irritation potential of functionally similar read across substance, C.I. Acid Red 52(sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3 -disulfonate) [CAS: 3520-42-1]. 0.1 g of Acid Red 52 was instilled into the conjunctival sac of the left eye of six Albino-Himalaya rabbits. The right eye remained untreated and served as reference control. Scoring of irritation was performed 1, 7, 24, 48 and 72 hours after application with a magnifying glass. After 24 hours all eyes were rinsed with physiological saline. Because of colour interference, an exact judgement was not possible in the area of the cornea (1 and 7 hours after post application).

The overall irritation score after 72 hours was as follows: Cornea = 0.00, iris = 0.00, conjunctiva redness = 0.67, conjunctiva chemosis = 0.06.

Hence it can be considered that Acid Red 52 was not irritating to rabbit eyes.

These results are also 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 as per OECD 405 Guidelines. 3 male New Zealand White rabbits, thirteen to sixteen weeks old were used for the study.

The eyes of each animal were examined prior to administration instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Approximately 70 mg of the test substance, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated as control. Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48, and 72 hours) after instillation. Additional observations were made for two animals four days after treatment. : Observation of the eyes was aided by the use of a handheld light. Ocular irritation was assessed on the cornea, iris, conjunctivae, and chemosis. There were no signs of toxicity or ill health in any rabbit during the observation period. No corneal damage or iridial inflammation was observed. Transient hyperemia of blood vessels to a diffuse crimson coloration of the conjunctivae with slight swelling or partial eversion of the eyelids was observed in all animals. These responses had resolved completely by two days after instillation.

Since, the effects were completely resolved by 2 days, 2'-anilino-6'-(diethylamino)-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one can be considered to be not irritating to New Zealand White rabbit eyes.

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 irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Based on the available information, Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate is not likely to cause severe irritation to eyes and skin.

Hence, Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate can be classified under the category “Not Classified”.