Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate

Endpoint summary

Description of key information

Acute Oral Toxicity: 

Acute oral toxicity dose was predicted based on OECD QSAR toolbox for target substance Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) was estimated to be 5268.33 mg/kg bw for rat,and for different studies available on the functionally similar read across substance disodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate (518-47-8) was considered to be 4740 mg/kg bw for mouse and for 2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate (3520-42-1) was considered to be 2200 mg/kg bw for mouse. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw.Thus, comparing this value with the criteria of CLP regulation, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) can be classified as category V of acute oral toxicity.

Acute Inhalation Toxicity: 

The test substance Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) has very low vapor pressure (4.19E-011 Pa). Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur and therefore repeated dose toxicity via the inhalation route was considered for waiver.

Acute Dermal Toxicity:

Acute dermal toxicity dose was predicted based on OECD QSAR toolbox for target substance Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) was estimated to be 4575.52 mg/kg bw for rat ,and for different studies available on structurally similar read across substance6-Dibutylamino-2-(2'-4'-Dimethylanilino)-3-Methylfluoran (36431-22-8)was considered to be >2000 mg/kg bwfor rat and for the closely related read across substance1-[2-(benzoyloxy)propoxy]propan-2-yl benzoate (27138-31-4) was considered to be >2000 mg/kg bw for rat.All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-,molybdatetungstatephosphate (12224-98-5)can be classified as category V of acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate
- Common name: C.I. Pigment Red 81
- Molecular formula: C28H31N2O3.xUnspecified
- Molecular weight: 443.5639 g/mol
- Smiles notation: CCNc1cc2c(cc1C)c(c3cc(c(cc3[o+]2)NCC)C)c4ccccc4C(=O)OCC
- InChl:1S/C28H31N2O3/c1-6-29-23-15-25-21(13-17(23)4)27(19-11-9-10-12-20(19)28(31)32-8-3)22-14-18(5)24(30-7-2)16-26(22)33-25/h9-16,29-30H,6-8H2,1-5H3/q+1
- Substance type: Organic

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

5268.33 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 268.33 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and "n" )  and "o" )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Chronic toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Sultones OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR 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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates  OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  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 >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  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 Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN1 OR SN1 >> Carbenium ion formation (enzymatic) OR SN1 >> Carbenium ion formation (enzymatic) >> Carbenium ion OR SN2 OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  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: "k"

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

Domain logical expression index: "l"

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 >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon OR Allyl OR Cyclo conjugated system OR Cycloalkane OR Cycloalkene OR Fused saturated carbocycles OR Fused unsaturated carbocycles OR Isopropyl OR Rosins OR tert-Butyl by Organic Functional groups

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.57

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 11.5

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 5268.33 mg/kg bw,when male and female wistar rats were orally exposed with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) via gavage.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5).The LD50 was estimated to be 5268.33 mg/kg bw,when male and female wistar rats were orally exposed with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5)via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 268.33 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: no data avaialble

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate
- Common name: C.I. Pigment Red 81
- Molecular formula: C28H31N2O3.xUnspecified
- Molecular weight: 443.5639 g/mol
- Smiles notation: CCNc1cc2c(cc1C)c(c3cc(c(cc3[o+]2)NCC)C)c4ccccc4C(=O)OCC
- InChl:1S/C28H31N2O3/c1-6-29-23-15-25-21(13-17(23)4)27(19-11-9-10-12-20(19)28(31)32-8-3)22-14-18(5)24(30-7-2)16-26(22)33-25/h9-16,29-30H,6-8H2,1-5H3/q+1
- Substance type: Organic

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

4575.52 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 575.52 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed

Mortality:

no data available

Clinical signs:

other: no data available

Gross pathology:

no data available

Other findings:

no data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Chronic toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

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, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  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 >> alpha,beta-Carbonyl compounds with polarized double bonds  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: "k"

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

Domain logical expression index: "l"

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 >> Acetates by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "p"

Similarity boundary:Target: CCNc1cc2c(cc1C)C(c1ccccc1C(=O)OCC)c1cc(C)c(NCC)cc1O2
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.83

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 10.4

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 4575.52 mg/kg bw,when male and female Sprague-Dawley rat were exposed occlusively with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate(12224-98-5).The LD50 was estimated to be 4575.52 mg/kg bw,when male and female Sprague-Dawley rats were exposed occlusively with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate(12224-98-5) by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 575.52 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) along with the study available on the functionally similar read across substancedisodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate (518-47-8)and 2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate (3520-42-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5).The LD50 was estimated to be 5268.33 mg/kg bw,when male and female wistar rats were orally exposed with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) via gavage.

The above experimental study was supported by Ken-ichiro O’goshi et. al. (Skin Research and Technology 2006; 12: 155–161) for the functionally similar read across substancedisodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate (518-47-8).In a acute oral toxicity study, mice were treated with sodium fluorescein in the concentration of 2200 mg/kg bw. 50% mortality was observed at dose 2200 mg/kg bw.Therefore, LD50 value was considered to be 2200 mg/kg bw,when mice were treated with sodium fluorescein orally.

This is further supported by P.L. Smart (The NSS Bulletin, Volume 46 Number 2: 21-33 - October 1984, A publication of the National Speleological Society) and RTECS (RTECS (registry of toxic effect of chemical substance data base),2017) for the functionally similar read across substancedisodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate (518-47-8).In a acute oral toxicity study, mice were treated with Sodium fluoresce in the concentration of 4740 mg/kg bw. 50 % mortality was observed in treated mice at 4740 mg/kg bw. Clinical signs like behavioral changes in motor activity (specific assay), Ataxia, Dyspnea were observed.Therefore, LD50 was considered to be 4740 mg/kg bw when mice were treated with Sodium fluorescein orally following 14 days of observation period.

Also these results are further supported by the experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017) for the functionally similar read across substance2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate (3520-42-1).In a acute oral toxicity study,mice were treated with C.I. Acid Red 52 in the concentration of 10300 mg/kg bw orally. No mortality was observed in treated mice. Therefore,LD50 was considered to be 10300 mg/kg bw,when mice were treated with C.I. Acid Red 52 orally.

Thus, based on the above studies on Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) and it’s functionally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate (12224-98-5) can be classified as category V of acute oral toxicity.

Acute Inhalation Toxicity: 

The test substance Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) has very low vapor pressure (4.19E-011 Pa). Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur and therefore repeated dose toxicity via the inhalation route was considered for waiver.

Acute Dermal Toxicity:

In different studies, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5)along with the study available on structurally similar read across substance6-Dibutylamino-2-(2'-4'-Dimethylanilino)-3-Methylfluoran (36431-22-8) and on the closely related read across substance1-[2-(benzoyloxy)propoxy]propan-2-yl benzoate (27138-31-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate(12224-98-5).The LD50 was estimated to be 4575.52 mg/kg bw,when male and female Sprague-Dawley rats were exposed occlusively with Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdatetungstatephosphate(12224-98-5) by dermal application for 24 hours.

The above experimental study was supported byU.S. Environmental Protection Agency (Robust Summary & Test Plans: Color Former Category: Robust Summary,U.S. Environmental Protection Agency ,2 May 2003) for the structurally similar read across substance6-Dibutylamino-2-(2'-4'-Dimethylanilino)-3-Methylfluoran (36431-22-8).In acute dermal toxicity study, 10 male and female Sprague-Dawley rat were treated with 6-Dibutylamino-2-(2'-4'-Dimethylanilino)-3-Methylfluoran (36431-22-8) in the concentration of 2000 mg/kg bw by dermal applicationaccording to OECD Guideline 402 (Acute Dermal Toxicity).Undiluted test material was used. Skin of animals were moistened with arachis oil B.P. The appropriate amount of test material, as received,was pre-weighed into a glass vial, and applied uniformly to an area of shorn skin approximating to 10% of the total body surface area which had been previously moistened with arachis oil B.P. A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a piece of selfadhesive bandage (Hypertie) for 24 hours. After the 24 contact period the bandage was removed and the area wiped with cotton wool moistened with arachis oil B.P. to remove any residual test material. signs of toxicity recorded at 1/2, 1,2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded on the day of treatment and on days 7 and 14.No mortality was observed in treated rats at dose 2000 mg/kg bw.No signs of systemic toxicity or skin irritation were noted during the study. No toxicologically significant effects on bodyweight were noted in the males during the study. One female showed bodyweight loss during the study. No abnormalities were noted at necropsy of animals killed at the end of the study.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rats were treated with 6-Dibutylamino-2-(2'-4'-Dimethylanilino)-3-Methylfluoran (36431-22-8)by dermal application.

Also these results are further supported by U.S. Environmental Protection Agency(Robust Summary & Test Plans: Dipropylene Glycol Dibenzoate: Robust Summary, U.S. Environmental Protection Agency ,1999) for the closely related read across substance1-[2-(benzoyloxy)propoxy]propan-2-yl benzoate (27138-31-4).In acute dermal toxicity study,male and female Sprague-Dawley rats were treated with 1-[2-(benzoyloxy)propoxy]propan-2-yl benzoate(27138-31-4) in the concentration of 2000 mg/kg bw by dermal application.No mortality was observed in treated rats at dose 2000 mg/kg bw.No signs of systemic reaction to treatment were observed in any animal throughout the observation period.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rats were treated with 1-[2-(benzoyloxy)propoxy]propan-2-yl benzoate(27138-31-4)  by dermal application. 

Thus, based on the above studies on Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) and it’s structurally similar and closely related read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-, molybdate tungstate phosphate(12224-98-5) and it’s functionally, structurally similar and closely related read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Xanthylium, 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethyl-,molybdate tungstate phosphate(12224-98-5) can be classified as category V for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.