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

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity,LD50 value was predicted based on OECD QSAR toolbox for target substance C.I. Pigment Violet 1 (1326-03-0) was estimated to be 8236.78 mg/kg bw,and for differentstudies available on the structurally similar read across substance C.I. Acid Red 52 (3520-42-1) was considered to be 10300 mg/kg bw and on Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester (302776-68-7) was considered to be >2000 mg/kg bw. 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, C.I. Pigment Violet 1 (1326-03-0) cannot be classified for acute oral 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 v3.3,2018

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: 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:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

8236.78 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

Dose descriptor:

LD50

Effect level:

8 236.78 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" )  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" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

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 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 >> 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 >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes 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 Inorganic chemical AND Not covered by current version of the decision tree AND Not known precedent reproductive and developmental toxic potential AND Organophosphorus compounds (1b) by DART scheme v.1.0

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24c) OR Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Metals (1a) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

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 Not categorized by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Carboxylic acids (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Cation AND Phosphoric acid derivative AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "r"

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 AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Phosphates by OECD HPV Chemical Categories

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Copper metal and copper compounds OR Iron salts by OECD HPV Chemical Categories

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 259 Da

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 464 Da

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 8236.78 mg/kg bw,when male Sprague-Dawley rats were orally exposed with C.I. Pigment Violet 1 (1326-03-0) orally .

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for C.I. Pigment Violet 1 (1326-03-0).The LD50 was estimated to be 8236.78 mg/kg bw,when male Sprague-Dawley rats were orally exposed with C.I. Pigment Violet 1 (1326-03-0) orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 236.78 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity: 

In different studies, C.I. Pigment Violet 1 (1326-03-0) 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 C.I. Pigment Violet 1 (1326-03-0) along with the study available on the structurally similar read across substance C.I. Acid Red 52 (3520-42-1) and Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester (302776-68-7). 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 (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for C.I. Pigment Violet 1 (1326-03-0).The LD50 was estimated to be 8236.78 mg/kg bw,when male Sprague-Dawley rats were orally exposed with C.I. Pigment Violet 1 (1326-03-0) orally.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance C.I. Acid Red 52 (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 be10300 mg/kg bw when mice were treated with C.I. Acid Red 52 orally.

This is further supported by European Commission (EC) -SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS – SCCP (Opinion on: Diethylamino Hydroxybenzoyl Hexyl Benzoate (S83); European Commission (EC) - Scientific Committee on Consumer Products (SCCP); SCCP/1166/08; 15 April 2008) andEuropean Commission (EC) -SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS – SCCP (Opinion on Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester, European Commission (EC) -SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS – SCCP,SCCP/0996/06,20 June 2006) forthe structurally similar read across substance Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester (302776-68-7). Acute oral toxicity study was performed in groups of 3 male and female wistar rats using test material Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester(302776-68-7)according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).0.5% Tylose CB 30.000 in Aqua bi-distillated was used as vehicle.No mortality was observed at dose 2000 mg/kg bw. Hence,LD50 value was considered to be >2000 mg/kg bw,when rats were treated with Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester(302776-68-7)orally via gavage.

Thus, based on the above studies on C.I. Pigment Violet 1 (1326-03-0) and it’s structurally similar read across substances C.I. Acid Red 52 (3520-42-1) and Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester (302776-68-7), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, C.I. Pigment Violet 1 (1326-03-0) cannot be classified for acute oral toxicity.

Justification for classification or non-classification

Based on the above experimental studies and prediction on C.I. Pigment Violet 1 (1326-03-0) and it’s structurally similar read across substances C.I. Acid Red 52 (3520-42-1) and Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester (302776-68-7), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, C.I. Pigment Violet 1 (1326-03-0) cannot be classified for acute oral toxicity.