Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 6964 mg/kg bw when Tif:MAGf male and female rats were orally exposed with Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate.

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 the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate
- Molecular formula: C40H44N12O10S2.2K
- Molecular weight: 993.174 g/mol
- Smiles notation: [K+].[K+].C(=C\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-])\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-]
- InChl: 1S/C40H44N12O10S2.2K/c53-21-17-51(18-22-54)39-47-35(41-29-7-3-1-4-8-29)45-37(49-39)43-31-15-13-27(33(25-31)63(57,58)59)11-12-28-14-16-32(26-34(28)64(60,61)62)44-38-46-36(42-30-9-5-2-6-10-30)48-40(50-38)52(19-23-55)20-24-56;;/h1-16,25-26,53-56H,17-24H2,(H,57,58,59)(H,60,61,62)(H2,41,43,45,47,49)(H2,42,44,46,48,50);;/q;2*+1/p-2/b12-11+;;
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Tif:MAGf

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

not specified

Doses:

6964 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 964 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as C.I. Fluorescent Brightener 28 113 by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) 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 Acid moiety OR Salt OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

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 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alcohol AND Alkene AND Aromatic amine AND Melamine AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acetal OR Alkoxy OR Alkyl arenes OR Allyl OR Ammonium salt OR Aryl OR Azo OR Carboxamide OR Carboxylic acid OR Cycloalkane OR Cycloalkene OR Dihydroxyl group OR Ether OR Fused carbocyclic aromatic OR Isocyanate OR Naphtalene OR Saturated heterocyclic fragment OR Sulfide OR Triazine OR Triazinetrione OR Urea derivatives by Organic Functional groups (nested)

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.84

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.24

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 6964 mg/kg bw when Tif:MAGf male and female rats were orally exposed with Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate. .

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 Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate. The LD50 was estimated to be 6964 mg/kg bw when Tif:MAGf male and female rats were orally exposed with Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 964 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

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, Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate along with the study available on structurally similar read across substance Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, free acid (CAS no 4404-43-7) and Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, disodium salt (CAS no 4193-55-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

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 Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate. The LD50 was estimated to be 6964 mg/kg bw when Tif:MAGf male and female rats were orally exposed with Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate.

In another prediction done by SSS (2017) using the Danish QSAR, the acute oral toxicity was estimated for Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate. The LD50 was estimated to be 6800 mg/kg bw in rat and 8800 mg/kg bw in mice when rats and mice were orally exposed with Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate.

Further this is supported by experimental study summarized by OECD SIDS – SIAM (OECD SIDS Initial Assessment Report, SIAM 20, April 2005.) on structurally similar read across substance Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2-hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, free acid (CAS no 4404-43-7), 10 Wistar II female rat was treated with Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, free acid in the concentration of 15000 mg/kg bw orally by gavage in water (3 % solution). No mortality and clinical signs were observed in treated female rat at 15000 mg/kg bw. Therefore, LD50 was considered to be >15000 mg/kg bw when 10 Wistar II female rat was treated with Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, free acid orally by gavage.

This is supported by experimental study summarized by OECD SIDS – SIAM (OECD SIDS Initial Assessment Report, SIAM 20, April 2005.) on structurally similar read across substance Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, disodium salt (CAS no 4193-55-9), 10 Wistar I male rat was treated with Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, disodium salt in the concentration of 15000 mg/kg bw orally by gavage in peanut oil. No mortality and clinical signs were observed in treated male rat at 15000 mg/kg bw. Therefore, LD50 was considered to be >15000 mg/kg bw when 10 Wistar I male rat was treated with Benzenesulfonic acid,2-2’-(1,2-ethenediyl)bis(5-((4-(bis(2- hydroxyethyl)amino)-6-(phenylamino)-1,3,5-triazin-2-yl)amino)-, disodium salt orally by gavage.

Thus, based on the above studies and predictions on Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate and its 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, Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate can be classified as category V of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate and its 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, Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate can be classified as category V of acute oral toxicity.