Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, aluminium salt

Endpoint summary

Description of key information

Acute oral toxicity: 

LD50 was estimated to be 506 mg/kg bw when male and female Wistar rats were treated with Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt via oral gavage route.

Based on the prediction on Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1) and it’s read across substances, it can be concluded that LD50 value is between 300 - 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt can be classified as category IV 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:

key study

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 3.4 and the supporting QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt
- Mol. formula: C27H32N2O6S2.1/3Al
- Molecular Weight: 1658.0277 g/mole
- Smiles: CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+](CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+](CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].CCN(CC)c1ccc(cc1)C(=C2C=CC(=[N+](CC)CC)C=C2)c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-].[Al+3]
- InChI: 1S/3C27H32N2O6S2.Al/c3*1-5-28(6-2)22-13-9-20(10-14-22)27(21-11-15-23(16-12-21)29(7-3)8-4)25-18-17-24(36(30,31)32)19-26(25)37(33,34)35;/h3*9-19H,5-8H2,1-4H3,(H-,30,31,32,33,34,35);/q;;;+3/p-3

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

506 mg/kg

No. of animals per sex per dose:

not specified

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:

506 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(("a" or "b" or "c" or "d" or "e" )  and ("f" and "g" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as 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 Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Similarity boundary:Target: CCN(CC)c1ccc(C(=C2C=CC(=N{+}(CC)CC)C=C2)c2ccc(S(=O)(=O)O{-})cc2S(O)(=O)=O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.418

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.49

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LD50 was estimated to be 506 mg/kg bw when male and female Wistar rats were treated with Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt via oral gavage route.

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 Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1). LD50 was estimated to be 506 mg/kg bw when male and female Wistar rats were treated with Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

506 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR toolbox 3.4

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, Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1) 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 Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene) diethylammonium, aluminium salt along with the study available on structurally similar read across substance [4-[bis[4-(diethylamino)phenyl]methylene]-2,5-cyclohexadien-1-ylidene]diethylammonium chloride (2390-59-2) and [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride (548-62-9). 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 Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1). LD50 was estimated to be 506 mg/kg bw when male and female Wistar rats were treated with Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene)cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt via oral gavage route.

In another study supported by Catherine et al.(International Journal of Toxicology, 28 (Suppl 3) 193S-204S, 2009), for the structurally similar read across substance [4-[bis[4-(diethylamino)phenyl]methylene]-2,5-cyclohexadien-1-ylidene]diethylammonium chloride (2390-59-2). The acute oral toxicity study was conducted in Sprague- Dawley male and female rats of each sex for each dose group at the concentration of 250, 500, 595, 707, or 1000 mg/kg in Male rats and 62.5, 125, 250, 500, or 1000 mg/kg in Female rats. The test substance was mixed with acetic acid (Vehicle). Animals were observed for clinical signs.50% mortality was observed with the Clinical Symptoms like sluggishness, unsteady gait, red discharge around the nose, tremors, diarrhea, emaciation, and a moribund appearance was observed. Therefore, LD50 was considered to be 549 mg/kg in male rats and 308 mg/kg in females, when Sprague- Dawley rats were treated with Basic Violet 4 by oral gavage route.

The above study supported by Catherine et al.(International Journal of Toxicology 28(Suppl 3) 193S-204S, 2010), for the structurally similar read across substance [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride (548-62-9). The Acute oral toxicity study was done in 24 adult rats. The 1% or 2% solution of test material was prepared in water and given by oral gavage route. 50% mortality was observed at dose 650 mg/kg bw. Hence LD50 was considered to be 650 mg/kg body weight via oral gavage route.

This is further supported by U.S .National library of medicine, ChemIDplus (2017) and IFA GESTIS (2017), for the structurally similar read across substance [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride (548-62-9). The Acute oral toxicity study was done in rats. 50% mortality was observed at dose 420mg/kg bw. Hence LD50 was considered to be 420mg/kg body weight, when rats were treated with C.I.basic violet 3 by oral route.

Thus, based on the above studies on Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1) and it’s read across substances, it can be concluded that LD50 value is between 300 - 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt can be classified as category IV of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt (15876-40-1) and it’s read across substances, it can be concluded that LD50 value is between 300 - 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Hydrogen (4-(4-(diethylamino)-2',4'-disulphonatobenzhydrylidene) cyclohexa-2,5-dien-1-ylidene)diethylammonium, aluminium salt can be classified as category IV for acute oral toxicity.