[4-[[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium acetate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate
- Molecular formula: C24 H28 N3.C2 H3 O2
- Molecular weight: 417.5499 g/mol
- Smiles notation: CC(=O)[O-].CNc1ccc(cc1)C(=C2C=CC(=[N+](C)C)C=C2)c3ccc(cc3)N(C)C
- InChl : 1S/C24H27N3.C2H4O2/c1-25-21-12-6-18(7-13-21)24(19-8-14-22(15-9-19)26(2)3)20-10-16-23(17-11-20)27(4)5;1-2(3)4/h6-17H,1-5H3;1H3,(H,3,4)
- Substance type: Organic
- Physical state: liquid

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

0.505 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
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 "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acetoxy OR Alkene OR Ammonium salt OR Aromatic amine OR Aryl OR Carboxylic acid by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetoxy OR Alkene OR Ammonium salt OR Aromatic amine OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Amino, aliphatic attach [-N<] OR Aromatic Carbon [C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aliphatic Amines OR Alkoxy Silanes OR Anilines (amino-meta) OR Anilines (Unhindered) OR Esters OR Esters, Monothiophosphates OR Inorganic Compound OR Melamines OR Not classified OR Quinones OR Salt OR SHOULD NOT BE PROFILED OR Surfactants-Anionic OR Surfactants-Cationic OR Thiazolones (Iso-) OR Triazines, Aliphatic OR Triazines, Aromatic OR Vinyl/Allyl Alcohols OR Vinyl/Allyl Esters OR Vinyl/Allyl Ketones by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND -C=CH  [alkenyl hydrogen] AND Methyl  [-CH3] AND Quaternary amine AND Tertiary amine by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aliphatic acid   [-C(=O)-OH] OR Aromatic acid   [-C(=O)-OH] OR -CH2-  [cyclic] OR -CH2-  [linear] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.72

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.53

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on aquatic invertebrates was predicted for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9). EC50 value was estimated to be 0.505 mg/l for Daphnia magna for 48 hrs duration. Thus, based on the EC50 value, it can be concluded that the substance N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) can be considered as toxic to aquatic organisms and can be classified in aquatic acute 1 category as per the CLP regulations.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, the short term toxicity on aquatic invertebrates was predicted for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9). EC50 value was estimated to be 0.505 mg/l for Daphnia magna for 48 hrs duration. Thus, based on the EC50 value, it can be concluded that the substance N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) can be considered as toxic to aquatic organisms and can be classified in aquatic acute 1 category as per the CLP regulations.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, the short term toxicity on aquatic invertebrates was predicted for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9). EC50 value was estimated to be 0.505 mg/l for Daphnia magna for 48 hrs duration. Thus, based on the EC50 value, it can be concluded that the substance N-(4-{[4-(dimethylamino)phenyl][4-(methylamino) phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) can be considered as toxic to aquatic organisms and can be classified in aquatic acute 1 category as per the CLP regulations.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.505 mg/L

Additional information

Short term toxicity to aquatic invertebrates for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) was summaries with predicted data for target and experimental study of structural and functional read across are summaries as follows:

 

In the first weight of evidence study using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, the short term toxicity on aquatic invertebrates was predicted for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9). EC50 value was estimated to be 0.505 mg/l for Daphnia magna for 48 hrs duration. Thus, based on the EC50 value, it can be concluded that the substance N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) can be considered as toxic to aquatic organisms and can be classified in aquatic acute 1 category as per the CLP regulations.

 

 

Study was carried out on the read across chemical (548-62-9), Intox report which was structurally similar to the target chemical. Acute Immobilisation test in Daphnia magna was performed in compliance with the OECD Guidelines for Testing of Chemicals, Section 2, No. 202, "Daphnia Sp., Acute Immobilisation Test" . N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride was tested for acute toxic effects on the swimming capabilities of Daphnia magna employing a static test procedure. In the main study, six groups of daphnids, each comprising 5 daphnids per replicate, were exposed to the test article at concentration levels of 0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg/L. Observations were made for immobilisation at 24 hours and 48 hours of treatment. A concurrent blank control was also run simultaneously. Potassium Dichromate was employed as a positive control and tested at the concentration of   0.4 mg, 0.63 mg and 1 mg/L. The animals were observed for immobility after 24 hours and 48 hours of exposure. Those daphnids which were unable to swim within 15 seconds after gentle agitation of the test container were considered to be immobile. The rates of immobilisation observed at 24 hours were 0%, 0%, 0%, 10%, 25% and 75% at the test concentrations of 0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg/L respectively. The rates of immobilisation observed at 48 hours were 0%, 0%, 10%, 25%, 55% and 85% at the test concentrations of 0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg/L respectively. The Positive control, Potassium Dichromate induced immobilisation in 20%, 50% and 80% of the exposed daphnids at 24 hours and 25%, 65% and 100% immobilization at 48 hours at the concentrations of 0.4 mg, 0.63 mg and 1 mg/L respectively. No immobilisation was observed in blank control group. The acute immobilisation EC50value of N-(4-{bis[4-(dimethylamino) - phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride to Daphnia magna at 24 hour exposure period was determine to be 0.53 mg/L with fiducial limits between 0.41 to 0.69 mg/L at 95% confidence level. The acute immobilisation EC50 value of N-(4-{bis[4-(dimethylamino)phenyl] methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride to Daphnia magna at 48 hour exposure period was determine to be 0.35 mg/L with fiducial limits between 0.24 to 0.50 mg/L at 95% confidence level. On the basis of EC50 value obtained it can be concluded that the substance N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride is toxic to the aquatic environment and can be considered as "Aquatic Acute 1" as per CLP regulation.

 

 

Similarly in the third weight of evidence study for read across chemical N-(4 -{[4 -(dimethylamino)phenyl](phenyl)methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium chloride (569-64-2) from J-check, study was performed in daphnia magna for 48 hrs. After the experiment, the EC50 value for N-(4-{[4-(dimethylamino)phenyl](phenyl)methylene} cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride was determined to be 0.13 mg/l.

 

Another fourth weight of evidence study on read across diphenylarsinous cyanide (23525-22-6) from Ecotox database was performed in static salt water condition for 48 hrs in daphnia magna. 5 daphnia magna of <24 hrs were used. After 48 hrs, the EC 50 value for diphenylarsinous cyanide (23525-22-6) was determined to be 0.072 mg/l.

 

Based on the experimental studies of target and study of structural and functional read across, it was considered that N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene} cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (84434-47-9) was considered to be toxic to aquatic invertebrates and can be considered to be classified in aquatic acute 1 category as per the CLP regulations.