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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

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 (if other than submission substance): C24H28N3.C2H3O2
- Molecular weight (if other than submission substance): 417.5499 g/mol
- Smiles notation (if other than submission substance): CC(=O)[O-].CNc1ccc(cc1)C(=C2C=CC(=[N+](C)C)C=C2)c3ccc(cc3)N(C)C
- InChI: 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

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

0.135 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Population

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 "j" )  )

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 Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Halogens OR Metalloids OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.778

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.22

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 0.135 mg/L on the basis of effects on population..

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (CAS no. 84434 -47 -9). EC50 value was estimated to be 0.135 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this 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 is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1 as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (CAS no. 84434 -47 -9). EC50 value was estimated to be 0.135 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this 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 is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1 as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

0.135 mg/L

Additional information

Predicted data for the target chemical N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methyl methanaminium acetate (CAS No. 84434 -47 -9) and various weight of evidence study for its closest read across substancewere reviewed to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemicalN-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (CAS No. 84434 -47 -9) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017). EC50 value was estimated to be 0.135 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this 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 is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1 as per the CLP classification criteria.

 

In a supporting weight of evidence study from peer reviewed journal (E Kasai and S. Hatakeyama, 1993) for the read across chemical N,N'-diethyl-6 -(methylsulfanyl)-1,3,5 -triazine-2,4 -diamine (CAS no. 1014 -70 -6), short term toxicity to Chlorella vulgaris (CCAP 211/11b and NIES-227) study was carried out for 72 hrs. The study was based on the effects of the read across compound N,N'-diethyl-6 -(methylsulfanyl)-1,3,5 -triazine-2,4 -diamine on Chlorella vulgaris in a static fresh water system at a temperature of 25 -28⁰C.Two hundred-fold stock solutions in 75 % DMSO (dimethyl sulfoxide) were prepared to make six final concentrations in the media, respectively. Chlorella vulgaris (CCAP 211/11b and NIES-227) was used as a test organism obtained as axenic unialgal cultures. To obtain log-phase materials in population growth, a few drops of stock cultures were inoculated into 100 ml flasks, each containing 50 ml Medium C. These flasks were incubated for three days. An equal amount (0.5 ml) of respective stock solutions of the herbicides and 1 to 4.5 ml of the precultured algae were added to a freshly prepared Medium C. The final volume was adjusted to 100 ml, which contained 1 x 10(4) algal cells/ml. The untreated control received only 0.5 ml of 75 % DMSO. A final concentration of DMSO used for the herbicide solvent was 0.375 %. A preliminary experiment showed no adverse effects at this concentration on the population growth of the algae. For the assay, 50 ml conical flasks each containing 30 ml of the test solution, covered with a silicon cap was used. Three replicates were used at each herbicide concentration. Preculture and the assays were conducted at 25-28⁰C under continuous illumination at 100-150 µmol photon/m2/s. The flasks were shaken manually twice a day. After 72 hours the cell density was determined using a Coulter Counter ZM (Coulter Electronics Ltd.). Percentage growth was calculated comparing cell number in the culture containing the respective herbicides to that of untreated control culture. EC50 values were estimated by the linear regression of probit of percentage growth on log dose of herbicides. Comparison of regression lines was performed statistically. Based on effect on growth rate and cell density of the test organism Chlorella vulgaris(CCAP 211/11b and NIES-227),the 72 hr EC50 value was determined to be 0.494 and 0.464 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance N,N'-diethyl-6-(methylsulfanyl)-1,3,5-triazine-2,4-diaminecan be considered as toxic to aquatic organisms and thus can be considered to be classified in aquatic acute category 1 as per the CLP classification criteria.

 

For the same read across chemical N,N'-diethyl-6 -(methylsulfanyl)-1,3,5 -triazine-2,4 -diamine (CAS no. 1014 -70 -6), short term toxicity to green algae study was carried out for 72 hrs (J-CHECK, 2017). The study was based on the effects of the read across compound N,N'-diethyl-6 -(methylsulfanyl)-1,3,5 -triazine-2,4 -diamine on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 0.028 and 0.0046 mg/l, respectively and on the basis of biomass and area under the growth curve, the 72 hr EC50 and NOEC value was determined to be 0.012 and 0.0046 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance N,N'-diethyl-6 -(methylsulfanyl)-1,3,5 -triazine-2,4 -diamine can be considered as toxic to aquatic organisms and thus can be considered to be classified in aquatic acute category 1 as per the CLP classification criteria.

 

Another short term toxicity to green algae study was carried out for 72 hrs(J-CHECK, 2017). The study was based on the effects of the read across compound 4,4'-carbonimidoylbis (N,N-dimethylaniline) hydrochloride (CAS no. 2465 -27 -2) on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 0.34 and 0.026 mg/l, respectively and on the basis of AUG, the 72 hr EC50 and NOEC value was determined to be 0.093 and 0.026 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 4,4'-carbonimidoylbis(N,N-dimethylaniline) hydrochloride can be considered as toxic to aquatic organisms and thus can be considered to be classified in aquatic acute category 1 as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (from OECD QSAR toolbox version 3.3, 2017) and for its read across substance (from peer reviewed journal and authoritative database), it can be concluded that the test substance N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate can be considered as toxic to aquatic environment and can be considered to be classifiedin aquatic acute category 1 as per the CLP classification criteria.