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

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Endpoint:

toxicity to microorganisms

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 from OECD QSAR toolbox version 3.4 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.4.

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):

Tetrahymena pyriformis

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

No data available

Test temperature:

No data available

pH:

No data available

Dissolved oxygen:

No data available

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

other: IGC50

Effect conc.:

91.766 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Growth

Remarks on result:

other: Other details not known

The prediction was based on dataset comprised from the following descriptors: IGC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" )  and ("c" and ( not "d") )  )  and "e" )  and ("f" and "g" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.62

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.69

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth inhibition of tetrahymena, IGC50 value was estimated to be 91.765 mg/l when N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was exposed to Tetrahymena pyriformis for 48 hours.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on microorganisms was predicted for N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino) phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (84434-47-9), IGC50 value was estimated to be 91.765 mg/l when N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was exposed to Tetrahymena pyriformis for 48 hours.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on microorganisms was predicted forN-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino) phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (84434-47-9),IGC50 value was estimated to be 91.765 mg/l whenN-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate wasexposed to Tetrahymena pyriformis for 48 hours.

Key value for chemical safety assessment

EC50 for microorganisms:

91.765 mg/L

Additional information

Based on the various experimental data and prediction data for the target chemical study have been reviewed to determine the toxic nature of N-(4-{[4-(dimethylamino)phenyl] [4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methyl methanaminium acetate (CAS No. 84434 -47 -9) on the growth of microorganisms. The studies are as mentioned below:

In the first weight of evidence study for target chemical (SSS, 2017)Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on microorganisms was predicted for N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino) phenyl]methylene} cyclohexa -2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate (84434-47-9),IGC50 value was estimated to be 91.765 mg/l when N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino) phenyl] methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was exposed to Tetrahymena pyriformis for 48 hours.

In the second weight of evidence study for the read across chemical (1694-09-4) (From Toxicology and applied pharmacology, 1977) toxicity to micro-organisms study was conducted on Paramecium caudatum for 20 mins. The test chemical conc. used for the study was 10000 mg/l (0.1%) and 1000 mg/l (1%). The test organism Paramecium caudatum was maintained at 22°C on 0.15% dried lettuce infusion and fed with Aerobacter aerogenes. Food dye (test chemical) of 0.1% conc. was put in a hollow slide glass, and an equal volume of 0.04 M phosphate buffer, pH 7.0, was added. After 5 to 10 Paramecium caudatum were added, their survival times were measured microscopically. 30 to 40 test organism for each conc. were tested and the mean survival time and the death rate was calculated after 20 mins. The survival time was defined as the time required until death was observed for each concentration. Death was assumed to have occurred when there was no movement. The death rate was defined as the percentage of deaths observed during 20 min. The mean survival time of test organism Paramecium caudatum at 1% was 298 sec and at 0.1% was 865 sec. Based on the mean survival time and death rate of organism due to the exposure of chemical acid violet, the EC100 was 10,000 mg/l and EC83.3 was 1000 mg/l.

 

Similarly study was conducted for the third weight of evidence study for the read across chemical methyl violet (8004-87-3) (From Chemosphere, 2003) Determination of toxicity of methyl violet on the growth of 14 gram negative microorganisms. Inhibitory activity of test chemical (methyl violet) was determined by the traditional agar gel method. The conc. of test chemical used for the study was 0.6918 mg/l (1 µM). 14 different gram negative bact. were used for the study was Agrobacterium radiobacter, Agrobacterium tumefaciens, Bradyrhizobium japonicum, Escherichia coli, Erwinia atroseptica,Erwinia herbicola, Erwinia uredovora, Pseudomonas fluorescence, Pseudomonas phaseolicola, Pseudomonas syringae , Rhizobium trifolii, Xanthomonas malvacearum, Xanthomonas phaseoli and X. stewartii. These test organisms were taken from the collection of the Plant Protection Institute, Hungarian Academy of Sciences (Budapest, Hungary). The bacteria were maintained on Nutrient Agar (Oxoid CM3) completed with vitamins pyridoxine. HCl, thiamine. HCl, riboflavine and nicotinamide at 1, 10, 1 and 20 mg/l concentrations. Bacterial suspensions for screening were prepared by washing cells with sterile tap water containing 0.3% peptone from slants of 20 h old cultures grown at (21±1) °C. A layer of 5 mm depth of inoculated medium was dispensed into Petri dishes of 90 mm diameter. Filter paper discs of 5 mm diameter were impregnated with 1 µM solution of test compounds and placed centrally on the surface of the agar plate. Growth inhibition zones were measured after 24 h incubation at 21 ± 1 °C. After incubation colony diameters were determined and growth inhibition was calculated in percentage of dye free colony growth. Each determination was run in quadruplicate. Based on no effect ongrowth inhibition of gram negative test organisms, the NOEC value of methyl violet was determine to be 0.6918 mg/l for Erwinia herbicola and Pseudomonas syringae. Whereas the growth inhibition was observed on the other organisms so LOEC was 0.6918 mg/l for remaining 12 bacteria.

 

 

Similarly study was conducted for the fourth weight of evidence study for the read across chemical methyl violet (8004-87-3) from chemosphere 2003, Determination of toxicity of methyl violet on the growth of 8 gram positive microorganisms. Inhibitory activity of test chemical (methyl violet) was determined by the traditional agar gel method. The conc. of test chemical used for the study was 0.6918 mg/l (1 µM). 8 different gram positive bact. were used for the study was Corynebacterium fascians, Corynebacterium flaccumfaciens, Corynebacterium michiganense, Corynebacterium oortii, Stapylococcus aureus, Micrococcus luteus, Bacillus subtilis and Bacillus thuringiensis Berliner subp. Kurstaki. These test organisms were taken from the collection of the Plant Protection Institute, Hungarian Academy of Sciences (Budapest, Hungary). The bacteria were maintained on Nutrient Agar (Oxoid CM3) completed with vitamins pyridoxine. HCl, thiamine. HCl, riboflavine and nicotinamide at 1, 10, 1 and 20 mg/l concentrations. Bacterial suspensions for screening were prepared by washing cells with sterile tap water containing 0.3% peptone from slants of 20 h old cultures grown at (21±1) °C. A layer of 5 mm depth of inoculated medium was dispensed into Petri dishes of 90 mm diameter. Filter paper discs of 5 mm diameter were impregnated with 1 µM solution of test compounds and placed centrally on the surface of the agar plate. Growth inhibition zones were measured after 24 h incubation at 21 ± 1 °C. After incubation colony diameters were determined and growth inhibition was calculated in percentage of dye free colony growth. Each determination was run in quadruplicate. Based on growth inhibition of gram positive test organisms, the LOEC value of methyl violet was determine to be 0.6918 mg/l.