Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates

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:

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: Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates
SMILES:CCN(CC)c1ccc2c(c1)o{+}(.O{-}[Mo](=O)(=O)O{-}.o{+}1c3cc(N(CC)CC)ccc3c(-c3ccccc3C(=O)OCC)c3ccc(N(CC)CC)cc13)c1cc(N(CC)CC)ccc1c2-c1ccccc1C(=O)OCC_O[W](O)(=O)=O_OP(O)(O)=O

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Tetrahymena pyriformis

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

other: IGC50

Effect conc.:

5.857 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Growth

Remarks on result:

other: Other details not known

Details on results:

The IGC50 was 5.85 mg/l.

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" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phosphates, Inorganic by US-EPA New Chemical Categories

Domain logical expression index: "b"

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: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) ester group AND Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic-CH AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] AND No alert found AND Number of fused 6-carbon aromatic rings AND Tertiary amine by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Pyridine ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Similarity boundary:Target: CCN(CC)c1ccc2c(c1)o{+}(.O{-}[Mo](=O)(=O)O{-}.o{+}1c3cc(N(CC)CC)ccc3c(-c3ccccc3C(=O)OCC)c3ccc(N(CC)CC)cc13)c1cc(N(CC)CC)ccc1c2-c1ccccc1C(=O)OCC_O[W](O)(=O)=O_OP(O)(O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Similarity boundary:Target: CCN(CC)c1ccc2c(c1)o{+}(.O{-}[Mo](=O)(=O)O{-}.o{+}1c3cc(N(CC)CC)ccc3c(-c3ccccc3C(=O)OCC)c3ccc(N(CC)CC)cc13)c1cc(N(CC)CC)ccc1c2-c1ccccc1C(=O)OCC_O[W](O)(=O)=O_OP(O)(O)=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND No functional group found AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alkoxy by Organic Functional groups (nested)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND No functional group found AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups (nested)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.28

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.93

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition the IGC50 value was estimated to be 5.85 mg/l when Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) exposed to Tetrahymena pyriformis for 48hrs.

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 microorganism Tetrahymena pyriformis predicted for Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8). Based on the growth rate inhibition the IGC50 value was estimated to be 5.85 mg/l when Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) exposed to Tetrahymena pyriformis for 48hrs.

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 microorganism Tetrahymena pyriformis predicted for Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8). Based on the growth rate inhibition the IGC50 value was estimated to be 5.85 mg/l when Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) exposed to Tetrahymena pyriformis for 48hrs.

Key value for chemical safety assessment

EC50 for microorganisms:

5.85 mg/L

Additional information

Based on the prediction data for the target chemical and experimental data for read across chemical which was selected on the basis of structure similarity study have been reviewed to determine the toxic nature of Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates (68647-35-8) on the microorganisms. The studies are as mentioned below:     

 

In the first predicted weight of evidence report from OECD QSAR toolbox 3.4, 2018 toxicity was measured for Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates (68647-35-8). 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 microorganism Tetrahymena pyriformis predicted for Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8). Based on the growth rate inhibition the IGC50 value was estimated to be 5.85 mg/l when Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) exposed to Tetrahymena pyriformis for 48hrs.

 

Further first predicted study was supported by the second experimental study for read across chemical Basic violet 1 (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 on growth 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 in the third weight of evidence study for the same read across chemical (8004-87-3) from Chemosphere 2003 toxicity was measured on the gram positive bacteria. 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- Gram – positive bacteria 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.

Thus based on the toxicity data chemical was consider as toxic to microorganisms.