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

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:

QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Predicted 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):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

25 to 50 mg/L asd CaCO3

Test temperature:

20°C +/- 1°C

pH:

7.6 to 7.9

Salinity:

22%

Nominal and measured concentrations:

Estimated

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

0.54 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Intoxication

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 0.54 mg/l.

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 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 "l" )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Conjugated Nitro Compounds OR SN2 OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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 >> Sulfonylureas 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 Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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 AND No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Carbonyl heteroaryl amines OR Acylation >> Direct acylation involving a leaving group >> N-Carbonylsulfonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  OR AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 11 - Trans.Metals Cu,Ag,Au OR Group 13 - Metalloids B OR Group 15 - Metalloids As,Sb OR Group 16 - Selennm Se OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I OR Group 7 - Trans.Metals Mn,Tc,Re by Chemical elements

Domain logical expression index: "o"

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=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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: "q"

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 by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.61

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.37

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxication of test organism the EC50 value was estimated to be 0.54 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 daphnia magna for 48 hrs.

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 six closest read across substances, toxicity on daphnia magna was 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 intoxication of test organism the EC50 value was estimated to be 0.54 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 daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) is considered to be toxic to aquatic environment and classified as aquatic acute 1 category as per the criteria mentioned in CLP regulation.    

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 six closest read across substances, toxicity on daphnia magna was 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 intoxication of test organism the EC50 value was estimated to be 0.54 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 daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) is considered to be toxic to aquatic environment and classified as aquatic acute 1 category as per the criteria mentioned in CLP regulation.    

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.54 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 mobility of daphnia magna. The studies are as mentioned below:   

 

In the first predicted weight of evidence report from OECD QSAR toolbox 3.4, 2018 toxicity was measured. Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was 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 intoxication of test organism the EC50 value was estimated to be 0.54 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 daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdate silicates (68647-35-8) is considered to be toxic to aquatic environment and classified as aquatic acute 1 category as per the criteria mentioned in CLP regulation.    

 

Further first predicted study was supported by the second experimental study for read across (83803-79-6) chemical from ABITEC lab. Determination of the inhibition of the mobility of daphnids was carried out with the substance N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien- 1-ylidene)-N-methylmethanaminium acetate according to OECD Guideline 202. The test substance was tested at the concentrations 0, 0.006, 0.012, 0.025, 0.050, 0.100 mg/l. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N- methylmethanaminium acetate, in Daphnia magna was determined to be 0.037 mg/L for immobilisation effects. This value indicates that the substance is likely to be hazardous to aquatic invertebrates and can be classified as aquatic acute 1 as per the CLP criteria.

 

Similarly in the third weight of evidence study for the read across chemical (6358-36-7) (from ABITEC lab report 2017) toxicity was conducted on daphnia to determine the toxic nature of chemical. Determination of the inhibition of the mobility of daphnids was carried out with the substance 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride according to OECD Guideline 202. The test substance was tested at the concentrations 0, 0.01, 0.02, 0.04, 0.08, 0.16 and 0.32 mg/L. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride, in Daphnia magna was determined to be 0.016 mg/L for immobilisation effects. This value indicates that the substance is likely to be hazardous to aquatic invertebrates and can be classified as Aquatic acute category 1 as per the CLP criteria.

Thus based on the above data sources for target chemical Benzenamine, 4-[(4-aminophenyl)(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates (68647-35-8) from various experimental studies and predicted studies from QSAR, ABITEC report 2017, it was summarized that the chemical was toxic to aquatic invertebrates and thus can be classified as aquatic acute category 1 as per the CLP criteria.