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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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: 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):

Cyprinodon variegatus

Test type:

flow-through

Water media type:

saltwater

Total exposure duration:

96 h

Hardness:

25 to 50 mg/L asd CaCO3

Test temperature:

22°C +/- 1°C

pH:

7.6 to 7.9

Nominal and measured concentrations:

Estimated

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.946 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: Other details not known

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
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 ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and "v" )  and ("w" and "x" )  )

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 SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN2 OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates 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 SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines 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) 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 >> N-Carbonyl heteroaryl amines OR Acylation >> Direct acylation involving a leaving group >> N-Carbonylsulfonamides OR AN2 OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inorganic Compound AND SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Esters, Monothiophosphates by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Inorganic Compound AND SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Inorganic Compound AND SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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: "t"

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

Domain logical expression index: "u"

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: "v"

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: "w"

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

Domain logical expression index: "x"

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 mortality of fishes, the LC50 value was estimated to be 0.94 mg/l for Cyprinodon variegatus for 96 hrs of duration. 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.

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, the short term toxicity on fish Cyprinodon variegatus 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 mortality of fishes, the LC50 value was estimated to be 0.94 mg/l for Cyprinodon variegatus for 96 hrs of duration. 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, the short term toxicity on fish Cyprinodon variegatus 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 mortality of fishes, the LC50 value was estimated to be 0.94 mg/l for Cyprinodon variegatus for 96 hrs of duration. 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 fish

Fresh water fish

Effect concentration:

0.94 mg/L

Additional information

Based on the predicted data for the target chemical and experimental data for read across chemicals 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 mortality of fish. 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, the short term toxicity on fish Cyprinodon variegatus 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 mortality of fishes, the LC50 value was estimated to be 0.94 mg/l for Cyprinodon variegatus for 96 hrs of duration. 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 UERL lab. Fish Acute Toxicity test according to OECD Guideline 203 was conducted for (test item name) [4-[[4-anilino-1-naphthyl][4 -(dimethylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene] dimethylammonium acetate. The test solution was prepared by dissolving 100 mg of the test substance in 100 ml of potable water (passed through reverse osmosis system) with 1 hr. continuous stirring for achieving test concentrations of 1g/L. The nominal concentration selected for the experiment were 0.3125mg/L,0.625mg/L,1.25mg/L,2.5mg/L,5mg/Land test fish were exposed to these concentration for 96 hours. After 96hrs of exposure LC0, LC50 and LC100 was observed. The lethal concentrations LC50 was determine to be >0.3125 mg/L but <0.625 mg/L. LC0 (96 hours) (highest loading at which no mortality was observed) = 0.3125 mg/L. LC50 (96 hours) Experimental = >0.3125 mg/L but <0.625 mg/L. LC100 (96 hours) (lowest loading at which 100% mortality was observed) = 0.625 mg/L. Based on LC50 chemical was toxic and consider as classified in aquatic acute 1 as per the CLP classification criteria.

 

Similarly for the same read across chemical (83803-79-6) from BASF report Study was conducted to determine the toxic nature of chemical N-(4-{[4-(dimethylamino)phenyl][4 -(methylamino) phenyl] methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate on the growth of fish Leuciscus idus. Test was performed according to the OECD guideline. The doses were chosen based on two range finding studies between 0.3 and 1 mg/l) the concentrations, spaced by a factor of about 2.2. Control, 0.01, 0,022, 0.046, 0.1, 0.215, 0464, 1.0, 2.15 mg/L concentration was taken in the study. In the form of an aqueous solution (0.1 g/100 ml) the product was added to the test water, subsequently the fish were placed into the aquaria. Leuciscus idus (golden variety) used as a test organism collected from Fischzucht Paul Eggers, 2354 Hohenwestedt, Germany. Fish does not feed during test. Open glass aquaria having dimeter 30 x 22 x 24 cm, was used having the capacity of 10 liter. 2.8 g fish /L was added. 10 organisms per vessel was used. Chloracetamid added as a reference substance. After the exposure of 96hrs LC50 observed on the basis of Apathy and narcotic-like state was determine at test concentration 2.15 mg/L after 1 hour. In reference substance Chloracetamid the LC50 was 32 mg/L at 48 hr. Based on the mortality of fish the LC50 was 0.158 mg/l and the LC100 was 0.0464 mg/l. Based on the LC50 chemical was consider as toxic and can be consider to be classified as aquatic acute 1 category as per the CLP classification criteria.

 

Similarly in the fourth weight of evidence study for the read across chemical (6358-36-7) (from UERL 2017) toxicity was conducted on fish to determine the toxic nature of chemical. Fish Acute Toxicity test according to OECD Guideline 203 was conducted for (test item name) 4,4'-carbonimidoylbis [N,Ndiethylaniline] monohydrochloride. The test substance was soluble in water. Therefore, the test solution was prepared by dissolving 1g of the test substance in 1 liters of potable water (passed through reverse osmosis system) with 1 hour continuous stirring. After that analytically detect stock, solubility found 981.56 mg/L and calculations done accordingly. The nominal concentration selected for the experiment were 0.625mg/L,1.25mg/L,2.5mg/L,5mg/L, 10mg/L and test fish were exposed to these concentration for 96 hours. The lethal concentrations LC50 was determine to be 0.625 mg/L. LC50 (96 hours) Experimental = 0.625 mg/L. LC100 (96 hours) (lowest loading at which 100% mortality was observed) = 1.25 mg/L

 

The fifth study used for the read across chemical (84434-47-9) from UERL lab 2017, fish Acute Toxicity test according to OECD Guideline 203 was conducted for (test item name) [4-[[4 -(dimethylamino) phenyl][4-(methylamino)phenyl]methylene] cyclohexa-2,5-dien- 1-ylidene]dimethylammonium acetate The nominal concentration selected for the experiment were 0.3125mg/L, 0.625mg/L, 1.25mg/L, 2.5mg/L, 5mg/L and test fish were exposed to these concentration for 96 hours. The lethal concentrations LC50 was found to be >0.3125 mg/L but <0.625 mg/L.

LC0 (96 hours) (highest loading at which no mortality was observed) = 0.3125 mg/L

LC50 (96 hours) Experimental = >0.3125 mg/L but <0.625 mg/L

LC100 (96 hours) (lowest loading at which 100% mortality was observed) = 0.625 mg/L

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, UERL lab report and BASF data, it was summarized that the chemical was toxic to aquatic organisms fishes and thus can be classified as aquatic acute category 1 as per the CLP criteria.