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

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:

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):

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

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

24 ± 1°C

pH:

7.1 - 8.0

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

0.404 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

growth rate

Remarks on result:

other: Other details not known

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(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 Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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: "h"

Referential boundary:The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

Referential boundary:The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr by Chemical elements

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 16 - Selennm Se OR Group 16 - Sulfur S OR Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "o"

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: "p"

Referential boundary:The target chemical should be classified as Group 17 - Halogens Cl by Chemical elements

Domain logical expression index: "q"

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: "r"

Referential boundary:The target chemical should be classified as Group 7 - Trans.Metals Mn,Tc,Re by Chemical elements

Domain logical expression index: "s"

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: "t"

Referential boundary:The target chemical should be classified as Group 12 - Trans.Metals Zn,Cd,Hg by Chemical elements

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=10%,
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=20%,
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 >= 3.73

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.13

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition of Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) by the chemical Benzenamine,4-[(4-aminophenyl)(4-imino-2,5- cyclohexadien-1-ylidene)methyl]-, N-Me derivatives, molybdatesilicates the EC50 was determine to be 0.404 mg/l.

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 Pseudokirchneriella subcapitata 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 growth inhibition of test organism the EC50 value was estimated to be 0.404 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 pseudokirchneriella subcapitata for 72 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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata 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 growth inhibition of test organism the EC50 value was estimated to be 0.404 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 pseudokirchneriella subcapitata for 72 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

EC50 for freshwater algae:

0.404 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 mortality of aquatic algae and cyanobacteria. 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 Pseudokirchneriella subcapitata 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 growth inhibition of test organism the EC50 value was estimated to be 0.404 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 pseudokirchneriella subcapitata for 72 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 (6358-36-7) chemical from ABITEC lab. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride according to OECD Guideline 201. The stock solution (10 mg/L) was prepared by dissolving yellow powder in OECD growth medium. Test solutions of required concentration were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture and tested at the concentrations 0, 3, 6, 12, 24 and 50 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (EC50) for the test substance, 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride, in Desmodesmus subspicatus was determined to be 0.13 mg/L. This value indicates that the substance is likely to be hazardous to aquatic algae and can be classified as Aquatic acute category 1 as per the CLP criteria.

 

 

Similarly in the third weight of evidence study for the read across chemical (2465-27-2) (from j-check 2017) toxicity was conducted on algae to determine the toxic nature of chemical. Short term toxicity to green algae study was carried out for 72 hrs. The study was based on the effects of the test 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 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 and j-check, it was summarized that the chemical was toxic to aquatic algae and cyanobacteria and thus can be classified as aquatic acute category 1 as per the CLP criteria.