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Short-term toxicity to aquatic invertebrates

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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:
Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.
Qualifier:
according to
Guideline:
other: Predicted data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.
GLP compliance:
not specified
Specific details on test material used for the study:
Name of the test chemical: 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid
Molecular formula: C20H16ClN9O10S3
Molecular weight: 674.0504 g/mol
Smiles Notation: S(=O)(=O)(c1c(/N=N/c2c(NC(=O)N)cc(Nc3nc(nc(n3)Cl)N)cc2)cc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc2c1)O
InChI: 1S/C20H16ClN9O10S3/c21-17-26-18(22)28-20(27-17)24-9-1-2-12(13(5-9)25-19(23)31)29-30-14-7-11-8(4-16(14)43(38,39)40) 3-10(41(32,33)34)6-15(11)42(35,36)37/h1-7H,(H3,23,25,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H3,22,24,26,27,28)/b30-29+
Substance Type: Organic
Physical State: solid
Analytical monitoring:
not specified
Vehicle:
not specified
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
48 h
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
113.58 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Intoxication
Remarks on result:
other: not toxic

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" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Unhindered) OR Substituted Ureas OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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 OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones 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 diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic 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 >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

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: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic compound AND Azo compound AND Carbonic acid derivative AND CO2 derivative (general) AND Halogen derivative AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.882

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.962

Validity criteria fulfilled:
not specified
Conclusions:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to Daphnia magna was predicted 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9). Intoxication value was estimated to be 113.58 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9) was likely to be not toxic to aquatic invertebrate.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to Daphnia magna was predicted 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9). Intoxication value was estimated to be 113.58 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9) was likely to be not toxic to aquatic invertebrate.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to Daphnia magna was predicted 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9). Intoxication value was estimated to be 113.58 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9) was likely to be not toxic to aquatic invertebrate.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
113.58 mg/L

Additional information

Based on the various predicted data for the target chemical and experimental data for structurally and functionally similar read across chemicals study have been reviewed to determine the toxic nature of target chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naphthalene -1,3,6-trisulphonic acid (35642-64-9) on the mobility of aquatic invertebrates. The studies are as mentioned below:

 

In the first study for the target chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naphthalene -1,3,6-trisulphonic acid (35642-64-9) from OECD QSAR toolbox 2017, prediction was done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to Daphnia magna was predicted 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9). Intoxication value was estimated to be 113.58 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 7-[(E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphth.(CAS: 35642-64-9) was likely to be not toxic to aquatic invertebrate.

 

First predicted study was supported by the second experimental weight of evidence study for the read across chemical Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6) from ABITEC report. An acute immobilisation test was used to test how a range of concentrations of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate exerts different degrees of toxic effects on the swimming capability of Daphnia magna under otherwise identical test conditions. The test was performed in close resemblance to OECD guideline 202 by ABITEC in Prague. The testing aim was to determine a EC50 after 48 hours of exposure to D. magna. Daphnids were exposed to Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate in 50 ml beakers in a volume of 25 ml of liquid solution containing both the chemical and media as specified in OECD 202. The beakers were placed in a temperature controlled room at 20±1 degrees Celsius. The D. magna (age ≤24) used for the test had been breed at ABITEC. The breeding stock of D. Magna originated from University of Technology in Prague. The animals were exposed to medium (i.e. a beaker containing only medium) and/or the tested chemical during 48 hours (±1 hour). None of the exposed animal’s immobilization were affected by exposure to only medium. The nominal concentrations used were: 100 mg/L (limit test). There were 5 Daphnia per test vessels and 5 replicates per concentration. The pH in test vessels were 7.7-7.8 mg/L. The positive control/reference substance used in the tested showed an expected result and gave an EC50 that corresponded to previous exposures with this chemical in D. magna. The IC50 was defined as a concentration that immobilizes 50% of the exposed D. magna. Eight percent immobilization in D. magna was observed after 48 hours of exposure to 100 mg/L of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate. The IC8 was therefore estimated to be 100 mg/L. Based on the IC8, it can be concluded that the chemical was nontoxic and can be consider to be not classified as per CLP classification criteria.

 

In the third weight of evidence study for the read across chemical (915-67-3) from UERL report 2017, study on was conducted. Determination of the inhibition of the mobility of daphnids was carried out with the substance 2,7-Naphthalenedisulfonic acid, 3-hydroxy- 4-[(4-sulfo-1-naphthalenyl), sodium salt; Amaranth dye according to OECD Guideline 202. The limit test was performed at 100 mg/l. Effects on immobilisation were observed for 48 hours. The effective concentration (EC8) for the test substance, 2,7-Naphthalenedisulfonic acid, 3-hydroxy-4- [(4-sulfo-1 -naphthalenyl), sodium salt (Amaranth dye), in Daphnia magna was determined to be 100 mg/L on the basis of mobility inhibition effects in a 48 hour study. This value indicates that the substance is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

Similarly in the fourth study for another read across chemical (4548-53-2) from ABITEC lab supports the classification and nontoxic behavior of chemical. Determination of the inhibition of the mobility of daphnids was carried out with the substance Disodium 3-[(2,4-dimethyl- 5-sulpho- natophenyl) azo]-4-hydroxy naphthalene-1-sulphonateaccording to OECD Guideline 202. A limit test at sample concentration of 100 mg/L was performed. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene -1-sulphonate, in Daphnia magna was determined to be >100 mg/L for immobilisation effects. Based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance, Disodium 3-[(2,4-dimethyl -5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate does not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

 

The fifth study form ABITEC lab report 2016 for the read across chemical (68583-95-9) was carried out. Determination of the inhibition of the mobility of daphnids was carried out with the substance Aluminium,6-hydroxy-5- [(2-methoxy-5-methyl-4-sulfophenyl)azo ]-2-naphthalenesulfonic acid complex according to OECD Guideline 202. A limit test at sample concentration of 100 mg/L was performed. Effects on immobilisation were observed for 48 hours. At 100 mg/l only 8% inhibition was observed, thus it can be concluded that the EC50 was >100 mg/l. The median effective concentration (EC50) for the test substance, Aluminium, 6-hydroxy-5- [(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex, in Daphnia magna was determined to be >100 mg/L for immobilisation effects. Based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance, Aluminium, 6-hydroxy-5- [(2-methoxy-5-methyl-4-sulfophenyl)azo ]-2-naphthalenesulfonic acid complex does not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

 

Similarly the sixth study was used for the read across chemical (915-67-3) from peer reviewed journal (The Journal of Toxicological Sciences, 1977). The toxic effects of Amaranth were studied on Artemia salina larvae. Artemia salina (A. salina eggs) a crustacean, commonly known as brine shrimp eggs, are commercially available, and are easily cultured in the laboratory because they are resistant to environmental stresses. Active larvae can be obtained within 1 to 2 days and no live culture is required for a few days thereafter. A. salina eggs (encysted dried gastrulae) were commercially obtained, and were stored at -200°C. Eggs used in experiments were washed and stored at room temperature in a desiccators over anhydrous granular CaCl2. Larvae were obtained by incubating eggs in petri dishes containing muslin-filtered sea water at 30°C for 24 hours. The larvae were separated from shells, dead larvae and unhatched eggs by their phototactic movements towards a light source. Amaranth at concentrations of 6044.7mg/l and 604.47 mg/l were placed in a petri dish, and sea water containing 20 to 30 larvae was added. After this was incubated at 30°C for 24 hours and 48 hours, larvae surviving were measured by direct count. The same method was tested from 5 to 6 times for each concentration, and the death rate was calculated. Death was assumed to have occurred when there was no movement. The death rate was defined as the average of the percentage of deaths observed for 24 hours and 48 hours. 100% death rate was noted after 48 hours when 6044.7 mg/l of Amaranth was exposed to the test organism and 0% death rate after 24 hours in case of exposure to 604.47 mg/l of test chemical.

 

Based on the predicted data for the target chemical (from OECD QSAR 2017) and for the read across chemical from experimental lab reports (ABITEC reports), it can be concluded that the substance 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naphthalene -1,3,6-trisulphonic acid (35642-64-9) is considered to be not toxic to aquatic environment (aquatic invertebrates) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.