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Toxicity to aquatic algae and cyanobacteria

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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:
Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.
Reference:
Composition 0
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
Test material information:
Composition 1
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):
Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
72 h
Reference substance (positive control):
not specified
Key result
Duration:
72 h
Dose descriptor:
EC50
Effect conc.:
131.678 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
growth rate
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 ("m" and "n" )  )

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation 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 >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 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 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 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: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.51

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 algae 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). Growth rate inhibition value was estimated to be 131.678 mg/l for Desmodesmus subspicatus for 72 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 algae.
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 algae 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). Growth rate inhibition value was estimated to be 131.678 mg/l for Desmodesmus subspicatus for 72  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 algae.

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 algae 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). Growth rate inhibition value was estimated to be 131.678 mg/l for Desmodesmus subspicatus for 72  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 algae.

Key value for chemical safety assessment

EC50/LC50 for freshwater algae:
131.67 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 growth of aquatic algae. 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 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 algae 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). Growth rate inhibition value was estimated to be 131.678 mg/l for Desmodesmus subspicatus for 72 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 algae.

 

First predicted study was supported by the second experimental weight of evidence study for the read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) from UERL report. The effect of test item aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25mg/L, 12.5mg/L, 25mg/L, 50mg/L, 100mg/L, 200mg/L. The test solution was prepared in aseptic condition. The test item Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex was prepared by adding 50 mg of test item in 250 ml of BBM to get the final concentration of 200 mg/L. This stock solution was kept for stirring/sonication for 30 minutes to obtain a homogenous solution for the experiment. The test concentrations were chosen according to the available data of the test item. The concentrations chosen were set up to the water solubility limit. The remaining test solutions were prepared by dilution from the above stock solution. To have a better growth and visibility of cells, the initial of the culture was kept 1 X 104cells/ml. Care was taken to have a homogeneous solution for the experiment. Test was performed in static manner at proper requirement of pH and temperature. The microscopic observations were noted down in each of the control vessel. All the cells appeared healthy, round and green throughout the study duration in the control. Also, the drift in pH in the control vessels did not increase by >1.5 units when observed on 72 hours as compared to 0 hours. The average pH drift observed in the control vessels was 0 units. After 72 hours of exposure to aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) to various nominal test concentration, EC50 calculated from equation through probit analysis was determine to be > 200 mg/l. Based on the EC50, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

In the third supporting weight of evidence study for the read across chemical from UERL lab, 2016 toxicity was measured on algae. The effect of test item aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex, CAS No. 68583-95-9 was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25mg/L, 12.5mg/L, 25mg/L, 50mg/L, 100mg/L, 200mg/L. The test solution was prepared in aseptic condition. The test item aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]- 2-naphthalenesulfonic acid complex was prepared by adding 50 mg of test item in 250 ml of BBM to get the final concentration of 200 mg/L. This stock solution was kept for stirring for 24 hours and filter it to obtain a homogenous solution for the experiment. The test concentrations were chosen according to the available data of the test item. The concentrations chosen were set up to the water solubility limit. The remaining test solutions were prepared by dilution from the above stock solution. To have a better growth and visibility of cells, the initial of the culture was kept 1 X 104cells/ml. The microscopic observations were noted down in each of the control vessel. All the cells appeared healthy, round and green throughout the study duration in the control. Also, the drift in pH in the control vessels did not increase by >1.5 units when observed on 72 hours as compared to 0 hours. The average pH drift observed in the control vessels was 0.1 units. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be 136.57 mg/L. Based on the EC50, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

 

Similarly in the fourth study for RA chemical 2,7-Naphthalenedisulfonic acid, 3-hydroxy- 4-[(4-sulfo-1-naphthalenyl), sodium salt (Amaranth dye) (915-67-3), ABITEC lab report, 2016. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 2,7-Naphthalenedi- sulfonic acid, 3-hydroxy-4-[(4-sulfo- 1-naphthal - enyl), sodium salt (Amaranth dye) according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 12.5, 25, 50, 100, 200 mg/L. Effects on the growth rate of the organism were studied. The effective concentration (ErC50) for the test substance, 2,7-Naphthalen -edisulfonic acid, 3-hydroxy-4-[(4-sulfo-1- -naphthalenyl), sodium salt, in Desmodesmus subspicatus was determined to be 356.2 mg/L. This value indicates that the substance is likely to be non-hazardous to aquatic algae and cannot be classified as toxic as per the CLP criteria.

 

The fifth study for RA chemical 2,7-Naphthalenedisulfonic acid, 3-hydroxy- 4-[(4-sulfo-1-naphthalenyl), sodium salt (Amaranth dye) (915-67-3),UERL report, 2016 test conducted. The effect of test substance Trisodium 3-hydroxy-4-(4’-sulphonatonaphthylazo) naphthalene-2,7-disulphonate (CAS No. 915-67-3) was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga growth inhibition test. The test concentration chosen for the study were 6.25 mg/l, 12.5mg/l, 25mg/l, 50mg/l, 100mg/l and 200mg/l were prepared using stock solution of the test substance using de-ionized water. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of test substance. EC50 calculated from equation through probit analysis was observed to be > 200 mg/L. Thus based on the EC50 it was concluded that the chemical was nontoxic and can be consider to be not classified as toxic to aquatic environment as per the CLP classification criteria.

 

For further supporting the classification of target chemical read across chemical (3734-67-6) was used. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7- disulphonate according to OECD Guideline 201. The stock solution 100 mg/l was prepared by dissolving red powder in OECD growth medium. The solution was kept 30 min in ultrasonic bath. Test solutions of required concentration were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture. 5x10(3) cells /ml algal culture were use in the study for total exposure period of 72hrs. Test conducted in 50 ml glass vessel filled with 50 ml of sample volume and tested at the concentrations 0, 0, 20, 30, 45, 67, 100 mg/l. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate, in Desmodesmus subspicatus was determined to be 285.8 mg/L. This value indicates that the substance is likely to be non-hazardous to aquatic algae and cannot be classified as toxic as per the CLP criteria.

 

Similarly in the seventh study for another read across chemical (4548-53-2) from ABITEC lab supports the classification and nontoxic behavior of chemical. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance Disodium 3-[(2,4-dimethyl -5-sulphonatophenyl) azo]-4-hydroxynaphthalene-1-sulphonate according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 0, 12.5, 25, 50, 100 and 200 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance, Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]- 4-hydro xynaphthalene-1-sulphonate, in Desmodesmus subspicatus was determined to be 276.1 mg/L. Based on this ErC50 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 toxicity to aquatic algae (Desmodesmus subspicatus).

 

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 and UERL lab 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 algae and cyanobacteria) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.