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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:
QMRF report has been attached.
Guideline:
OECD Guideline 201 (Alga, Growth Inhibition Test)
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 of test material (IUPAC name): 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
- Molecular formula: C11H11NO4S
- Molecular weight: 253.2769 g/mol
- Smiles notation: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- InChl: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
- Substance type: Organic
- Physical state: Solid
Analytical monitoring:
not specified
Details on sampling:
No data available
Vehicle:
not specified
Details on test solutions:
No data available
Test organisms (species):
Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)
Test type:
static
Water media type:
freshwater
Total exposure duration:
72 h
Hardness:
No data available
Test temperature:
24 °C ±2°C.
pH:
6.7 to 7.4
Dissolved oxygen:
No data available
Salinity:
No data available
Conductivity:
No data available
Nominal and measured concentrations:
Estimated data
Details on test conditions:
No data available
Reference substance (positive control):
not specified
Key result
Duration:
72 h
Dose descriptor:
EC50
Effect conc.:
135.52 mg/L
Nominal / measured:
estimated
Conc. based on:
not specified
Basis for effect:
growth rate
Remarks on result:
other: Other details not known
Details on results:
The EC50 was 135.520 mg/l based on the growth rate inhibition

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 ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols 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 AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR 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 >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines 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) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

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 Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Hydrazines OR Neutral Organics by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Ketones by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Ethers by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.22

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.88

Validity criteria fulfilled:
not specified
Conclusions:
Based on the growth rate inhibition of algae, the EC50 value was estimated to be 135.52 mg/l when 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid exposed to Desmodesmus subspicatus for 72hrs.  
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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 135.52 mg/l when 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid exposed to Desmodesmus subspicatus for 72hrs.     

Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (6259-53-6) is considered to be not toxic to aquatic environment 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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 135.52 mg/l when 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid exposed to Desmodesmus subspicatus for 72hrs.     

Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (6259-53-6) is considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation.     

Key value for chemical safety assessment

EC50 for freshwater algae:
135.52 mg/L

Additional information

Various predicted data for the target compound 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) and supporting weight of evidence studies for its closest read across substance with structural similarity and log Kow as the primary descriptor were reviewed for the toxicity on the aquatic algae and cyanobacteria end point which are summarized as below: 

In a prediction done by SSS (2017), 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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 135.52 mg/l when 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid exposed to Desmodesmus subspicatus for 72hrs. Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (6259-53-6) is considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation.     

 

Similarly in the second predicted report from Danish QSAR database, for the toxicity to algae was used based on the prediction done using the three different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database, the short term toxicity on green algae was predicted for test substance  4-hydroxy-6-(methylamino) naphthalene -2-sulfonic acid (CAS: 6291 -53 -6). The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance  4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid is estimated to be 2698.016 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration. Thus, on the basis of EC50 value, it can be concluded that the test chemical  4-hydroxy- 6-(methylamino) naphthalene -2-sulfonic acid can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

Further weight of evidence studies for the read across chemicals supports the above predicted study for the target chemical. By considering data for supporting weight of evidence study from ABITEC report 2016 for read across chemical 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid (130-23-4) toxicity experiment was conducted for evaluating the effect of read across substance. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 4-amino-5-hydroxynaphthalene-1,7- disulphonic acid according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 2.2, 11, 25, 55 and 120 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance, 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid, in Desmodesmus subspicatus was determined to be 129.4 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 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid does not exhibit toxicity to aquatic algae (Desmodesmus subspicatus) and not classified as toxic as per the CLP classification criteria.

 

Similarly for the same read across chemical, toxicity study was conducted on algae and reported from UERL lab, 2016, The effect of test item 4-amino-5-hydroxynaphthalene -1,7-disulphonic acid, CAS No. 130-23-4 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 and 200mg/l. The test concentrations were prepared using stock solution of the test item using mineral media. 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 >200mg/l. Thus, based on the EC50 value, test substance 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid can be classified as not hazardous and nontoxic as per the criteria of CLP regulation.

 

Study in the study for the read across chemical (98-37-3) from Water Research Pergamon Press 1968, Short term toxicity to Chlorella pyrenoidosa (green algae) study was carried out for 72 hrs. Emerson strain of bacteria free, experimentally reproducible cultures of Chlorella pyrenoidosa was used as a test organism. The procedure involve the use of test tubes in both the screening and final tests. These test tubes contained 15 ml of inorganic culture medium, a predetermined amount of test chemical and 5 ml of algal culture. The tubes were incubated for 72 hrs andchlorophyll content of the algal suspensions was measured every 24 hrs. For chlorophyll measurement, the chlorophyll pigment was extracted with hot methanol in two separate extractions. An algal suspension, 2.5 ml, was removed from the test tube, centrifuged, washed with distilled water, and recentrifuged in preparation of chlorophyll analysis. After discarding the supernatant, the deposited cell material was coagulated by placing the cells in a boiling water bath for about 40 sec. About 2.5 ml of methanol were used in each extraction. Finally, the chlorophyll solution was diluted to a total volume of 10 ml with an acetone-water mixture (80 per cent by volume). A Beckman Spectrophotometer, Model DB, was used to measure the chlorophyll content according to MACKIN~v (1941) and ARNON (1949). For this a wavelength of 652 m/z was used because different proportions of chlorophyll a and b least affect the results at this wavelength. Control tubes containing no test chemical was also used in the experiment. Knop's solution, including the Hutner-EDTA microelement addition, was used as the culture medium.pH of culture medium was adjusted to 7.0 using KOH before use. The test organism was maintained under steady-state conditions, provided a chlorophyll content of 38 mg/l. Environmental control was rigidly maintained. The temp. of water bath was 25 ± 1°C. The test apparatus consisted of a constant-temperature water bath, a light source containing four 200W fluorescent lamps with attached aluminum reflectors, a gas manifold to supply an air-CO2 mixture to each test tube, and a rack to hold the test tubes. A stream of 5 % CO2 in air gas mixture was supplied to culture medium in order to provide the inorganic carbon source and also to keep the algal ceils in suspension. Based on destruction of chlorophyll of test organism by test chemical Amino-1-phenol-4-sulfonic acid, the LOEC value was determine to be1500 mg/l and as no toxic effect at 1000 mg/l was observed, the NOEC value was determine to be 1000 mg/l. Thus, based on this value, it can be concluded that the substance can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

Similarly for the another read across chemical D & C Red no. 7 (5281-04-9) from HPVIS and SIDS report, Detection of the effect of D & C Red no. 7 on the growth of Selenastrum capricornutum ATCC 22662 was done by following standard 202 OECD guideline. The test was performed in static system by following the OECD guideline. Selenastrum capricornutum ATCC 22662 exposed with the chemical for 72hrs. Based on the biomass inhibition of Selenastrum capricornutum ATCC 22662 by the chemical 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl)azo]-, calcium salt (D & C Red no. 7) for 72hrs, the NOEC was 5.8 mg/l, and the EC50 was 190 mg/l. Based on the EC50 value it was concluded that the chemical D & C Red no 7 was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

On the basis of above results for target 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) (from OECD QSAR toolbox version 3.4 and Danish QSAR) and for its read across substance from ABITEC report, UERL report, peer reviewed journal Water Research Pergamon Press 1968 and HPVIS, SIDS report, it can be concluded that the test substance 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) was not toxic to algae and can be consider to be not classified as toxic as per the CLP classification criteria.