2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate

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:

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 is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate
- Molecular formula : C9H13NO7S2
- Molecular weight : 311.3337 g/mol
- Smiles notation : COC1=C(C=CC(=C1)S(=O)(=O)CCOS(=O)(=O)O)N
- InChl : 1S/C9H13NO7S2/c1-16-9-6-7(2-3-8(9)10)18(11,12)5-4-17-19(13,14)15/h2-3,6H,4-5,10H2,1H3,(H,13,14,15)
- 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

Total exposure duration:

72 h

Test temperature:

21 – 24 °C

pH:

6.1 - 9.6

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

202.111 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 202.110 mg/l after the exposure period of 72hrs.

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 ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and "ag" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

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 >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

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  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Strong binder, NH2 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, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aromatic chloride   [-CL] by Bioaccumulation - metabolism alerts

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Pyridine ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Alkoxy AND Aniline AND Aryl AND Ether AND Sulfate AND Sulfone by Organic Functional groups

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Alkoxy AND Aniline AND Aryl AND Ether AND Sulfate AND Sulfone by Organic Functional groups

Domain logical expression index: "ae"

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

Domain logical expression index: "af"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.14

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.965

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition, the EC50 value was estimated to be 202.110 mg/l when 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate exposed to Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) for 72 hrs.

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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (26672-22-0). The EC50 value was estimated to be 202.110 mg/l when 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate exposed to Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) for 72 hrs. Thus, based on this value, it can be concluded that the test chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate can be considered as nontoxic to aquatic organisms (aquatic algae) and thus cannot be classified as per the CLP classification criteria.

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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (26672-22-0). The EC50 value was estimated to be 202.110 mg/l when 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate exposed to Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) for 72 hrs. Thus, based on this value, it can be concluded that the test chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate can be considered as nontoxic to aquatic organisms (aquatic algae) and thus cannot be classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

202.11 mg/L

Additional information

Based on the various prediction data for the target chemical and experimental data for the read across chemical study have been reviewed to determine the toxic nature of 2-[(4-amino-3-methoxyphenyl) sulphonyl]ethyl hydrogen sulphate (26672-22-0) on the growth of aquatic algae. The studies are as mentioned below:

 

First predicted study used for the target chemical used from the OECD QSAR toolbox version 3.3, 2017. 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 Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (26672-22-0). The EC50 value was estimated to be 202.110 mg/l when 2-[(4-amino-3-methoxyphenyl) sulphonyl]ethyl hydrogen sulphate exposed to Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) for 72 hrs. Thus, based on this value, it can be concluded that the test chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate can be considered as nontoxic to aquatic organisms (aquatic algae) and thus cannot be classified as per the CLP classification criteria.

 

In second predicted study for the target chemical used on the basis of 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 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS:26672 -22 -0). 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 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate is estimated to be 2594.421 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 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate 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.

Experimental study for the read across chemical 4-amino-m-toluenesulfonic acid (98-33-9) from ABITEC report, 2017 was studied. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 4-amino-3- methylbenzenesulfonic acid according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 0, 30, 45, 67, 100, 150 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (EC50) for the test substance 4-amino-3- methylbenzene- sulfonic acid, in Desmodesmus subspicatus was determined to be 110.6 mg/L. This value indicates that the substance is likely to be non-hazardous to aquatic algae and cannot be classified as per the CLP criteria.

 

Similarly in the fourth weight of evidence study for the structurally similar read across chemical 1,3-Phenylenediamine-4-sulfonic (88-63-1 ) from ABITEC lab report 2017. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 1,3-Phenylenediamine-4-sulfonic Acid according to OECD Guideline 201. The stock solution 150 mg/l was prepared by dissolving light brown powder in OECD growth medium. The solution was kept in ultrasonic bath for 20 min. Test solutions of required concentration were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture. Sample tested at the concentrations 0, 0, 30, 45, 67, 100 and 150 mg/L. Test performed by the static system for 72hrs of exposure period. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance 1,3-Phenylenediamine-4-sulfonic Acid, in Desmodesmus subspicatus was determined to be 110 mg/L on the basis of effects on growth rate in a 72 hour study. This value indicates that the substance 1,3-Phenylenediamine-4-sulfonic Acid is likely to be non-hazardous to aquatic algae and cannot be classified as toxic as per the CLP classification criteria. 

 

Similarly in the fifth weight of evidence study for the structurally similar read across chemical (98-37-3) 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 and chlorophyll 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 MACKINv (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.

 

Based on the predicted data for the target chemical (OECD QSAR, Danish QSAR, 2017) and experimental studies for the read across chemical obtain from various sources (ABITEC report, 2017) toxicity on algae was studied due to the exposure of 2-[(4-amino-3-methoxyphenyl) sulphonyl]ethyl hydrogen sulphate (26672-22-0), and it was concluded that the substance 2-[(4-amino-3-methoxyphenyl) sulphonyl]ethyl hydrogen sulphate was consider as nontoxic and can be consider to be not classified as toxic to aquatic invertebrates as per CLP classification criteria.