N-(2-phenoxyphenyl)methanesulphonamide

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): N-(2-phenoxyphenyl)methanesulfonamide
- Molecular formula (if other than submission substance): C13H13NO3S
- Molecular weight (if other than submission substance): 263.316 g/mol
- Smiles notation (if other than submission substance): S(Nc1c(Oc2ccccc2)cccc1)(=O)(=O)C
- InChI: 1S/C13H13NO3S/c1-18(15,16)14-12-9-5-6-10-13(12)17-11-7-3-2-4-8-11/h2-10,14H,1H3
- Substance type: Organic
- Physical state: Solid

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:

23.9-24.4°C

pH:

at start of test: 7.29-7.38
at end of test: 10.6 to 10.8 expect in the highest test concentration which had a pH of 7.25

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

21.835 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Ether AND Sulfonamide by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Ether AND Overlapping groups AND Sulfonamide by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Oxygen, two aromatic attach [-O-] AND Aromatic Carbon [C] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, two olefinic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfamide, aliphatic attach [-SO2-N] AND Sulfonyl amide, aliphatic attach [-S(=O)N-] AND Sulfur, nitrogen attach [-S-] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Oxygen, two aromatic attach [-O-] AND Aromatic Carbon [C] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, two olefinic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfamide, aliphatic attach [-SO2-N] AND Sulfonyl amide, aliphatic attach [-S(=O)N-] AND Sulfur, nitrogen attach [-S-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Oxygen, two aromatic attach [-O-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, two olefinic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfamide, aliphatic attach [-SO2-N] OR Sulfonyl amide, aliphatic attach [-S(=O)N-] OR Sulfur, nitrogen attach [-S-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aromatic compound OR Diarylether OR Ether OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) 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 Primary Aromatic Amines 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) >> Hydrazine Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.71

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.78

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for N-(2-phenoxyphenyl)methanesulfonamide on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 21.83 mg/L on the basis of effects on growth rate.

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 five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-(2-phenoxyphenyl)methanesulfonamide

 (CAS no. 51765-51-6). EC50 value was estimated to be 21.83 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance N-(2 -phenoxyphenyl)methanesulfonamide is considered to be toxic to aquatic environment and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.

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 five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-(2-phenoxyphenyl)methanesulfonamide

 (CAS no. 51765-51-6) (2017). EC50 value was estimated to be 21.83 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance N-(2 -phenoxyphenyl)methanesulfonamide is considered to be toxic to aquatic environment and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

21.83 mg/L

Additional information

Predicted data for the target chemical N-(2-phenoxyphenyl)methanesulfonamide (CAS No. 51765-51-6) and weight of evidence study for its read across substancewere reviewed to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical N-(2-phenoxyphenyl)methanesulfonamide (CAS No. 51765-51-6) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017).EC50 value was estimated to be 21.83 mg/l for Pseudokirchneriella subcapitata for 72 h duration.

 

In another prediction done using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance N-(2-phenoxyphenyl)methanesulfonamide(CAS No. 51765-51-6).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 47.984 mg/l for green algae for 96 h duration.

 

In a weight of evidence study of the read across chemical 2-methylbut-2-ene (CAS no. 513-35-9), short term toxicity to Pseudokirchneriella subcapitata (formerly Selenastrum capricornutum) study was carried out for 96 hrs (OECD SIDS, 2004 and High Production Volume Challenge Program, 2016). The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test), EC Directive 92/69 C3, US EPA TSCA 797.1050 & 797.1060, respectively. The study was based on the effects of the read across compound 2-methylbut-2-ene on Selenastrum capricornutum(green algae)in a static fresh water system at a temperature of 22.3 – 23.4°C, pH range of 7.2-7.4 with continuous light illumination, respectively. Pseudokirchneriella subcapitata was used as a test organism. Initial cell density of the test organism was1 × 10(4) cells/ml. Test chemical conc. used for the study was in the range of 22-29% (nominal conc.) and 19-27% of their nominal values at the start of the test (measured conc.), respectively. Based on an arithmetic mean, the overall mean measured levels of 2-methyl-2-butene were 0.689, 1.53, 3.61, 7.22 and 21.1 mg/l. Nominal test substance conc. used was 3.20, 7.04, 15.5, 34.1 and 75 mg/l, respectively. The test media were prepared, either directly or by dilution, from an aqueous preparation in which the test substance was stirred in a sealed vessel for approximately 23 hours in the dark. After being allowed to stand for at least one hour to obtain an equilibrium concentration of 2-methyl-2-butene, aliquots of medium were removed from the middle of the vessel and after dilution and inoculated with alga cells, was used to fill the test vessels. The area under the growth curve and the average specific growth rate are taken to be an index of growth and are calculated mathematically. The EbC50 ("x" h) is the median effect concentration for inhibition of growth based on a comparison of areas under the growth curves after "x" hours. The EbC50 was calculated using the moving average method of a computer program which uses percentage effect and the nominal and measured test concentration in test samples. The ErC50 ("x"-"y" h) is the median effect concentration for inhibition of growth based on a comparison of growth rates from "x" to "y" hours. The ErC50 was calculated by either the moving average method or by nonlinear interpolation between the two concentrations which bracket the 50% effect level of a computer program; the program uses percentage effect and the nominal and measured test concentration in test samples. The "no observed effect concentrations" (NOEC) was determined using Dunnett's multicomparison test to compare the percentage inhibition in the test group with that for the control cultures. After 72 and 96 hours of exposure to 2-methyl-2-butene, the EbC50 values were 10.5 and 10.1 mg/l respectively; the ErC50 values were 12.0 and 13.2 mg/l respectively. The "no observed effect concentration" (NOEC) for area under the growth curve and growth rate respectively, were 3.61 and 7.22 mg/l, respectively.

 

Thus, based on the overall reported results for target chemical N-(2-phenoxyphenyl)methanesulfonamide (OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance (fromsecondary source), it can be concluded that the test substance N-(2-phenoxyphenyl)methanesulfonamide can be considered as toxic to aquatic environment and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.