N-(2-phenoxyphenyl)methanesulphonamide

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of N-(2-phenoxyphenyl)methanesulfonamide was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.

Eye Irritation:

The ocular irritation potential of N-(2-phenoxyphenyl)methanesulfonamide was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to eye and can be classified under the category "Not Classified" as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

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)methanesulphonamide
- Molecular formula : C13H13NO3S
- Molecular weight : 263.316 g/mol
- Smiles notation: S(Nc1c(Oc2ccccc2)cccc1)(=O)(=O)C
- InChl : 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed

Estimation method: Takes mode 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(not "l")) ) and("m" and(not "n")) ) and("o" and(not "p")) ) and "q") and("r" and(not "s")) ) and("t" and "u") )

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 AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides 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 >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 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 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 OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines by Protein binding by OECD

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.547

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.02

Interpretation of results:

other: not irritating

Conclusions:

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of N-(2-phenoxyphenyl)methanesulfonamide was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

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)methanesulphonamide
- Molecular formula : C13H13NO3S
- Molecular weight : 263.316 g/mol
- Smiles notation: S(Nc1c(Oc2ccccc2)cccc1)(=O)(=O)C
- InChl : 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

24, 48, 72 hours and 4,7 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Interpretation of results:

other: not irritating

Conclusions:

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

 

The ocular irritation potential of N-(2-phenoxyphenyl)methanesulfonamide was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

N-(2-phenoxyphenyl)methanesulfonamide was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to eye and can be classified under the category "Not Classified" as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies, N-(2-phenoxyphenyl)methanesulfonamide has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and closely related read across substances N-butylbenzenesulphonamide [NBSS] (CAS: 3622-84-2) and Trimethoxyphenyl silane (CAS: 2996-92-1) . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated forN-(2 -phenoxyphenyl)methanesulfonamide. N-(2-phenoxyphenyl)methanesulfonamidewas not irritating to New Zealand White rabbit skin.

This result was supported by the experimental study conducted by Antonella Marrocco et.al (J Toxicol Environ Health A; 2015; 78(17): 1122–1132), for theclosely related read across substance N-butylbenzenesulphonamide [NBSS] (CAS: 3622-84-2). A combined irritancy/local lymph node assay (LLNA) on Female BALB/c mice was performed according to the method described in the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Peer Review Panel report. Mice (3 per group) were exposed topically on each ear to 25 μl vehicle (acetone) or 25,50 or 100% NBSS. Dinitrofluorobenzene [DNFB] (0.3%) was used as a positive control. Animals were allowed to rest for 2 d following the last exposure and then euthanized via CO2 inhalation. Mice were observed daily for signs of distress or extreme irritation, for any signs of chemical-induced toxicity (ruffled fur, abnormal posture, isolation in the cage, abnormal exudates from the eyes, nose, or anus), and for local signs of irritation, including ear erythema and swelling. Animals were weighed the day prior to the first exposure and on d 4 prior to euthanasia.

Dermal exposure of female BALB/c mice to the high concentration of NBBS (100%) produced no signs of overt toxicity or visual signs of inflammation at the exposure sites. A numerical increase in ear swelling was observed following exposure to NBBS (8.4, 7.2, and 5.6% for 25, 50, and 100% respectively). DNFB (0.3%), used as a positive control, showed a mean significant rise of 241% ear swelling after exposure.

Hence,N-butylbenzenesulphonamide[NBSS] can be considered not irritating to skin of BALB/c mice.

 

The above studies are also supported by the experimental study summarized in SIDS Dossier_2996921; OECD HPV Chemicals Programme, SIDS Dossier, approved at SIAM 30 (20-22 April 2010) for the closely related read across substance Trimethoxyphenyl silane (CAS: 2996-92-1). Undiluted trimethoxyphenyl silane wasapplied on ear, intact and abraded skin of the abdomen of one male rabbit. The rabbit was observed for signs of irritation till 14 days. No significant irritation was observed following single application of trimethoxyphenylsilane.

Hence, trimethoxyphenyl silane can be considered not irritating to rabbit skin.

 

Based on the available data for the target and read across substances and applying the weight of evidence approach, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye Irritation:

In different studies, N-(2-phenoxyphenyl)methanesulfonamide has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and closely related read across substances  Trimethoxyphenyl silane [CAS: 2996-92-1] and 6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide (DOPO) [CAS: 35948-25-5] . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated forN-(2 -phenoxyphenyl)methanesulfonamide. N-(2-phenoxyphenyl)methanesulfonamidewas not irritating to New Zealand White rabbit eyes.

This result was supported by the experimental studythe experimental study summarized in SIDS Dossier_2996921; OECD HPV Chemicals Programme, SIDS Dossier, approved at SIAM 30 (20-22 April 2010), for the closely related read across substance Trimethoxyphenyl silane (CAS: 2996-92-1).

2 drops of undiluted trimethoxyphenyl silane was instilled into the eyes of one female rabbit. The left eye was washed with tepid water within 30 seconds following instillation. Instillation of undiluted material into the eye of a rabbit produced pain response and very slight irritation. Direct contact with the test material resulted moderate pain and conjunctival response. This effect was transient in nature and subsided in an hour.

Since the effects were reversible after 1 hour, trimethoxyphenyl silane can be considered not irritating to rabbit eyes.

 

The above studies are also supported by the experimental study summarized in EPA Publication 744-R-15-001; August 2015, for the closely related read across substance 6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide (DOPO) [CAS: 35948-25-5]. Neat test material (0.1 mL) was instilled in left eye of 3 female albino rabbits. Eyes were monitored for up to 7 days. Moderate signs of eye irritation that cleared in 7 days were observed among the rabbits. Since the effects were reversible by 7 days, 6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide (DOPO) can be considered not irritating to rabbit eyes.

Based on the available data for the target and read across substances and applying the weight of evidence approach, N-(2-phenoxyphenyl)methanesulfonamide can be considered to be not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

Available studies for suggest N-(2-phenoxyphenyl)methanesulfonamide that it is not irritating to eyes and skin. Hence,N-(2-phenoxyphenyl)methanesulfonamide can be classified under the category “Not Classified” as per CLP regulation.