N-(2-phenoxyphenyl)methanesulphonamide

Endpoint summary

Description of key information

The skin sensitization potential of N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 ) was predicted to be not sensitizing to the skin of female Hartley HsdPOC: DH guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Remarks:

in vivo

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:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3.

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

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:

guinea pig

Strain:

other: Hartley HsdPOC: DH

Sex:

female

Details on test animals and environmental conditions:

No data available.

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 ml

Day(s)/duration:

24 hour

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 ml

Day(s)/duration:

24 hour

No. of animals per dose:

20 animals

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: No data available.
- Exposure period: 24 hour
- Test groups: 20
- Control group: No data available.
- Site: No data available.
- Frequency of applications: No data available.
- Duration: 24 hour
- Concentrations: 0.5 ml

B. CHALLENGE EXPOSURE
- No. of exposures: No data available.
- Day(s) of challenge: No data available.
- Exposure period: No data available.
- Test groups: 20
- Control group: No data available.
- Site: No data available.
- Concentrations: 0.5 ml
- Evaluation (hr after challenge): No data available.

OTHER:

Challenge controls:

No data available.

Positive control substance(s):

not specified

Statistics:

No data available.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no erythema or edema

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 6 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 ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and "u" )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and "aa" )  )

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain 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 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 >> Hydroquinones 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 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo 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 OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  by Protein binding by OASIS v1.3

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Ac-SN2 OR Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group OR Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group >> Arenesulphonamides OR AN2 OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulphonamides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkoxysilanes OR Benzotriazoles (Acute toxicity) OR Substituted Triazines (Acute toxicity) OR Substituted Triazines (Chronic toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic compound AND Diarylether AND Ether AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.346

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.05

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 ) was predicted to be not sensitizing to the skin of female Hartley HsdPOC: DH guinea pig.

Executive summary:

The skin sensitization potential of N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) estimated by using OECD QSAR toolbox v 3.3 with log kow as the primary descriptor and considering the six closest read across substances. N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 ) was predicted to be not sensitizing to the skin of female Hartley HsdPOC: DH guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 )has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig for target chemical N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 )and its structurally similar read across substancesNicotinonitrile (100-54-9) andPyridine (110 -86 -1). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across .

The skin sensitization potential of N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6 ) was predicted to be not sensitizing to the skin of female Hartley HsdPOC: DH guinea pig.

Supported by experimental data conducted by Majka K (UNEP)(Med P ,1979) )on structurally similar read across substance Nicotinonitrile (100-54-9) in rabbit .The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Skin sensitizing test was conducted for Pyridine-3-carbonitrile in rabbit. Allergic effect was not observed. ThereforeNicotinonitrile (100-54-9)was considered to be non sensitizing to rabbit skin

It is further supported by an experimental study conducted  by Reinhardt, C.F (Patty's Industrial Hygiene and Toxicology, 1981)on structurally similar read across substance N(2phenoxyphenyl)methanesulfonamide (110 -86 -1)on guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Skin sensitizing potential of Pyridine (110 -86 -1) was evaluated in Guinea pig. According to the text Pyridine (110 -86 -1) was considered to be non sensitizing in Guinea pig.

Thus based on the above predictions on N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) as well as its read across substances and applying weight of evidence, it can be concluded that N-(2-phenoxyphenyl)methanesulfonamide (51765-51-6) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, N-(2-phenoxyphenyl) methanesulfonamide (51765-51-6)can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, N-(2-phenoxyphenyl) methanesulfonamide (51765-51-6)can be considered as not classified for skin sensitization effects.