4-amino-N-(4-aminophenyl)benzenesulphonamide

Endpoint summary

Description of key information

The skin sensitization potential of 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.          

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 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

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name: 4-Amino-N-(4-aminophenyl)benzenesulphonamide
InChI:1S/C12H13N3O2S/c13-9-1-3-10(4-2-9)15-11-5-7-12(8-6-11)18(14,16)17/h1-8,15H,13H2,(H2,14,16,17)
SMILES:O=S(=O)(c1ccc(cc1)Nc1ccc(cc1)N)N
Molecular Weight: 263.32 g/mole
Molecular Formula:C12H13N3O2S

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was obsered in treated animals.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was obsered in treated animals.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Amino Anthraquinones 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) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives 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 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Amino Anthraquinones 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 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.53

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.23

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.          

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) and its structurally similar read across substancesSulphanilic Acid (CAS no: 121-57-3) and Dapsone (CAS no: 80-08-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

The D. A. Basketter et.al., conducted {Contact Dermatitis, Volume 27, Issue 4, April 1992, Pages 209–213} the cumulative contact enhancement test (CCET) of read across substance Sulphanilic Acid (CAS no: 121-57-3)to study the sensitization potential. To induce sensitization a group of 10 guinea pig were albino Dunkin-Hartley strain and weighed approximately 350 g at the start of testing were treated twice weekly for 2 weeks using 24 hrs occluded patches containing 25% sulphanilic acid in vehicle 0.9% PEG 400 (50/50, w/w) over the shoulder region. Immediately before the third application, the test and 4 control guinea pigs were injected with Freund's complete adjuvant in the shoulder region at the site to be patched. Test and control animals were challenged after a 12 days rest period by open application at the maximum nonirritant concentration (25%). Challenge sites were scored for erythema (scale 0-3) at 24- h and 48 h. Sulphanilic Acid did not produce any positive reaction and failed to induce any evidence of sensitization at higher concentrations in the cumulative contact enhancement test (CCET). Therefore Sulphanilic Acid was considered to non-sensitizing.

 

 The above results were further supported by the experimental report reported by the National Technical Reports library (NTRL) {National Technical Reports library (NTRL),AMER CYANAMID CO, Microfiche Number: OTS0534436,1991} for read across chemicalDapsone (CAS no: 80-08-0).In a preliminary dose-range finding study, four animals (two males and two females) were exposed to one concentration (as received) of Dapsone at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %. Dapsone was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration.An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicitedin the animals receiving the positive control article, 1-chloro-2,4-dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge. No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in guinea pigs.Hence Dapsone is not sensitizer o the skin of Guinea pig.

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) is unable to cause skin sensitization and considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) and its structurally similar read across substancesSulphanilic Acid (CAS no: 121-57-3) and Dapsone (CAS no: 80-08-0)were observed in various studies. From the results obtained from these studies it is concluded that the chemical 4-amino-N-(4-aminophenyl)benzenesulphonamide (CAS no: 16803-97-7) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.