Sodium 2-(p-aminoanilino)-5-nitrobenzenesulphonate

Endpoint summary

Description of key information

The skin sensitization potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3)was 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 of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

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:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

Name of the test chemical: sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate
Molecular Formula: C12H10N3NaO5S
Molecular Weight: 331.283 g/mol
Smiles Notation: c1cc(ccc1N)Nc2ccc(cc2S(=O)(=O)[O-])[N+](=O)[O-].[Na+]
Substance type: Organic
Physical State:

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

No data available

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

Dose level:

undiluted

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Skin sensitization reaction was not oberved

Remarks on result:

no indication of skin sensitisation

Remarks:

not sensitising

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 5 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 ("k" and ( not "l") )  )  and "m" )  and "n" )  and "o" )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

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 Amine OR Anion OR Aromatic compound OR Cation OR Nitro compound OR Primary amine OR Primary aromatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitro, aromatic attach [-NO2] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Nitrobenzene OR Overlapping groups OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aniline OR Aryl OR Nitrobenzene OR Precursors quinoid compounds OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

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 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters 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 >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes 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) >> Nitroalkanes 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 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 >> 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 metabolic 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 SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Nucleophilic substitution after nitrite formation OR SN2 >> Nucleophilic substitution after nitrite formation >> Nitroalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides 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  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding by OASIS v1.3

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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: "l"

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 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines 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: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Nitro compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Nc1ccc(Nc2ccc(N(=O)=O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic mono- and dialkylamine OR Hydrazine OR Nitro-aromatic OR No alert found OR Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.14

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.5

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3) was 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 of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate (14846-08-3) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3)was 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 of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) and its structurally similar read across substancesBenzyl benzoate (120-51-4)and Acid orange 3(6373-74-6), the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) was 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 of sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Supported by experimental study conducted by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset-European Chemicals Bureau- 18–FEB–2000) to evaluate the skin sensitizing potential of read across substance sodium 2-methylprop-2-ene-1-sulfonate (1561-92-8) in guinea pig . The skin sensitization study of sodium 2-methylprop-2-ene-1-sulfonate (1561-92-8) was performed on 20 guinea pigs. No indication of skin sensitization was observed. Hence sodium 2-methylprop-2-ene-1-sulfonate (1561-92-8) was considered to be not sensitizing in guinea pig.

Supported by experimental study conducted by Joe Dinardo, Raleigh Nc And Zoe Diana Draelos (j. Cosmet, Sci 58, 209-214 (May/June2 007)) to evaluate the skin sensitizing potential of read across substance Acid orange 3(6373-74-6) in guinea pig . The skin sensitization study of Basic Violet 3(548-62-9) was performed by Buehler test and the Klecak method for open epicutaneous testing (OET) in 10 guinea pigs. In induction phase, induction given using 0.1ml of 1% solution in polyethylene glycol (PG) on left flank(1.8-cm circular area) by topical application for three times weekly ( Monday, Wednesday Friday) for three consecutive weeks. 0.5% 2,4-dinitrochlorobenzene (DNCB) in ethanol used as positive control. In challenge phase, After 2 weeks rest period, challenge application given in dose concentration0.1ml of10% , 5%, 2.5% in PG on right flank.Evaluation done 24hr and 48 hr after challenge application. No indication of skin sensitization was observed. Hence it is considered that Acid orange 3(6373-74-6) was not skin sensitizing in guinea pig by Buehler test and the Klecak method for open epicutaneous testing (OET)

Thus based on the above predictions on sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) as well as its read across and applying weight of evidence, it can be concluded that sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) can be considered as not classified for skin sensitization.

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, sodium 2-[(4-aminophenyl)amino]-5-nitrobenzene-1-sulfonate(14846-08-3) can be considered as not classified for skin sensitization.