2-amino-3,5-xylenesulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of 2-amino-3,5-dimethylbenzene-1-sulfonic acid was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 2-amino-3,5-dimethylbenzene-1-sulfonic acid was predicted to be non sensitizing to the skin of male and female Pirbright - Hartley guinea pigs.

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 v3.4 and the 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 3.3

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 of test material: 2-amino-3,5-dimethylbenzene-1-sulfonic acid
- Molecular formula: C8H11NO3S
- Molecular weight: 201.245 g/mol
- Smiles notation: O=S(=O)(O)c1c(N)c(cc(C)c1)C
- InChl: 1S/C8H11NO3S/c1-5-3-6(2)8(9)7(4-5)13(10,11)12/h3-4H,9H2,1-2H3,(H,10,11,12)
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Dose level:

no data available

Clinical observations:

no data available

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

no data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 9 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amines OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Hindered) by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aromatic amines AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) 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) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 by DNA alerts for AMES by OASIS v.1.4

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "l"

Similarity boundary:Target: Cc1cc(C)cc(S(O)(=O)=O)c1N
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Cc1cc(C)cc(S(O)(=O)=O)c1N
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

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 log Kow < 0.5 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: "o"

Referential boundary: The target chemical should be classified as Group CNHal Aqueous Solubility < 0.1 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.15

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.89

Interpretation of results:

other: not sensitizing

Conclusions:

2-amino-3,5-dimethylbenzene-1-sulfonic acid was predicted to be non sensitizing to the skin of male and female Pirbright - Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 2-amino-3,5-dimethylbenzene-1-sulfonic acid was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 2-amino-3,5-dimethylbenzene-1-sulfonic acid was predicted to be non sensitizing to the skin of male and female Pirbright - Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2)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 chemical2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2) and its structurally similar read across substances Sulphanilic Acid(CAS no:121-57-3)andMethallyl sulfonate (CAS No:-1561-92-8).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 Sodium hydrogen 8-aminonaphthalene-1,6-disulfonate was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Sodium hydrogen 8-aminonaphthalene-1,6-disulfonate was predicted to be non sensitizing to the skin of male and female Hartley guinea pigs.

 

The D. A. Basketter, E. W. Scholes, M. Cumberbatch, C. D. Evans, I. Kimber (1992) conducted the cumulative contact enhancement test (CCET) to study the sensitization potential ofstructurally similar read across substanceSulphanilic Acid(CAS no:121-57-3). 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 failedto induce any evidence of sensitization at higher concentrations in the cumulative contact enhancement test (CCET). Therefore Sulphanilic Acid (CAS no: 121-57-3) was considered to be non sensitizing.

 

The above results were further supported by maximization test conducted byEUROPEAN COMMISSION – European Chemicals Bureau (2000) on ofstructurally similar read acrosschemicalMethallyl sulfonate(CAS No:-1561-92-8) in 20 guinea pigs. The guinea pigs did not produce any sensitization reactions. Thus Methallyl sulfonate(CAS No:-1561-92-8) was considered to be non sensitizing to the guinea pigs.

 

Thus on the basis of available data for thetarget chemical2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2) and its structurally similar read across substancesSulphanilic Acid(CAS no:121-57-3)and Methallyl sulfonate (CAS No:-1561-92-8),it can be concluded thatchemical 2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2) is unable to cause skin sensitization and considered as non skin sensitizer.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 2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2) and its structurally similar read across substancesSulphanilic Acid(CAS no:121-57-3)and Methallyl sulfonate (CAS No:-1561-92-8)were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-amino-3,5-dimethylbenzene-1-sulfonic acid (CAS No: 88-22-2) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.