2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) was assessedin various experimental studies which were conducted on guinea and mouse for target chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) and its structurallysimilar read across substances Sulphanilic Acid(CAS no:121-57-3) and Sulphanilamide (CAS No: 63-74-1).. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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

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 (IUPAC name): 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate
- Molecular formula: C9H13NO7S2
- Molecular weight: 311.3337 g/mol
- Smiles notation: COC1=C(C=CC(=C1)S(=O)(=O)CCOS(=O)(=O)O)N
- InChl: 1S/C9H13NO7S2/c1-16-9-6-7(2-3-8(9)10)18(11,12)5-4-17-19(13,14)15/h2-3,6H,4-5,10H2,1H3,(H,13,14,15)
- Substance type: Organic
- Physical state: Solid

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:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

10

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 reaction was observed in trested guinea pigs.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization reaction was observed in trested guinea pigs.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 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 ("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) AND Vinyl Sulfones 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 SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated 1,3,5-triazine derivatives OR Low reactive OR Low reactive >> Activated haloarenes OR Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR No alert found OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> 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 SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds 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 by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.14

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.05

Interpretation of results:

other: Not sensitizing

Conclusions:

The substance 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)failed to induce skin sanitization effects and hence is considered to be not sensitizing to 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:

Various studieshas been investigated for the test chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and mouse for target chemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)and its structurally similar read across substancesSulphanilic Acid(CAS no:121-57-3) and Sulphanilamide (CAS No: 63-74-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs

 

The D. A. Basketter et.al., {Contact Dermatitis, Volume 27, Issue 4, April 1992, Pages 209–213} conducted cumulative contact enhancement test (CCET) for read across substance Sulphanilic Acid (CAS no:121-57-3) that supported the above mentioned result. 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 (CAS no: 121-57-3) was considered to be non -sensitizing.

 

The above results were further supported by the Local Lymph Node Assay (LLNA) carried out by D. A. BASKETTR et, al., {Food and Chemical Toxicology Vol. 32. No. 6. pp. 543-547. 1994} on Female CBA/Ca mice to assess the skin sensitization potential of read across chemical Sulphanilamide (CAS No: 63-74-1). The LLNA was conducted on groups of CBA/Ca mice (8-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl of one of three concentrations (10%, 25% and 50% )of the test chemical. 5 days after the first topical application, all mice were injected iv with 250µl phosphate buffered saline (PBS) containing 20µCi of [³H]methyl thymidine (³HTdR) .The mice were killed 5 hr later and the draining auricular lymph nodes excised and pooled for each experimental group. A single cell suspension of lymph node cells (LNC) was prepared by gentle disaggregation through 200 mesh stainless steel gauze. Pooled LNC were pelleted by centrifugation at 190g for 10 min, washed twice with 10 ml PBS and resuspended in 3 ml 5% trichloroacetic acid (TCA). After incubation overnight at 4°C, the precipitate was recovered by centrifugation, resuspended in I ml 5% TCA and transferred to 10 ml scintillation fluid. Incorporation of³HTdR was measured by p-scintillation counting.The proliferative response of LNC was expressed as mean radioactive disintegrations per minute per lymph node (dpm/node for each experimental group and as the ratio of³HTdR incorporation into LNC of test nodes relative to control nodes [test: control (T:C) ratio]. A chemical was regarded as a sensitizer in the LLNA if at least one concentration resulted in a T:C ratio of 3 or greater and the data were not incompatible with a biological dose response. The test: control (T:C) ratios were estimated to be 1.0, 1.0 and 0.9 at concentration of 10% ,25% and 50% respectively. Since the resulted test: control (T:C) ratio was less than 3 at each concentration, the chemical Sulphanilamide (CAS No: 63-74-1) was considered to be not sensitizing in Local Lymph Node Assay (LLNA).

 

Thus on the basis of available data for thetarget chemical2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0)and its structurally similar read across substancesSulphanilic Acid (CAS no:121-57-3) and Sulphanilamide (CAS No: 63-74-1),it can be concluded thatchemical 2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) 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 substance2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) and its structurally similar read across substancesSulphanilic Acid (CAS no:121-57-3) and Sulphanilamide (CAS No: 63-74-1) were observed in various studies. From the results obtained from these studies it is concluded that the chemical2-[(4-amino-3-methoxyphenyl)sulphonyl]ethyl hydrogen sulphate (CAS No: 26672-22-0) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.