5-amino-2-methoxybenzenesulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was assessed in various experimental studies which were conducted on guinea pigs and humans for target chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) and its structurally similar read across substance Vanillin (CAS No: 121-33-5) and functionally similar read across substance2-Methoxybenzyl alcohol (CAS no: 612-16-8). The predicted data using QSAR 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 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) 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

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 of test material : 5-amino-2-methoxybenzene-1-sulfonic acid
- Common name : 5-Amino-2-methoxybenzenesulphonic acid
- Molecular formula : C7H9NO4S
- Molecular weight : 203.217 g/mol
- Smiles notation : O=S(=O)(O)c1c(OC)ccc(N)c1
- InChl : 1S/C7H9NO4S/c1-12-6-3-2-5(8)4-7(6)13(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
- 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:

20

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 observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed.

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" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 >> Hydroquinones 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 >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Ether AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary by Organic Functional groups

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Thioether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.508

Interpretation of results:

other: not sensitizing

Conclusions:

The chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) 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 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) 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:

Various studieshas been investigated for the test chemical5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs, mouse and humans for target chemical5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) and its structurally similar read across substanceVanillin (CAS No: 121-33-5)andfunctionallysimilar read across substance2-Methoxybenzyl alcohol (CAS no: 612-16-8).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 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

 

The Gerberick GF et al., {Dermatitis, 2005 Dec; 16(4):157-202} assessed skin sensitizing potential of read across chemical Vanillin (CAS No: 121-33-5) by using the Mouse Local Lymphnode Assay that supports the result of target chemical. The LLNA was conducted on groups of CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute.  An SI was calculated as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer , if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3) .The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value. The relative potency index of Vanillin (CAS No: 121-33-5) was not calculated but on the basis of classification system it was considered to be >100. Thus the chemical Vanillin (CAS No: 121-33-5) was considered as non-skin sensitizer.

 

The above results were further supported by the skin sensitization study of read across chemical2-Methoxybenzyl alcohol (CAS no: 612-16-8)carried out by D. Belsito et al., {Food and Chemical Toxicology, Vol. 50, Pg. no. S52-S99, 2012} via ahuman repeated insult patch test (HRIPT) on 39 volunteers. During the study, each subject was induced with1.2% of2-Methoxybenzyl alcohol inEtOH three times per week for 3 weeks under occlusive condition. After induction, all the treated subjects were challenged at same concentration used in induction and later observed for skin reactions after 24 hours.None of the volunteers showed any signs of skin sensitization. Hence the chemical2-Methoxybenzyl alcohol (CAS no: 612-16-8) was considered to be not sensitizing to the skin of human subjects.

 

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) 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 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) and its structurally similar read across substances its structurally similar read across substanceVanillin (CAS No: 121-33-5)andfunctionallysimilar read across substance2-Methoxybenzyl alcohol (CAS no: 612-16-8)were observed in various studies. From the results obtained from these studies it is concluded that the chemical 5-amino-2-methoxybenzene-1-sulfonic acid (CAS no: 6470-17-3) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.