Sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate

Endpoint summary

Description of key information

The skin sensitization potential of target chemical sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was assessedin various experimental studies which were conducted on guinea and humans for target chemicalsodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) and its functionally similar read across substances Acid red 50 (CAS No: 5873-16-5)andFD and C Green No. 3 (CAS no: 2353-45-9). 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 sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) 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

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

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 (IUPAC name): 2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-Indole-5-sulfonic acid, disodium salt- Common name: Indigo Carmine- Molecular formula: C16H8N2Na2O8S2- Molecular weight: 466.3572g/mol-Smiles: C1(=C2\C(=O)c3c(N2)ccc(c3)S(=O)(=O)[O-])/C(=O)c2c(N1)ccc(c2)S(=O)(=O)[O-].[Na+].[Na+]- InChl: 1S/C16H10N2O8S2.2Na/c19-15-9-5-7(27(21,22)23)1-3-11(9)17-13(15)14-16(20)10-6-8(28(24,25)26)2-4-12(10)18-14;;/h1-6,17-18H,(H,21,22,23)(H,24,25,26);;/q;2*+1/p-2/b14-13+;;- Substance type: Organic- Physical state: Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data

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

Details on study design:

No data

Challenge controls:

No data

Positive control substance(s):

not specified

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 in treated guinea pigs.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed in treated guinea pigs.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation",EC3,"S M W N"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Esters AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkylarylether AND Amine AND Anion AND Aromatic compound AND Carbonic acid derivative AND Cation AND Ether AND Heterocyclic compound AND Lactone AND Secondary amine AND Secondary mixed amine (aryl, alkyl) AND Sulfonamide AND Sulfonic acid derivative AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "d"

Similarity boundary:Target: CCN(CC)c1ccc2C=C(C3(S(=O)(=O)O{-}.[Na]{+})Nc4cc(S(N)(=O)=O)ccc4O3)C(=O)Oc2c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  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 SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "g"

Similarity boundary:Target: CCN(CC)c1ccc2C=C(C3(S(=O)(=O)O{-}.[Na]{+})Nc4cc(S(N)(=O)=O)ccc4O3)C(=O)Oc2c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.51

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.15

Interpretation of results:

other: Not sensitizing

Conclusions:

The substance sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated results odium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated results odium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6)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 chemicalsodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6)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 chemicalsodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) and itsfunctionallysimilar read across substances Acid red 50 (CAS No: 5873-16-5)andFD and C Green No. 3 (CAS no: 2353-45-9).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 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

The JOE DINARDO at el., (Journal of Cosmetic Science, 58, no. 3 (2007): 209-214) conducted skin sensitization study for read cross chemical Acid red 50 (CAS No: 5873-16-5) in guinea pig using modified Buehler and Klecak method for open Epicutaneous testing. For the induction phase, the left flanks of 10 albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentration (10.0%, 5.0%, and 2.5%of the induction concentration). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. The test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale (0 = no reaction, 1 -- slight reaction, 2 = moderate reaction, 3 = severe reaction. A positive reaction was defined as an erythema/edema value during the challenge phase of at least one skin grade higher than during the last induction phase.  No erythema/edema was observed after 24 and 48 hours post-application. Hence the test substance Acid red 50 (CAS No:5873-16-5)was considered as not sensitizing to the guinea pigs skin.

 

 

The above results were further supported by the patch test performed by Guin JD. (Contact Dermatitis 2003: 49: 217–218) of read across chemical FD and C Green No. 3 (CAS no: 2353-45-9) to determine the allergic contact dermatitis caused by the chemical on human patients. The dye was applied on 29 patients in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories.  None of the treated patients showed any signs of allergic contact dermatitis. Hence the chemical FD and C Green No. 3 (CAS no: 2353-45-9) can be considered as non-sensitizer to human skin.

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) 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 sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) and itsfunctionallysimilar read across substances Acid red 50 (CAS No: 5873-16-5)andFD and C Green No. 3 (CAS no: 2353-45-9) were observed in various studies. From the results obtained from these studies it is concluded that the chemical sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate (CAS No: 93859-32-6) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.