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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Prediction model based estimation for the target chemical and data from read across have been summarized to evaluate the mutagenic nature of the test material Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate: Genetoxicity of Sodium 5-(aminosulphonyl)-2-( 7-(diethylamino) -2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonateis predicted using QSAR toolbox version 3.3, 2016.The substance Sodium 5-(aminosulphonyl)-2-(7- diethylamino)- 2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox version 3.3

Justification for type of information:

Prediction is done using OECD QSAR Toolbox version 3.3 and the supporting 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 assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material (IUPAC name): sodium 2-[7-(diethylamino)-2-oxo-2H-chromen-3-yl]-5-sulfamoyl-2,3-dihydro-1,3-benzoxazole-2-sulfonate- Common name: sodium 5-(aminosulphonyl)-2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazolesulphonate- Molecular formula: C20H20N3NaO8S2- Molecular weight: 517.513 g/mol- InChl: 1S/C20H21N3O8S2.Na/c1-3-23(4-2)13-6-5-12-9-15(19(24)30-18(12)10-13)20(33(27,28)29)22-16-11-14(32(21,25)26)7-8-17(16)31-20;/h5-11,22H,3-4H2,1-2H3,(H2,21,25,26)(H,27,28,29);/q;+1/p-1- Substance type: Organic- Physical state: Solid- Batch No./ Lot no.: FG/16-17/0003- Physical Appearance: Yellow colored Powder- Stability: Stable in recommended storage conditions- Storage Conditions: 1. Ambient Temp (23 to 27 °C) √ (Store in a cool place. Keep containers tightly closed in a dry and well ventilated place). 2. In Refrigerator (4 °C) and 3. In Freezer (-10 To 0 °C)

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

Water

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Remarks:

No details available

Details on test system and experimental conditions:

No data

Evaluation criteria:

No data

Statistics:

No data

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
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" or "f" or "g" or "h" )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and "m" )  )

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 Acid moiety AND Amides AND Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "k"

Similarity boundary:Target: CCN(CC)c1ccc2C=C(C3(S(=O)(=O)O{-}.[Na]{+})Nc4cc(S(N)(=O)=O)ccc4O3)C(=O)Oc2c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.53

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.715

Conclusions:

The substance Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay

Executive summary:

Genetoxicity of Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate is predicted using QSAR toolbox version 3.3, 2016. The substance Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene mutation in vitro:

Prediction model based estimation for the target chemical and data from read across have been summarized to evaluate the mutagenic nature of the test material Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate: Genetoxicity of Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonateis predicted using QSAR toolbox version 3.3, 2016.The substance Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl)benzoxazolesulphonate is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay.

Gene mutation study was performed by Wuebbles et al (1985) to evaluate the mutagenic nature of the test compound Coumarin 30 (RA CAS no 41044 -12 -6) using Salmonella typhimurium strain TA1538, TA98 and TA100 with and without S9 metabolic activation system. Bacteria were grown overnight in Oxoid nutrient broth, then refrigerated at 4-5^OC for a few hours before use. 0.1 ml of bacterial culture was added to 2 ml of 45°C molten top agar containing 0.01 mg histidine HCI and 0.012 mg biotin/ml, followed by the test sample in ≤0.2 ml DMSO. Finally, 0.5 ml of sodium phosphate buffer, pH 7.4 (no activation), or 0.5 ml of Aroclor-induced rat S9 mixture was added, and the mixture was poured on minimal glucose agar plates. Histidine revertant colonies were counted on a Biotran II automated colony counter after a 2-day incubation at 37°C. A sample was judged mutagenic if it produced greater than twice the spontaneous background colonies at more than one dose or at the highest dose tested. In the above mentioned study, coumarin 30, the test material failed to induce gene mutation in theSalmonella typhimuriumstrains TA1538, TA98 and TA100 with and without metabolic activation. Hence the given test material, Coumarin 30, is not likely to be a gene mutant in vitro.

Based on the weight of evidence data presented, the test material Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl) benzoxazole sulphonate is not mutagenic in vitro.

In the same study by Wuebbles et al (1985) gene mutation study was performed for the test chemical Coumarin 7 (RA CAS no 27425 -55 -4). Bacteria were grown overnight in Oxoid nutrient broth, then refrigerated at 4-5^OC for a few hours before use. 0.1 ml of bacterial culture was added to 2 ml of 45°C molten top agar containing 0.01 mg histidine HCI and 0.012 mg biotin/ml, followed by the test sample in ≤0.2 ml DMSO. Finally, 0.5 ml of sodium phosphate buffer, pH 7.4 (no activation), or 0.5 ml of Aroclor-induced rat S9 mixture was added, and the mixture was poured on minimal glucose agar plates. Histidine revertant colonies were counted on a Biotran II automated colony counter after a 2-day incubation at 37°C. A sample was judged mutagenic if it produced greater than twice the spontaneous background colonies at more than one dose or at the highest dose tested. To estimate mutagenic potency (revertant/µg) from linear dose-response curves, we used the method of Moore and Felton. All compounds were tested to a level at which they were toxic or to the limits of solubility. Duplicate plates were run on all tests except high-performance liquid chromatography (HPLC) fractions. All results were verified in repeat experiments. In the above mentioned study, coumarin 7, the test material failed to induce gene mutation in the Salmonella typhimurium strains TA1538, TA98 and TA100 with and without metabolic activation. Thus the given test material, Coumarin 7, is negative for gene mutation in vitro.

Based on the weight of evidence data presented, the test chemical Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl) benzoxazole sulphonate (CAS no 93859 -32 -6) is not likely to be mutagenic in nature.

Justification for selection of genetic toxicity endpoint
Data is from prediction model

Justification for classification or non-classification

Based on the weight of evidence data presented, the test material Sodium 5-(aminosulphonyl)-2-(7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl) benzoxazole sulphonate (CAS no 93859 -32 -6) is not mutagenic in vitro.