3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

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 predicted by OECD QSAR Toolbox version 3.3. The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Data is predicted by OECD QSAR Toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: 3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
- Molecular formula: C28H30N2O3
- Molecular weight: 442.556 g/mol
- Substance type: Organic
- Smiles: C12(c3c(Oc4c1ccc(c4)N(CC)CC)cc(N(CC)CC)cc3)c1c(cccc1)C(O2)=O

Radiolabelling:

not specified

Analytical monitoring:

not specified

Remarks:

Not specified

Positive controls:

not specified

Negative controls:

not specified

Transformation products:

not specified

Key result

DT50:

5.888 d

Remarks on result:

other: other details not available

Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ring opening acylation at a carbonyl OR Acylation >> Ring opening acylation at a carbonyl >> Anhydrides OR Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Discrete chemical by Substance Type ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides OR Moderate reactive OR Moderate reactive >> Five-membered heterocyclic urea by DPRA Cysteine peptide depletion

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 288 Da

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 475 Da

Validity criteria fulfilled:

not specified

Conclusions:

The estimated half-life of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 5.88 days, indicating that it is very slowly hydrolysable.

Executive summary:

Hydrolysis of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was predicted using OECD QSAR toolbox version 3.3 (2017). The estimated half-life of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 5.88 days, indicating that it is very slowly hydrolysable.

Description of key information

The estimated half-life of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 5.88 days, indicating that it is very slowly hydrolysable

Key value for chemical safety assessment

Half-life for hydrolysis:

5.88 d

Additional information

Hydrolysis of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was predicted using OECD QSAR toolbox version 3.3 (2017). The estimated half-life of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 5.88 days, indicating that it is very slowly hydrolysable.