[4-[[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium acetate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate; 4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylidene}-N,N-dimethylcyclohexa-2,5-dien-1-iminium acetate
- Molecular formula: C24H28N3.C2H3O2
- Molecular weight: 417.5499 g/mol
- Smiles notation: CC(=O)[O-].CNc1ccc(cc1)C(=C2C=CC(=[N+](C)C)C=C2)c3ccc(cc3)N(C)C
- InChI: 1S/C24H27N3.C2H4O2/c1-25-21-12-6-18(7-13-21)24(19-8-14-22(15-9-19)26(2)3)20-10-16-23(17-11-20)27(4)5;1-2(3)4/h6-17H,1-5H3;1H3,(H,3,4)
- Substance type: Organic
- Physical state: Liquid

Radiolabelling:

not specified

Analytical monitoring:

not specified

Positive controls:

not specified

Negative controls:

not specified

Transformation products:

not specified

Key result

DT50:

13.824 d

Type:

other: estimated data

Remarks on result:

other: Other details not known

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

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

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 >> Secondary aromatic amine 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 AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 220 Da

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 627 Da

Validity criteria fulfilled:

not specified

Conclusions:

The estimated half-life of N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate was estimated to be 13.82 days, indicating that it is not hydrolysable.

Executive summary:

Hydrolysis of N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (CAS no. 84434 -47 -9) is predicted using OECD QSAR toolbox version 3.4 with logKow as the primary descriptor. The estimated half-life of N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclo hexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was estimated to be 13.82 days, indicating that it is not hydrolysable.

Description of key information

Hydrolysis of N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (CAS no. 84434 -47 -9) is predicted using OECD QSAR toolbox version 3.4 (2017) with logKow as the primary descriptor. The estimated half-life of N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene} cyclo hexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was estimated to be 13.82 days, indicating that it is not hydrolysable.

Key value for chemical safety assessment

Half-life for hydrolysis:

13.82 d

Additional information

Various predicted data for the target chemical N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (CAS No. 84434-47-9) and supporting weight of evidence study from authoritative database for its read across substance were reviewed for the hydrolysis end point which are summarized as below:

 

In a prediction done by SSS (2017) using OECD QSAR toolbox version 3.4 with logKow as the primary descriptor, the hydrolysis of N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino) phenyl]methylene}cyclohexa-2,5 -dien-1-ylidene)-N-methylmethanaminium acetate (CAS no. 84434 -47 -9) was predicted. The estimated half-life of N-(4 -{[4 -(dimethylamino)phenyl] [4 -(methylamino)phenyl]methylene}cyclo hexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate was estimated to be 13.82 days, indicating that it is not hydrolysable.

 

In an anotherprediction done using the HYDROWIN v2.00 program of Estimation Programs Interface (EPI Suite, 2017) prediction model, the hydrolysis half-life of test compound N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate(CAS No. 84434-47-9) was estimated.The estimated half-life of test chemical was estimated to be 43.449 and 4.345 days at pH 7 and 8 (at 25 deg C) respectively. Based on the half-life value (43.449 days at pH 7.0), it indicates that chemical is not hydrolysable.

 

In a supporting weight of evidence study from authoritative database (HSDB, 2017) for the read across chemical (4 -(4,4'-Bis(dimethylamino)benzhydrylidene)cyclohexa-2,5 -dien-1 -ylidene)dimethylammonium, chloride (CAS no. 548-62-9),the half-life and base catalyzed second order hydrolysis rate constant was determined using a structure estimation method of the read across chemical (4 -(4,4'-Bis(dimethylamino) benzhydrylidene)cyclohexa-2,5 -dien-1 -ylidene)dimethylammonium, chloride. The second order hydrolysis rate constant of (4 -(4,4'-Bis(dimethylamino) benzhydrylidene)cyclohexa-2,5-dien-1-ylidene)dimethylammonium, chloride was determined to be 3.707L/mol-sec with a corresponding half-lives of 22 and 2 days at pH 7 and 8, respectively. Based on the half-life values (22 days at pH 7.0), it is concluded that the chemical (4 -(4,4'-Bis(dimethylamino)benzhydrylidene)cyclohexa-2,5 -dien-1 -ylidene)dimethylammonium, chloride is not hydrolysable.

 

On the basis of the above results for target chemical N-(4-{[4-(dimethylamino)phenyl][4-(methylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium acetate (from OECD QSAR toolbox version 3.4 and EPI Suite, 2017) and for its read across substance (from authoritative database HSDB, 2017), it can be concluded that the test chemical N-(4 -{[4 -(dimethylamino)phenyl][4 -(methylamino)phenyl]methylene}cyclohexa-2,5 -dien-1 -ylidene)-N-methylmethanaminium acetate is not hydrolysable.