2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride

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:

Data is from OECD QSAR toolbox version 3.3 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride
- Molecular formula : C24H30Cl2N2
- Molecular weight : 417.421 g/mol
- Smiles notation : C1(=[N+](c2ccccc2C1(C)C)C)\C=C/c1c(cc(N(CCCl)CC)cc1)C.[ClH-]
- InChl : 1S/C24H30ClN2.ClH/c1-6-27(16-15-25)20-13-11-19(18(2)17-20)12-14-23-24(3,4)21-9-7-8-10-22(21)26(23)5;/h7-14,17H,6,15-16H2,1-5H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid

Radiolabelling:

not specified

Analytical monitoring:

not specified

Details on sampling:

No data available

Buffers:

No data available

Estimation method (if used):

No data available

Details on test conditions:

No data available

Number of replicates:

No data available

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

No data available

Preliminary study:

No data available

Test performance:

No data available

Transformation products:

not specified

Details on hydrolysis and appearance of transformation product(s):

No data available

Key result

DT50:

147.899 d

Type:

not specified

Remarks on result:

other: Non hydrolysable

Other kinetic parameters:

No data available

Details on results:

No data available

Results with reference substance:

No data available

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Alkylation, direct acting epoxides and related after cyclization AND SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine AND SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium Ion Formation >> Mustards by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  by Protein binding by OASIS v1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Ka, pH 8)(Hydrowin) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 188 Da

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 474 Da

Validity criteria fulfilled:

not specified

Conclusions:

The estimated half-life of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be 147.8 days, indicating that 2-[2-[4-[(2-chloroethyl)- ethylamino] -o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was non hydrolysable.

Executive summary:

Hydrolysis of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441 -82 -3) was predicted using OECD QSAR toolbox version 3.3 (2017). The estimated half-life of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be 147.8 days, indicating that 2-[2-[4-[(2-chloroethyl)- ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was non hydrolysable.

Description of key information

Hydrolysis of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441 -82 -3) was predicted using OECD QSAR toolbox version 3.3 (2017). The estimated half-life of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be 147.8 days, indicating that 2-[2-[4- [(2-chloroethyl)- ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was non hydrolysable.

Key value for chemical safety assessment

Half-life for hydrolysis:

147.8 d

Additional information

Hydrolysis:

Various predicted and experimental data for the target compound 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]- 1,3,3-trimethyl-3H-indolium chloride (CAS No. 6441 -82 -3) and supporting weight of evidence studies for its closest read across substance with logKow as the primary descriptor were reviewed for the hydrolysis end point which are summarized as below:  

 

In the first weight of evidence study, hydrolysis of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441 -82 -3) was predicted using OECD QSAR toolbox version 3.3 (2017). The estimated half-life of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was estimated to be 147.8 days, indicating that 2-[2-[4- [(2-chloroethyl)- ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was non hydrolysable.

Similarly second study was conducted on the read across chemical which was selected on the basis of logKow as the primary descriptor. Chemical 1,2,3-Trichloropropane (96-18-4) from authoritative database study was conducted for the estimation of hydrolysis rate constant and Half-life of hydrolysis at pH 7 of test chemical 1,2,3-Trichloropropane by base catalyzed first order reaction and structure estimation method. The hydrolysis rate constant of chemical 1,2,3-Trichloropropane was 1.8X10-6 /h based on the first order reaction. The half-life of hydrolysis obtained at pH 7 was 44 years. Since half-life of hydrolysis at pH is more than 10 days so it is concluded that test chemical 1,2,3-Trichloropropane was non hydrolyzing.

 

Similarly thirdstudy was conducted on another read across chemical 1,2-Dibromethan (106-93-4) which was selected on the basis of logKow as the primary descriptor. To estimate hydrolysis rate constant and Half-life of hydrolysis at pH 7 of test chemical 1,2-Dibromethan at 60degree C. The aqueous hydrolysis rate constant for ethylene dibromide was measured at pH 7 to be 0.00187/hr at 60 deg C. The half-life of 1,2-Dibromethan obtained at pH 7 was 15.44 days. Since half-life of hydrolysis at pH 7 is more than 10 days so it is concluded that test chemical 1,2-Dibromethan was non hydrolyzing.

 

Thus based on the above data for the target chemical and read across chemical it was concluded that the chemical was not hydrolysable as it exceeds the half-life of at pH 7 is more than 10 days.