Silicic acid (H4SiO4), tetraethyl ester, reaction products with bis(acetyloxy)dioctylstannane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

July 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Laboratory Internal Standard

Version / remarks:

Exhibit A - Amendment 7a, Simulated Gastric Hydrolysis Tests of Oxides, Maleate, Dilaurate: Scope, Schedule, and Cost, Parametrix, 3 September 2002, Project No. 555-3451-003/03/03b

Deviations:

not specified

Principles of method if other than guideline:

The purpose of the study was to perform a series of hydrolysis tests at low pH (-1-2. in 0.07N HCl) at 37 °C in order to simulate mammalian gastric systems. The test compounds included in the study were DBTL, DBTM, DBTO and DOTO. Under acidic conditions it is expected that the tin-ligand bond breaks, leading to formation of the corresponding alkyltin chloride and release of the ligand.
Under acidic conditions, the liberated ligands maleate and laurate are not expected to hydrolyze or react further.
The rate and degree of hydrolysis were studied by analysis of the amounts of DBTC and DOTC, and in case of DBTM and DBTL, simultaneously the amounts of the ligands formed in the hydrolysis reactions of the test substances after 0.5, 1.0, 2.0 and 4.0 hours. The concentrations of the hydrolysis products were determined with GC-FPD (DBTC), HPLC-UV (maleate) and GC-MS (laurate and DOTC).

GLP compliance:

not specified

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

All samples were derivatized and extracted with hexane within 20 minutes after transfer of the contents of the hydrolysis sample. The hexane extracts of the derivatized organotin compounds were stored at 2-10 °C until GC-MS analysis.

Buffers:

Not specified

Estimation method (if used):

As the simulated gastric hydrolysis study with DOTO was not carried out, no calculations have been described.

Details on test conditions:

The study with DOTO was originally of a different design because the determination of DOTC with GC-FPD was not possible, in contrast to DBTC. As an alternative a procedure was used in which DOTO could be separated from the expected hydrolysis product DOTC by extraction with dichloromethane. DOTC was determined by GC-MS after derivatisation with STEB, analogous to the analysis of water samples (method used for the analysis of media used in ecotoxicity testing).

Remarks:

Not specified

Number of replicates:

Not specified

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

Not specified

Transformation products:

not specified

Remarks on result:

not measured/tested

Remarks on result:

not measured/tested

Details on results:

The extraction of DOTC from 0.07 N HCl with dichloromethane yielded a recovery of< 5%. Therefore, this procedure was not found suitable for the study.
A number of additional verification experiments were carried out to develop an improved method. The results of the experiments all yielded comparable results.
Based on the results of the verification of the method for the determination of DOTO in water (ecotoxicity testing), it was decided by the sponsor not to continue the simulated gastric hydrolysis for DOTO, as it was apparent that DOTO would not sufficiently hydrolyze under simulated gastric hydrolysis conditions.
In this section, the results of three verification experiments are summarized. Multiple factors make it difficult to directly compare the results of the different experiments.
However, the data suggest that DOTO is relatively resistant to the simulated gastric hydrolysis.
A)DOTO was added (weighed amount) to 200 ml of water (DSWL-E, medium used in ecotoxicity testing) and shaken overnight at room temperature. After addition of 8.5 ml 36% HCl, the solution was heated 1 h at 55 °C. Following the addition of the internal standards and adjustment of the pH, DOTC was analyzed with the GC-MS STEB method.
Result: approximately 55% hydrolysis of DOTO into DOTC.
B) DOTO was added (weighed amount) to 100 ml of water (DSWL-E medium used in ecotoxicity testing) and shaken overnight at room temperature. After addition of internal standards and the addition of 4.25 ml 36% HCl, the solution was heated 1 h at 60 °C. Following adjustment of the pH, DOTC was analyzed with the GC-MS STEB method.
Result: approximately 27% hydrolysis of DOTO into DOTC.
C) DOTO was added (weighed amount) to 100 ml of 0.07N HCl and shortly shaken at room temperature. After addition of the internal standards, DOTC was analyzed with the GC-MS STEB method.
Result: approximately 2% hydrolysis into DOTC

Results with reference substance:

Not specified

DOTO is also a remarkably insoluble test substance. The only way it could be dissolved was by hydrolyzing it to its acetate with acetic acid. Therefore, similar to DBTO, the addition of the test substance to the acidic solution had to take place in the undissolved form.

In contrast to DBTC, the analysis of the DOTC, which is formed during the acidic hydrolysis of DOTO, with GC-FPD was not possible. Therefore, the GC-MS method after STEB ethylation was chosen for the detection of DOTC. To make sure that no unreacted DOTO would also be derivatized and analyzed, a step was foreseen in which DOTO and DOTC were to be separated by an extraction. Unfortunately, the extraction of DOTC from 0,07 N HCl with dichloromethane only yielded very low recoveries.

 

During the development of a method for the determination of DOTO in water for the analysis of the media used for ecotoxicity testing, some data on the acidic hydrolysis of DOTO were obtained. It was clear that particle size of the test substance had a obvious influence on the level of DOTC formed and was the likely source of the high variability between replicates. Increased temperatures higher than 37°C (up to 60°C) increased the speed of hydrolysis. Summarizing, the percentages of hydrolysis measured never exceeded 55% and were in most cases much lower (i.e., 2% and 27%).

 

Taking into account these various difficulties, it was decided, in consultation with the sponsor, that the end result would not be meaningful and further efforts to measure the simulated gastric hydrolysis of DOTO were terminated.

Validity criteria fulfilled:

not specified

Conclusions:

For DOTO it was not possible to measure the hydrolysis due to analytical difficulties and the physical-chemical properties of the test substance. From data available, it was concluded that DOTO would not fully hydrolyze in the test system.

Executive summary:

The purpose of the study was to perform a series of hydrolysis tests at low pH (-1-2. In 0.07N HCl) at 37 °C in order to simulate mammalian gastric systems. Under acidic conditions it is expected that the tin-ligand bond breaks, leading to formation of the corresponding alkyltin chloride and release of the ligand.

Under acidic conditions, the liberated ligands maleate and laurate are not expected to hydrolyze or react further.

The concentrations of the hydrolysis products were determined with GC-MS (laurate and DOTC).

 

DOTO is also a remarkably insoluble test substance. The only way it could be dissolved was by hydrolyzing it to its acetate with acetic acid. Therefore, similar to DBTO, the addition of the test substance to the acidic solution had to take place in the undissolved form.

In contrast to DBTC, the analysis of the DOTC, which is formed during the acidic hydrolysis of DOTO, with GC-FPD was not possible. Therefore, the GC-MS method after STEB ethylation was chosen for the detection of DOTC. To make sure that no unreacted DOTO would also be derivatized and analyzed, a step was foreseen in which DOTO and DOTC were to be separated by an extraction. Unfortunately, the extraction of DOTC from 0,07 N HCl with dichloromethane only yielded very low recoveries.

 

During the development of a method for the determination of DOTO in water for the analysis of the media used for ecotoxicity testing, some data on the acidic hydrolysis of DOTO were obtained. It was clear that particle size of the test substance had a obvious influence on the level of DOTC formed and was the likely source of the high variability between replicates. Increased temperatures higher than 37°C (up to 60°C) increased the speed of hydrolysis. Summarizing, the percentages of hydrolysis measured never exceeded 55% and were in most cases much lower (i.e., 2% and 27%).

 

Taking into account these various difficulties, it was decided, in consultation with the sponsor, that the end result would not be meaningful and further efforts to measure the simulated gastric hydrolysis of DOTO were terminated.

 

It was not possible to carry out the simulated gastric hydrolysis study for dioctyltin oxide (DOTO, CAS # 870-08-6). From the information available, it was concluded that DOTO only partially hydrolyzed in the test system and the estimated percentage of hydrolysis was 20 to 55%.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Principles of method if other than guideline:

Test procedure is largely consistent with OECD 111, hydrolysis as a function of pH. Breakdown products were analysed using solid state Sn NMR. Known samples of Dioctyltin oxide and Dioctyltin chloride were subjected to the same procedure and analysis and the resultant charts compared.

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

Solid State Tin NMR

Positive controls:

no

Negative controls:

no

Transformation products:

yes

No.:

#1

Key result

Remarks on result:

other: Results provided in tables below

·DOTO : - 177.5 Ppm

 

Measurement	1.0074g
filter paper	0.7960g
After filtration and drying	1.8004g
Collection amount	1.0044g
Recovery rate	99.7%

·DOTC : - 46.8 Ppm

 

Measurement	1.0017g
filter paper	0.7834g
After filtration and drying	1.7676g
Collection amount	0.9842g
Recovery rate	98.3%

·S-1 : - 179.5 Ppm

 

Measurement	1.1231g
filter paper	0.7976g
After filtration and drying	1.3852g
Collection amount	0.5876g
Recovery rate	52.3%

The low recovery rate of S-1 is due to the presence of solids that decomposed solids stick to bottle and cannot be recovered

SN NMR charts attached

A.    DOTO

B.     DOTC

C.     S-1 Hydrolysis with H₂O

D.    S-1 Hydrolysis with Conc. HCl

E.     DOTO Hydrolysis with 0.07N HCl aq (pH1.2)

F.      DOTC Hydrolysis with 0.07N HCl aq (pH1.2)

G.    S-1 Hydrolysis with 0.07N aq (pH1.2)

Validity criteria fulfilled:

yes

Conclusions:

Based on the SN NMR, the aqueous and gastric hydrolysis products of Silicic acid tetraethyl ester,dioctylstannane forms Dioctyltin Oxide and does not degrade to Dioctyltin Chloride

Executive summary:

Silicic acid tetraethyl ester,dioctylstannane has been subjected to hydrolysis under aqueous and gastric conditions. Furthermore, know samples of dioctyltin oxide and dioctyltin chloride were subjected to hydrolysis under aqueous and gastric conditions.

The resultant hydrolysis products were collected and dried; the dried samples were analysed by SN NMR.

Comparison of the resultant charts demonstrate that Silicic acid tetraethyl ester,dioctylstannane hydrolyses to dioctyltin oxide and does not hydrolyses to dioctyltin chloride.

Description of key information

Hydrolysis of the registered substance, has demonstrated that the substance degrades by hydrolysis. By means of Sn NMR it has been demonstrated that the substance hydrolyses to dioctyltin oxide (DOTO)

Additional information

Silicic acid tetraethyl ester,dioctylstannane has been subjected to hydrolysis under aqueous and gastric conditions. Furthermore, know samples of dioctyltin oxide and dioctyltin chloride were subjected to hydrolysis under aqueous and gastric conditions.

The resultant hydrolysis products were collected and dried; the dried samples were analysed by SN NMR.

Comparison of the resultant charts demonstrate that Silicic acid tetraethyl ester,dioctylstannane hydrolyses to dioctyltin oxide and does not hydrolyses to dioctyltin chloride.