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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Experiments conducted by NMR spectrometry investigated the behaviour of aqueous solutions of MBTCl over time, at varying concentrations and in the presence of varying concentrations of hydrochloric acid.
GLP compliance:
not specified
Remarks:
GLP status not specified in study report
Radiolabelling:
not specified
Analytical monitoring:
no
Details on sampling:
PREPARATION OF NMR SAMPLES
- Stability test of 10 % solution: Internal LIMS: 241221. Into a clean NMR vial, D2O (0.577 g) was weighed in and MBTCl (0.066 g) was added and mixed by shaking after capping the vial. A clear colourless solution resulted with a calculated mass percentage w(MBTCl) = 10.3 %.
- Dilution series 50 % to 10 % (see Table 1): Using syringes with needles, MBTCl and deuterated water (D2O) were weighed in accurately using GC vials. From these, both portions were transferred quantitatively into a clean NMR vial. In order to avoid loss of materials and cross contamination, further portions of D2O were added to the NMR vial to obtain the next desired concentration step. At the 20 % MBTCl stage, the solution had to be partitioned because the total volume had reached the capacity of the vial. Therefore, the 10 % stage was prepared in another vial adding the proper aliquot of D2O. The masses were as shown in with corresponding mass percentages given. Another aliquot from the 20 % MBTCl stage was subjected to addition of further MBTCl to return the concentration to 50 % MBTCl.
- MBTCl in DCl/D2O 9 M: Internal LIMS: 240590. Into a clean NMR vial, 9 M DCl/D2O (0.569 g) was weighed in and MBTCl (0.082 g) was added and mixed by shaking after capping the vial. A clear colourless solution resulted with a calculated mass percentage w(MBTCl) = 12.6 %.
- MBTCl in DCl/D2O 1 M: Internal LIMS: 240529. Into a clean NMR vial, 1 M DCl/D2O (0.551 g) was weighed in and MBTCl (0.074 g) was added and mixed by shaking after capping the vial. A clear colourless solution resulted with a calculated mass percentage w(MBTCl) = 11.8 %.
- MBTCl in DCl/D2O 0.1 M: Internal LIMS: 240859. Into a clean NMR vial, 0.1 M DCl/D2O (0.485 g) was weighed in and MBTCl (0.063 g) was added and mixed by shaking after capping the vial. A clear colourless solution resulted with a calculated mass percentage w(MBTCl) = 11.5 %.
- MBTCl in CDCl3: Internal LIMS: 240858. Into a clean NMR vial, CDCl3 (0.700 g) was weighed in and MBTCl (0.117 g) was added and mixed by shaking after capping the vial. A clear colourless solution resulted with a calculated mass percentage w(MBTCl) = 14.3 %.
Transformation products:
no
Remarks on result:
other: The study showed that formation of one or several individual distinct species from MBTCl in the presence of neutral water is slow under the conditions observed in this study and is too slow to be observed under same conditions in acidic solution.
Details on results:
Observation of MBTCl in D2O over time
- A solution of MBTCl in D2O at a concentration of approx. 10 % was investigated by 1H and 13C NMR spectroscopy over a time period of 11 days.
- There was no significant change observed in the 1H and 13C spectra recorded over a time span of 11 days. The spectrum directly after preparation of the solution is essentially identical with the ones measured after 6 and 11 days both for protons and carbons of MBTCl. No precipitation was observed in the NMR vial after 6 days; however, after 11 days, tiny bits of white precipitate were seen and the corresponding spectra indicate slight signal broadening due to the presence of solids.

Observation of MBTCl in D2O at varying concentrations
- Solutions of MBTCl in D2O at contents varying from 50 % to 10 % were observed by 1H and 13C NMR spectroscopy and the resulting spectra were compared. Experimentally, first a 1:1 mixture of MBTCl in D2O was prepared by weighing and further D2O was added to the same NMR vial to furnish mass percentages of MBTCl in D2O of approximately 40 %, 30 %, 20 %. For the 10 % experiment, the sample had to be partitioned because of total volume constraints in the vial. However, the five concentration levels constitute a dilution series, i.e. the sample of MBTCl observed was identical over these concentrations.
- The proton spectra show a shift of all signals to the right with increasing concentration of MBTCl when the residual solvent peak is used as reference. Apart from that, the proton spectra do not deliver conclusive insights. In contrast, the comparison of the 13C NMR spectra is showing a significant concentration dependent change in line width of the signals, specifically the resonance of carbon number 1 is broadening extremely with decreasing concentration, i.e. it is observed at similar linewidth as carbons 2-4 at 50 % but it almost disappears into noise at a content of 10 %.
- An aliquot from the 20 % MBTCl stage was enriched with additional MBTCl and thus returned to the concentration of 50 % MBTCl in order to test whether the spectral change was reversible. This reversibility was indeed observed and the spectra of the two 50 % solutions are very much in agreement.

Observation of MBTCl in different concentrations of DCl in D2O
- Spectral investigations were extended to solutions of MBTCl at a mass content of approximately 10 % in different concentrations of DCl in D2O, i.e. deuterated hydrochloric acid in deuterated water. The molar concentrations used were 0.1 mol/L (0.1 M), 1.0 mol/L (1 M) and 9.2 mol/L (9 M), which were prepared from commercially available 20 % deuterium chloride in deuterium oxide. Dilutions were prepared by weight because of the limited amount of both D2O and DCl/D2O.
The results were displayed in comparison to 1H spectra of MBTCl in D2O without addition of any hydrochloric. For greater clarity, magnified sections of the same spectra of the region containing the MBTCl resonances were displayed, the same comparison is displayed for the case of 13C spectra.
- The MNR samples of MBTCl at different concentrations of acids were also monitored for change over time, but as in the case of the solution in neutral D2O, no change in the spectra was observed over an extended time period. Spectra were compared directly after preparation and after time spans varying between 14 and 19 days depending on the sample, for concentrations of 0.1 M, 1 M and 9 M DCl/D2O.
- Even after three weeks, none of the acidic solutions (i.e. DCl at 0.1 M, 1 M and 9 M) showed any signs of precipitation or turbidity. The samples were still clear and colourless.

Figures (Please refer to attached)

> Orientation: MBTCl in CDCl3

Figure 1: LIMS# 240858 EXP 22: Section of 1H NMR spectrum of MBTCl in CDCl3.

Figure 2: LIMS# 240858 EXP 21: Section of 13C NMR spectrum of MBTCl in CDCl3.

> Observation of MBTCl in D2O over time

Figure 3: LIMS# 241221 EXP 13/30/42: 1H spectra of MBTCl in D2O after preparation, after 6 days, and after 11 days

Figure 4: LIMS# 241221 EXP 14/31/41: 13C spectra of MBTCl in D2O after preparation, after 6 days, and after 11 days

> Observation of MBTCl in D2O at varying concentrations

Figure 5: LIMS# 236652 EXP 41/36/34/32/30: Comparison of 1H spectra of MBTCl in D2O at mass percentages from bottom to top of 10, 20, 30, 40 and 50 %

Figure 6: LIMS# 236652 EXP 12/37/35/33/31: Comparison 13C spectra of MBTCl in D2O at mass percentages from bottom to top of 10, 20, 30, 40 and 50 %

Figure 7: LIMS# 236652 EXP 30/36/50: 1H spectra of initial solution of 50 % MBTCl in D2O (blue, bottom), diluted solution of 20 % MBTCl in D2O (red, middle) and enriched solution of 50 % MBTCl in D2O (green, top). It is visible that dilution changes the spectral properties (e.g. chemical shifts) and reenrichment with MBTCl returns the spectrum to the initial appearance. Chemical shifts are calibrated using the HDO resonance (4.79 ppm).

Figure 8: LIMS# 236652 EXP 31/37/51: 13C spectra of initial solution of 50 % MBTCl in D2O, diluted solution of 20 % MBTCl in D2O, and enriched solution of 50 % MBTCl in D2O

> Observation of MBTCl in different concentrations of DCl in D2O

Figure 9: LIMS# 236652 EXP 20; LIMS# 240500 EXP 13; LIMS 240529 EXP 11; LIMS# 240590 EXP 13: Display of full 1H NMR spectra of 10 % MBTCl in different concentrations of DCl in D2O, from bottom to top 0 M (blue), 0.1 M (red), 1 M (green), 9 M (magenta). Chemical shifts are calibrated using the HDO resonance (4.79 ppm). The seemingly extreme change in chemical shift in the spectrum at 9 M indicates that at low pH, this practice is no longer perfectly adequate, but it was maintained for the sake of consistency.

Figure 10: LIMS# 236652 EXP 20; LIMS# 240500 EXP 13; LIMS 240529 EXP 11; LIMS# 240590 EXP 13: Display of C1-C4 sections of 1H NMR spectra of 10 % MBTCl in different concentrations of DCl in D2O (0 M, 0.1 M, 1 M, 9 M).

Figure 11: LIMS# 236652 EXP 21; LIMS# 240500 EXP 15; LIMS 240529 EXP 12; LIMS# 240590 EXP 14: Display of C1-C4 sections of 13C NMR spectra of 10 % MBTCl in different concentrations of DCl in D2O (0 M, 0.1 M, 1 M, 9 M).

Figure 12: LIMS# 240859 EXP 10/14, LIMS# 240529 EXP 11/26, LIMS# 240590 EXP 13/28: Sections of 1H spectra of MBTCl in D2O with increasing concentrations of DCl present and comparing day 1 with after 2 weeks or more: 0.1 M DCl after preparation and after 14 days; 1 M DCl after preparation and after 19 days; 9 M DCl after preparation and after 17 days

Figure 13: LIMS# 240859 EXP 11/15, LIMS# 240529 EXP 12/27, LIMS# 240590 EXP 14/29: 13C spectra of MBTCl in D2O with increasing concentrations of DCl present and comparing day 1 with after 2 weeks or more: 0.1 M DCl after preparation and after 14 days; 1 M DCl after preparation and after 19 days; 9 M DCl after preparation and after 17 days

Validity criteria fulfilled:
not applicable
Conclusions:
The results of this study are providing a basis to justify an in vivo testing protocol where live mice were being fed MBTCl with a digestible vehicle for resorption through the gastrointestinal tract. The results of the present study show that it is reasonable to assume that MBTCl will survive exposure to water and gastric acid on the timeframe that is relevant for the testing scenario because gastric acid is composed of hydrochloric acid at concentrations between 0.1 mol/L and 1 mol/L, depending on species. Therefore, MBTCl will reach the organ where resorption takes place intact.
Executive summary:

The stability of monobutyltin trichloride in aqueous media was investigated through experiments conducted by NMR spectrometry. The behaviour of aqueous solutions of MBTCl was investigated over time, at varying concentrations and in the presence of varying concentrations of hydrochloric acid.

As a starting point of the investigation, the spectral properties of MBTCl dissolved in an inert solvent, i.e. CDCl3, were investigated through spectral assignment of 1H and 13C resonances. Special attention was directed to the presence of pronounced satellite resonances caused by heteronuclear spin-spin coupling of both protons and carbons in the butyl chain to the central tin atom in those molecules where NMR-active nuclei of tin are present. Therefore, they are observed in both 1H and 13C spectra.

The integrated interpretation of the experiments conducted throughout this study combines findings from solutions of MBTCl in inert solvent (CDCl3) as well as in strongly interacting solvents D2O and DCl/D2O to make a statement about the stability of MBTCl against irreversible hydrolytic attack by water molecules.

This study finds no indication that such an irreversible hydrolysis occurs on a timeframe of one to six days upon dissolution of MBTCl in neutral water, mildly or strongly acidic aqueous solutions of hydrochloric acid in water. After more than six days, precipitates form in neutral water, but the same is not observed in acidic solution. The experimental data provide support to the assumption that in these solutions an equilibrium exists between strong complexes of water with MBTCl and chemical species where one or several chloride ions are abstracted. In neutral water, it takes at least seven days for any fully hydrolysed species to occur that would oligomerise and be removed from the equilibrium by precipitation. The position of this equilibrium is shifting continuously both with the concentration of MBTCl in water and with the concentration of hydrochloric acid, i.e. the concentration of additional chloride ions. This indicates that formation of one or several individual distinct species from MBTCl in the presence of neutral water is slow under the conditions observed in this study and is too slow to be observed under same conditions in acidic solution. 

The results of this study are providing a basis to justify an in vivo testing protocol where live mice were being fed MBTCl with a digestible vehicle for resorption through the gastrointestinal tract. The results of the present study show that it is reasonable to assume that MBTCl will survive exposure to water and gastric acid on the timeframe that is relevant for the testing scenario because gastric acid is composed of hydrochloric acid at concentrations between 0.1 mol/L and 1 mol/L, depending on species. Therefore, MBTCl will reach the organ where resorption takes place intact.

Description of key information

Kleinmaier and Heitmann (2018)

The integrated interpretation of the experiments conducted throughout this study combines findings from solutions of MBTCl in inert solvent (CDCl3) as well as in strongly interacting solvents D2O and DCl/D2O to make a statement about the stability of MBTCl against irreversible hydrolytic attack by water molecules.

This study finds no indication that such an irreversible hydrolysis occurs on a timeframe of one to six days upon dissolution of MBTCl in neutral water, mildly or strongly acidic aqueous solutions of hydrochloric acid in water. After more than six days, precipitates form in neutral water, but the same is not observed in acidic solution. The experimental data provide support to the assumption that in these solutions an equilibrium exists between strong complexes of water with MBTCl and chemical species where one or several chloride ions are abstracted. In neutral water, it takes at least seven days for any fully hydrolysed species to occur that would oligomerise and be removed from the equilibrium by precipitation. The position of this equilibrium is shifting continuously both with the concentration of MBTCl in water and with the concentration of hydrochloric acid, i.e. the concentration of additional chloride ions. This indicates that formation of one or several individual distinct species from MBTCl in the presence of neutral water is slow under the conditions observed in this study and is too slow to be observed under same conditions in acidic solution. 

 

Until very recently, the substance was indeed considered to be highly insoluble in water and to hydrolyse rapidly and as such the statement below had been submitted as a data waiver. As part of the ongoing CoRAP evaluation additional investigations are currently being conducted and studies are still ongoing. Anecdotal evidence suggests that the substance may be more soluble and stable than originally thought. Work is currently ongoing to clarify the properties of the substance and once the appropriate data are available and have been fully assessed, the CSR and the corresponding Key Information will be updated accordingly once all the relevant information on the behavior of the substance in the environment are available.

According to Annex XI section 2 of the Regulation EC 1907/2006; testing for a specific endpoint may be omitted, if it is technically not possible to conduct the study as a consequence of the properties of the substance. Furthermore, according to Annex VIII, section 9.2.2.1 column 2, the study does not need to be conducted if the substance is highly insoluble in water. A statement concerning the hydrolysis of the test substance as a function of pH was included in the physico-chemical testing battery by Baltussen (2010): “The test substance rapidly decomposes in contact with water forming a range of breakdown products. The test substance can only be analysed after derivatisation, but using derivatisation, a distinction between intact test substance and breakdown products can no longer be made, this is a prerequisite for the hydrolysis study. In addition, the expected water solubility is very low and at these low levels it is often difficult if not impossible to prevent adsorption of test substance to the vials or containers used” A hydrolysis as a function of pH study was deemed impossible due to the properties of the test material. This is supported by the results from the de Wolf (2005) study. References: -Baltussen E (2010) Baltussen E (2010) Determination of Physico-Chemical Properties of Monobutyltin Trichloride. NOTOX project no. 492798 - de Wolf, J.M. & Schilt, R. (2005) Abiotic degradation of butyltrichlorostannane (MBTC, CAS # 1118-46-3) according to OECD Test guideline 111 - a preliminary test (Tier 1) Report V6017

Key value for chemical safety assessment

Additional information

Kleinmaier and Heitmann (2018)

The stability of monobutyltin trichloride in aqueous media was investigated through experiments conducted by NMR spectrometry. The behaviour of aqueous solutions of MBTCl was investigated over time, at varying concentrations and in the presence of varying concentrations of hydrochloric acid.

As a starting point of the investigation, the spectral properties of MBTCl dissolved in an inert solvent, i.e. CDCl3, were investigated through spectral assignment of 1H and 13C resonances. Special attention was directed to the presence of pronounced satellite resonances caused by heteronuclear spin-spin coupling of both protons and carbons in the butyl chain to the central tin atom in those molecules where NMR-active nuclei of tin are present. Therefore, they are observed in both 1H and 13C spectra.

The integrated interpretation of the experiments conducted throughout this study combines findings from solutions of MBTCl in inert solvent (CDCl3) as well as in strongly interacting solvents D2O and DCl/D2O to make a statement about the stability of MBTCl against irreversible hydrolytic attack by water molecules.

This study finds no indication that such an irreversible hydrolysis occurs on a timeframe of one to six days upon dissolution of MBTCl in neutral water, mildly or strongly acidic aqueous solutions of hydrochloric acid in water. After more than six days, precipitates form in neutral water, but the same is not observed in acidic solution. The experimental data provide support to the assumption that in these solutions an equilibrium exists between strong complexes of water with MBTCl and chemical species where one or several chloride ions are abstracted. In neutral water, it takes at least seven days for any fully hydrolysed species to occur that would oligomerise and be removed from the equilibrium by precipitation. The position of this equilibrium is shifting continuously both with the concentration of MBTCl in water and with the concentration of hydrochloric acid, i.e. the concentration of additional chloride ions. This indicates that formation of one or several individual distinct species from MBTCl in the presence of neutral water is slow under the conditions observed in this study and is too slow to be observed under same conditions in acidic solution. 

The results of this study are providing a basis to justify an in vivo testing protocol where live mice were being fed MBTCl with a digestible vehicle for resorption through the gastrointestinal tract. The results of the present study show that it is reasonable to assume that MBTCl will survive exposure to water and gastric acid on the timeframe that is relevant for the testing scenario because gastric acid is composed of hydrochloric acid at concentrations between 0.1 mol/L and 1 mol/L, depending on species. Therefore, MBTCl will reach the organ where resorption takes place intact.