Reaction mass of dodecyl 4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannaicosanoate and tetradecyl 4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannadocosanoate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

21 September 2016 to 07 November 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

no

Radiolabelling:

not specified

Analytical monitoring:

yes

Details on sampling:

Sample preparation: 370 µL/ 330 µL toluene-d8 (10 mg/mL CrAcAc)

Buffers:

pH 1.2: HCl 0.1 M
pH 4.0: HCl/NaCl/Citric acid
pH 7.0: Na2HPO4/NaH2PO4
pH 9.0: H3BO3/KCl/NaOH

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 250 mL Erlenmeyer flask with ground in stopper

HIGH PH TESTING (pH 4.0, 7.0, 9.0)
- The test material was used without a co-solvent or a detergent.
- 1 g (1.1 mMol) of the test material was added to 100 mL of the respective buffer solution in a 250 mL Erlenmeyer flask.
- The flask was closed with a stopper and heated in a heating cabinet for 5 days (120 hours) at 50 °C.
- The mixture was stirred by a magnetic stirrer using a 40 x 7 mm stir bar at approx. 100 rpm.
- After the pre-determined reaction time, the solution was allowed to cool down to room temperature; 10 mL of each reaction mixture was taken by a syringe and placed in a headspace glass for TOC analysis. The rest of each reaction mixture was extracted with 20 mL hexane, the phases were separated using a separatory funnel. The organic phase was transferred into a pre-weighed flask and the solvent was removed in a rotary evaporator (< 40°C, 10 mbar). The weight difference was recorded for the mass balance, and the samples were analysed by 119Sn-NMR.

GASTRIC PH TESTING (pH 1.2/ 37 °C)
- The test material was used without a co-solvent or a detergent.
- 1 g (1.1 mMol) of the test material was added to 100 mL of 0.1 M aqueous solution of hydrochloric acid that was preheated to 37 °C in a 250 mL Erlenmeyer flask with ground in stopper.
- The flask was closed with a stopper and heated in a heating cabinet for 4 hours at 37 °C.
- The mixture was stirred by a magnetic stirrer using a 40 x 7 mm stir bar at approximately 100 rpm.
- After the pre-determined exposure time, the solution was allowed to cool down to room temperature; extracted 2 times with 25 mL hexane; the phases were separated using a separatory funnel. The organic phase was transferred into flask, and the solvent was removed in a rotary evaporator (<40 °C, 10 mbar). The sample was analysed by 119Sn-NMR.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

100 other: %

Remarks:

The test material was used without a solvent

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

100 other: %

Remarks:

The test material was used without a solvent

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

100 other: %

Remarks:

The test material was used without a solvent

Duration:

4 h

pH:

1.2

Temp.:

37 °C

Initial conc. measured:

100 other: %

Remarks:

The test material was used without a solvent

Number of replicates:

1

Positive controls:

no

Negative controls:

no

Transformation products:

yes

Remarks:

Dioctyltin chloro lauryl-myristyl thioglycolate (DOTC-LMTG) the monochloroester of the test material.

% Recovery:

99

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

98

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

91

pH:

9

Temp.:

50 °C

Duration:

5 d

% Recovery:

98

pH:

1.2

Temp.:

37 °C

Duration:

4 h

Key result

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

at pH 4 and 7

Details on results:

HYDROLYSIS AT pH 4, 7 AND 9
- The unhydrolysed test material was characterised by a single signal at 76 ppm. Although the test material is composed of two constituents, the difference in the alkylchains of the ligands does not influence the chemical shift of the central tin-atom.
- At pH 4 and 7 the 119Sn-NMR spectra was not different compared to the unhydrolised test material.
- The pH 9 spectrum of the extracted hydrolysate shows a significant decrease of the product peak at 76 ppm (10 Mol%) and a sharp peak appears at -45 ppm (90Mol%)
- -45 ppm is a characteristic chemical shift for DOTTG, which can be formed by initial hydrolysis of one ligand and and a subsequent nucleophilic attack of the ester function of the second thioglycolate ligand leading to a ring closure to DOTTG.


HYDROLYSIS AT pH 1.2
- The 119Sn-NMR spectrum of the organic extract the substance signal decreased to 27 Mol% in intensity.
- An additional broad peak appeared at 32 ppm (72 Mol%).
- The new peak can be attributed to the dioctyltin chloro lauryl-myristyl thioglycolate (DOTC-LMTG) the monochloroester of the test material. This hydrolytical behaviour is well known from other dialkyltin thioglycolates.
- No DOTC was formed under the conditions of the study

MASS BALANCE RECOVERY RATES
pH 4: 99 %
pH 7: 98 %
pH 9: 91 %
pH 1.2: 98 %

ATOMIC ABSORPTION SPECTOMETRY
- The aqueous phase of the low pH hydrolysis has been analysed after extraction with hexane by AAS and contained < 5mg/L Sn. So the formation of an organotin substance better soluble in water than in hexane can be excluded.

Validity criteria fulfilled:

not specified

Conclusions:

The test material can be considered hydrolytically stable at pH 4 and 7. After 5 days of hydrolysis at 50 °C at pH 4 and 7 no reaction could be identified based on the 119Sn NMR spectra of the extracted hydrolysates.
At pH 9 under the same conditions the DOTTG formed was the only breakdown product.
Under simulated gastric conditions the test material was found to break down to its monochloroester, dioctyltin chloro laurylmyritylthioglycolate.
The formation of DOTC can be excluded.
The tin content in the aqueous phase of the hydrolysis remained under the detection limit of < 5 mg/L in AAS, thus the formation of a water soluble organotin species can be excluded.

Executive summary:

The hydrolysis of the test material as a function of pH was investigated in accordance with the standardised guidelines OECD 111 and EU Method C.7.

The stability of the test material was investigated at pH 4, 7 and 9 and pH 1.2 using NMR spectroscopy.

Under the conditions of the study, the test material was considered hydrolytically stable at pH 4 and 7. After 5 days of hydrolysis at 50 °C at pH 4 and 7 no reaction could be identified based on the 119Sn NMR spectra of the extracted hydrolysates.

At pH 9 under the same conditions DOTTG was formed and was considered to be the only breakdown product.

Under simulated gastric conditions the test material was found to break down to its monochloroester, dioctyltin chloro laurylmyritylthioglycolate.

The formation of DOTC can be excluded.

The tin content in the aqueous phase of the hydrolysis remained under the detection limit of < 5 mg/L in AAS, thus the formation of a water soluble organotin species can be excluded.

Description of key information

The test material can be considered hydrolytically stable at pH 4 and 7. After 5 days of hydrolysis at 50 °C at pH 4 and 7 no reaction could be identified based on the 119Sn NMR spectra of the extracted hydrolysates.

At pH 9 under the same conditions the DOTTG formed was considered to be the only breakdown product.

Under simulated gastric conditions the test material was found to break down to its monochloroester, dioctyltin chloro laurylmyritylthioglycolate.

The formation of DOTC can be excluded.

The tin content in the aqueous phase of the hydrolysis remained under the detection limit of < 5 mg/L in AAS, thus the formation of a water soluble organotin species can be excluded.

Additional information

The hydrolysis of the test material as a function of pH was investigated in accordance with the standardised guidelines OECD 111 and EU Method C.7. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

The stability of the test material was investigated at pH 4, 7 and 9 and pH 1.2 using NMR spectroscopy.

Under the conditions of the study, the test material was considered hydrolytically stable at pH 4 and 7. After 5 days of hydrolysis at 50 °C at pH 4 and 7 no reaction could be identified based on the 119Sn NMR spectra of the extracted hydrolysates.

At pH 9 under the same conditions DOTTG was formed and was considered to be the only breakdown product.

Under simulated gastric conditions the test material was found to break down to its monochloroester, dioctyltin chloro laurylmyritylthioglycolate.

The formation of DOTC can be excluded.

The tin content in the aqueous phase of the hydrolysis remained under the detection limit of < 5 mg/L in AAS, thus the formation of a water soluble organotin species can be excluded.