Diisooctyl 2,2'-[(dioctylstannylene)bis(thio)]diacetate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 January 2016 to 05 April 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

(Non-GLP)

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The test material has been used as neat material, not as solution

GLP compliance:

no

Remarks:

(this is not a toxicological or ecotoxicological test)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

1 g (1.3 mMol) test item 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*7 mm stir bar at approx. 100 rpm.
The test at pH 1.2 was carried out at 37 °C
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 analyzed by 119Sn-NMR

Buffers:

Commercially available solutions purchased from VWR International GmbH
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:

Performing Tier 1 testing:

Tier 1 Testing (pH 1.2, 4.0, 7.0, 9.0):
1 g (1.3 mMol) test item 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*7 mm stir bar at approx. 100 rpm. The test was carried out at pH 1.2 and 37 °C

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 analyzed by 119Sn-NMR.

Tier 2 Testing (pH 1.2/37°C)
1 g (1.3 mMol) Test Item was added to 100 ml of 0.1 M hydrochloric acid that was preheated to 37 °C in an 250 ml Erlenmeyer flask with ground. For the initial time of the experiment (15 seconds), the reaction products were extracted with hexane immediately according to the below-described procedure. For longer exposure/hydrolysis times, the flask was closed with a stopper and heated in a heating cabinet for 1, 2, 4, 8, 24, and 48 hours at 37°C. The mixture was stirred by a magnetic stirrer using a 40*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 the 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 analyzed by 119Sn-NMR.

The experiments were run in duplicates.

Duration:

120 h

pH:

4

Temp.:

50 °C

Duration:

120 h

pH:

7

Temp.:

50 °C

Duration:

120 h

pH:

9

Temp.:

50 °C

Duration:

120 h

pH:

1.2

Temp.:

37 °C

Duration:

0.004 h

pH:

1.2

Temp.:

37 °C

Number of replicates:

The test at pH 1.2 have been run in duplicates for 0.004/1/2/4/8/24/48 hours

Transformation products:

yes

No.:

#1

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

Transformation product of the hydrolysis at low pH is dioctyltin chloro 2-ethylhexylmecaptoacetate
At pH 4 / 7 / 9 the substance was considered hyrolytically stable

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

1.2

Temp.:

37 °C

DT50:

< 1 min

Validity criteria fulfilled:

yes

Conclusions:

The study showed that DOTE at pH 9, 7 and 4 can be considered hydrolytically stable. After 5 days at 50 °C less than 10% DOTE was hydrolyzed (t 0.5 25°C > 1 year).
Under the simulated gastric conditions (0.1 M HCl / pH 1.2 / 37 °C) DOTE was hydrolyzed to DOTEC, its monochloride ester.
It can be concluded that DOTEC is the only metabolite of DOTE that was formed in the simulated mammalian gastric environment. No DOTC was formed under the conditions of this study.

Executive summary:

The study was performed to determine the hydrolysis of the test material as a function of pH, the study was performed in accordance with the standardised guideline OECD 111.

The study showed that DOTE is hydrolytically stable at pH 9, 7 and 4. After 5 days of hydrolysis at 50 °C less than 10% DOTE was hydrolyzed (t 0.5_25°C> 1 year).

Amount of hydrolyzed DOTE was increased at lower pH values from 1.85% at pH 9 to 5.33% at pH 7 and 7.01% at pH 4.

At the simulated gastric conditions (0.1 M HCl/pH 1.2 /37°C) 75% DOTE was hydrolyzed to it’s monochloride (DOTCE).

Hydrolysis of DOTE can be monitored by the decrease in the relative intensity of the respective 119Sn-NMR signal at 73.4 ppm and the increase of the DOTCE signal at 33.3 ppm. The sum of both intensities agrees well with DOTE signal intensity of the untreated test item.

DOTC could not be identified in any of the hydrolyzed DOTE samples atd_DOTC= 133 ppm using the 119Sn-NMR spectroscopy.Detection limit for DOTC has been experimentally found to be 0.5% w/w .It was shown that when spiked with DOTC, DOTE signal present in a partially hydrolyzed DOTE sample containing DOTCE, disappeared but still no peak characteristic to DOTC was detected. These results provide direct evidence that DOTC readily reacts with DOTE and forms DOTCE.

TOC analysis has been conducted to ensure completeness of the analysis and recover all organic carbon in aqueous phases including all possible water-soluble organotin substances and their breakdown components.The analyses detected some organic carbon content (from 1.4 to 4.2 % of the total available organic carbon) in the aqueous phases of the experiments. These traces of organic carbon could be attributed to 2-EHTG (a hydrolyzed ligand of DOTE) and its breakdown products EH and TGA. Therefore, it can be concluded that DOTCE is the only tin-containing metabolite of DOTE that is formed under the simulated mammalian gastric environment.

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read-across to structurally similar substance Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.

Reason / purpose for cross-reference:

read-across source

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

1.2

Temp.:

37 °C

DT50:

< 1 min

Description of key information

Read-across performed on structurally similar substance

The study showed that DOTE (CAS No 15571 -58 -1) is hydrolytically stable at pH 9, 7 and 4. After 5 days of hydrolysis at 50 °C less than 10% DOTE was hydrolyzed (t 0.5_25°C> 1 year).

Additional information

Read-across to structurally similar substance Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1).

The study was performed to determine the hydrolysis of the test material as a function of pH, the study was performed in accordance with the standardised guideline OECD 111.

The study showed that DOTE is hydrolytically stable at pH 9, 7 and 4. After 5 days of hydrolysis at 50 °C less than 10% DOTE was hydrolyzed (t 0.5_25°C> 1 year).

Amount of hydrolyzed DOTE was increased at lower pH values from 1.85% at pH 9 to 5.33% at pH 7 and 7.01% at pH 4.

At the simulated gastric conditions (0.1 M HCl/pH 1.2 /37°C) 75% DOTE was hydrolyzed to it’s monochloride (DOTCE).

Hydrolysis of DOTE can be monitored by the decrease in the relative intensity of the respective 119Sn-NMR signal at 73.4 ppm and the increase of the DOTCE signal at 33.3 ppm. The sum of both intensities agrees well with DOTE signal intensity of the untreated test item.

DOTC could not be identified in any of the hydrolyzed DOTE samples atd_DOTC= 133 ppm using the 119Sn-NMR spectroscopy.Detection limit for DOTC has been experimentally found to be 0.5% w/w .It was shown that when spiked with DOTC, DOTE signal present in a partially hydrolyzed DOTE sample containing DOTCE, disappeared but still no peak characteristic to DOTC was detected. These results provide direct evidence that DOTC readily reacts with DOTE and forms DOTCE.

TOC analysis has been conducted to ensure completeness of the analysis and recover all organic carbon in aqueous phases including all possible water-soluble organotin substances and their breakdown components.The analyses detected some organic carbon content (from 1.4 to 4.2 % of the total available organic carbon) in the aqueous phases of the experiments. These traces of organic carbon could be attributed to 2-EHTG (a hydrolyzed ligand of DOTE) and its breakdown products EH and TGA. Therefore, it can be concluded that DOTCE is the only tin-containing metabolite of DOTE that is formed under the simulated mammalian gastric environment.