Diisotridecyl 3,3'-[(dibutylstannylene)bis(thio)]dipropionate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

In-vitro metabolism as part of a OECD 111 type study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27.10-27.11.2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

not under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 111 (Hydrolysis as function of pH)

Deviations:

yes

Remarks:

The poorly soluable neat material was added without co-solvent to the buffer solutions

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diisotridecyl 3,3'-[(dibutylstannylene)bis(thio)]dipropionate

EC Number:

284-461-5

EC Name:

Diisotridecyl 3,3'-[(dibutylstannylene)bis(thio)]dipropionate

Cas Number:

84896-44-6

Molecular formula:

C40H80O4S2Sn

IUPAC Name:

2-methyldodecyl 3-{[dibutyl({3-[(2-methyldodecyl)oxy]-3-oxopropyl}sulfanyl)stannyl]sulfanyl}propanoate

Test material form:

other: liquid

Radiolabelling:

no

Administration / exposure

Details on study design:

yes
Details on sampling
the respective reaction mixtures were extracted with hexan after pre defined times. The solvent was
removed and analysed by 119Sn NMR
aqueous phase were analysed for tin content by AAS
Details on analytical methods
119-Sn-NMR for hexan solubla fraction
AAS fot tin content in aqueous phase
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 item was incubated at pH 4 / 7 / 9 for 150 h at 50 °C resp at pH 1.2 for 150 h at 37 °C
At pH 1.2 / 37 °C the test item was incubated for 30 seconds, 30 minutes, 1, 2, 4, 8 hours
Number of replicates
The tests at low pH were run in duplicate

Results and discussion

Preliminary studies:

DBT-MPTD Hydrolysis at pH 1.2
A sample of the test item was added to an excess 0.1 M Hydrochloric Acid at 37 °C for 5 days (120
h). The 119Sn-NMR spectrum of the recovered reaction product showed that DBT-MPTD is hydrolyz
ed to DBTC-MPTD. Both substances were present in an equilibrium in a 15/85 DBT-MPTD / DBTCMPTD
mol. % ratio.
DBTC-MPTD, the product of hydrolysis, has been identified based on the 119 Sn-NMR signal. Pure
DBTC-MPTD substance was synthesized separately.
No signal corresponding to DBTC (typically present at 130 ppm) was detected.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Dibutyltin monochloro isotridecylmercaptopropionate / Dibutyltin tridecyl 3-mercaptopropionate
chloride was found as the only metabolite of the exposure to 0.1 M HCl in an equiibrium with the unreacted test item

Any other information on results incl. tables

Tier 1 Testing:

Hydrolysis at pH 4.0, 7.0, and 9.0:

Samples of the test item were added to the respective buffer solutions at 50 °C for 5 days (120 h). Th

e 119Sn-NMR spectra of the reaction products (Annex 2) show only slight signs of hydrolysis. The NM

R peak characteristic to the DBT-MPDT molecule at about 120 ppm decreased from 99 Mol% in the

untreated staring material to a minimal value of 90.7 Mol% in the pH 4 buffer solution. In all cases the

degree of hydrolysis was lower than 10 %. Thus, the higher tier testing was not considered for these

pH-value buffers.

DBT-MPTD Hydrolysis at pH 1.2

A sample of the test item was added to an excess 0.1 M Hydrochloric Acid at 37 °C for 5 days (120

h). The 119Sn-NMR spectrum of the recovered reaction product showed that DBT-MPTD is hydrolyz

ed to DBTC-MPTD. Both substances were present in an equilibrium in a 15/85 DBT-MPTD / DBTCMPTD

mol. % ratio.

DBTC-MPTD, the product of hydrolysis, has been identified based on the 119 Sn-NMR signal. Pure

DBTC-MPTD substance was synthesized separately.

No signal corresponding to DBTC (typically present at 130 ppm) was detected.

Tier 2 testing at pH 1.2

Additional 1 g (1.2 mmol) samples of the test item were hydrolyzed over 6 different time periods (from

30 seconds to 8 hours) in an excess of 0.1 M Hydrochloric Acid at 37 °C. The recorded 119Sn-NMR

spectra detected DBTC-MPTD (# ~ 71 ppm) as the only product of DBT-MPTD hydrolysis.

Kinetics of the hydrolysis was studied measuring intensities of the NMR-signals for DBT-MPTD and

DBTC-MPTD. The sum of both signal intensities remains constant The kinetics of the first and the

second test series were nearly identical so following the average of both test series are used.

After 30 seconds of contact with the preheated buffer (an aqueous solution of hydrochloric acid), the

test item was worked up immediately. The 119Sn-NMR showed that the DBT-MPTD signal was r

educed by about 60 % of its initial signal intensity. Conversion of DBT-MPTD continued during 30

minutes of hydrolysis to about 20 % of the initial signal intensity, whereas the DBTC-MPTD signal in

creased proportionally at the same rate.

The rate of hydrolysis remained constant – with slight variation – at ~ 20 % of DBT-MPTD between 1

and 8 hours of incubation. The long term incubation from Tier 1 resulted in a 15 % DBT-MPTD / 85

% DBTC-MPTD equlibribrium..

Applicant's summary and conclusion

Conclusions:

The study showed that DBT-MPTD at pH 9, 7 and 4 can be considered hydrolytically stable. After 5
days at 50 °C less than 10% DBT-MPTD was hydrolyzed (t 0.5 25°C > 1 year).

Under the simulated gastric conditions (0.1 M HCl / pH 1.2 / 37 °C) DBT-MPTD was hydrolyzed to
DBTC-MPTD, its monochloro ester.
It can be concluded that DBTC-MPTD is the only metabolite of DBT-MPTD that was formed in the si
mulated mammalian gastric environment.

No DBTC was formed under the conditions of this study.

Executive summary:

The study showed that DBT-MPTD is hydrolytically stable at pH 9, 7 and 4. After 5 days of hydrolysis

at 50 °C less than 10% DBT-MPTD was hydrolyzed (t 0.525°C> 1 year).

At the simulated gastric conditions (0.1 M HCl/pH 1.2 /37°C) 75% DBT-MPTD was hydrolyzed to it’s

monochloride DBTC-MPTD

No formation of DBTC was detected under the conditions of the study.

Hydrolysis of DBT-MPTD can be monitored by the decrease in the relative intensity of the respective

119Sn-NMR signal at ~ 120 ppm and the increase of the DBTC-MPTD signal at ~ 71 ppm. The sum of

both intensities agrees well with DBT-MPTD signal intensity of the untreated test item.

DBTC could not be identified in any of the hydrolyzed DBT-MPTD samples atdDBTC= 130 ppm using

the 119Sn-NMR spectroscopy.

A comparable result for Dioctyltin bis-2-ethylhexyl mercaptoacetate (DOTE) is described in literature for

the fate of DOTE in PVC [6]

AAS analysis has been conducted to ensure completeness of the analysis and recover all tin compounds

in aqueous phases including all possible water-soluble organotin substances and their breakdown

components.

The analyses detected tin in amounts of 25-40 ppm, which demonstrates that only traces of the water

soluble tin compounds remain in the aqueous phase.

This is consistent with the high, nearly quantitative, recovery rates found in all experiments.

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