Dihydro-2,2-dioctyl-6H-1,3,2-oxathiastannin-6-one

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was performed using a non pre-validated in vitro method. The method was designed in line with good scientific principles and reported to a sufficiently high standard to assess the quality of the data presented. As such the study was considered reliable with restriction.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Objective of study:

other: biotransformation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A series of hydrolysis tests were performed at low pH (~1-2 in 0.07 N HCl) at 55-60 °C (due to problems with the solubility of the test material) to simulate the mammalian gastric system. The rate and degree of hydrolysis were studied by analysing the amount of DOTC. The concentrations of the hydrolysis products were determined with gas chromatrography mass spectroscopy (GC-MS).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dioctyltin oxide

EC Number:

212-791-1

EC Name:

Dioctyltin oxide

Cas Number:

870-08-6

Molecular formula:

C16H34OSn

IUPAC Name:

Stannane, dioctyloxo-

Details on test material:

- Name of test material (as cited in study report): Dioctyltin oxide (DOTO)
- Storage condition of test material: In the dark at <-18 °C

Radiolabelling:

no

Test animals

Species:

other: Test material exposed to low pH to simulate gastric hydrolysis

Administration / exposure

Route of administration:

other: Test material was added to two different media

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

The actual times for the exposure of the test substance to the test media was not reported.

Doses / concentrations

Remarks:

Doses / Concentrations:
The mass of test substance added to the media was not reported

Results and discussion

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

The extraction of DOTC from 0.07 N HCl with dichloromethane yielded a recovery of less than 5 %, the procedure was found to be unsuitable. The additional verification experiments carried out to improve the method all yielded comparable results.
Several additional verification experiments were carried out to develop an improved method. Based collectively on prior knowledge of ecotoxicity testing on the substance and the observations in this study, the author concluded (with consultation with the sponsor) that DOTO would not sufficiently hydrolyse under gastric conditions. DOTO appeared to be relatively resistant to the simulated gastric hydrolysis.
Experiment:
A) Approximately 5 % hydrolysis of DOTO to DOTC occurred
B) Approximately 27 % hydrolysis of DOTO to DOTC occurred
C) Approximately 2 % hydrolysis of DOTO to DOTC occurred

During the course of the study it was found that the only way the test substance could be dissolved was hydrolysing to the acetate using acetic acid.
It was noted that the particle size of the test substance influenced the level of DOTC formed and was considered to be the cause of the high variability between replicates. Increased temperatures higher than 37 °C (up to 60 °C) increased the speed of hydrolysis.
The percentage of hydrolysis never exceeded 55 % and in most cases were considerably lower.
A gastric hydrolysis study on the test substance was found not to be possible.

Applicant's summary and conclusion

Conclusions:

No meaningful results were obtained, DOTO was extremely insoluble in the test system and only partially hydrolysed.
It was not possible to measure the hydrolysis of the test substance due to the difficulties presented with the analytical procedures and the physico-chemical properites of the test substance. It was concluded that DOTO would not fully hydrolyse in the test system.

Executive summary:

A series of hydrolysis tests were performed at low pH (~1-2 in 0.07 N HCl) at 55-60 °C (due to problems with the solubility of the test material) to simulate the mammalian gastric system. The rate and degree of hydrolysis were studied by analysing the amount of DOTC. The concentrations of the hydrolysis products were determined with gas chromatrography mass spectroscopy (GC-MS). Low recovery was noted, and several verification studies were performed in an attempt to improve the method used. It was not possible to measure the hydrolysis of the test substance due to the difficulties presented with the analytical procedures and the physico-chemical properites of the test substance. It was concluded that DOTO would not fully hydrolyse in the test system.