Dibutyltin oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Objective of study:

other: to simulate the hydrolytic action by mammalian gastric contents and to determine if the tin-ligand bond breaks, leading to formation of the corresponding alkyltin chloride and release of the ligand.

Principles of method if other than guideline:

DBTO was tested under low pH (~1-2) conditions (0.07 N HCl) at 37 °C in order to simulate the hydrolytic action by mammalian gastric contents. The degree of hydroloysis for the test substance was studied by determination of the amount of DBTC formed after 0.5, 1, 2, and 4 hours, using GC-FPD.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyltin oxide

EC Number:

212-449-1

EC Name:

Dibutyltin oxide

Cas Number:

818-08-6

Molecular formula:

C8H18OSn

IUPAC Name:

dibutylstannanone

Details on test material:

- Name of test material (as cited in study report): Dibutyltin oxide (DBTO)
- Molecular formula (if other than submission substance): (C4H9)2SnO
- Molecular weight (if other than submission substance): 248.92
- Analytical purity: 99.2%
- Lot No: 1704

Radiolabelling:

no

Test animals

Species:

other: No species were used - simulated gastric hydrolysis

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

DBTO was tested under low pH (~1-2) conditions (0.07 N HCl) at 37 °C in order to simulate the hydrolytic action by mammalian gastric contents. The degree of hydroloysis for the test substance was studied by determination of the amount of DBTC formed after 0.5, 1, 2, and 4 hours, using GC-FPD.

Administration / exposure

Route of administration:

other: test to simulate mammalian gastric contents

Vehicle:

other: insoluble in solvent; 'diluted' by thoroughly mixing with 811.17 mg of lactose

Details on exposure:

No information available.

Duration and frequency of treatment / exposure:

No information available.

Doses / concentrations

Remarks:

Doses / Concentrations:
50 mg of DBTO/lactose mixture (0.199 mg/mg) was added to 1000 ml of 0.07 N HCl.

No. of animals per sex per dose / concentration:

No information available.

Control animals:

no

Positive control reference chemical:

No further information required.

Details on study design:

Into a series of 4 PTFE vessels, 50 mg (accurately weighed) of the DBTO/lactose mixture (0.199 mg/mg) was added to 1000 ml of 0.07 N HCl (already at 37 degrees Celsius). In this way, the concentration of DBTO in the final 0.07 N HCl solution was approximately 10 mg/L. The solution was stirred, and the temperature was maintained using an oven.

Details on dosing and sampling:

A sample was taken from one of the Teflon vessels after 0.2, 1, 2, and 4 hours. Once a vessel was sampled, no other sample was collected from that vessel. Experiments were performed in duplicate.

Statistics:

The percentage of hydrolyzed organotin test substance based on the DBTC measurement was calculated as follows: The total amount of DBTC in solution that can be formed upon complete hydrolysis of the test substance was approximately 12 mg/l (DBTO) was weighed and thus varied slightly per sample. This level was calculated using the following formula:

50 (mg) * 0.20 (mg/mg)/1000 ml * Mw(DBTC)/Mw(DBTO).

Results and discussion

Preliminary studies:

The mean percentage of hydrolysis of DBTO is summarized in Table 7 (see below). Under chemical conditions intended to simulate mammalian gastric contents, as described in this report, DBTO was hydrolyzed to a great extent. Approximately 80% hydrolysis to DBTC occurred in 2 hours and percent hydrolysis to DBTC in 4 hours was 87%. The half life of DBTO was 3.5 hours.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No information available.

Details on distribution in tissues:

No information available.

Details on excretion:

No information available.

Toxicokinetic parameters

Toxicokinetic parameters:

half-life 1st: 3.5 hours

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The percentage of hydrolyzed organotin test substance was determined. DBTC in solution can be formed upon complete hydrolysis of DBTO.

Any other information on results incl. tables

Table 7. Summary of the results of the simulated gastric hydrolysis of DBTO
Time	Mean percentage of hydrolysis (DBTC values) %
0.5	42.6
1	64.8
2	80.3
4	87.3

Applicant's summary and conclusion

Conclusions:

DBTO may be hydrolyzed to a great extent in simulated mammalian gastric contents.
Under chemical conditions intended to simulate mammalian gastric contents, for DBTO the percent hydrolysis was 87.3% and the half life was 3.5 hours.

Executive summary:

Dibutyltin oxide was tested under pH 1 -2 conditions (0.07 N HCl) at 37 degrees C in order to simulate the hydrolytic action by mammalian gastic contents. The hypothesis was that in the hydrochloric acid solution, the tin-ligand bond breaks, leading to formation of the corresponding alkyltin chloride and simultaneous liberation of the ligand. The degree of hydrolysis was tested by GC-FPD. Where possible, the ligand was also analyzed. The analytical approach to the individual ligands, maleate, laurate and oxide, was different due to the unique chemical properties of each. It was not possible to carry out the simulated gastic hydrolysis study for dioctyltin oxide. DBTO hydrolyzed to 87.3% after 4 hours, with a half-life at 3.5 hours.