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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

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:
No further information required.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dibutyltin dilaurate (DBTL)
- Molecular formula (if other than submission substance): (C4H9)2S(C12H23O2)2
- Molecular weight (if other than submission substance): 631.55
- Analytical purity: 98.2%
- Lot No: 0020
Radiolabelling:
no

Test animals

Species:
other: No species were used - simulated gastric hydrolysis
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
DBTL was tested under low pH (~1-2) conditions (0.07 N HCl) at 37 degrees Celsius in order to simulate they 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, uusing 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 ul of the stock solution of DBTL (5.15 mg/ml) was added to 25 ml of 0.07 N HCl.
No. of animals per sex per dose:
No information available.
Control animals:
no
Positive control:
No further information required.
Details on study design:
Into a series of 4 polypropylene vessels, 50 ul of the stock solution of DBTL (5.15 mg/ml) was added to 25 ml of 0.07 N HCl (already at 37 degrees Celsius). In this way, the concentration of DBTL in the final 0.07 N HCl solution was 10.31 mg/L. The solution was stirred for predetermined 37 degrees C, and the temperature was maintained using an oven.
Details on dosing and sampling:
A sample was taken from one of the Teflon vessels after 0.5, 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 4.96 mg/l. This level was calculated using the following formula:

50 (ul) * 5.15 (mg/ml)/25 ml * Mw(DBTC)/Mw(DBTL).

Results and discussion

Preliminary studies:
The mean percentage of hydrolysis of DBTL is summarized in Table 6 (see below). Under chemical conditions intended to simulate mammalian gastric contents, as described in this report, DBTL to DBTC was rapid. The percentage of hydrolysis was 87.8% after 2 hours. The half-life was < 0.5 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: <0.5 hours

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The percentage of hydrolyzed organotin test substance was determined. Most of the DBTL was hydrolyzed to DBTC in 2 hours.

Any other information on results incl. tables

Table 6: summary of the results of the simulated gastric hydrolysis

Time (h) Mean % of hydrolysis (DBTC values) (%) Mean % of hydrolysis (Lauric acid values) (%)
0.5 82.3 21.5
1 77.9 7.4
2 87.8 11.2
4 87.1 23.4

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: DBTL may be hydrolyzed to a great extent in simulated mammalian gastric contents
Under chemical conditions intended to simulate mammalian gastric contents, for DBTL the percent hydrolysis was 87.8% after two hours and the half life was < 0.5 hours.
Executive summary:

Dibutyltin laurate 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 hdrochloric 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 ligand was analysed by GC-MS. DBTL was hydrolysed to DBTC by 87.8% after 2 hours. The half-life was <0.5 hours.