Tributyltin chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Similar to OECD 417 but with deviations. No GLP, but peer reviewed.

Data source

Reference

Reference Type:

publication

Title:

INTESTINAL UPTAKE SITE, ENTEROHEPATIC CIRCULATION, AND EXCRETION OF TETRA AND TRIALKYLTIN COMPOUNDS IN MAMMALS

Author:

Iwai et al

Year:

1982

Bibliographic source:

Journal of Toxicology and Environmental Health. 9: 41-49

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

See principles of method if other than guideline

Principles of method if other than guideline:

Main deviations:
- Not enough animals used.
- No information on feeding and housing conditions.
- Different vehicles used for different routes of entry.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tributyltin chloride

EC Number:

215-958-7

EC Name:

Tributyltin chloride

Cas Number:

1461-22-9

Molecular formula:

C12H27ClSn

IUPAC Name:

tributylstannanylium chloride

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Three male Wistar rats weighing 400-450 g were used for one group.

Administration / exposure

Route of administration:

other: Oral & subcutaneous

Vehicle:

other: Oral: sesame oil; subcutaneous: ethanol & saline (2:1)

Duration and frequency of treatment / exposure:

Oral: five times at 12 h intervals.
Subcutaneous: twice at a 2 h intervals.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

3 other: mg/kg

Remarks:

Oral

Doses / concentrations 2

Dose / conc.:

10 other: mg/kg

Remarks:

Oral

Doses / concentrations 3

Dose / conc.:

5 other: mg/kg

Remarks:

Subcutaneous

Doses / concentrations 4

Dose / conc.:

10 other: mg/kg

Remarks:

Subcutaneous

No. of animals per sex per dose / concentration:

3 rats.

Control animals:

yes, concurrent vehicle

Details on dosing and sampling:

Oral Doses of the test material (10 mg/kg each) dissolved in sesame oil were simultaneously administered orally to the rats five times at 12 h intervals. Another group of rats received simultaneously the test material (3 mg/kg each) dissolved in sesame oil at the same time intervals. Rats of the control group were given only sesame oil at these time intervals. Four hours after the last dose, all rats were sacrificed and the organs (gastrointestinal tract, liver, kidney, blood, and brain) were removed. The gastrointestinal tract was cut open and rinsed in succession with saline, 70 % ethanol, and 100 % ethanol to avoid contamination by the contents of the lumen. The small intestine was divided into duodenum for the upper fourth, ileum for the lower fourth, and jejunum for the rest.

Subcutaneous Doses of the test material (10 mg/kg each) dissolved in 2 mL ethanol and saline (2:1) solution were administered sc to three rats twice at a 2 h interval. Doses of the test material (5 mg/kg each) were administered to another group of rats in the same way. One hour after the last injection, the animals were sacrificed and their ogans [small intestine (contents of small intestine), liver, and blood] examined.

Faeces and Urine of Rats: Test material (l0 mg/kg each) dissolved in ethanol were administered sc to three rats. Test material (5 mg/kg each); dissolved in ethanol were administered to another three rats. Each group of rats, were housed in a separate metabolic cage. Faeces and urine were collected for 3d.

Results and discussion

Preliminary studies:

No data

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The main uptake sites in the small intestine were the ileum and the jejunum

Main ADME results 2

Type:

distribution

Results:

See figure 3

Main ADME results 3

Type:

excretion

Results:

The test material (5 mg/kg) administered sc were detected in higher concentrations in urine than in faeces. This result may be explained by the chemical properties of the test material, which are less susceptible to metabolism and more soluble in water.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The main uptake sites in the small intestine were the ileum and the jejunum.

Details on distribution in tissues:

When the test material was orally administered, their concentrations in the gastrointestinal tract increased in the order of jejunum, duodenum, and ileum.
A moderately high amount of TBT+ was found in the brain after oral administration of the test material.
When the test material was injected sc, TBT+ was recovered in the small intestine and contents of the lumen (Fig. 5).

Details on excretion:

The test material (5 mg/kg) administered sc were detected in higher concentrations in urine than in feces. This result may be explained by the chemical properties of the test material, which are less susceptible to metabolism and more soluble in water.

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

No data

Applicant's summary and conclusion

Conclusions:

The main uptake sites in the small intestine were the ileum and the jejunum.
When the test material was orally administered, their concentrations in the gastrointestinal tract increased in the order of jejunum, duodenum, and ileum.
A moderately high amount of TBT+ was found in the brain after oral administration of the test material. When the test material was injected sc, TBT+ was recovered in the small intestine and contents of the lumen.
The test material (5 mg/kg) administered sc were detected in higher concentrations in urine than in faeces. This result may be explained by the chemical properties of the test material, which are less susceptible to metabolism and more soluble in water.

Executive summary:

The intestinal uptake site, enterohepatic circulation, and excretion into faeces, and urine of alkyltins were investigated after oral and sc administration of the test material to rats. Assays of trialkyltins in biological materials were carried out by gas chromatography.

The main uptake sites in the small intestine were the ileum and jejunum for trialkyltins. When the test material was injected sc, TBT+ was recovered in the small intestine and contents of the lumen (Fig. 5). These facts suggest that trialkyltins are transported in the body through enterahepatic circulation.