Dioctyltin oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: guideline study, glp, impurities unknown

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD~,May 12, 198. (C (81) 30 Final )

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

di-n-octyltin dichloride

IUPAC Name:

di-n-octyltin dichloride

Test material form:

solid - liquid: suspension

Remarks:

migrated information: dispersion

Details on test material:

-

Radiolabelling:

yes

Remarks:

113Sn

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Duration and frequency of treatment / exposure:

single exposure; 72h

Doses / concentrations

Remarks:

Doses / Concentrations:
25 mg/kg bw

No. of animals per sex per dose / concentration:

5

Control animals:

no

Results and discussion

Preliminary studies:

not relevant

Main ADME results

Type:

distribution

Results:

see free text > Distribution under pharmacokinetics)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

t(1/2) = 3h

Details on distribution in tissues:

The proportions of concentrations (in ng DOTC-equivalents/g tissue) at 1 h post administration were as follows blood (1) < kidneys (1.7) < brain (2.6) < thymus {5.3) < liver (21.1), and at 24 h brain (1) < blood (2.9) < thymus {4,5) < kidneys {32.5} < liver (131.3). Relative to Plasma levels, the ranking at C_max was liver (58) kidneys {18} thymus (2.8} z brain (1.4) blood (1.3) Plasma (1.0).

Transfer into organs

Test no.:

#1

Transfer type:

secretion via gastric mucosa

Observation:

slight transfer

Details on excretion:

-

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

AUC: 67 h

Toxicokinetic parameters 2

Test no.:

#2

Toxicokinetic parameters:

Tmax: 13 h

Toxicokinetic parameters 3

Test no.:

#3

Toxicokinetic parameters:

other: half live absprption: 3h

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

monooctyltin

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

-

Any other information on results incl. tables

-

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
t(1/2) = 67 h; t_abs(1/2)=3h
low absorption ~ 1.2 %
temp. accum.in liver

Executive summary:

Most of the 113_Sn_DOTC was found in the liver, where at 1 h post administration 0.2 % and after 24 h 1.2 % of the initial dose was measured. The activity in liver did not decrease within 72 h, which was the same for the other organs; expect for brain, repeated once-a-day administrations would lead to considerable accumulation. The blood levels were comparatively low but still increasing up to the last measurement at 24 h. The evaluation of the time dependencies as e.g. DOTC showed a slight affinity to the corpuscular compartments of blond: the solid/liquid partition factor, calculated far three paints of measure, was about 2 and seemed to decrease slowly.