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Toxicological information

Basic toxicokinetics

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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:
other: OECD~,May 12, 198. (C (81) 30 Final )
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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:
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 parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
AUC: 67 h
Test no.:
#2
Toxicokinetic parameters:
Tmax: 13 h
Test no.:
#3
Toxicokinetic parameters:
other: half live absprption: 3h

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
monooctyltin

Bioaccessibility

Bioaccessibility 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.