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Diss Factsheets

Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
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:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The percutaneous absorption of 113Sn-labelled ZK 21 955 through the intact abdominal skin was studied in vivo in baboons. Two male baboons (animal no. A89, 16.8 kg and no. A92 14.6 kg) were fixed lying on the back and 0.5 mL (=370 kBq) was applied to two areas of 25 cm² intact abdominal skin.
After 7 hours of exposure the unabsorbed substance on the surface of the skin was wiped off by swabs of cotton-wool and the stratum corneum removed by 20 strips of adhesive tape. Urine and faeced were collected up to 16 days after application. Radioactivity in swabs, horny layer strips and in excreta (urine and faeces) was determined by direct counting of an aliquot in the auto-gamma scintillation spectrometer (Type 5285, Mess. Packard, Illinois, USA).
GLP compliance:
yes
Remarks:
40 CFR Part 792

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(tributyltin) oxide
EC Number:
200-268-0
EC Name:
Bis(tributyltin) oxide
Cas Number:
56-35-9
Molecular formula:
C24H54OSn2
IUPAC Name:
tributyl[(tributylstannyl)oxy]stannane
Details on test material:
- Name of test material : Tributyltin oxide (TBTO)
- Locations of the label (if radiolabelling): (n-C4H9)3-Sn*-O-Sn*-(n-C4H9)3
Radiolabelling:
yes
Remarks:
113 Sn

Test animals

Species:
primate
Strain:
other: baboon
Sex:
male

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
7 hours
Doses:
0.5mL of radiolabled Sn TBTO on two 25 cm² area of abdominal skin (250 uL/25cm²); [NOTE - table indicates it was only 20 µl so some discrepancy between text and table.]
No. of animals per group:
2
Control animals:
no
Details on study design:
Baboons (2) were fixed lying on the back and 0.5 mL (~370 kBq) of 113SnZk21.955 was applied to two areas of 25 cm² on the intact abdominal skin. After 7 hours of exposure, the unabsorbed substance on the skin was wiped off by swabs of cotton-wool and the stratum corneum removed by 20 strips of adhesive tape. Urine and feces were collected up to 16 d after application. Radioactivity in swabs horny layer and in excreta were determined by direct counting of an aliquot in the auto gamma-scilntillation spectrometer.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
yes
Remarks:
within 3 days after application, severe inflammation of the skin accompanied by exsudation and partial separation of the epdiermis. Lesions were larger than area of application indicating that substance easily spreads over skin
Absorption in different matrices:
After 7 h,
~15.4% of the applied dose could be removed with cotto/wool swab
~17.5% of the applied dose was found in the horny layer; radioactivity within the stratum corneum decreased from most distal to proximal layers by approximately 1 deade; the horny layer works as a penetration barrier for TBTO
~8.9% of applied dose was eliminated within 16 d in the feces
~1.37% of the applied dose was exreted within 13 d in urine
Note: fecal to:urine excretion rate was similar in both animals but great variation in excretion rates was observed between them.
Animal 1 excretion half life was 3-3.5 d; Animal 2 excretion half life was~8 d
>90% of the absorbed dose was eliminated from animal 1 (~12% of the applied dose) (higher excretion rate)
~75% of the absorbed dose was eliminated from animal 1 (~7.5% of the applied dose)
Total recovery:
The poor total recoveryof radioactivity of < 50% may be mainly the result of incomplete remova of unabsorbed substance on the skin surface due to the extensive spreading of the substance beyond the marked site of application
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

Summary of recovery of radiolabel on the skin, in horny layer (strips), urine and feces

% of dose per skin area

Animal No. 1a 1b 2a 2b Mean

recovery from surface of skin 15.56 17.17 14.15 13.60 15.12

Horny layer of skin (sum of 20 strips) 19.37 18.90 14.52 17 17.45

Urine (half life) 1.45 (3.71) 1.29 (7.67) 1.37 (5.69)

Feces 10.55 (3.18) 6.22 (8.87) 8.39 (6.02)

Applicant's summary and conclusion

Conclusions:
Radiolabeled 113Sn tri-n-butyltin oxide was percutaneously aborobed (10-15%) after 7 h abdominal dermal application on baboons. Severe skin irritation was observed and spread beyond the site of application. The test material was removed from the body, with a half life ranging from 3 to 8 days.
Executive summary:

In a non-guideline study, after dermal application of undiluted 113Sn radiolabelled tri-n-butytin oxide (TBTO) to the intact abdominal skin of two baboons, severe skin reactions occurred and the substance spread beyond its marked site of application. Undiluted TBTO was percutaneously absorbed. Within and exposure time of 7 h, 10 -15% of the dose became systemically available. Absorbed TBTO is slowly removed from the body with half lives ranging from 3 to 8 days in baboons. Daily dermal contact could lead to an accumulation of substance in the body if similar excretion half-lives are anticipated in humans.