Registration Dossier

Toxicological information

Dermal absorption

Currently viewing:

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well-conducted and reported study

Data source

Reference
Reference Type:
publication
Title:
The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin.
Author:
Gamer, A.O.; et al.
Year:
2006
Bibliographic source:
Toxicology in Vitro 20, 301-307

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): titanium dioxide
No further details are given.
Radiolabelling:
no

Test animals

Species:
pig
Strain:
other: Pietrain-Deutsche Landrasse-Hybrid
Sex:
not specified
Details on test animals and environmental conditions:
not applicable

Administration / exposure

Type of coverage:
other: diffusion cell
Vehicle:
physiological saline
Duration of exposure:
up to 24 hours
Doses:
The test formulations were applied to 1cm^2 exposed skin at nominal doses of 4 mg/cm^2 for 24 hours corresponding to nominal doses of about 400 µg/cm^2 of zinc oxide or titanium dioxide or to nominal doses of 360 and 240 µg/cm^2 of zinc or titanium, respectively.
No. of animals per group:
The skin absorption studies were performed with three pigs per formulation, and the test formulations were applied to 8 (ZnO) or 3 (TiO2) skin preparations from each pig in a parallel experimental setup
Control animals:
no
Remarks:
in vitro testing
Details on study design:
no
Details on in vitro test system (if applicable):
Full thickness skin samples of visually intact skin from the lateral abdominal region of 5 months old pigs were dermatomed to a thickness of around 500 µm. The samples were mounted in modified Franz static dermal penetration cells consisting of an upper donor compartment and a lower receptor compartment with the external surface of the stratum corneum facing the donor chamber.
The receptor chambers were filled with approx. 4 ml of the receptor fluid and the cells were placed on a magnetic stirrer (32°C). Each skin sample was checked for integrity by measuring its electrical resistance with a LCR bridge prior testing.
Samples of receptor fluid were taken at various time intervals (3, 6, 12 and 24 hours) after application of the test formulation to the skin and retained for analysis. The skin was removed from the diffusion cell and put onto parafilm. Titanium was removed from the skin preparations by washing with sponge pieces dipped into soap solution, and subsequent tape stripping was used to remove titanium together with the superficial layers of the stratum corneum.
The pools of tape strips, the skin remaining after tape stripping, and all retained receptor fluid samples were acid-treated and analysed for titanium by atomic spactroscopy (AS). Depending on the concentration of the samples, inductively coupled plasma-atomic emission spectrometry or - mass spectrometry was applied for Ti analyses.

Results and discussion

Signs and symptoms of toxicity:
not examined
Remarks:
in vitro absorption was investigated
Dermal irritation:
not examined
Remarks:
in vitro absorption was investigated
Absorption in different matrices:
Reported results include full mass-balance (recovery 86-100%), tape stripping and epidermal and receptor medium analysis.
Absorbed dose (receptor ): 0%
Potentially absorbable dose (skin): 0.1-0.5 %
(excl. surface tape strippings)
Total recovery:
see table
Mean total recoveries of Ti ranged from 98% to 100% (T-Lite SF-S) and 86% to 93% (T-Lite SF) of the total Ti applied, respectively.
Percutaneous absorptionopen allclose all
Dose:
10%
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: after 24 hours
Remarks:
T-Lite SF-S (TiO2) formulation
Dose:
10%
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: after 24 hours
Remarks:
T-Lite SF (TiO2) formulation

Applicant's summary and conclusion

Conclusions:
Results show that the test substance was not able to penetrate porcine stratum corneum.