Titanium dioxide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

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

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Titanium dioxide

EC Number:

236-675-5

EC Name:

Titanium dioxide

Cas Number:

13463-67-7

Molecular formula:

O2Ti

IUPAC Name:

dioxotitanium

Test material form:

solid: nanoform

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: Pietrain-Deutsche Landrasse-Hybrid

Sex:

not specified

Details on test animals or test system 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 1cm² exposed skin at nominal doses of 4 mg/cm² for 24 hours corresponding to nominal doses of about 400 µg/cm² of zinc oxide or titanium dioxide or to nominal doses of 360 and 240 µg/cm² 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 spectroscopy (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 absorption

Percutaneous absorption 1

Dose:

10%

Parameter:

percentage

Absorption:

0 %

Remarks on result:

other: after 24 hours

Remarks:

T-Lite SF-S (TiO2) formulation

Percutaneous absorption 2

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.