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NIOSH Home > Safety and Health Topics >Skin Exposures and Effects >Occupational & Environmental Exposures of Skin to Chemicals- 2005> Abstracts

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Abstract for Poster 43

 

 

The use of PIXE analysis to determine penetration and distribution within the skin of metals and ultra-fine particles. Method development using Titanium dioxide (TiO2) as a model

M. Lindberg*1, I. Anveden1, J. Pallon2, M. Garmer3
1Department of Occupational and Environmental Health, Stockholm, Sweden
2Division of Nuclear Physics, Department of Physics, Lund, Sweden, Division of Nuclear 3Physics, Department of Physics, Lund, Sweden

Background

Modern man is exposed to ultra-fine particles both in occupational settings and in daily life, e.g. through skin application of physical sun-screens containing TiO2. The size of such particles is in the range of 25-70 nm and it has been considered that particles of this size do not penetrate intact, normal skin. The development is in the direction of decreasing the particle size in e.g. sun-screens to increase the cosmetic properties of such products. According to the Cosmetic directive in European Union (EU) it is today allowed to use TiO2 in cosmetics and skin care products in concentrations up to 25 %. In a recently initiated EU funded research project “Quality of skin as a barrier to ultra-fine particles” (1) the question has been raised if and under what circumstances penetration can take place and if it does, what is the health risk. Can ultra-fine particles penetrate down to the viable part of epidermis if the skin barrier (stratum corneum) is disrupted due to harmful skin exposure or due to diseases such as eczema? The objective of this study was to determine the localisation of titanium in epidermis following skin exposure to TiO2 under occlusion for 24 hours. To mimic barrier disruption exposure was performed on normal skin, skin in persons with atopic eczema and on tape-stripped normal and atopic skin.

Methods

A 25 % TiO2 mixture in petrolatum was applied on the skin under occlusion for 24 hours using patch tests with Finn Chambers. Exposure was performed on intact and tape-stripped normal skin (n=4) and on intact and tape stripped skin in persons with atopic eczema (n=4). After removal of the patch tests the exposed skin was wiped clean and punch biopsies were taken and were snap frozen in liquid nitrogen and stored at – 70o C. A cryo-microtome was used to produce 16 mm thick sections. The sections were placed on a holder using tape and were freeze-dried for PIXE (proton induced X-ray emission) analysis. The analytic method for detection of titanium in thin human skin sections had been optimized in a pre-study. The concentration of the naturally occurring major elements phosphorus, chlorine, sulphur, calcium and potassium were determined together with titanium. Performing the analysis vertically across the epidermis and dermis enables the use of phosphorus and sulphur as internal standards as these elements have steep gradients, different from each other across epidermis. Sulphur concentration is high in stratum corneum whereas phosphorous is virtually absent in stratum corneum but high in stratum granulosum.

Results

Analysis of intact normal and atopic skin showed concentration profiles of calcium, phosphorous, sulphur and potassium across the skin compatible with previously published results. There was a high sulphur concentration in stratum corneum, decreasing in the viable epidermis and we could also demonstrate the normal phosphorous distribution with low values in stratum corneum and increasing concentration in stratum granulosum. Using sulphur and phosphorous concentration profiles as internal standards it was possible to locate the outer side of stratum corneum and the transition from stratum corneum to stratum granulosum and to relate titanium concentrations to this. Following application of TiO2 to intact normal and atopic skin we found titanium located outside (on the surface) of stratum corneum.

In the analysis of un-exposed tape-stripped normal and atopic skin we found a more narrow (thinner) sulphur peak corresponding to stratum corneum probably due to the removal of stratum corneum components by tape-stripping. In sections of the TiO2-exposed tape-stripped skin we found titanium located on the surface of stratum corneum. However, in some of the sections there was an overlap between the titanium and the phosphorous peaks not found in the sections from intact, non-stripped skin.

Conclusions

In the present study it was demonstrated that the PIXE-technique is a useful tool for analysis of penetration and local distribution of titanium in skin sections. The sensitivity of PIXE is better than 10 ppm, e.g. detection of trace elements is possible. The spatial resolution is better than 5 µm which allows the detection of different strata within epidermis. The technique can thus also be used for studies of skin penetration and local distribution of metal ions such as nickel, cobalt and chromium.

Using TiO2 as a model for ultra-fine particle we found that if the barrier (stratum corneum) is disrupted there is a theoretical possibility that TiO2 can be distributed in viable parts of epidermis following application to the skin surface. This is an important finding further studied in the framework of the NANODERM-project.

References

NANODERM, QLK4-CT-2002-02678, http://www.uni-leipzig.de/~nanoderm

 

Content last modified: 18 May 2005

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