Abstract #955 Board #336 Comparison of a new skin penetration system containing a toxicokinetic modul with Franz diffusion cells D. GERSTEL, I. HERBERZ, M. AKHIANI, S. MUELLER , H. WENCK, A. SCHEPKY* Beiersdorf AG, Toxicology, Hamburg, Germany*Correspondence/SOT Full Member: Andreas.Schepky@Beiersdorf.comIntroduction
Critical endpoints in in vitro testing of cosmetic ingredients are the
We could show that the recovery rates of caffeine and benzophenone-3
determination of the bioavailability of test substances in different skin
recorded by SPS are highly comparable to those in GDC. No significant
layers and the examination of the toxicokinetic profile. Skin penetration
studies are so far performed in Franz diffusion cells using pig skin1.
percutaneously, benzophenone-3 remained mainly on the surface
Unfortunately with these cells an automated toxicokinetic determination is
(Fig. 2 a, b). It is also possible to take samples from the receptor fluid
not receivable. To record a full toxicokinetic profile we developed a
automatically . Fig. 2 c shows a toxicokinetic profile of caffeine. One can
semiautomated skin penetration system (SPS) that collects samples from
see that the samples taken from different cells within the SPS are
the receptor fluid automatically. This skin exposure module is a prototype.
reproducible. Percutaneous penetration of caffeine is observable after a
We developed it on the basis of a penetration cell from VITROCELL®
Systems and tested it for comparability to Franz diffusion cells. Conclusion
To perform toxicokinetic studies, we developed the SPS with eight
In conclusion, the new SPS is highly comparable to glass diffusion cells.
parallel running diffusion cells. To substitute the glass diffusion cells with
We observed percutaneous penetration for caffeine after 7 h. Sampling
the SPS it is important to compare both systems in terms of performance
from the receptor fluid of different penetration cells within the SPS leads
Fig. 2 Comparison of the penetration of caffeine (a) and benzophenone-3 (b) in the skin
and reproducibility. Therefore we investigated the penetration of caffeine
penetration system (SPS) and glass diffusion cells (GDC) after 24h. Both assays are highly
to reproducible results. The SPS has the advantage that manual
and benzophenone-3 after 24 h through full-thickness pig skin using
comparable for hydrophilic and lipophilic substances. 16 skin discs from three pigs were used in
sampling from the receptor fluid is no longer necessary. Therefore one
each penetration assay. c) Recovery of caffeine in the receptor fluid in a time dependent manner.
normal glass diffusion cells (GDC) and the SPS (Fig. 1). In total 16 skin
can record a full toxicokinetic profile, even over night.
The toxicokinetic profile has been recorded with the SPS using 16 skin discs from two pigs. It
discs from 3 different pigs where investigated in each system. After
shows a good reproducibility between different diffusion cells within the SPS.
Currently we are refining the SPS in terms of liberation studies. This
successful comparison of the penetration we recorded a full toxicokinetic
means the determination of the liberation of a test substance from
profile of caffeine. Currently we are refining the SPS for liberation
different formulations could be tested semi automatically. Reference and Acknowledgement
1W. Diembeck, H. Beck, F. Benech-Kieffer, P. Courtellemont, J. Dupuis,
W. Lovell, M. Paye, J. Spengler, W. Steiling: Test guidelines for in vitro
assessment of dermal absorption and percutaneous penetration of
cosmetic ingredients. Food Chem Toxicol. 1999, 37(2-3):191-205.
The authors would like to acknowledge the contribution of VITROCELL®
Systems for support and construction of the SPS.
Fig. 1 Semiautomated skin penetration system (SPS) for toxicokinetic studies. a) Complete overview b) Inside view showing the experimental setup with syringes, Franz cells and storage vessels for
receptor fluid c) Enlargement of experimental setup showing HPLC vials, receptor fluid in- and outlet and integrated Franz diffusion cells.
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