An OECD TG 428 study ring trial with 14C-Caffeine demonstrating repeatability and robustness of the dermal absorption in vitro method

Regulatory Toxicology and Pharmacology, vol. 132, pp. 105184

Abstract

finite dose) was investigated in six laboratories under Good Laboratory Practice conditions using an OECD TG 428-compliant in vitro assay with flow-through cells and split-thickness human skin. Potential sources of variation were reduced by a standardized protocol, test item and skin source. Particularly, skin samples from same donors were distributed over two repeats and between labs in a non-random, stratified design. Very similar recovery was achieved in the various assay compartments between laboratories, repeats and donors, demonstrating that the assay can be robustly and reliably performed. The absorption in one laboratory was 5-fold higher than in the others. This did not clearly correlate with skin integrity parameters but might be associated with an accidental COVID-19 pandemic-related interruption in sample shipment. It is possible that other factors may affect dermal absorption variation not routinely assessed or considered in the current method. The mean receptor fluid recovery, potential absorption (recovery in receptor fluid and skin except tape strips 1 and 2) and mass balance of caffeine was 6.99%, 7.14% and 99.13%, respectively, across all and 3.87%, 3.96% and 99.00% in the subset of five laboratories.

Authors 21

1. Felix M. Kluxen
   Affiliation as printed

   ADAMA Deutschland GmbH, Cologne, Germany

2. Styliani Totti

   University of Surrey

   Affiliation as printed

   University of Surrey, Guildford, United Kingdom

3. Wilfred Maas Aachen Charles River Laboratories

   Charles River Laboratories (Netherlands)

   Affiliation as printed

   Charles River Laboratories, Den Bosch, the Netherlands

4. Frank Toner

   Charles River Laboratories (United Kingdom)

   Affiliation as printed

   Charles River Laboratories, Tranent, United Kingdom

5. Leanne Page

   Charles River Laboratories (United Kingdom)

   Affiliation as printed

   Charles River Laboratories, Tranent, United Kingdom

6. Kathryn Webbley

   Pharmaron (United Kingdom)

   Affiliation as printed

   Pharmaron, Rushden, United Kingdom

7. Rajendra M. Nagane
   Affiliation as printed

   Jai Research Foundation, Valvada, India

8. Robert T. Mingoia

   Corteva (United States)

   Affiliation as printed

   Corteva Agriscience, Newark, United States

9. Christine Whitfield

   Corteva (United States)

   Affiliation as printed

   Corteva Agriscience, Newark, United States

10. John S. Kendrick

    Corteva (United States)

    Affiliation as printed

    Corteva Agriscience, Indianapolis, United States

11. Claire Valentine
    Affiliation as printed

    Labcorp Drug Development, Harrogate, United Kingdom

12. Jeanne Bernal Dorange

    Eurofins (France)

    Affiliation as printed

    Eurofins Agroscience Services Chem SAS, Vergeze, France

13. Camille Egron

    Syngenta (Switzerland)

    Affiliation as printed

    Syngenta Crop Protection AG, Basel, Switzerland

14. Camille Imart

    Syngenta (Switzerland)

    Affiliation as printed

    Syngenta Crop Protection AG, Basel, Switzerland

15. Jeanne Y. Domoradzki

    Corteva (United States)

    Affiliation as printed

    Corteva Agriscience, Indianapolis, United States

16. Philip Fisher
    Affiliation as printed

    Bayer SAS, Bayer Crop Science, Sophia, Antipolis, France

17. Christine Lorez

    Syngenta (Switzerland)

    Affiliation as printed

    Syngenta Crop Protection AG, Basel, Switzerland

18. Steve McEuen

    FMC (United States)

    Affiliation as printed

    FMC Corporation, Philadelphia, PA, USA

19. Edgars Felkers
    Affiliation as printed

    ADAMA Deutschland GmbH, Cologne, Germany

20. Tao Chen

    University of Surrey

    Affiliation as printed

    University of Surrey, Guildford, United Kingdom

21. Christiane Wiemann
    Affiliation as printed

    BASF Österreich GmbH, Vienna, Austria. Electronic address: christiane.wiemann@basf.com