A key approach to harmonizing animal care and use standards throughout the world is through the application of knowledge gained from peers. A peer can be defined as one that is of equal standing with another, especially one belonging to the same societal group (Merriam-Webster dictionary) or, more specific to this discussion, a colleague who shares the same experiences or works in a similar field of science. Peer interactions occur at scientific meetings, through collaborations, through the publication of research data, and through institutional systems of review of animal care and use practices and procedures that encompass internal and/or external expertise. The dissemination of information derived from peers regarding current good standards of practice and refinements to existing procedures leads to a harmonization strategy that is grounded in quality science, considers ethical issues, and is performance-based.
We have proposed a cell transformation assay using the Bhas 42 cells (Bhas 42 CTA) as an in vitro method for predicting the carcinogenicity of chemicals. The Bhas 42 CTA consists of two assays: one is the initiation assay and the other is the promotion assay. An in-house study on Bhas 42 CTA had been performed using approximately a hundred test chemicals. In that study, seven chemicals induced the severe cell killing in the promotion assays and their promoting activities were unable to be evaluated. The aim of this study was to find the cause of severe cell killing that occasionally occurred in the promotion assay. We presumed that the severe cell killing was attributed to the failure of dose setting caused by the difference of treatment periods between the cell growth assay (for 3 days) and the promotion assay (for 10days). In this study, we compared the inhibition rates in the cell growth assays between the chemical treatments for 3 days and 10 days. For seven chemicals that had induced the severe cell killing in the promotion assays, a larger inhibition was caused by the treatment for 10 days than for 3 days. For the chemicals whose promotion assays had succeeded, the growth inhibition was similar between two treatment conditions. These results demonstrated that the severe cell killing in the promotion assays was attributed to the failure of dose setting arising from the difference of the period of chemical treatment between the cell growth assay for dose setting and the promotion assay.
Polydimethyl siloxane (PDMS) membrane has been widely used to evaluate the permeation of drugs, instead of human or animal skin, in screening for drug candidates for new transdermal drug delivery systems. However, PDMS membrane is not suitable for predicting the permeation of hydrophilic drugs, although human skin is permeable to hydrophilic drugs like mannitol. Thus, we aimed to prepare novel copolymer membranes which could be used for prediction of the skin permeability of hydrophilic drugs. We synthesized the copolymers by a radical polymerization technique using methyl methacrylate, glycidyl methacrylate and macro-azoinitiator with a polyoxyethylene chain for mimicking drug permeation behavior through human skin. Gel permeation chromatography, 1H-NMR, X-ray diffraction and thermal analysis were conducted to characterize the synthesized copolymers. Results suggested that artificial membranes changed the balance of hydrophilic and lipophilic properties depending on the copolymer composition. In vitro permeation studies of 9 model compounds having different lipophilicities were performed using the artificial membranes and excised human skin. The results suggest that the synthetic copolymer membranes can be useful as an alternative to predict human skin permeability of not only lipophilic drugs but also hydrophilic drugs during the development of transdermal drug delivery systems.