To gain experience concerning the effect of formulation on the ISTD, additional experiments using ISTD in parallel to standard routine experiments without ISTD are feasible. If no data of intentionally damaged skin is available for setting a cut-off limit (as done in the current work, Fig. 2), routine data could be used to depict a frequency histogram and

use the 95th percentile threshold as previously done for TWF (Fasano et al., 2002 and Meidan and Roper, 2008). In conclusion the standard integrity tests TEER, TEWL and TWF are useful to distinguish between impaired and intact human skin samples prior to a dermal absorption experiment, if limit values of 10 g m−2 h−1, Buparlisib order 4.5 ∗ 10−3 cm h−1 and

2 kΩ, respectively, are applied. The application of one of these tests is recommended for routine experiments. Furthermore, adding an internal reference standard to the test compound allows a continuous assessment of the barrier functionality over the entire experimental period. Combining both, an effective and non-invasive pre-test like TEWL and the concept of ISTD could improve the quality of dermal absorption experiments in the future. However, the routine application of ISTD is hampered by the need of a historical dataset which is required to define thresholds of integrity and develop a general protocol. Katharina Guth, Eric Fabian, Robert Landsiedel and Ben van Ravenzwaay are employees of BASF SE – a chemical company which may use the described models in the development of commerical click here products. Transparency document. We would like to

thank Geoffrey Pigott for providing the test compounds MCPA and MCPA-2EHE as well as ingredients for the MCPA formulation. “
“Clearer understanding of the toxicological behavior of nanomaterials (NM) is emerging with an increasing number of studies utilizing in vitro methodologies for toxicological assessments ( Rodriguez-Yanez Ribose-5-phosphate isomerase et al., 2012 and Yang and Liu, 2012). Many of the assays utilize colorimetric and fluorimetric detection methods. One such assay, the resazurin assay is utilized to measure cell viability, based on the reduction of blue, non-fluorescent resazurin to pink, fluorescent resorufin by metabolically active cells ( O’Brien et al., 2000). The cellular reduction of resazurin occurs by metabolic enzymes located in the mitochondria, cytosol and the microsomal fractions ( De Fries and Mitsuhashi, 1995 and Gonzalez and Tarloff, 2001). The decrease in the magnitude of resazurin reduction below control levels indicates cytotoxicity (loss of cell viability). The test is simple, rapid, versatile, cost-effective and shows a high degree of correlation with cytotoxicity assessed by other methods, such as MTS ( Riss and Moravec, 2004).