g. during washing of the skin). To obtain a complete picture of the barrier integrity, an advanced integrity test would detect the continuum of barrier impairments and barrier defects may correlate with the absorption of the test compound through the very skin preparation. To address

the binary differentiation of human skin samples into valid and invalid, we compared the absorption results (AD and maxKp) of four test compounds (caffeine, testosterone, MCPA and MCPA-EHE) applied to excised or reconstructed human skin. The results were grouped by integrity Adriamycin clinical trial test classification (valid/invalid) according to the three standard tests TEER, TEWL and TWF operated at two cut-off levels. Mean values

for valid human skin samples sorted by TEWL or TWF were generally higher than means for invalid skin samples. The valid absorption results for 14C-caffeine and 14C-testosterone (Table 5 and Table 6) were in good accordance with absorption studies for (14C-) caffeine 56 ± 36 ∗ 10−5 cm h−1 (maxKp) and 30 ± 14% (AD) and (14C-) testosterone 41 ± 48 ∗ 10−5 cm h−1 selleck chemical (maxKp) and 20 ± 15% (AD) through human skin (van de Sandt et al., 2004). 29 out of 30 reconstructed human skin samples were identified as invalid by TEWL measurements, which was in accordance to obviously higher absorption values in comparison to excised human skin samples. Generally higher absorption through reconstructed human epidermis and reconstructed human full-thickness skin in comparison to native human skin and pig skin was reported previously (Ackermann et al., 2010 and Schäfer-Korting et al., 2008). The outlined observations confirm a meaningful differentiation of skin samples using integrity tests TEWL or TWF. However, some single skin samples with average permeability were identified as invalid and a few as valid which presented obvious

too high maxKp and AD values. Deterioration of the skin during the experiment just due to time or caused by detergent and manipulation during washing procedure can be reasons for false valid classifications (Buist et al., 2005). Such effects can tuclazepam only be considered and evaluated by concurrent or post-experimental integrity tests. Interestingly the EFSA “Guidance on Dermal Absorption” recommends to avoid post experimental integrity tests (EFSA Panel on Plant Protection Products and their Residues, 2012). Prevention of inappropriate skin rejection due to compound related barrier damages could be reasons for this recommendation. However, diminished barrier function of single skin preparations after an experiment may provide valuable information, for instance, hints for an inappropriate over-prediction of dermal absorption.