A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN®, EpiDerm™ and SkinEthic®, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.

Isotope shifts in dielectronic recombination spectra were studied for Li-like A Nd 57+ ions with A=142 and A=150. From the displacement of resonance positions energy shifts δE 142,150 (2s − 2p 1/2 ) = 40.2(3)(6) meV ((stat)(sys)) and δE 142,150 (2s − 2p 3/2 ) = 42.3(12)(20) meV of 2s − 2p j transitions were deduced. An evaluation of these values within a full QED treatment yields a change in the mean-square charge radius of 142,150 δ r 2 = -1.36(1)(3) fm 2 . The approach is conceptually new and combines the advantage of a simple atomic structure with high sensitivity to nuclear size.

Term energies for dielectronic-recombination Rydberg resonances below 0.07 eV are determined for Sc18+ with absolute accuracies below 0.0002 eV by electron collision spectroscopy in an ion storage ring, using the twin-electron-beam technique and a cryogenic photocathode. The lithiumlike 2s_{1/2}-2p_{3/2} transition energy for Z=21 is determined to 4.6 ppm, less than 1% of the few-body effects on radiative corrections. Features from the hyperfine structure of the 2s state could be resolved in the dielectronic-recombination spectrum.

Recent spectroscopic models of active galactic nuclei (AGN) have indicated that the recommended electronion recombination rate coefficients for iron ions with partially filled M-shells are incorrect in the temperature range where these ions form in photoionized plasmas. We have investigated this experimentally for Fe XIV forming Fe XIII. The recombination rate coefficient was measured employing the electron-ion merged beams method at the Heidelberg heavy-ion storage-ring TSR. The measured energy range of 0 − 260 eV encompassed all dielectronic recombination (DR) 1s 2 2s 2 2p 6 3l 3l ′ 3l ′′ nl ′′′ resonances associated with the 3p 1/2 → 3p 3/2 , 3s → 3p, 3p → 3d and 3s → 3d core excitations within the M-shell of the Fe XIV (1s 2 2s 2 2p 6 3s 2 3p) parent ion. This range also includes the 1s 2 2s 2 2p 6 3l 3l ′ 4l ′′ nl ′′′ resonances associated with 3s → 4l ′′ and 3p → 4l ′′ core excitations. We find that in the temperature range 2-14 eV, where Fe XIV is expected to form in a photoionized plasma, the Fe XIV recombination rate coefficient is orders of magnitude larger than previously calculated values.

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During the past decade, several validation studies have been conducted on in vitro methods for discriminating between skin irritating and non-irritating chemicals. The reconstructed human skin models, EpiDerm and EPISKIN, provided the most promising results. Based on experience of the similar performance of the two skin models, it was suggested that a common test protocol and prediction model should be developed for the prediction of skin irritation potential with the two models. When the EPISKIN protocol was applied with the EpiDerm model, an acceptable specificity (80%) was achieved, whereas the sensitivity (60%) was low. In 2003, the EPISKIN protocol was further refined by extending the post-incubation period following exposure to test chemicals. This extension and additional technical improvements to the EpiDerm protocol were evaluated with 19 chemicals from the prevalidation study. With the new test design, high sensitivity (80%) and specificity (78%) were obtained. The statistical probability for correct classifications was high, so the test was considered to be ready for formal validation. However, since test optimisation had been conducted with the same test chemicals as were used in the ECVAM prevalidation study, it was decided that the optimisation of the protocol had to be verified with a new set of chemicals. Thus, in the current study, 26 additional chemicals (10 rabbit irritants and 16 non-irritants), which had previously been selected and tested by L'ORΈAL with EPISKIN, were evaluated in three independent experiments with EpiDerm. With this unbalanced testing set, a specificity of 94%, and a sensitivity of 60% were obtained, while the positive and negative predictivity and accuracy remained almost unchanged (around 80%) in comparison to the in vivo rabbit data. Overall, 45 chemicals (20 irritants and 25 non-irritants) were tested according to the final protocol. The resulting high positive (82%) and negative predictive values (79%) confirmed the reliability (accuracy of 80%) of the improved test protocol of the EpiDerm model.

Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.

We have measured resonance strengths and energies for dielectronic recombination (DR) of Mg-like Fe xv forming Al-like Fe xiv via N ¼ 3 ! N 0 ¼ 3 core excitations in the electron-ion collision energy range 0Y45 eV. All measurements were carried out using the heavy-ion test storage ring at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. We have also carried out new multiconfiguration Breit-Pauli (MCBP) calculations using the AUTOSTRUCTURE code. For electron-ion collision energies P25 eV we find poor agreement between our experimental and theoretical resonance energies and strengths. From 25 to 42 eV we find good agreement between the two for resonance energies. But in this energy range the theoretical resonance strengths are %31% larger than the experimental results. This is larger than our estimated total experimental uncertainty in this energy range of AE26% (at a 90% confidence level). Above 42 eV the difference in the shape between the calculated and measured 3s3p( 1 P 1 )nl DR series limit we attribute partly to the nl dependence of the detection probabilities of high Rydberg states in the experiment. We have used our measurements, supplemented by our AUTOSTRUCTURE calculations, to produce a Maxwellian-averaged 3 ! 3 DR rate coefficient for Fe xv forming Fe xiv. The resulting rate coefficient is estimated to be accurate to better than AE29% (at a 90% confidence level) for k B T e ! 1 eV. At temperatures of k B T e % 2:5Y15 eV, where Fe xv is predicted to form in photoionized plasmas, significant discrepancies are found between our experimentally derived rate coefficient and previously published theoretical results. Our new MCBP plasma rate coefficient is 19%Y28% smaller than our experimental results over this temperature range.