The permeability barrier disruption by acetone treatment and TEWL measurements significantly correlated with the percutaneous absorption of the hydrophilic and lipophilic drugs sucrose, caffeine, and hydrocortisone. However acetone treatment did not alter the percutaneous penetration of the highly lipophilic compounds estradiol and progesterone, hence, suggesting that there is no correlation between TEWL and the percutaneous absorption of highly lipophilic compounds. The results imply the need to use both TEWL and drug lipophilicity to predict alterations in skin permeability.

Chilcott et al. (2002) investigated the relationship between TEWL and skin permeability to tritiated water (³H₂O) and the lipophilic sulfur mustard (³⁵SM) in vitro. No correlation was found between basal TEWL rates and the permeability of human epidermal membrane to ³H₂O (p = 0.72) or sulfur mustard (p = 0.74). Similarly, there was no correlation between TEWL rates and the ³H₂O permeability on full-thickness pig skin (p = 0.68). There was also no correlation between TEWL rates and ³H₂O permeability following up to 15 tape strips (p = 0.64) or up to four needle stick punctures (p = 0.13). Taken together these results from this experiment indicate that under these experimental circumstances (i.e., in vitro human and pig skin) TEWL cannot be used as a measure of the skin’s permeability to topically applied lipophilic or hydrophilic compounds.

Elkeeb et al. (2010) compared TEWL to the percutaneous absorption/flux rate of ³H₂O in in vitro dermatomed clinically healthy human cadaver skin using three different evaporimeters to measure TEWL. Measurements were taken at baseline (i.e., at the start of the experiment) and then again at several time points over 24 h. The evaporimeters included an open chamber evaporimeter A (TEWameter® TM 210 (Courage and Khazaka, Cologne, Germany)) and two closed chamber evaporimeters B (VapoMeter™ (Delfin Technologies, Kuopio, Finland)) and C (AquaFlux AF200, Biox Systems, Ltd, London, UK). Open chamber evaporimeters are open to the ambient air, while closed chamber evaporimeters are closed systems that are not open to the environment. There has been controversy over the years as to whether open and closed chamber evaporimeters are equivalent in given accurate and precise TEWL measurements TEWL. Baseline TEWL measurements with evaporimeters A (p = 0.04, r ²  = 0.34) and C (p = 0.00, r ²  = 0.50) correlated with the percutaneous absorption or flux rate of tritiated H₂O, while evaporimeter B showed no statistically significant correlation (p = 0.07, r ²  = 0.31). However, the pattern of changing TEWL values over 24 h was similar to that of the percutaneous absorption or tritiated water flux for all three evaporimeters A, B, and C (p = 0.04, r ²  = 0.34,). The reason why evaporimeter B showed no significant correlation for baseline TEWL measurement remains unknown. Elkeeb et al. (2010) state that the results of this experiment imply the validity of using both open and closed chamber evaporimeters in the evaluation of skin barrier function.

Atrux-Tallau et al. (2007) demonstrated significant correlation between TEWL and the percutaneous absorption of caffeine (a hydrophilic compound) during an ex vivo experiment on heat separated epidermis and dermatomed human skin (p < 0.001, r ²  = 0.88). Since caffeine is a hydrophilic compound and has a relatively small molecular weight of 194 Da, it was not surprising to the authors that the permeation behavior resembles that of tritiated water (22 Da).

Hui et al. (2012) investigated the correlation between TEWL and the percutaneous absorption of clonidine (a lipophilic compound) and ³H₂O (a hydrophilic compound) in in vitro human cadaver skin. The partition coefficient of clonidine is reported in Table 6.1. TEWL measurements were made with a closed chamber TEWL meter (AquaFlux AF200). With the goal of discerning the potential differences in the correlation between TEWL and lipophilic clonidine, the correlation between TEWL and hydrophilic ³H₂O percutaneous absorption and general differences in the percutaneous absorption of clonidine and ³H₂O, the flux rate, skin distribution, and total amount of absorption for clonidine and tritiated water were recorded and compared. Statistical analysis indicated that the baseline TEWL values weakly correlated with the flux of [14C]-clonidine (p < 0.03, r ²  = 0.36) and ³H₂O (r ²  = 0.34, p = 0.04). The correlation between fluxes of ³H₂O and [14C]-clonidine was moderate (correlation coefficient = 0.675, p < 0.001). In addition, TEWL and permeation data of ³H₂O expressed as a percent dose of the amount in the receptor fluid correlated well throughout the experiment. However, the permeation curve of [14C]-clonidine as a percent dose in the receptor fluid differed from that of ³H₂O and TEWL. The difference in the curves is likely secondary to differences in the hydrophilic/lipophilic properties of clonidine versus water. Therefore as Hui suggests, it may be necessary to combine the TEWL values with factors such as molecular weight and/or hydrophilicity/lipophilicity to gauge percutaneous absorption.

Elmahjoubi et al. (2009) investigated TEWL (using the AquaFlux evaporimeter) and the percutaneous absorption/flux of ³H₂O in full-thickness in vitro porcine skin both at baseline and after physical and chemical barrier disruption in multiple different experiments. The aim of these experiments was to further investigate the relationship between TEWL and ³H₂O flux using the AquaFlux evaporimeter® (Bio Systems Ltd, USA) and to evaluate the use of porcine skin in vitro as a model to study the human skin barrier.

The first experiment investigated the relationship between basal TEWL rates and ³H₂O flux in in vitro healthy full-thickness porcine skin. The results showed that basal TEWL values were linearly correlated with basal ³H₂O flux values (r ²  = 0.80, n = 63).

The second experiment examined the effect of physical barrier disruption with skin punctures on TEWL measurements. The results did not show a perfect correlation between skin punctures and TEWL measurements. TEWL increased significantly after the first skin puncture and then remained constant for punctures 2, 3, and 4. Another large increase in TEWL was seen with the fifth puncture. However no changes in TEWL values were seen with the sixth or seventh puncture suggesting that a threshold may have been reached after the fifth puncture.

The third and fourth experiments examined TEWL changes after chemical barrier disruption with surfactants. In the third experiment, anionic surfactants of differing alkyl chain lengths were applied to the full-thickness porcine skin in vitro to determine if measuring TEWL values could discern between mild and severe perturbations to the barrier function. TEWL was largely unaffected following cutaneous exposure to short and long alkyl chain surfactants and, however, was significantly elevated over control levels following exposure to those with intermediate chain lengths. Exposure to sodium lauryl sulfate (SLS), with an intermediate 12 carbon alkyl chain, produced the greatest increase in TEWL.

In the fourth experiment, the effect of varying SLS concentration, volume, and contact time on the TEWL in vitro in porcine skin was measured. The results showed a linear trend between TEWL and SLS concentration in the 0–1 % w/v concentration range. However, following treatment with 5 % w/v SLS, TEWL readings were only slightly higher than those following treatment with 1 % w/v surfactant. A linear correlation was also demonstrated between TEWL and surfactant solution volume (r ²  = 0.87), which was statistically significant (p < 0.01). TEWL also increased as a function of increasing SLS treatment time, when concentration was fixed at 1 % w/v and volume fixed at 200 μl.

In conclusion, Elmahjoubi et al. (2009) found that baseline TEWL values correlated with the percutaneous absorption of ³H₂O in vitro in healthy porcine skin and the TEWL measurements linearly correlated with the exposure of porcine skin in vitro to increasing concentrations, time, and volumes of SLS. TEWL measurements did not demonstrate a linear correlation between skin punctures (i.e., skin damage) and TEWL. The authors feel that TEWL measurements in vitro in porcine skin may serve as a model for future studies in this area in contrast to the previous findings by Chilcott et al. (2002).