PURPOSE

The permeability coefficient (K) is often used for prediction of the dermal penetration of chemicals. Mathematical models have mostly been derived on K data basis. However, confusing K values are reported, questioning the general reliability of this parameter. In this study, we tested the plausibility of K values expressing the dermal penetration velocity (cm h) of chemicals on a larger dataset from literature.

METHODS

K was applied for the calculation of the time for penetration through skin membranes of defined thickness (t). K values were obtained from Flynn's dataset (1990), containing data determined mostly under similar experimental conditions using diffusion cells. Further skin penetration parameters, e.g., times at which the chemicals were firstly measured in the receptor phase, lag times, steady-state times, and exposure duration, where available, were related to K values. The data congruence was tested comparing K values from Flynn's dataset with those reported in the EDETOX database. Variables, which could bias the results, such as different experimental protocols and research groups were also considered.

RESULTS

K data for 94 chemicals matched the inclusion criteria were evaluated. According to the K values, 21 (22%) compounds would require longer than 100 h, and 20 (21%) further compounds longer than 10 h of exposure to penetrate skin membranes of ~ 0.01-2.5 mm thickness. Obviously, erroneous K were found in studies of almost all research groups in Flynn's database, indicating that neither the observer nor the experimental conditions alone biased the values.

CONCLUSIONS

Our evaluation demonstrates high implausibility of K values to represent the dermal penetration velocity and supports general invalidity of the parameter for implementation in studies using skin membranes. The K should not be used to characterize the percutaneous penetration of chemicals or in risk assessment without verification.