Evaluation on the reliability of the permeability coefficient (Kp) to assess the percutaneous penetration property of chemicals on the basis of Flynn's dataset.
Int Arch Occup Environ Health
; 91(4): 467-477, 2018 May.
Article
em En
| MEDLINE
| ID: mdl-29468312
ABSTRACT
PURPOSE:
The permeability coefficient (Kp) is often used for prediction of the dermal penetration of chemicals. Mathematical models have mostly been derived on Kp data basis. However, confusing Kp values are reported, questioning the general reliability of this parameter. In this study, we tested the plausibility of Kp values expressing the dermal penetration velocity (cm h-1) of chemicals on a larger dataset from literature.METHODS:
Kp was applied for the calculation of the time for penetration through skin membranes of defined thickness (tCrossSkin). Kp 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 Kp values. The data congruence was tested comparing Kp 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:
Kp data for 94 chemicals matched the inclusion criteria were evaluated. According to the Kp 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 Kp 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 Kp values to represent the dermal penetration velocity and supports general invalidity of the parameter for implementation in studies using skin membranes. The Kp should not be used to characterize the percutaneous penetration of chemicals or in risk assessment without verification.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Absorção Cutânea
/
Xenobióticos
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Int Arch Occup Environ Health
Ano de publicação:
2018
Tipo de documento:
Article