Modelling skin permeability in risk assessment––the future

Fitzpatrick, Dara; Corish, J.; Hayes, Brian

doi:10.1016/j.chemosphere.2003.11.051

Cited by 63 publications

(31 citation statements)

References 22 publications

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“…This principle is applied in recent mathematical models used to describe the dermal absorption through the stratum corneum [32,34,35]. The stratum corneum lipid matrix is viewed as a homogeneous medium surrounding keratinocytes where a substance diffuses from high to low concentration according to…”

Section: Fick's First Lawmentioning

confidence: 99%

See 1 more Smart Citation

Dermic diffusion and stratum corneum: A state of the art review of mathematical models

Couto

Fernandes

Cordeiro

et al. 2014

Journal of Controlled Release

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A B S T R A C TTransdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

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Section: Fick's First Lawmentioning

confidence: 99%

“…As previously mentioned, current mathematical models use the Fick's Law of diffusion to describe dermal absorption through the stratum corneum [32,34,35]. Chemicals, in the stratum corneum lipid matrix, diffuse from high to low concentration according to Fick's First Law.…”

Section: Hybrid Approach: First and Second Law Of Fickmentioning

confidence: 99%

Dermic diffusion and stratum corneum: A state of the art review of mathematical models

Couto

Fernandes

Cordeiro

et al. 2014

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…9 However QSARs of the Potts and Guy form continue to dominate the field and have been shown to perform as well as other more complex models, particularly when larger and more comprehensive data sets are treated. 10 Ultimately the quality of any QSAR, and hence its ability to produce accurate predictions is completely dependent on the quality of the data from which the relationship is developed. More specifically for the dermal permeation QSARs, the proper analysis and interpretation of the data obtained in the dermal permeation studies is a prerequisite for arriving at improved and especially mechanistically better founded QSARs.…”

Section: Introductionmentioning

confidence: 99%

Analysis, Interpretation, and Extrapolation of Dermal Permeation Data Using Diffusion-Based Mathematical Models

Krüse

Golden

Wilkinson

et al. 2007

Journal of Pharmaceutical Sciences

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“…These models are most often based on physicochemical properties related to partition coefficients between octanol and water, MW, and different measures of molecular volume and steric structures [55][56][57]. The original algorithm from 1992 based on the Flynn database has been revisited several times, but the overall r 2 values for the quantitative structure-activity relationship (QSAR) models related to percutaneous penetration seldom exceed 0.7 except when excluding specific outliers, in which case the r 2 value may approach 0.9.…”

Section: From Experimental Observations To the Real Worldmentioning

confidence: 99%

Percutaneous Penetration ‐ Methodological Considerations

Holmgaard

Benfeldt

Nielsen

2014

Basic Clin Pharma Tox

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Studies on percutaneous penetration are needed to assess the hazards after unintended occupational skin exposures to industrial products as well as the efficacy after intended consumer exposure to topically applied medicinal or cosmetic products. During recent decades, a number of methods have been developed to replace methods involving experimental animals. The results obtained from these methods are decided not only by the chemical or product tested, but to a significant degree also by the experimental set-up and decisions made by the investigator during the planning phase. The present MiniReview discusses some of the existing and well-known experimental in vitro and in vivo methods for studies of percutaneous penetration together with some more recent and promising methods. After this, some considerations and recommendations about advantages and limitations of the different methods and their relevance for the prediction of percutaneous penetration are given. Which method to prefer will depend on the product to be tested and the question asked. Regulatory guidelines exist for studies on percutaneous penetration, but researchers as well as regulatory bodies need to pay specific attention to the vehicles and solvents used in donor and sampling fluids so that it reflects in-use conditions as closely as possible. Based on available experimental data, mathematical models have been developed to aid predictions of skin penetration. The authors question the general use of the present mathematical models in hazard assessment, as they seem to ignore outliers among chemicals as well as the heterogeneity of skin barrier properties and skin conditions within the exposed populations. This MiniReview will discuss some of the existing and wellknown experimental in vitro and in vivo models together with some more recent and promising models and give some considerations and recommendations about advantages and limitations of the various models and their relevance for predictions of percutaneous penetration. An overview of the methodologies discussed can be found in table 1.Dermal exposure may be unintentional after environmental or occupational exposure or intentional after the use of topically applied medication or use of cosmetic products. In all cases, the assessment of the potential for percutaneous penetration or temporary deposition within the skin is an essential element in assessing risk as well as efficacy after dermal exposures.Decades of preventive efforts have decreased the inhalational exposures at work places. At the same time, topically applied pharmaceuticals are being used ever more often. Together, this has increased the relative importance of dermal exposures.Knowledge concerning percutaneous penetration and the potential to reach target sites closes the gap from exposure assessment and hazard identification to risk assessment. If a substance is unable to penetrate the stratum corneum (SC) or affect the skin barrier function in any way, then the need for further assessment of risk becomes less evide...

show abstract

Modelling skin permeability in risk assessment––the future

Cited by 63 publications

References 22 publications

Dermic diffusion and stratum corneum: A state of the art review of mathematical models

Dermic diffusion and stratum corneum: A state of the art review of mathematical models

Analysis, Interpretation, and Extrapolation of Dermal Permeation Data Using Diffusion-Based Mathematical Models

Percutaneous Penetration ‐ Methodological Considerations

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