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Analyzing dermal absorption data of chemicals

: Scholz, Roland

Naunyn-Schmiedebergs archives of pharmacology 387 (2014), Supplement 1, S.S86, A347
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <80, 2014, Hannover>
Zeitschriftenaufsatz, Konferenzbeitrag
Fraunhofer ITEM ()

Knowledge about the exposure to chemical substances forms an inevitable part of risk assessments and is as such required for many regulatory authorization processes. In the past, the focus was on inhalation and oral uptake; the dermal route was often disregarded. This might have been guided by the general assumption that skin provides a robust barrier to the external environment.
However, the skin forms a large surface for chemical exposure and thus, dermal absorption could be a crucial dimension that contributes to internal exposure. Penetration through skin is a complex process depending on very different factors such as 1) physicochemical properties of the test compound, 2) solvent/vehicle, 3) skin condition, 4) interactions between chemical and skin or metabolism in skin 5) test conditions (dose, area, duration, etc.). Thus, a general prediction on the basis of one single test might be misleading. In addition, measured endpoints differ with the used test system (in-vitro: steady-state flux and permeability coefficient, in-vivo: absorption rate in % of applied dose). Theoretical equations and models have been developed to describe transport of chemicals through the skin but so far they have limited acceptance.
Within the new EU legislations (e.g. BPD/BPR, PPP) the dermal exposure got enhanced attention and dermal exposure including absorption data has to be considered. If there is a lack of absorption data for biocides a skin absorption rate of 100% has to be used as default. This prediction assumes complete absorption of the total amount of the substance getting in contact to the skin surface independent of the load and duration which seems to be rather implausible.
Therefore, we gathered publicly available information e.g. from the EDETOX Database (1) and the eChemPortal (2) and built-up a separate database. This database should allow to match chemicals to certain absorption ranges and to identify common structural features which might trigger higher skin absorption. In addition information about concentration effects and other influencing factors can be extracted from this data pool.
As dermal absorption depends not only on substance inherent property, but also on the exposure situation, a reasonable prediction of dermal absorption requires consistent and comparable data from various exposure situations and can consequently be achieved by a comprehensive database.