Chemische Penetrationsförderung und deren Relevanz für den Arbeitsplatz
MAK-Begründung
Bernd Roßbach1Rüdiger Bartsch2
Hans Drexler3
Manigé Fartasch4
Thomas Göen3
Julia Hiller3
Thomas Jäger5
Michael Bader5
Andrea Hartwig2 (Vorsitz der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft)
MAK Commission6
1 Institut für Arbeits-, Sozial- und Umweltmedizin, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Kilian-Weg, Geb. 308B, 55131 Mainz, Deutschland
2 Institut für Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut für Technologie (KIT), Adenauerring 20a, Geb. 50.41, 76131 Karlsruhe, Deutschland
3 Friedrich-Alexander-Universität Erlangen-Nürnberg, Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Henkestraße 9–11, 91054 Erlangen, Deutschland
4 Kaiserstraße 34, 53721 Siegburg, Deutschland
5 BASF SE, Corporate Health Management, Carl-Bosch-Straße 38, 67056 Ludwigshafen, Deutschland
6 Ständige Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Deutschland
7 Deutschland
8 Deutschland
9 Deutschland
Abstract
Dermal absorption is a major route of exposure to hazardous substances in the workplace and is subject to numerous influencing factors. For example, exposure to substances known as “chemical penetration enhancers” can facilitate the absorption of a substance through the skin. While this effect has long been utilised to improve the absorption of topically applied drugs, little is currently known about such influencing factors in the workplace. This study aimed to compile existing knowledge on chemical penetration enhancement through a literature review, and evaluate its significance for occupational health and safety when handling hazardous substances. Chemical penetration enhancement is underpinned by various mechanisms, such as structural changes to the stratum corneum (the primary skin barrier), an increase of solubility of the penetrating substance within the stratum corneum, or an increase of the effective substance concentration interacting with the skin barrier. Several effects may occur simultaneously and influence one another. Research into the development of transdermal therapeutic systems has identified several hundred substances with penetration-enhancing properties, which can be classified into a variety of chemical compound classes. These include well-known hazardous substances (e. g. solvents and solubilisers), as well as ingredients commonly found in cosmetics and products for skin protection, cleansing and care. However, it is difficult to make quantitative estimates as to the extent of penetration-enhancing effects even in this field due to combination effects (active ingredient to be delivered, penetration enhancer, co-formulants) and influencing factors (e. g. site and amount of application, condition of the skin). Compared to pharmaceutical active ingredients and cosmetics, the promotion of penetration is investigated less frequently in relation to workplace-relevant hazardous substances, mostly being limited to in-vitro studies on skin preparations. Here, the focus is on the possible effects of skin protection products (e. g. sun creams and insect repellents), for which there are also initial indications of potentially penetration-enhancing properties from field studies. From an occupational health and safety perspective, it would be useful to identify and label penetration-enhancing substances. However, due to the complexity of the underlying mechanisms and the large number of chemical penetration enhancers, quantitative predictions are particularly difficult to make. Deriving an algorithm, such as that used by the German Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (“MAK-Commission”) to evaluate the skin absorption of hazardous substances, is currently not possible for the property “penetration-enhancing”. From a preventive perspective, however, it seems sensible to take dermal co-exposures into account in a risk assessment. This should not be limited to typical hazardous substances, but should also include conditions that may promote penetration, such as the use of skin protection products or disinfectants, wet work and occlusion. Furthermore, within the framework of occupational health surveillance, determining internal exposure via human biomonitoring can provide valuable insights into relevant dermal uptake of hazardous substances, which may be further facilitated by penetration-enhancing substances or conditions.
