Arch Dermatol Res (2007) 299:423–431 DOI 10.1007/s00403-007-0788-z 123 ORIGINAL PAPER Defense against dermal exposures is only skin deep: signiWcantly increased penetration through slightly damaged skin Jesper Bo Nielsen · Flemming Nielsen · Jens Ahm Sørensen Received: 15 March 2007 / Revised: 30 July 2007 / Accepted: 27 August 2007 / Published online: 20 September 2007  Springer-Verlag 2007 Abstract The OECD guideline for studies on percutane- ous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to diVerent medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline proce- dures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caVeine, benzoic acid, malathion) covering a range of solu- bilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin sig- niWcantly increases the permeability coeYcient (K p ) as well as total percutaneous penetration of chemicals, and most signiWcantly for those compounds that due to their physico- chemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only conWrms the proportionality between lipophilicity and potential for per- cutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the diVerent skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is aVected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This obser- vation may have implications when evaluating the possibil- ity of removing chemicals from the skin through diVerent cleansing procedures following unintended dermal exposures. Keywords Percutaneous penetration · In vitro · Damaged skin · Lipophilicity · Skin deposition Introduction Dermal exposure to chemicals occurs on a daily basis in most humans, intended as well as unintended. Intentional exposure may take place through the use of cosmetics and pharmaceuticals among which most chemicals are intended for systemic absorption whereas other chemicals are expected to remain on the outside or within the upper layers of the skin. Thus, in case of remedies against lice or fungus, the active ingredients in form of pesticides have their target site on top of the skin with no intention of systemic absorp- tion and distribution to systemic targets. However, systemic absorption may occur, and studies on dermal penetration are among the key studies when regulating topical use of such chemicals with a potential for systemic toxicity. Like- wise, rules and regulations, including skin notations, gov- erning the unintentional occupational dermal exposures depend on knowledge on dermal absorption. J. B. Nielsen (&) · F. Nielsen Environmental Medicine, University of Southern Denmark, Winsløwparken 17, 5000 Odense C, Denmark e-mail: jbnielsen@health.sdu.dk J. A. Sørensen Department of Plastic and Reconstructive Surgery, Odense University Hospital, Odense C, Denmark