title: Human skin permeation of emerging mycotoxins (beauvericin and enniatins).
abstract: Currently, dermal exposure data of cyclic depsipeptide mycotoxins are completely absent. There is a lack of understanding about the local skin and systemic kinetics and effects, despite their widespread skin contact and intrinsic hazard. Therefore, we provide a quantitative characterisation of their dermal kinetics. The emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) were used as model compounds and their transdermal kinetics were quantitatively evaluated, using intact and damaged human skin in an in vitro Franz diffusion cell set-up and ultra high-performance liquid chromatography (UHPLC)-MS analytics. We demonstrated that all investigated mycotoxins are able to penetrate through the skin. ENN B showed the highest permeation (kp,v=9.44 × 10(-6) cm/h), whereas BEA showed the lowest (kp,v=2.35 × 10(-6) cm/h) and the other ENNs ranging in between. Combining these values with experimentally determined solubility data, Jmax values ranging from 0.02 to 0.35 μg/(cm(2) h) for intact skin and from 0.07 to 1.11 μg/(cm(2) h) for damaged skin were obtained. These were used to determine the daily dermal exposure (DDE) in a worst-case scenario. On the other hand, DDE's for a typical occupational scenario were calculated based on real-life mycotoxin concentrations for the industrial exposure of food-related workers. In the latter case, for contact with intact human skin, DDE's up to 0.0870 ng/(kg BW × day) for ENN A were calculated, whereas for impaired skin barrier this can even rise up to 0.3209 ng/(kg BW × day) for ENN B1. This knowledge is needed for the risk assessment after skin exposure of contaminated food, feed, indoor surfaces and airborne particles with mycotoxins.
authors.affiliation: Drug Quality and Registration (DruQuaR) Group, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Taevernier
authors.affiliation: Drug Quality and Registration (DruQuaR) Group, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Veryser
authors.affiliation: Department of Plastic and Reconstructive Surgery, University Hospital Ghent, De Pintelaan 185, Ghent, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Roche
authors.affiliation: Department of Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
authors.affiliation: Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Burvenich
authors.affiliation: Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Delesalle
authors.affiliation: Drug Quality and Registration (DruQuaR) Group, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
mesh_terms: D002851:Chromatography, High Pressure Liquid; D047630:Depsipeptides / Q000493:pharmacokinetics*; D006801:Humans; D013058:Mass Spectrometry; D009183:Mycotoxins / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*
chemical_list: D047630:Depsipeptides; D009183:Mycotoxins; C100264:enniatins; C004456:beauvericin