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Human skin permeation of emerging mycotoxins (beauvericin and enniatins)

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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/(cm2 h) for intact skin and from 0.07 to 1.11 μg/(cm2 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.
Keywords
dermal risk assessment, enniatins, IN-VITRO, CACO-2 CELLS, DENDRITIC CELLS, cyclic depsipeptides, beauvericin, human skin transdermal permeation, mycotoxins, FUNGUS VERTICILLIUM-HEMIPTERIGENUM, PRECURSOR-DIRECTED BIOSYNTHESIS, FUSARIUM-MYCOTOXINS, TRANSDERMAL ABSORPTION, CANCER-CELLS, TAT PEPTIDE, T-2 TOXIN

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Chicago
Taevernier, Lien, Lieselotte Veryser, Nathalie Roche, Kathelijne Peremans, Christian Burvenich, Catherine Delesalle, and Bart De Spiegeleer. 2016. “Human Skin Permeation of Emerging Mycotoxins (beauvericin and Enniatins).” Journal of Exposure Science and Environmental Epidemiology 26 (3): 277–287.
APA
Taevernier, L., Veryser, L., Roche, N., Peremans, K., Burvenich, C., Delesalle, C., & De Spiegeleer, B. (2016). Human skin permeation of emerging mycotoxins (beauvericin and enniatins). JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY, 26(3), 277–287.
Vancouver
1.
Taevernier L, Veryser L, Roche N, Peremans K, Burvenich C, Delesalle C, et al. Human skin permeation of emerging mycotoxins (beauvericin and enniatins). JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY. 2016;26(3):277–87.
MLA
Taevernier, Lien, Lieselotte Veryser, Nathalie Roche, et al. “Human Skin Permeation of Emerging Mycotoxins (beauvericin and Enniatins).” JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 26.3 (2016): 277–287. Print.
@article{5846537,
  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 {\texttimes} 10\ensuremath{-}6\,cm/h), whereas BEA showed the lowest (kp,v=2.35 {\texttimes} 10\ensuremath{-}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\,\ensuremath{\mu}g/(cm2\,h) for intact skin and from 0.07 to 1.11\,\ensuremath{\mu}g/(cm2\,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{\textquoteright}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{\textquoteright}s up to 0.0870\,ng/(kg BW {\texttimes} day) for ENN A were calculated, whereas for impaired skin barrier this can even rise up to 0.3209 ng/(kg BW {\texttimes} 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.},
  author       = {Taevernier, Lien and Veryser, Lieselotte and Roche, Nathalie and Peremans, Kathelijne and Burvenich, Christian and Delesalle, Catherine and De Spiegeleer, Bart},
  issn         = {1559-0631},
  journal      = {JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY},
  keyword      = {dermal risk assessment,enniatins,IN-VITRO,CACO-2 CELLS,DENDRITIC CELLS,cyclic depsipeptides,beauvericin,human skin transdermal permeation,mycotoxins,FUNGUS VERTICILLIUM-HEMIPTERIGENUM,PRECURSOR-DIRECTED BIOSYNTHESIS,FUSARIUM-MYCOTOXINS,TRANSDERMAL ABSORPTION,CANCER-CELLS,TAT PEPTIDE,T-2 TOXIN},
  language     = {eng},
  number       = {3},
  pages        = {277--287},
  title        = {Human skin permeation of emerging mycotoxins (beauvericin and enniatins)},
  url          = {http://dx.doi.org/10.1038/jes.2015.10},
  volume       = {26},
  year         = {2016},
}

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