title: Cytotoxicity of folpet fungicide on human bronchial epithelial cells.
abstract: Folpet, a widely used dicarboximide fungicide, has been detected in the ambient air of several vine-growing regions of France. It is present in particle form in the environment; however, no study exploring its potential health impact on airways and the respiratory system has been published. Here, the biological effect of these particles was investigated in vitro on human bronchial epithelial cells (16HBE14o-). To be close to the real-life conditions of exposure, Folpan 80WG, a commercial form of folpet, was tested. Folpan 80WG particles showed dose- and time-dependent cytotoxic effects on 16HBE14o- cells. This effect was compared to that produced by technical-grade folpet and both were found to induce a toxicity with similar IC(50) values after 24h of exposure. After 4h and at least until 48h of exposure, the IC(50) values of Folpan 80WG particles were between 2.4 and 2.8 microg/cm(2). Investigation of the cytotoxicity found that Folpan 80WG particles at 1.85 microg/cm(2) induced an increase in ROS production from the first hour of exposure. Evidence that oxidative processes occur in folpet-exposed cells was confirmed by the presence of membrane lipid peroxidation. Furthermore, early apoptosis and late apoptosis/necrosis were both present after the first hour of exposure. These findings indicate that exposure to Folpan 80WG particles result in a rapid cytotoxic effect on human bronchial epithelial cells in vitro that could be in part explained by oxidative stress, characterised by membrane lipid peroxidation and ROS production.
authors.affiliation: EA 3672, Laboratoire Santé-Travail-Environnement, Université Bordeaux 2, Bordeaux, France. mireille.canal@pharmaco.u-bordeaux2.fr
authors.forename: Mireille
authors.initials: M
authors.lastname: Canal-Raffin
authors.forename: Béatrice
authors.initials: B
authors.lastname: l'Azou
authors.forename: Joana
authors.initials: J
authors.lastname: Jorly
authors.forename: Annabelle
authors.initials: A
authors.lastname: Hurtier
authors.forename: Jean
authors.initials: J
authors.lastname: Cambar
authors.forename: Patrick
authors.initials: P
authors.lastname: Brochard
mesh_terms: D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D004396:Coloring Agents; D004847:Epithelial Cells / Q000187:drug effects*; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009499:Neutral Red; D010797:Phthalimides / Q000633:toxicity*; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017304:Annexin A5; D004396:Coloring Agents; D005659:Fungicides, Industrial; D010797:Phthalimides; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D009499:Neutral Red; D011419:Propidium; C005020:folpet