Toxicology 2008-01-01

Cytotoxicity of folpet fungicide on human bronchial epithelial cells

Mireille Canal-Raffin, Béatrice l’Azou, Joana Jorly, Annabelle Hurtier, Jean Cambar, Patrick Brochard, Mireille Canal-Raffin, Béatrice l’Azou, Joana Jorly, Annabelle Hurtier, Jean Cambar, Patrick Brochard, Mireille Canal-Raffin, Béatrice l’Azou, Joana Jorly, Annabelle Hurtier, Jean Cambar, Patrick Brochard

Index: Toxicology 249(2-3) , 160-6, (2008)

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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 24 h of exposure. After 4 h and at least until 48 h of exposure, the IC 50 values of Folpan 80WG ® particles were between 2.4 and 2.8 μg/cm 2. Investigation of the cytotoxicity found that Folpan 80WG ® particles at 1.85 μg/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.