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Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG(R) and Myco 500(R), two commercial forms of folpet.

Canal-Raffin M, L'azou B, Martinez B, Sellier E, Fawaz F, Robinson P, Ohayon-Courtès C, Baldi I, Cambar J, Molimard M, Moore N, Brochard P - Part Fibre Toxicol (2007)

Bottom Line: Folpet degradation products and vehicles of Folpan 80 WG(R) did not show any cytotoxicity at tested concentrations.At non-cytotoxic and subtoxic concentrations, Folpan 80 WG(R) was found to increase DCFH-DA fluorescence.This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire Santé-Travail-Environnement (EA 3672), Université Bordeaux 2, Bordeaux, France. mireille.canal@pharmaco.u-bordeaux2.fr.

ABSTRACT

Background: Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 mug/m3 during its spraying, 0.16-1.2 mug/m3 in rural air and around 0.01 mug/m3 in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells.

Results: Granulometry of two commercial forms of folpet (Folpan 80WG(R) and Myco 500(R)) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 mum, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC50) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 mug/cm2 for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG(R) did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG(R) was found to increase DCFH-DA fluorescence.

Conclusion: These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.

No MeSH data available.


Related in: MedlinePlus

Folpet and its degradation products adapted from Gordon [24]. Folpet (a) is hydrolyzed to give (b) phthalimide and (c) thiophosgene. Phthalimide is then further hydrolyzed to give (d) phthalamic acid which is it-self hydrolyzed to give (e) phthalic acid.
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Figure 1: Folpet and its degradation products adapted from Gordon [24]. Folpet (a) is hydrolyzed to give (b) phthalimide and (c) thiophosgene. Phthalimide is then further hydrolyzed to give (d) phthalamic acid which is it-self hydrolyzed to give (e) phthalic acid.

Mentions: Folpet (N-[(trichloromethyl)thio)phthalimide]) is a contact fungicide belonging to the dicarboximide family. It has been used for the past 50 years and is still widely employed in Europe as a preventive or curative treatment against mildew, gray mold, spoilage fungi and wood rot fungi [11]. Folpet is able to inhibit spore germination [12], its mode of action is centred on its reaction with thiol groups [13]. The folpet degradation pathway consists of hydrolysis with cleavage of the sulfur-nitrogen bond to give thiophosgene and phthalimide [14]. Phthalimide is hydrolyzed to phthalamic acid and then to phthalic acid (Fig. 1). Thiophosgene is a highly reactive short-lived compound, rapidly degraded to form HCl and SH2 in water.


Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG(R) and Myco 500(R), two commercial forms of folpet.

Canal-Raffin M, L'azou B, Martinez B, Sellier E, Fawaz F, Robinson P, Ohayon-Courtès C, Baldi I, Cambar J, Molimard M, Moore N, Brochard P - Part Fibre Toxicol (2007)

Folpet and its degradation products adapted from Gordon [24]. Folpet (a) is hydrolyzed to give (b) phthalimide and (c) thiophosgene. Phthalimide is then further hydrolyzed to give (d) phthalamic acid which is it-self hydrolyzed to give (e) phthalic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211752&req=5

Figure 1: Folpet and its degradation products adapted from Gordon [24]. Folpet (a) is hydrolyzed to give (b) phthalimide and (c) thiophosgene. Phthalimide is then further hydrolyzed to give (d) phthalamic acid which is it-self hydrolyzed to give (e) phthalic acid.
Mentions: Folpet (N-[(trichloromethyl)thio)phthalimide]) is a contact fungicide belonging to the dicarboximide family. It has been used for the past 50 years and is still widely employed in Europe as a preventive or curative treatment against mildew, gray mold, spoilage fungi and wood rot fungi [11]. Folpet is able to inhibit spore germination [12], its mode of action is centred on its reaction with thiol groups [13]. The folpet degradation pathway consists of hydrolysis with cleavage of the sulfur-nitrogen bond to give thiophosgene and phthalimide [14]. Phthalimide is hydrolyzed to phthalamic acid and then to phthalic acid (Fig. 1). Thiophosgene is a highly reactive short-lived compound, rapidly degraded to form HCl and SH2 in water.

Bottom Line: Folpet degradation products and vehicles of Folpan 80 WG(R) did not show any cytotoxicity at tested concentrations.At non-cytotoxic and subtoxic concentrations, Folpan 80 WG(R) was found to increase DCFH-DA fluorescence.This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire Santé-Travail-Environnement (EA 3672), Université Bordeaux 2, Bordeaux, France. mireille.canal@pharmaco.u-bordeaux2.fr.

ABSTRACT

Background: Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 mug/m3 during its spraying, 0.16-1.2 mug/m3 in rural air and around 0.01 mug/m3 in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells.

Results: Granulometry of two commercial forms of folpet (Folpan 80WG(R) and Myco 500(R)) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 mum, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC50) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 mug/cm2 for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG(R) did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG(R) was found to increase DCFH-DA fluorescence.

Conclusion: These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.

No MeSH data available.


Related in: MedlinePlus