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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

Cytotoxic effect on 16HBE14o-cells after 24 h exposure. The 16HBE14o-cells were exposed to Folpan 80WG® (n = 31), vehicles of Folpan 80WG® (n = 6), Myco 500® (n = 15), phthalimide (n = 9), phthalamic acid (n = 9) and phthalic acid (n = 3) and micronic titanium dioxide (n = 3) during 24 h. A neutral red release assay was performed to quantify viable cells. The proportion of dead cells was calculated using the formula (100 - (Absorbance540 nm–630 nm drug-treated sample × 100/Absorbance540 nm–630 nm control sample)) and is expressed as mean ± se.
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Figure 7: Cytotoxic effect on 16HBE14o-cells after 24 h exposure. The 16HBE14o-cells were exposed to Folpan 80WG® (n = 31), vehicles of Folpan 80WG® (n = 6), Myco 500® (n = 15), phthalimide (n = 9), phthalamic acid (n = 9) and phthalic acid (n = 3) and micronic titanium dioxide (n = 3) during 24 h. A neutral red release assay was performed to quantify viable cells. The proportion of dead cells was calculated using the formula (100 - (Absorbance540 nm–630 nm drug-treated sample × 100/Absorbance540 nm–630 nm control sample)) and is expressed as mean ± se.

Mentions: The 16-Human Bronchial Epithelial 14o-cells (16HBE14o-) were treated with various concentrations of folpet particles from Folpan 80WG® and Myco 500® for 24 h (Fig. 7). After 24 h exposure, folpet in its commercial forms induced cytotoxicity in a dose-dependent manner. The concentration of folpet in Folpan 80 WG® and Myco 500® required to induce 50% non viable cells compared with the control (IC50) was 2.89 μg/cm2 (± 0.16) and 5.11 μg/cm2 (± 0.36) respectively. The IC50between Folpan 80WG® and Myco 500® differed significantly (Student's t test, p < 0.0001). Vehicles of Folpan 80WG® and the degradation products of folpet (phthalimide, phthalamic acid and phthalic acid) were tested separately under the same conditions. No cytotoxic effect was observed in the range of concentrations tested (0.185–18.5 μg/cm2) for both degradation products and vehicles of Folpan 80WG® (Fig. 7). Micronic titanium dioxide used as negative control particles showed no cytotoxicity in the same range of folpet concentrations (0.185–18.5 μg/cm2).


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)

Cytotoxic effect on 16HBE14o-cells after 24 h exposure. The 16HBE14o-cells were exposed to Folpan 80WG® (n = 31), vehicles of Folpan 80WG® (n = 6), Myco 500® (n = 15), phthalimide (n = 9), phthalamic acid (n = 9) and phthalic acid (n = 3) and micronic titanium dioxide (n = 3) during 24 h. A neutral red release assay was performed to quantify viable cells. The proportion of dead cells was calculated using the formula (100 - (Absorbance540 nm–630 nm drug-treated sample × 100/Absorbance540 nm–630 nm control sample)) and is expressed as mean ± se.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Cytotoxic effect on 16HBE14o-cells after 24 h exposure. The 16HBE14o-cells were exposed to Folpan 80WG® (n = 31), vehicles of Folpan 80WG® (n = 6), Myco 500® (n = 15), phthalimide (n = 9), phthalamic acid (n = 9) and phthalic acid (n = 3) and micronic titanium dioxide (n = 3) during 24 h. A neutral red release assay was performed to quantify viable cells. The proportion of dead cells was calculated using the formula (100 - (Absorbance540 nm–630 nm drug-treated sample × 100/Absorbance540 nm–630 nm control sample)) and is expressed as mean ± se.
Mentions: The 16-Human Bronchial Epithelial 14o-cells (16HBE14o-) were treated with various concentrations of folpet particles from Folpan 80WG® and Myco 500® for 24 h (Fig. 7). After 24 h exposure, folpet in its commercial forms induced cytotoxicity in a dose-dependent manner. The concentration of folpet in Folpan 80 WG® and Myco 500® required to induce 50% non viable cells compared with the control (IC50) was 2.89 μg/cm2 (± 0.16) and 5.11 μg/cm2 (± 0.36) respectively. The IC50between Folpan 80WG® and Myco 500® differed significantly (Student's t test, p < 0.0001). Vehicles of Folpan 80WG® and the degradation products of folpet (phthalimide, phthalamic acid and phthalic acid) were tested separately under the same conditions. No cytotoxic effect was observed in the range of concentrations tested (0.185–18.5 μg/cm2) for both degradation products and vehicles of Folpan 80WG® (Fig. 7). Micronic titanium dioxide used as negative control particles showed no cytotoxicity in the same range of folpet concentrations (0.185–18.5 μg/cm2).

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