Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

Abstract

Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce. In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100µM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca(2+)]i and strong depolarization of mitochondrial membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo.

Strobilurin fungicides in house dust: is wallboard a source?

“…Interestingly, a meta-analysis included in the paper found pyraclostrobin and azoxystrobin to have the highest risk quotients. Other studies highlighted the potential for these chemicals to cause neurotoxicity in vitro [8,9]. In addition, pyraclostrobin has been demonstrated to stimulate mitochondrial dysfunction and adipogenic activity in human cell lines [10,11]; however, effects by other strobilurins have not been evaluated.…”

Use of the Model Organism Caenorhabditis elegans to Elucidate Neurotoxic and Behavioral Effects of Commercial Fungicides

“…This class of fungicide, developed in the 1990s has rapidly become the second most prevalent type of fungicide, accounting for a $600 million industry that includes treatment of soybean, wheat and other cereal crops. Compounds like kresoxim-methyl and pyraclostrobin are broad-spectrum fungicides that have long-term stability [19] and were recently shown to be neurotoxic to cultured mammalian neurons [20]. Pyraclostrobin fed to rodents was also associated with stomach ulcerations, reduced weight gain and decreased food consumption [21].…”

Determination of metrafenone in bitter gourd and soil by GC with ECD

“…To date, most studies were focused on the field effectiveness of metrafenone (Capriotti, Gentili, Vecchio, Balzaretti, & Fagnani, 2006;Felsenstein, Semar, & Stammler, 2010;Opalski et al, 2006;Regueiro, Olguin, Simal-Gandara, & Sunol, 2015). Same effects regarding of metrafenone applied to vines on the color, fermentation, aroma and so on were reported (Briz-Cid, FigueiredoGonzalez, Rial-otero, Cancho-Grande, & Simal-Gandara, 2014;Noguerol-Pato, Sieiro-Sampredro, Gonzalez-Barreiro, CanchoGrande, & Simal-Gandara, 2014;Noguerol-Pato, Torrado-Agrasar, Gonzalez-Barreiro, Cancho-Grande, & Simal-Gandara, 2014), the results showed that metrafenone could produce an increase in the ripe fruit odorant series and higher biomass.…”