This recent paper, coauthored by RSA consultants Kim Travis and Remi Bars and published in Archives of Toxicology, assesses the mammalian toxicology studies available for the succinate dehydrogenase inhibitor (SDHI) fungicide fluopyram. The assessment was made as a case study, in light of suggestions that standard regulatory studies may not identify key toxicities related to the SDHI mode of action. The regulatory toxicity studies with fluopyram identify primary effects on the liver and thyroid, with additional renal findings in male rats. The mechanisms of toxicity for these findings are shown to be both unrelated to succinate dehydrogenase inhibition and not of human relevance. Most toxicity studies with fluopyram are untargeted, but include a huge number of endpoints in order to detect toxic effects. While effects consistent with succinate dehydrogenase inhibition would most likely be seen in the nervous system, heart and muscle; these effects are notably absent in the multiple studies available for fluopyram across different mammalian species. It is therefore concluded that the human safety of fluopyram has been thoroughly investigated in the available studies. The absence of effects related to succinate dehydrogenase inhibition is likely to be a consequence of the low affinity of fluopyram for the mammalian enzyme, and the rapid metabolism of fluopyram in mammalian species.
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