Drugs are potentially dangerous environmental contaminants, as they are designed to have biological effects at low concentrations. Monepantel (MOP), an amino-acetonitrile derivative, is frequently used veterinary anthelmintics, but information about MOP environmental circulation and impact is almost non-existent. We studied the phytotoxicity, uptake and biotransformation of MOP in two fodder plants, Plantago lanceolata and Medicago sativa. The seeds and whole plant regenerants were cultivated with MOP. The plant roots and the leaves were collected after 1, 2, 3, 4, 5 and 6 weeks of cultivation. The lengths of roots and proline concentrations in the roots and leaves were measured to evaluate MOP phytotoxicity. The UHPLC-MS/MS technique with a Q-TOF mass analyser was used for the identification and semi-quantification of MOP and its metabolites. Our results showed no phytotoxicity of MOP. However, both plants were able to uptake, transport and metabolize MOP. Comparing both plants, the uptake of MOP was much more extensive in Medicago sativa (almost 10-times) than in Plantago lanceolate. Moreover, 9 various metabolites of MOP were detected in Medicago sativa, while only 7 MOP metabolites were found in Plantago lanceolata. Based on metabolites structures, scheme of the metabolic pathways of MOP in both plants was proposed. MOP and its main metabolite (MOP sulfone), both anthelmintically active, were present not only in roots but also in leaves that can be consumed by animals. This indicates the potential for undesirable circulation of MOP in the environment, which could lead to many pharmacological and toxicological consequences.

Department of Analytical Chemistry Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Biochemical Sciences Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 500 05 Hradec Králové Czech Republic

Laboratory of Plant Biotechnologies Institute of Experimental Botany The Czech Academy of Sciences Rozvojová 263 165 02 Praha 6 Lysolaje Czech Republic

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