The ecotoxicological effects of metformin and its metabolite, guanylurea, on Japanese medaka (Oryzias latipes)
Abstract
Human pharmaceutical waste threatens many natural processes of non-target aquatic organisms, through the introduction of such contaminants into the environment. Pharmaceuticals are a large and diverse groups of medicinal compounds that are used for the diagnosis, cure, mitigation, treatment, and/or prevention of diseases in humans and animals. In recent years, the occurrence and fate of pharmaceuticals in the aquatic environment have become an emerging issue in aquatic toxicology, with one of the most prevalent contaminants being the type-2 diabetic drug, metformin, and its metabolite guanylurea. Metformin and guanylurea have been measured in surface waters in the ng- ??g??L-1 range. This study aimed to investigate the toxicological effects of metformin and guanylurea on Japanese medaka (Oryzias medaka). \nA first experimental step was to determine the potential for uptake, bioaccumulation, and depuration of metformin in early-life stage (ELS) medaka using 14C-metformin. Results from this study showed that both embryo and larval medaka can take up, bioaccumulate, and successfully depurate metformin from the aquatic environment. Furthermore, egg chorion hardening (~6 hpf) prevented the uptake of metformin from by developing embryos. \nAdditionally, we show that waterborne exposure to metformin and guanylurea significantly impacted the growth metrics in ELS fish, showing that guanylurea caused growth retardation at exposure concentrations an order of magnitude lower that those…
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