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加拿大安大略省和魁北克省地表水和沉积物中 2 型糖尿病药物二甲双胍及其转化产物胍基脲的环境浓度。

Environmental Concentrations of the Type 2 Diabetes Medication Metformin and Its Transformation Product Guanylurea in Surface Water and Sediment in Ontario and Quebec, Canada.

机构信息

London Research and Development Centre, Agriculture and Agri-Food Canada, London, Ontario, Canada.

Department of Chemistry, Western University, London, Ontario, Canada.

出版信息

Environ Toxicol Chem. 2023 Aug;42(8):1709-1720. doi: 10.1002/etc.5684. Epub 2023 Jul 19.

DOI:10.1002/etc.5684
PMID:37283207
Abstract

Metformin, used to treat Type 2 diabetes, is the active ingredient of one of the most prescribed drugs in the world, with over 120 million yearly prescriptions globally. In wastewater-treatment plants (WWTPs), metformin can undergo microbial transformation to form the product guanylurea, which could have toxicological relevance in the environment. Surface water samples from 2018 to 2020 and sediment samples from 2020 were collected from six mixed-use watersheds in Quebec and Ontario, Canada, and analyzed to determine the metformin and guanylurea concentrations at each site. Metformin and guanylurea were present above their limits of quantification in 51.0% and 50.7% of all water samples and in 64% and 21% of all sediment samples, respectively. In surface water, guanylurea was often present at higher concentrations than metformin, while the inverse was true in sediment, with metformin frequently detected at higher concentrations than guanylurea. In addition, at all sites influenced solely by agriculture, concentrations of metformin and guanylurea were <1 µg/L in surface water, suggesting that agriculture is not a significant source of these compounds in the investigated watersheds. These data suggest that WWTPs and potentially septic system leaks are the most likely sources of the compounds in the environment. Guanylurea was detected at many of these sites above environmental concentrations of concern, where critical processes in fish may be affected. Due to the scarcity of available ecotoxicological data and the prominence of guanylurea across all sample sites, there is a need to perform more toxicological investigations of this transformation product and revisit regulations. The present study will help provide toxicologists with environmentally relevant concentration ranges in Canada. Environ Toxicol Chem 2023;42:1709-1720. © 2023 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

摘要

二甲双胍用于治疗 2 型糖尿病,是世界上使用最广泛的药物之一的有效成分,全球每年处方量超过 1.2 亿张。在废水处理厂(WWTP)中,二甲双胍可以发生微生物转化形成产物胍基脲,这在环境中可能具有毒理学相关性。2018 年至 2020 年期间,从加拿大魁北克省和安大略省的六个混合使用流域采集地表水样本,2020 年采集沉积物样本,并对每个地点的二甲双胍和胍基脲浓度进行分析。在所有水样中,有 51.0%和 50.7%的水样以及所有沉积物样本中 64%和 21%的样本超过了定量限,存在二甲双胍和胍基脲。在地表水样本中,胍基脲的浓度通常高于二甲双胍,而在沉积物样本中则相反,二甲双胍的浓度经常高于胍基脲。此外,在所有仅受农业影响的地点,地表水和沉积物中的二甲双胍和胍基脲浓度均<1μg/L,这表明农业不是调查流域中这些化合物的重要来源。这些数据表明,废水处理厂和可能的化粪池泄漏是环境中这些化合物的最可能来源。胍基脲在许多这些位点的检测浓度高于关注的环境浓度,这可能会影响鱼类的关键过程。由于可用的生态毒理学数据稀缺,以及胍基脲在所有采样点的突出地位,需要对这种转化产物进行更多的毒理学研究,并重新审查法规。本研究将帮助毒理学家提供加拿大环境相关的浓度范围。Environ Toxicol Chem 2023;42:1709-1720. © 2023 加拿大国王陛下及其作者。由 Wiley Periodicals LLC 代表 SETAC 出版的《环境毒理学与化学》。经加拿大农业和农业食品部许可转载。

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