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

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.

Surface functionalization, particle size and pharmaceutical co-contaminant dependent impact of nanoplastics on marine crustacean – Artemia salina

“…42 It is widely released into aquatic systems because of its many applications, which include suppressing cancer, reducing plasma cholesterol levels, aiding in weight loss, and treating polycystic ovarian syndrome (PCOS). 43 Its elevated levels can lead to vitamin B12 insufficiency, 44 lactic acidosis, 45 etc. Metformin concentrations in the environment vary substantially depending on the area and the number of diabetic people, with a maximum concentration of 189 mg ml −1 reported in Ontario, Canada.…”

“…Metformin concentrations in the environment vary substantially depending on the area and the number of diabetic people, with a maximum concentration of 189 mg ml −1 reported in Ontario, Canada. 45 While MH was shown to have the expected no-effect concentration of 1 mg L −1 , its ongoing exposure and bioaccumulation characteristics terrify scientists worldwide. 46 Possibility of causing endocrine disruption in aquatic organisms has also drawn attention to concerns regarding the effect on reproduction.…”

Metformin and guanylurea reduce survival, but have limited sublethal effects in larval zebrafish (Danio rerio)

“…Similarly to metformin, guanylurea is expected to be highly hydrophilic (estimated K ow of -1.22 to -2.22; Straub et al 2019) and mobile in aquatic environments (Scheurer et al 2012). Metformin is among the most abundant pharmaceuticals detected in waters receiving wastewater effluent, with surface water concentrations ranging between 0.1-30 µg·L −1 (Oosterhuis et al 2013; Niemuth and Klaper 2015; Littlejohn et al 2023). Guanylurea is also detected in surface waters, albeit in some cases, at higher concentrations than its parent compound (Scheurer et al 2012).…”