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

Author:

Littlejohn Cameron12,Renaud Justin B.1,Sabourin Lyne1,Lapen David R.3,Pappas Jane J.4,Tuteja Bindu4,Hughes Dianne4,Ussery Erin5,Yeung Ken K.‐C.26,Sumarah Mark W.12ORCID

Affiliation:

1. London Research and Development Centre Agriculture and Agri‐Food Canada London Ontario Canada

2. Department of Chemistry Western University London Ontario Canada

3. Ottawa Research and Development Centre Agriculture and Agri‐Food Canada Ottawa Ontario Canada

4. New Substances Assessment and Control Bureau Safe Environments Directorate, Health Canada Ottawa Ontario Canada

5. Aquatic Contaminants Research Division Environment and Climate Change Canada Burlington Ontario Canada

6. Department of Biochemistry Western University London Ontario Canada

Abstract

AbstractMetformin, 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.

Funder

Health Canada

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Environmental Chemistry

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