Developmental and Full-Life Cycle Exposures to Guanylurea and Guanylurea-Metformin Mixtures Results in Adverse Effects on Japanese Medaka (Oryzias latipes)

Metformin is currently thought to be the highest drug by weight released into the aquatic environment, as a direct result of its widespread use in the treatment of a number of human health disorders. The removal of metformin from wastewaters is directly related to the formation of guanylurea (metformin's only known persistent degradation product), which is generally present at higher concentrations in surface waters than the parent compound. With metformin use rising steadily, it is important to characterize the effects of guanylurea on nontarget aquatic organisms. We recently demonstrated the effects of developmental exposure to environmentally relevant concentrations of metformin on the growth of early life stage (ELS) medaka as well as effects on the body weight of adult male fish following full-life cycle exposures. In the present study, we describe similar effects of guanylurea exposure on these endpoints and life stages. Guanylurea led to effects on growth in a 28-d ELS assessment that were similar to those of metformin; however, these effects occurred at concentrations in the ng/L range compared with the mu g/L range for metformin. A possible sex-dependent association with body weight changes was also observed in adults following a 165-d full-life cycle exposure to guanylurea alone or in a mixture with metformin. To our knowledge, the present is the first study to report the toxicity of guanylurea to nontarget aquatic organisms. Environ Toxicol Chem 2019;00:1-6. (c) 2019 SETAC