Ecotoxicological assessment of cimetidine and determination of its potential for endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa, and Danio rerio

•Cimetidine is not acutely toxic at levels occurring in the aquatic environment.•Chronic exposure to cimetidine leads to alteration of steroidogenesis pathway.•ELS exposure to cimetidine is associated with changes in gonadal histology in fish. Cimetidine is a histamine H2-receptor antagonist used for treatment of gastrointestinal disorders. It is often detected in aquatic environments, but its ecotoxicological effects have not been well studied. Thus, ecotoxicity of cimetidine was evaluated using Daphnia magna and Moina macrocopa, and zebrafish (Danio rerio), and a predicted no effect concentration (PNEC) was derived. In D. magna, 48h immobilization EC50 was determined at 394.9mgL−1. However, reproduction damages in D. magna were not found even at the maximum exposure level (30mgL−1). For M. macrocopa, 48h EC50 was found at 175.8mgL−1 and the 7d reproduction no observed effect concentration (NOEC) was 1.1mgL−1. For D. rerio, 40d growth NOEC was determined at 100mgL−1, the highest experimental concentration. The PNEC of cimetidine was estimated at 0.1mgL−1 based on M. macrocopa 7d reproduction NOEC. In 14d adult zebrafish exposure, endocrine disruption potentials of cimetidine were observed. In male, decrease in plasma 17β-estradiol and testosterone levels, up-regulation of gonadal cyp17, and down-regulation of hepatic erα were observed at 300mgL−1. In female, increase in plasma E2 level and down-regulation of hepatic cyp1a were noted at 3mgL−1. Endocrine disruption effects were also observed in early life stage exposure. Up-regulation of erβ at 17d, and cyp19a and vtg at 40d post fertilization were detected at 100mgL−1, and co-occurrence of ovary and putative testis was observed at as low as 1.1mgL−1. The results indicate that there is little evidence for cimetidine to cause direct ecological impact at the current ambient levels in the aquatic environment. However potential consequences of endocrine disruption following long-term exposure in aquatic environment deserves further investigation.