title: Ecotoxicological assessment of cimetidine and determination of its potential for endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa, and Danio rerio.
abstract: 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, 48 h immobilization EC50 was determined at 394.9 mg L(-1). However, reproduction damages in D. magna were not found even at the maximum exposure level (30 mg L(-1)). For M. macrocopa, 48 h EC50 was found at 175.8 mg L(-1) and the 7 d reproduction no observed effect concentration (NOEC) was 1.1 mg L(-1). For D. rerio, 40 d growth NOEC was determined at 100 mg L(-1), the highest experimental concentration. The PNEC of cimetidine was estimated at 0.1 mg L(-1) based on M. macrocopa 7d reproduction NOEC. In 14 d 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 300 mg L(-1). In female, increase in plasma E2 level and down-regulation of hepatic cyp1a were noted at 3 mg L(-1). Endocrine disruption effects were also observed in early life stage exposure. Up-regulation of erβ at 17d, and cyp19a and vtg at 40 d post fertilization were detected at 100 mg L(-1), and co-occurrence of ovary and putative testis was observed at as low as 1.1 mg L(-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.
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Saeram
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: dawoon@snu.ac.kr.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.affiliation: Department of Health, Environment and Safety, Eulji University, Seongnam 461-713, Republic of Korea.
authors.forename: Younglim
authors.initials: Y
authors.lastname: Kho
authors.affiliation: Department of Occupational and Environmental Health, Yongin University, Yongin 449-714, Republic of Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Ji
authors.affiliation: National Institute of Environmental Research, Incheon 404-708, Republic of Korea.
authors.forename: Pilje
authors.initials: P
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Byeongwoo
authors.initials: B
authors.lastname: Ahn
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D002927:Cimetidine / Q000633:toxicity*; D033361:Cladocera / Q000187:drug effects; D003621:Daphnia / Q000187:drug effects; D015536:Down-Regulation; D054750:Ecotoxicology; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006066:Gonads / Q000187:drug effects; D008297:Male; D012098:Reproduction / Q000187:drug effects; D015854:Up-Regulation; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology
chemical_list: D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical; D002927:Cimetidine
keywords: Chronic exposure; Ecotoxicity; H2-receptor antagonist; Steroidogenesis; Zebrafish