Endocrine disruption and consequences of chronic exposure to ibuprofen in Japanese medaka (Oryzias latipes) and freshwater cladocerans Daphnia magna and Moina macrocopa.
Despite frequent detection of ibuprofen in aquatic environments, the hazards associated with long-term exposure to ibuprofen have seldom been investigated. Ibuprofen is suspected of influencing sex steroid hormones through steroidogenic pathways in both vertebrates and invertebrates. In this study, the effect of ibuprofen on sex hormone balance and the associated mechanisms was investigated in vitro by use of H295R cells. We also conducted chronic toxicity tests using freshwater fish, Oryzias latipes, and two freshwater cladocerans, Daphnia magna and Moina macrocopa, for up to 144 and 21d of exposure, respectively. Ibuprofen exposure increased 17beta-estradiol (E2) production and aromatase activity in H295R cells. Testosterone (T) production decreased in a dose-dependent manner. For D. magna, the 48 h immobilization EC50 was 51.4 mg/L and the 21 d reproduction NOEC was <1.23 mg/L; for M. macrocopa, the 48 h immobilization EC50 was 72.6 mg/L and the 7d reproduction NOEC was 25mg/L. For O. latipes, 120 d survival NOEC was 0.0001 mg/L. In addition, ibuprofen affected several endpoints related to reproduction of the fish, including induction of vitellogenin in male fish, fewer broods per pair, and more eggs per brood. Parental exposure to as low as 0.0001 mg/L ibuprofen delayed hatching of eggs even when they were transferred to and cultured in clean water. Delayed hatching is environmentally relevant because this may increase the risk of being predated. For O. latipes, the acute-to-chronic ratio of ibuprofen was estimated to be greater than 1000. Overall, relatively high acute-to-chronic ratio and observation of reproduction damage in medaka fish at environmentally relevant ranges of ibuprofen warrant the need for further studies to elucidate potential ecological consequences of ibuprofen contamination in the aquatic environment.
Han
Sunyoung
S
School of Public Health, Seoul National University, 28 Yunkeon, Chongro, Seoul 110-799, Republic of Korea.
Choi
Kyungho
K
School of Public Health, Seoul National University, 28 Yunkeon, Chongro, Seoul 110-799, Republic of Korea. Electronic address: kyungho@snu.ac.kr.
Kim
Jungkon
J
School of Public Health, Seoul National University, 28 Yunkeon, Chongro, Seoul 110-799, Republic of Korea.
Ji
Kyunghee
K
School of Public Health, Seoul National University, 28 Yunkeon, Chongro, Seoul 110-799, Republic of Korea.
Kim
Sunmi
S
School of Public Health, Seoul National University, 28 Yunkeon, Chongro, Seoul 110-799, Republic of Korea.
Ahn
Byeongwoo
B
College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Yun
Junheon
J
National Institute of Environmental Research, Incheon 404-708, Republic of Korea.
Choi
Kyunghee
K
National Institute of Environmental Research, Incheon 404-708, Republic of Korea.
Khim
Jong Seong
JS
Division of Environmental Science and Ecological Engineering, Korea University, Seoul 136-713, Republic of Korea.
Zhang
Xiaowei
X
Toxicology Centre and Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7J 5B3, Canada; State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing 210093, China.
Giesy
John P
JP
Toxicology Centre and Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7J 5B3, Canada; State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing 210093, China; Zoology of Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China; State Key Laboratory of Marine Environmental Science, College of Oceanography and Environmental Science, Xiamen University, Xiamen, China.
D018268:Adrenocortical Carcinoma / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D033361:Cladocera / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003621:Daphnia / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism; D005618:Fresh Water; D006801:Humans; D007052:Ibuprofen / Q000633:toxicity*; D009990:Oryzias / Q000002:abnormalities / Q000378:metabolism* / Q000502:physiology; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase; D007052:Ibuprofen