title: Toxicity and endocrine disruption in zebrafish (Danio rerio) and two freshwater invertebrates (Daphnia magna and Moina macrocopa) after chronic exposure to mefenamic acid.
abstract: Pharmaceuticals have been frequently detected in the aquatic environment. Their potential effects on the endocrine system in wildlife are of special concern because these alterations could lead to impaired reproduction. We evaluated ecotoxicities associated with long-term exposure to mefenamic acid (MFA) and potential endocrine disruption. For this purpose, acute and chronic toxicities of MFA on several aquatic organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and a teleost, Danio rerio were evaluated. The 48 h acute median effective concentration (EC50) of D. magna and M. macrocopa was 17.16 mg/L and 2.93 mg/L, respectively. In chronic toxicity test, D. magna and M. macrocopa showed significant changes in reproduction (number of young per adult) after the exposure to 1.0 mg/L and 0.25 mg/L MFA, respectively. In early life stage exposure using D. rerio, significant decrease of larval survival was observed at 1 mg/L. Changes in vitellogenin (VTG) protein concentrations in 32 day post fertilization fish and vtgI mRNA expression in adult male fish suggest endocrine disruption potentials of MFA. Among the genes of hypothalamus-pituitary-gonad axis, transcriptions of gnrh, gnrhr, cyp19a, and cyp19b increased, supporting estrogenic potential of MFA. Along with histological changes in ovaries, the results of this study provide evidences of endocrine disruption capacity of MFA. However, the effective concentrations are orders of magnitude greater than those occurring in the ambient aquatic environment.
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hyo-rin Jung
authors.initials: HR
authors.lastname: Collard
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Ji
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Lee
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Liu
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kang
authors.forename: Younglim
authors.initials: Y
authors.lastname: Kho
authors.forename: Byeongwoo
authors.initials: B
authors.lastname: Ahn
authors.forename: Jisung
authors.initials: J
authors.lastname: Ryu
authors.forename: Jaean
authors.initials: J
authors.lastname: Lee
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D033361:Cladocera; D003621:Daphnia; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects*; D005618:Fresh Water; D007814:Larva / Q000378:metabolism; D008297:Male; D008528:Mefenamic Acid / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D012098:Reproduction; D036401:Toxicity Tests, Chronic; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D052244:Endocrine Disruptors; D012333:RNA, Messenger; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D008528:Mefenamic Acid