title: Fish embryo toxicity of carbamazepine, diclofenac and metoprolol.
abstract: Frequently measured pharmaceuticals in environmental samples were tested in fish embryo toxicity (FET) tests with Danio rerio, based on the draft OECD test protocol. In this FET test 2-h-old zebrafish embryos were exposed for 72 h to carbamazepine, diclofenac and metoprolol to observe effects on embryo mortality, gastrulation, somite formation, tail movement and detachment, pigmentation, heartbeat, malformation of head, otoliths and heart, scoliosis, deformity of yolk, and hatching success at 24, 48 and 72 h. We found specific effects on growth retardation above 30.6 mg/l for carbamazepine, on hatching, yolk sac and tail deformation above 1.5mg/l for diclofenac, and on scoliosis and growth retardation above 12.6 mg/l for metoprolol. Scoring all effect parameters, the 72-h-EC(50) values were: for carbamazepine 86.5mg/l, for diclofenac 5.3mg/l and for metoprolol 31.0mg/l (mean measured concentrations). In conclusion, our results for carbamazepine and metoprolol are in agreement with other findings for aquatic toxicity, and also fish embryos responded in much the same way as rat embryos did. For diclofenac, the FET test performs comparably to Early Life Stage testing.
authors.affiliation: Laboratory for Ecological Risk Assessment, RIVM, PO Box 1, Bilthoven 3720 BA, The Netherlands. Evert-Jan.van.den.Brandhof@rivm.nl
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: van den Brandhof
authors.forename: Mark
authors.initials: M
authors.lastname: Montforts
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000959:Antihypertensive Agents / Q000633:toxicity; D018692:Antimanic Agents / Q000633:toxicity; D002220:Carbamazepine / Q000633:toxicity*; D004008:Diclofenac / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008790:Metoprolol / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D018692:Antimanic Agents; D014874:Water Pollutants, Chemical; D004008:Diclofenac; D002220:Carbamazepine; D008790:Metoprolol