title: Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.).
abstract: Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L(-1) to μg L(-1). In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC50 values of verapamil were estimated at 16.4±9.2, 7.3±1.5 and 4.8±0.2 mg L(-1) for embryos (E5-E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L(-1). Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L(-1) of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF>500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2±1.6 days and 44.2±8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations.
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany, Czech Republic. steinbach@frov.jcu.cz
authors.forename: Christoph
authors.initials: C
authors.lastname: Steinbach
authors.forename: Ganna
authors.initials: G
authors.lastname: Fedorova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Prokes
authors.forename: Katerina
authors.initials: K
authors.lastname: Grabicova
authors.forename: Jana
authors.initials: J
authors.lastname: Machova
authors.forename: Roman
authors.initials: R
authors.lastname: Grabic
authors.forename: Olga
authors.initials: O
authors.lastname: Valentova
authors.forename: Hana Kocour
authors.initials: HK
authors.lastname: Kroupova
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002347:Carps / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004350:Drug Residues / Q000493:pharmacokinetics* / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D007928:Lethal Dose 50; D013997:Time Factors; D023382:Toxicity Tests, Acute; D014700:Verapamil / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D014700:Verapamil
keywords: Bioconcentration; Embryo-larval test; Half-life time; Heart rate; Verapamil