title: Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.
abstract: The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic drugs were characterized by low toxicity in zebrafish in acute and sub-chronic tests.
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Kovács
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Bakos
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Urbányi
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Kövesi
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Gazsi
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Csepeli
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Ádám János
authors.initials: ÁJ
authors.lastname: Appl
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Bencsik
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csenki
authors.affiliation: Department of Aquaculture, Szent István University, 2100, Gödöllő, Páter Károly u. 1., Hungary. ahorvath73@icloud.com.
authors.forename: Ákos
authors.identifier: http://orcid.org/0000-0001-9760-2478
authors.initials: Á
authors.lastname: Horváth
mesh_terms: D000818:Animals; D054697:Cytostatic Agents / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D007928:Lethal Dose 50; D008136:Longevity / Q000187:drug effects; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology
chemical_list: D054697:Cytostatic Agents; D014874:Water Pollutants, Chemical
keywords: Acute; Cytostatic drugs; Sub-chronic; Toxicity; Zebrafish