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.

The non‐steroidal anti‐inflammatory drug diclofenac sodium induces abnormal embryogenesis and delayed lethal effects in early life stage zebrafish (Danio rerio)

“…In contrast, no negative effects of diclofenac on embryo development have been reported in common carp (Stepanova et al, ) and brown trout (Schwarz et al, ). In ecotoxicological assays of chemicals, zebrafish are increasingly used to examine abnormal embryogenesis, and there are many reports that abnormal embryogenesis is induced in zebrafish by various chemicals including agricultural chemicals (Cao et al, ; Jia, Mao, Zhang, Zhang, & Jiang, ; Maharajan, Muthulakshmi, Nataraj, Ramesh, & Kadirvelu, ; Sulukan et al, ; Yao, Yu, Zhou, Xiang, & Xu, ), pharmaceuticals (Chen et al, ; Félix et al, ; Kovács et al, ; present study) and metals (Horie, Yamagishi, Koshio, et al, ; Sun et al, ; Yin et al, ). These studies suggest that zebrafish embryos are particularly sensitive to chemical exposure.…”

Ecotoxicity of disinfectant benzalkonium chloride and its mixture with antineoplastic drug 5-fluorouracil towards algaPseudokirchneriella subcapitata

“…However, due to their mechanisms of action most of these drugs are genotoxic, carcinogenic, and/or teratogenic and can cause adverse effects in aquatic organisms, especially upon chronic exposure ( Kuemmerer & Ruck, 2014 ; Toolaram, Kuemmerer & Schneider, 2014 ). Several recent studies demonstrated that certain antineoplastic drugs cause adverse effects to different aquatic species even at concentrations relevant for aquatic environment ( Brezovšek, Eleršek & Filipič, 2014 ; Elersek et al, 2016 ; Kovacs et al, 2015 ; Kovacs et al, 2016 ; Misik et al, 2014 ; Parrella et al, 2014 ; Parrella et al, 2015 ).…”

A novel screening method for transition metal‐based anticancer compounds using zebrafish embryo‐larval assay and inductively coupled plasma‐mass spectrometry analysis

“…Dose‐response studies were conducted with the aforementioned nominal waterborne concentrations of cisplatin based on previous findings in the literature (Kovács et al, ). Lethality and a delayed hatching endpoint were analytically evaluated (Figure ).…”