With the increasing use of pharmaceuticals, their concentrations in the environment are increasing, posing a risk to the environment. A group of pharmaceuticals, with a remarkable boom in the last few years, are also anti-cancer drugs. Due to the prevalence and frequency of the disease – cancer – a lot has been invested in the development of new drugs and techniques, where great progress has been made with tyrosine kinase inhibitors (TKIs). They're classified as targeted drugs because they act directly on certain tumor tyrosine kinases that they inhibit. In our study, we wanted to evaluate the toxic effect of sorafenib, nilotinib, and regorafenib on an experimental model of the zebrafish embryo (Danio rerio). Individual embryos were exposed to selected concentrations of these inhibitors for 96 hours, and their development was recorded daily. We also determined lethal, sub-lethal and teratogenic effects. We found that sorafenib and nilotinib didn't increase lethal, sub-lethal or teratogenic effects in embryos up to the highest tested concentration. Regorafenib didn't cause lethal effects, but it significantly increased the sub-lethal and teratogenic characters after 48 hours at a concentration of 1,9 mg/L and after 96 hours at a concentration of 0,6 mg/L onwards. Sorafenib and regorafenib also significantly reduced the hatching rate of embryos after 96 hours, namely sorafenib at 1,8 mg/L and regorafenib at 0,6 mg/L and 1,9 mg/L. According to the ratio of predicted environmental concentration and predicted no effect concentration, none of the tested TKIs present an environmental risk. It should also be emphasized that our research is the first in Slovenia for these TKIs.
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