Assessment of genotoxicity and acute toxic effect of the imatinib mesylate in plant bioassays

• Imatinib mesylate is at present one of the most wildly used cytostatic drugs in Europe.
• The paper describes the findings of genotoxic and acute toxic properties in plants.
• Positive results were obtained in two widely used plant micronucleus bioassays.
• Additionally acute toxic effects and induction of abortive pollen grains were detected.
• The PEC value of imatinib is ⩾5 orders of magnitude lower as the LOELs in plants.

Imatinib mesylate (IM) is at present one of the most widely used cytostatic drugs in developed countries but information on its ecotoxicological activities is scarce. This article describes the results of the first investigation in which genotoxic and acute toxic properties of the drug were studied in higher plants. IM was tested in two widely used plant bioassays namely in micronucleus (MN) assays with meiotic tetrad cells of Tradescantia (clone #4430) and in mitotic root tip cells of Allium cepa. Additionally, acute toxic effects (inhibition of cell division and growth of roots) were monitored in the onions. Furthermore, we studied the impact of the drug on the fertility of higher plants in pollen abortion experiments with three wildlife species (Chelidonium majus, Tradescantia palludosa and Arabidopsis thaliana). In MN assays with Tradesacantia a significant effect was seen with doses ⩾10 μM; the Allium MN assay was even more sensitive (LOEL ⩾ 1.0 μM). A significant decrease of the mitotic indices was detected at levels ⩾10 μM in the onions and reduction of root growth with ⩾100 μM. In the pollen fertility assays clear effects were observed at doses ⩾147.3 mg kg−1. Data concerning the annual use of the drug in European countries (France, Germany, Slovenia) enable the calculation of the predicted environmental concentration (PEC) values which are in the range between 3.3 and 5.0 ng L−1. Although comparisons with the genotoxic potencies of other commonly used cytostatic drugs and with highly active heavy metal compounds show that IM is an extremely potent genotoxin in higher plants, it is evident that the environmental concentrations are ⩾5 orders of magnitude lower as the levels which are required to cause adverse effects.