Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate - K2 (B3 O3 F4 OH) in Rats and Mice

Abstract Biological activity of boron-containing compounds (BCCs) has been well-known. Growing interest and numerous applications for BCCs have been reported. Boron and boron-containing acids show low acute toxicity in mammals but data on halogenated boroxine (HB) - dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH) acute toxicity have not been reported before. This compound, characterized as a potential therapeutic for skin changes, exhibits no observable genotoxicity in doses lower that 0.1 mg/ml in vitro and 55 mg/kg in vivo. It has also been confirmed as an antitumour agent both in vitro and in vivo as well as an inhibitor of enzymes involved in antioxidant mechanisms. The aim of this study was to assess the acute toxicity of HB and to determine the maximum tolerated dose as well as a dose free of any signs of toxicity in different test organisms. Acute toxicity of HB was tested in Sprague-Dawley and Wistar rats and BALB/c mice after single parenteral application of different doses. We determined doses free of any sign of toxicity and LD50 after single dose administration. LD50 of HB ranges from 63 to 75 mg/kg in different test models, meaning that HB shows moderate toxicity

Genotoxicity Evaluation of Dipotassium -Trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), in Human Lymphocyte Cultures and Mice Reticulocytes

ABSTRACT Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH) in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH). In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH) was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH) is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations.