Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate -K2(B3O3F4OH) in Rats and Mice

Haveric, Anja; Haveric, Sanin; Hadzic, Maida; Ezic, Jasmin; Cetković, Tamara; Galic, Borivoj

doi:10.1590/s2175-97902023e21384

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Article • Braz. J. Pharm. Sci. 59 • 2023 • https://doi.org/10.1590/s2175-97902023e21384 copy

Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate -K₂(B₃O₃F₄OH) in Rats and Mice

Authorship SCIMAGO INSTITUTIONS RANKINGS

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.

Keywords:
Halogenated boroxine; BALB/c mice; Wistar rats; Sprague-Dawley rats; drug development

Animal strain	Dose mg/kg	Clinical findings	Necropsy
Sprague-Dawley rats	60; 75	body sag or decrease in grip strength, cyanosis, hind limb reflex or loss of pinna reflex, increased drinking or change in body posture, lacrimation, noisy breathing, piloerection, tremors,
	75	polypnea, reduced spontaneous locomotion with abnormal gait,
	75; 100	polypnea, reduced spontaneous locomotion with abnormal gait, vocalization	enlarged spleen enlarged adrenals
Wistar rats	40	hypothermia, leg stretching, passivity,
	40; 60	lying on the side
	60	body stretching, dyspnea, vocalization
	80; 90	absence of spontaneous locomotor activity, cyanosis, tremors, absence of reactivity	bleeding in abdomen and heart, lung clots
	40; 80; 90	bradypnea
BALB/c mice	30	lying on the side, scab around the site of administration, hypothermia,
	30; 60	body stretching
	60	bradypnea, convulsions, tail pitching, vocalization
	70		blood in lungs and pleura, severe abdominal bleeding

Test system	Dose per day (mg/kg)	Treated animals			Mortality (x/N)
Test system	Dose per day (mg/kg)	Male (♂)	Female (♀)	Total	Male (♂)	Female (♀)	Total (%)
Sprague-Dawley rats	50	0	1	1	0/0	0/1	0/1 (0%)
	60	0	3	3	0/0	0/3	0/3 (0%)
	75	0	3	3	0/0	1/3	1/3 (33.33%)
	100	0	1	1	0/0	1/1	1/1 (100%)

Test system	Dose per day (mg/kg)	Mortality (x/N)
Test system	Dose per day (mg/kg)	Male (♂)	Female (♀)	Total (%)
Wistar rats	30	0/3	0/3	0/6 (0%)
	40	0/3	0/3	0/6 (0%)
	50	2/3	3/3	5/6 (83.33%)
	60	2/3	1/3	3/6 (50%)
	70	2/3	2/3	4/6 (66.67%)
	80	2/3	3/3	5/6 (83.33%)
	90	2/3	3/3	5/6 (83.33%)

Test system	Dose per day (mg/kg)	Mortality (x/N)
Test system	Dose per day (mg/kg)	Male (♂)	Female (♀)	Total (%)
BALB/c mice	30	0/3	0/3	0/6 (0%)
	40	0/3	0/3	0/6 (0%)
	50	1/3	1/3	2/6 (33.33%)
	60	2/3	1/3	3/6 (50%)
	70	3/3	1/3	4/6 (66.67 %)

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: A. Haveric. Institute for Genetic Engineering and Biotechnology. University of Sarajevo. Zmaja od Bosne 8. 71000 Sarajevo. Bosnia and Herzegovina. Phone: +38733220926. E-mail: anja.haveric@ ingeb.unsa.ba; anjahaveric@gmail.com.