Acute and subchronic toxicities in dogs and genotoxicity of honokiol microemulsion

Abstract

This article aims to conduct toxicity test research on honokiol microemulsion(HM) to provide reference frame for the safe dose design as well as the toxic and adverse reaction monitoring in clinic. High performance liquid chromatography (HPLC) method was adopted to determine the concentration, stability and uniformity of HM and the results indicated that the test sample was conformed to the toxicity test requirements. In the acute toxicity test, six intravenous drip dosages, namely, 100.0, 66.7, 44.4, 19.8, 8.8, and 3.9 mg/kg were set, with one beagle dog in each dosage, respectively. In addition, the results also demonstrated that the approximate lethal dose range of HM was 66.7–100.0 mg/kg. In the subchronic toxicity test, beagle dogs were intravenously dripped with HM at doses of 1.25, 0.25 and 0.05 mg/kg for 30 days. During the test period, signs of gross toxicity, behavioral changes, body weight, rectal temperature, food consumption, ophthalmoscopy, electrocardiography, urinalysis, blood biochemistry, coagulation, hematology, organ weights and histopathology were examined. Under the present study conditions, the no-observed-adverse-effect level for HM was estimated to be 0.25 mg/kg. According to the results of bacterial reverse mutation, chromosomal aberration and micronucleus assays, HM exhibited no notable genotoxicity both in vivo and in vitro.