Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02

Kon-Young Ji, Ki Mo Kim, Jeong-Ja Oh, Jung-Woo Kim, Woo-Joo Lee, Hyeon Cho, Hyun-Kul Lee, Joo Young Lee, Sungwook Chae, Kon-Young Ji, Ki Mo Kim, Jeong-Ja Oh, Jung-Woo Kim, Woo-Joo Lee, Hyeon Cho, Hyun-Kul Lee, Joo Young Lee, Sungwook Chae

Abstract

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

Trial registration: ClinicalTrials.gov NCT03310385.

Keywords: 28-day repeated-dose toxicity study; GHX02; genotoxicity; herbal medicine; single oral dose toxicity study.

Conflict of interest statement

The authors have no conflict of interests to declare.

© 2019 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Body weight (mean ± SD) of male and female rats treated with 0, 1250, 2500 and 5000 mg/kg/day in the 28‐day repeated‐dose oral toxicity study of GHX02 with a 14‐day recovery period. *Significantly different from the vehicle control at P < .05 [Colour figure can be viewed at http://wileyonlinelibrary.com]
Figure 2
Figure 2
Effect of GHX02 on the weekly food and water consumption after oral administration in male and female rats for 28 days. A, Weekly food consumption. B, Weekly water consumption. Data are expressed as the mean ± SD [Colour figure can be viewed at http://wileyonlinelibrary.com]

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