Following OECD GLP guidelines: preliminary in vivo safety assessment of Brucea javanica fruit aqueous extract in Sprague Dawley rats

Abstract

This study evaluates the acute toxicity of Brucea javanica fruit following a single oral administration in female Sprague Dawley rats, with clinical assessments conducted over 14 days, in line with the Organisation for Economic Co-operation and Development Guideline for the Testing of Chemicals, Section 4, Test No. 420: Acute Oral Toxicity - Fixed Dose Procedure. The chemical profile of the B. javanica raw material used in this study was investigated, and its authenticity was confirmed with bruceine A detection. Two doses, 300 mg/kg and 2,000 mg/kg body weight (BW), were tested, with five rats receiving 300 mg/kg BW and one rat receiving 2,000 mg/kg BW, which displayed clinical signs of toxicity. Rats given 300 mg/kg BW had increased body weight at the end of the observation period, along with increased food intake. Macroscopic evaluations revealed no significant abnormalities except a dilated uterine horn (n = 3) and whitish discolouration on the liver’s caudate lobe. Histological evaluation revealed mild, dose-dependent lesions in the liver and ileum at both 300 and 2,000 mg/kg BW, whereas moderate lesions were observed in the kidneys, duodenum, and jejunum were confined to the 2,000 mg/kg BW group. Gastrointestinal lesions in the 300 mg/kg BW rats were likely due to fasting-related erosion, and liver and kidney lesions may be associated with physiological changes during euthanasia. Further investigation into the mortality of the rat given 2,000 mg/kg BW dose revealed slightly pronounced organ lesions. The current result indicates the median lethal dose (LD50) value for the freeze-dried aqueous extract of B. javanica fruits is likely below 2,000 mg/kg BW. Follow-up studies with prolonged exposure and repeated dosing are warranted to fully characterise the toxicity of this medicinal plant.