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

Bee Ping Teh¹, Nor Syaidatul Akmal Mohd Yousof^1*, Umi Rubiah Sastu@Zakaria¹, Siti Zubaidah Che Lem², Azlina Zulkapli², Inirah Che Ishak², Tavinraj Rajendran¹, Bazilah Jusoh¹, Nurul Syahira Shabudin¹, Dalnitha Lea Nicol¹, Norzahirah Ahmad¹

1. Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, 40170 Shah Alam, Selangor, Malaysia 

2. Special Resource Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, 50588 Kuala Lumpur, Malaysia

*Corresponding author: Nor Syaidatul Akmal Mohd Yousof, This email address is being protected from spambots. You need JavaScript enabled to view it.

CITATION: Teh, B. P., Mohd Yousof, N. S. A., Sastu@Zakaria, U. R., Che Lem, S. Z., Zulkapli, A., Che Ishak, I., Rajendran, T., Jusoh, B., Shabudin, N. S., Nicol, D. L., & Ahmad, N. (2025). Following OECD GLP guidelines: preliminary in vivo safety assessment of Brucea javanica fruit aqueous extract in Sprague Dawley rats. International Medical Research Journal, 11(2). https://doi.org/https://doi.org/10.63719/imrj.2025.11.02.008

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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 a nd 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 white 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.

KEYWORDS: Brucea javanica, melada pahit, acute toxicity, OECD GLP, median lethal dose (LD₅₀)