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Establishment of safety and toxicity profiles of metabolites of endophytic organisms from known medicinal plants are crucial in their pharmacological and biological applications. The aim of this study was to evaluate the oral acute toxicity (LD50) of crude extract of endophytic fungi isolated from Annona senegalensis Pers. The endophytic fungal metabolite was extracted with ethyl acetate. The LD50 was estimated following the method described by Lorke. Three dose levels (10, 100, and 1000 mg/kg) of the crude extract were administered to three mice each for the first phase using oral gavage needle in a single dose disposable syringe. The animals were observed for possible deaths or other side effects of the test substance in each group within 24 hours of the treatment. In the second phase, which was deduced from the first phase, eight mice were sub-divided into four groups of two mice each and they were treated with doses of 1200, 1600, 2900 and 5000 mg/kg orally. They were also observed within 24 hours and final LD50 value was determined. Results showed that the endophytic fungal extract exhibited no mortality or any histological defect in the liver tissues of the mice. More so, the immunological parameter tested showed significant increase in neutrophils and lymphocytes relative to the control in all the fungal isolates. Additionally, the LD50 for the crude metabolites was > 5000 mg/kg. This study has revealed that crude extract of endophytic fungi isolated from Annona senegalensis Pers did not show oral acute toxicity in mice. Further studies will evaluate long term-toxicity of the crude extract. Keywords: Endophytes, LD50, Annona senegalensis, Metabolites, Fungi