BackgroundThe safety potential of the methanol extract of Trema orientalis (TOM) leaf was evaluated in albino Wistar rats using biochemical, haematological, and histological indices in both acute and sub-chronic toxicity studies. MethodsThe animals were managed following the National Institute of Health (NIH) stipulated protocols for handling laboratory animals. The weight of each animal was recorded upon arrival and monitored throughout the study. The animals were allowed to acclimatize for 14 days, after which they were reweighed and randomly distributed into four groups of three female rats (n=12) for acute toxicity studies. Group A was given distilled water, and Groups B, C, and D were given a single dose of 2000, 4000, and 5000 mg/kg bw TOM extract, respectively. On day 15, each animal was anaesthetized and then euthanized. For the sub-chronic toxicity study, animals were randomly distributed into five groups of eight female rats (n=40). They were dosed daily for 28 days. Group A (Negative control group) was given distilled water. Groups B, C, and D had 200, 400, and 800 mg/kg bw TOM extract and Group E (Vehicle control group) were given 0.25 % of sodium carboxyl methyl cellulose (CMC). Five animals were anaesthetized and then euthanized on day 29, while three animals were kept for recovery evaluation for another two weeks without further administration of the extract. Ten organs were excised from each animal and weighed. The liver and kidney were processed for histopathological studies, while the blood samples were collected for biochemical and haematological assays. ResultsFrom acute toxicity studies, the LD50 value of TOM extract was estimated to exceed 5000 mg/kg bw via oral passage. From Sub-chronic toxicity studies, biochemical results showed a significant (p < 0.05) reduction in total protein, albumin, globulin, AST, ALP, and ALT in a dose-dependent manner. Histology of the liver and kidney tissues of all the animals except the kidney of the 800 mg/kg group had no visible lesions; this sets the safety dose for TOM at above 400 mg/kg but below 800 mg/kg. Recovery animals had significantly (p < 0.05) increased total protein, total bilirubin, and ALP and decreased albumin and direct bilirubin levels. ConclusionThis study reports the safety dose of TOM, a reputable medicinal plant extract. This is the first study reporting that the LD50 value of TOM extract exceeds 5000 mg/kg bw via oral passage.