BACKGROUND: E. hirta or tawa-tawa is a small annual herb common to tropical countries. In the Philippines, the decoction of the whole plant is used for the treatment of dengue because of its apparent platelet increasing property. While efforts are ongoing to determine the role of E. hirta for dengue, this study focused on its safety.

OBJECTIVE: This study determined the median lethal dose (LD50), toxidromes and reversibility of toxic effects following the acute oral administration of the crude aqueous extract in Sprague-Dawley rats.

METHODS: The Up-and-Down Procedure (Organization for Economic Cooperation and Development (OECD) Test Guideline 425) was conducted after the preliminary tests for the aqueous extract such as phytochemical and pesticide residue analyses and tests for aflatoxin and heavy metals.

RESULTS: Phytochemical screening showed the presence of tannins, glycosides and alkaloids in the plant extract. The aqeous extract contained allowable aflatoxin levels. Organochlorines, organophosphates and heavy metals such as arsenic, cadmium, lead and mercury were not detected in the aqueous extract. The LD50 of the aqueous extract was greater than 5000 mg/kg. The test animals did not experience significant body weight alterations. Gross necropsy revealed a hematoma on top of the skull and in the large intestine and a small, round protrusion in the stomach of the test animals. Histopathological examination showed foci of perivascular hemorrhages and neuronal degeneration in the brain, multifocal submucosal hemorrhages in the large intestine and fragmented very dark staining nuclei and fibrin stands with red blood cells in the stomach of test animals.

CONCLUSION: While the acute oral LD50 of the aqueous extract is greater than 5000 mg/kg, there is a need to pay attention to the toxidromes showing evidence of dose-dependent CNS depression. Histopathological examination showed multifocal submucosal hemorrhages and foci of perivascular hemmorrhages and neuronal necrosis indicating an acute hemorrhagic enteritis and cerebral hemorrhage, respectively. These findings and crucial in the light of the anecdotal use of E. hirta for the treatment of dengue hemorrhagic fever.