Acute and sub-acute toxicity study reveals no dentrimental effect of formononetin in mice upon repeated i.p. dosing.

ABSTRACT

AIM: Formononetin is a phytoestrogen which possess different pharmacological activities. The intraperitoneal route permits the identification of target organs involved in toxicity without compromising the molecule's bioavailability. The current study investigated the safety profile of intraperitoneal formononetin in Swiss albino mice. MATERIAL AND METHODS: For acute toxicity study, formononetin administered intraperitoneally to mice at the doses of 5, 50, 100, 150, 200, and 300 mg/kg for 14 days. For the subacute toxicity study, mice were intraperitoneally administered with formononetin (12.5, 25, and 50 mg/kg) daily for 28 days. RESULTS: During the acute study, no deteriorating effect was observed on body weight, food and water intake, no behavioral changes were observed in animals. The lethal dose 50% (LD50) of formononetin was determined to be 103.6 mg/kg of BW, with a no observed adverse effect level (NOAEL) of 50 mg/kg of BW. Mortality was observed in the 300 mg/kg dose group and histopathological changes such as a mild degree of diffuse granular degeneration in the liver but for rest all doses did not have any adverse effect. In subacute study, no signs of adverse effects, mortality, no changes in body weight, food and water intake, and hematological and biochemical parameters were observed. Histopathology of subacute study indicates, formononetin did not have any noxious effect on organs. CONCLUSION: Formononetin shows mortality at acute dose 300 mg/kg and LD50 at 103.6 mg/kg of BW, with a NOAEL of 50 mg/kg of BW, rest all doses for acute and sub-acute are safe when given intraperitoneally.