ASSESSMENT OF ACUTE AND SUB CHRONIC TOXICITY OF DEOXYCHOLIC ACID ON ORAL ADMINISTRATION IN RODENTS

Abstract

Deoxycholic acid (DCA) is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria and used traditionally to treat immune related disorders. The objective of the present study was to evaluate acute and sub-acute toxicity of DCA in mice and rats after oral administration following OECD test guidelines. Toxicological profile of DCA were evaluated by single-oral toxicity (5, 10, 100 and 200 mg/kg), 14-day repeated oral dose toxicity (1, 2.5 and 5 mg/kg) in mice and 28-days repeated-oral dose toxicity (30, 100, 300 and 1000 mg/kg) in healthy SD rats. Oral single dose of DCA caused decreased body weight and the mice were found lethargic. DCA was lethal at doses ≥ 10 mg/kg and caused mortality/morbidity by 48 hours post dosing. In 14-days repeated oral toxicity study with DCA as oral gavage at 1, 2.5 and 5 mg/kg, no effects on body weight and no treatment related clinical signs were observed. 28-day repeated oral toxicity demonstrates dose-dependent significant increase in WBC (up to 43%), absolute neutrophil (up to 61%) and absolute lymphocyte (up to 42%) counts suggesting an immunostimulatory role on humoral immunity. DCA at doses >1000 mg/kg was toxic and caused anemia. Minimum lethal dose (MLD) and MTD of DCA in mice was estimated to be equal or greater than 10 mg/kg and 5 mg/kg/day, respectively. Oral NOAEL of DCA was30 mg/kg/day in SD rats. DCA did not cause any delayed effects. DCA appears to be safe for human consumption.