Acute and Repeated Dose 28-Day Oral Toxicity Studies of Phlorotannin Rich Fraction of Sargassum tenerrimum, A Marine Brown Algae

Abstract

Sargassum tenerrimum is a marine brown algae rich in phlorotannins, a class of marine polyphenols with significant biological activities. The present study aimed to prepare a phlorotannin-rich fraction from S. tenerrimum (PST) and evaluate its acute and subacute oral toxicity in Wistar albino rats according to the procedures and methods of the OECD test guidelines for acute and repeated dose 28-day oral toxicity studies. S. tenerrimum powder was extracted with ethanol and further fractionated with ethylacetate, 1-butanol, and water. The ethyl acetate fraction was found to have the highest total phlorotannin concentration and was evaluated for its safety. In the acute oral toxicity study, a single dose of PST at 2000 mg/kg body weight did not result in any treatment-related clinical symptoms of toxicity or mortality. Therefore, the median lethal dose (LD50) of PST was identified as greater than 2000 mg/kg. The subacute oral toxicity investigation at 200, 400, and 800 mg/kg doses administered for 28 days with a 14-day recovery period revealed no treatment-related adverse clinical symptoms or mortality/morbidity. The treated animals exhibited normal weight gain, feed intake and did not result in clinically significant toxicity as measured by clinical blood chemistry and hematological markers. Gross and histological examinations of selected tissues did not reveal any notable adverse alterations associated with the intervention. Under the study's findings, the LD50 for PST was determined to be >2000 mg/kg b.wt. and No Observed Adverse Effect Level (NOAEL) to be 800 mg/kg rat b.wt.