NTP technical report on the toxicity studies of (+)-usnic acid (CASRN 7562-61-0) administered in feed to F344/N nctr rats and B6C3F1/Nctr mice / National Toxicology Program (U.S.).

Format:

Book

Author/Creator:

National Toxicology Program (U.S.), author, issuing body.

Series:

Toxicity report series.

Toxicity report series

Language:

English

Subjects (All):

Toxicity testing.

Physical Description:

1 online resource.

Other Title:

NTP technical report on the toxicity studies of

Place of Publication:

North Carolina, USA : National Toxicology Program, 2022.

Summary:

(+)-Usnic\sacid is a secondary metabolite of lichens belonging to the Usnea genus. Usnea lichens and purified usnic\sacids have been used historically in traditional herbal medicine as bactericidal and antimicrobial agents. (+)-Usnic\sacid exhibits membrane proton uncoupling activity, which not only forms the mechanistic basis of its bactericidal action, but also has provided a rationale for its use as a fat-burning, weight-loss agent. Purified (+)-usnic\sacid has been marketed in the United States for this purpose either alone or in combination with other chemical agents. Use of some of these fat-burning products that contain (+)-usnic\sacid has resulted in serious liver damage. This study investigated the potential toxicity of (+)-usnic\sacid in male and female F344/N Nctr rats and B6C3F1/Nctr mice that were exposed via feed for 3\smonths. F344/N Nctr rats were administered 0, 30, 60, 120, 360, or 720\sppm in feed, while B6C3F1/Nctr mice were administered 0, 15, 30, 60, 180, or 360\sppm in feed. Exposure of F344/N Nctr rats and B6C3F1/Nctr mice to (+)-usnic\sacid in feed for 3 months resulted in hepatotoxicity in male rats at exposure levels above 120\sppm. Mild toxicity as demonstrated by increased serum enzyme activity was observed in female rats at exposure levels of 720 ppm. In male mice, moderate but significant increases in alanine aminotransferase and alkaline phosphatase were observed at exposure levels of 360\sppm, moderate significant increases in blood urea nitrogen were observed at exposure levels of 180 and 360\sppm, whereas moderate significant increases in serum creatinine were observed at exposure levels of 60, 180, and 360\sppm. There were significantly fewer female rats cycling in the 720\sppm group than in the control group, due to extended diestrus. Significant body weight decreases were achieved at exposure levels of 720\sppm in male and female rats. Exposure to 600\sppm (+)-usnic\sacid for 14\sdays significantly increased the incidence of micronuclei in erythrocytes or reticulocytes from both male and female B6C3F1/Nctr mice; exposure to 1,200\sppm significantly increased the incidence of micronuclei in reticulocytes in male B6C3F1/Nctr mice. No-observed-adverse-effect levels (NOAELs) of 120\sppm and 30\sppm of (+)-usnic acid administered in feed were established for F344/N Nctr rats and B6C3F1/Nctr mice, respectively, on the basis of the results of these subchronic studies.SYNONYMS: 2,6-diacetyl-7,9-dihydroxy-8,9b(R)-dimethyldibenzofuran-1,3(2H,9bH)-dione; (d)-usnic acid; usneine; usninic acid; usniacin TRADE NAMES: usnea extract, usnic acid.

Notes:

Description based on online resource; title from PDF title page (National Toxicology Program, viewed April 22, 2023).