Citrus aurantium (bitter orange) extract: Safety assessment by acute and 14-day oral toxicity studies in rats and the Ames Test for mutagenicity

摘要

Abstract The primary active constituent in bitter orange extract (BOE) is p -synephrine. This study assessed the safety of a BOE standardized to 50% p -synephrine following short-term exposure to rats and by the Ames Test. Following 5000?mg/kg of the extract orally to female rats all animals survived. Administration at 2000?mg/kg to female rats for four days yielded no signs of toxicity. Five male and five female rats were administered the BOE at 0, 250, 500, 1000 and 2000?mg/kg/day for 14 days. No significant effects were observed at any dose with respect to body weights, food intake, absolute and relative organ weights, hematology, clinical chemistry, and pathology. Two male rats died after 2000?mg/kg with gastrointestinal impaction at necropsy. During week two of 1000?mg/kg and 2000?mg/kg/day, rats exhibited transient signs of repetitive burrowing of heads in the bedding material (hypoactivity) for about 15 and 45?min, respectively. The no-observed-effect-level (NOEL) was 500?mg/kg/day. The mutagenic potential was assessed at and up to the limit dose of 5000 μg/plate in a Salmonella typhimurium reverse mutation (Ames) test, performed in duplicate as a pre-incubation assay in the presence and absence of metabolic activation (S9). The BOE did not induce an increase in the frequency of revertant colonies at any dose in the five tester strains, and was therefore non-mutagenic. Highlights ? The LD50 of a bitter orange extract containing 50% p-synephrine was greater than 5000?mg/kg. ? The NOEL of the bitter orange extract was 500?mg/kg/day. ? Bitter orange extract was non-mutagenic in the S.?typhimurium reverse mutation assay.