Assessment of safety through mutagenicity and subchronic toxicity studies with black pepper extract preparation.

Introduction: Black pepper (Piper nigrum) is a rich source of natural and bioactive components such as N-trans-feruloyltyramine (NFT). In this paper, we discuss the results of the subchronic toxicity and mutagenicity studies conducted to understand the potential for adverse effects if any, of Black Pepper Extract Preparation (BPE).

Methods: To evaluate mutagenicity, an Ames test was conducted with BPE in the presence and absence of S9 metabolic activation. Long-term safety was inferred through a 90-day subchronic toxicology study using adult rats. Dose levels were selected with expected human intake levels of NFT (120 mg/kg/day), with an acceptable safety factor, for preclinical safety and tolerability. Sprague Dawley rats were fed diets targeting dietary intakes (doses) of 0, 125, 350, or 700 mg/kg/day of BPE for 90 days, an NFT dose level equivalent to 68, 190, and 380 mg/kg/day.

Results: In vitro Ames test up to 5000 µg/plate with and without S9 metabolic activation showed no BPE-related increases in revertant colony numbers and was non-mutagenic. There were no BPE-related changes in viability, clinical signs, body weight, food consumption, and organ weights. BPE dietary administration did not induce any treatment-related changes in hematology, clinical chemistry, other macroscopic or microscopic endpoints.

Discussion and conclusion: The highest dose tested with BPE (700 mg/kg/day) was the no-observed-adverse-effect level (NOAEL) that revealed no adverse effects. Based on toxicological endpoints evaluated, this NOAEL for BPE corresponded to a human equivalent NFT dose level of 380 mg/kg/day, dependent upon a (∼50%) concentration of NFT in BPE.