Safe usage levels of aqueous Hippophae rhamnoides fruit extract in cosmetics estimated by threshold of toxicological concern, point of departure, and history of safe consumption

Abstract

Botanical ingredients pose challenges to cosmetic safety assessors due to complex and variable composition. We estimated the safe usage levels of aqueous Hippophae rhamnoides fruit extract (HRFE) in cosmetics using Threshold of Toxicological Concern (TTC), Point of Departure (PoD) estimation, and history of safe consumption approaches. Skin and eye irritation and genotoxicity of HRFE were excluded through in vitro tests, first. The safe usage level of HRFE was estimated using TTC approach through identifying 85 constituents accounting for 98.46 % of HRFE on mass basis, and calculating systemic exposure dosage levels. PoD from the rodent 90-day oral repeated-dose toxicity study and history of safe food consumption of Hippophae rhamnoides fruit were also utilized to derive safe usage levels of HRFE in cosmetics. Maximum safe usage levels of HRFE were estimated to be 0.125 mg/kg bw/day (extract powder), 0.5 mg/kg bw/day, and 166 mg/kg bw/day with TTC, PoD and history of safe consumption approach respectively, showing that TTC is the most conservative and history of safe consumption, the least. However, questions of material equivalence and route-difference remained for PoD and history of safe consumption. Collectively, this study may help to understand the pros and cons of current safety assessment methodologies for botanical ingredients. © 2025 Elsevier Inc.