Almond hull, a substantial byproduct constituting more than half of almond fresh weight, has garnered recent attention due to its abundance in fiber and bioactive content. Despite this huge interest, data on its toxicity remain scarce. In line with the Organization for Economic Cooperation and Development (OECD) 423 guidelines, this study conducted an acute oral toxicity test using almond hull powders processed from three major almond varieties of Butte, Monterey, and Nonpareil on BALB/c female mice, administering dosages of 300 mg/kg body weight (bw), 2000 mg/kg bw, and 5000 mg/kg bw, with observations over a 14-day period. The results indicated that almond hull powders were non-toxic, aligning with the Globally Harmonized System’s classification. Administering up to 5000 mg/kg bw of all three varieties of almond hull powders (female BALB/c mice) and 10,000 mg/kg bw of Monterey almond hull powders (both female and male mice) induced no adverse effects in terms of mortality, body weight changes, food intake, organ to weight ratio, and clinical biochemistry. Additionally, histopathological examination revealed no organ abnormalities. This study demonstrates the non-toxic nature of almond hull as an edible food ingredient under experimental conditions, encouraging the further exploration of its potential for safe consumption and its health benefits.

Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required.