Due to their antibacterial and antiviral effects, silver nanoparticles (AgNP) are one of the most widely used nanomaterials worldwide in various industries, e.g., in textiles, cosmetics and biomedical-related products. Unfortunately, the lack of complete physicochemical characterization and the variety of models used to evaluate its cytotoxic/genotoxic effect make comparison and decision-making regarding their safe use difficult. In this work, we present a systematic study of the cytotoxic and genotoxic activity of the commercially available AgNPs formulation Argovit™ in Allium cepa. The evaluated concentration range, 5–100 µg/mL of metallic silver content (85–1666 µg/mL of complete formulation), is 10–17 times higher than the used for other previously reported polyvinylpyrrolidone (PVP)-AgNP formulations and showed no cytotoxic or genotoxic damage in Allium cepa. Conversely, low concentrations (5 and 10 µg/mL) promote growth without damage to roots or bulbs. Until this work, all the formulations of PVP-AgNP evaluated in Allium cepa regardless of their size, concentration, or the exposure time had shown phytotoxicity. The biological response observed in Allium cepa exposed to Argovit™ is caused by nanoparticles and not by silver ions. The metal/coating agent ratio plays a fundamental role in this response and must be considered within the key physicochemical parameters for the design and manufacture of safer nanomaterials.

Background/Objectives: Silver nanoparticles (AgNPs) hold great promise for antimicrobial, antiviral, and anticancer applications; however, concerns about their toxicity remain a major barrier to their medical use. This study systematically evaluates the acute oral toxicity of five well-characterized AgNP formulations from the Argovit™ family, which previously showed remarkable biomedical properties. Methods: We determine the median lethal dose (LD50), assess clinical signs, and identify the histopathological alterations in mice following oral administration for each formulation. The LD50 was calculated for AgNPs (metallic silver plus stabilizing agent) and for the complete formulation (including water). Results: All formulations showed exceptionally high LD50 values (86,020–150,535 mg/kg) considering the complete formulation, surpassing those reported for other AgNPs in the literature (typically ≤5,000 mg/kg). Clinical signs and toxicological assessment reveal differences in the response of the AgNPs formulations, but all exhibit extremely low toxicity. Histopathological changes were minimal compared to those caused by other AgNP formulations, even though we used doses several times higher. The estimated human LD50 values for the assessed Argovit AgNPs formulations are 17-30 times higher than those reported for other AgNP formulations in the literature. Conclusions: The remarkably low toxicity found in this work contradicts the prevailing assumption that only biogenically synthesized AgNP are biocompatible, highlighting these synthetic PVP-AgNP formulations as a highly safe alternative. The study suggests that the low LD50 may be due to the peculiar structure of Argovit AgNP formulations, which, according to recent data, consists of Ag cores incorporated into PVP nano- and microgels. A high percentage of rapid elimination of Argovit AgNPs from organisms (>98%) via feces also contributes to low LD50. To our knowledge, the present work is the first to study the LD50 of AgNPs-nanogel systems.