Exploring the Allium cepa Model in Nanotoxicology: A Scoping Review Protocol of Biological and Ecotoxicological Outcomes

In recent years, the development of nanostructured systems, particularly in nanomedicine and nanocosmetics, has surged. With the increasing use of nanocarriers, concerns have also arisen about their toxicity to human health and the environment. Nanocarriers, when released into the environment, can pose ecological risks. To mitigate these concerns, alternative models have been implemented in the early stages of nanocarrier development, following the 3Rs principle—Reduction, Refinement, and Replacement—in using animals for toxicological testing. One notable model is Allium cepa, or the onion root model, which assesses substances' cytotoxic, genotoxic, and ecotoxicological effects, including nanocarriers. This scoping review aims to map and analyze the literature on the Allium cepa model in toxicity studies, focusing on the biological and ecotoxicological effects of nanocarriers developed for therapeutic or cosmetic applications. The review will follow the methodological guidelines set by the Joanna Briggs Institute (JBI) and the results will be reported by the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Electronic databases, such as PubMed, Scopus, and Web of Science, will be searched to identify relevant studies. To guide this review, we have formulated the question: "How has the Allium cepa model served as an alternative to assessing the toxicity of nanocarriers?" This scoping review will focus on the types of nanocarrier tested and assess key toxicity parameters, including cytotoxicity, genotoxicity, oxidative stress, and mitotic alterations. Additionally, we will summarize findings from various studies to determine whether the Allium cepa model is primarily used to predict toxicity in higher organisms or to study ecotoxicity. We will also identify methodological variations and gaps in the literature to enhance our understanding of Allium cepa's role in nanotoxicity. Therefore, this review will highlight the model's applications, methodologies, and potential for future research in nanotoxicology and ecotoxicity using the Allium cepa assay.