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The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

Key Points Microbial pathogens require nutrient metals in order to grow and cause disease. However, excess metals are toxic, so metal levels must be tightly regulated during infection. Vertebrates have evolved to exploit this metal dependence and metal toxicity through strategies that either prevent access to nutrient metal or direct excess metals towards invading pathogens. Collectively, these processes are known as nutritional immunity. The struggle between host and pathogen for nutrient metals is best studied in the area of Fe. Fe is sequestered from invading pathogens either intracellularly or in high-affinity Fe-binding proteins. To combat host-mediated Fe sequestration, microbial pathogens elaborate several high-affinity Fe acquisition systems. Recently, vertebrate proteins of the innate immune system have been identified that prevent microbial infection through the chelation of nutrient Mn and Zn. These proteins are members of the S100 family of Ca-binding proteins and are abundant at sites of inflammation. In addition to Mn and Zn sequestration, vertebrates can use strategies to direct toxic levels of Mn and Zn towards microbial pathogens. Bacterial measures to combat Mn and Zn sequestration, as well as the toxicity that is associated with excess levels of these metals, are beginning to be uncovered. It is becoming increasingly evident that host-mediated direction of excess Cu towards microbial pathogens is a crucial aspect of vertebrate defence against infection. This observation has provided an explanation for the broad conservation of Cu detoxification systems across disease-causing microorganisms. The importance of nutritional immunity for defence against infection is highlighted by the observation that inherited defects in transition metal homeostasis dramatically affect host susceptibility to certain infectious diseases. This fact underscores the tremendous therapeutic potential of targeting bacterial metal acquisition systems. Vertebrates protect against infection through the sequestration of nutrient metals, and bacterial pathogens have evolved sophisticated acquisition strategies to circumvent this host defence. In this Review, Hood and Skaar describe this molecular arms race for nutrients. Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen–host interface.

Ensuring food security is essential for achieving sustainable global development, requiring a balance between sufficient food production and maintaining its safety and nutritional value. However, this objective faces considerable challenges due to the infiltration of toxic metal species into the food supply. Heavy metals and metalloids, depending on their molecular form and daily dose, exhibit varying degrees of toxicity, making the precise identification of their species essential for assessing their impact on human health and the environment. This study focuses on identifying the primary anthropogenic sources and dissemination pathways of heavy metal pollutants, with an emphasis on their speciation and bioavailability. It examines how toxic metal species, such as Pb2+, Cd2+, Hg2+, and various arsenic species (AsIII and AsV), infiltrate ecosystems, bioaccumulate within the food chain, and ultimately compromise food safety and nutritional value. Furthermore, the research explores the physiological and biochemical disruptions caused by these toxic metal species, including the displacement of essential ions from enzymatic active sites and transport proteins due to competitive binding by pollutants, oxidative stress induced by reactive oxygen species generation, and cellular dysfunction affecting metabolic pathways and signaling cascades, all of which contribute to both chronic and acute health conditions. By providing a detailed analysis of exposure routes and toxicological processes, this paper highlights the far-reaching consequences of heavy metal contamination on public health and agricultural sustainability. Special attention is given to the need for precise terminology, as the toxicity of metals is inherently linked to their daily dose and chemical species rather than their elemental form. Finally, this study advocates for integrated, multidisciplinary strategies aimed at mitigating these risks, enhancing ecosystem stability, and ensuring long-term food security in the face of environmental challenges.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives: branching glycosyltransferase from Rhodothermus obamensis expressed in Bacillus subtilis, cassia gum, cyclamic acid and its salts (dietary exposure assessment), cyclotetraglucose and cyclotetraglucose syrup, ferrous ammonium phosphate, glycerol ester of gum rosin, glycerol ester of tall oil rosin, lycopene from all sources, lycopene extract from tomato, mineral oil (low and medium viscosity) class II and class III, octenyl succinic acid modified gum arabic, sodium hydrogen sulfate and sucrose oligoesters type I and type II.Specifications for the following food additives were revised: diacetyltartaric acid and fatty acid esters of glycerol, ethyl lauroyl arginate, glycerol ester of wood rosin, nisin preparation, nitrous oxide, pectins, starch sodium octenyl succinate, tannic acid, titanium dioxide and triethyl citrate.Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.

Abstract Ochratoxin A (OTA), a mycotoxin primarily produced by Aspergillus and Penicillium species, poses significant risks to food safety due to its nephrotoxic, immunosuppressive, and carcinogenic effects. This review presents an in-depth analysis of OTA’s presence in food commodities, toxicity, regulatory standards, and current decontamination strategies. Physical methods, including heat treatment and adsorption using activated carbon or bentonite, offer mitigation avenues but often face challenges in food quality preservation. Chemical methods like ozone (O3) treatment and alkaline hydrolysis show promise in reducing OTA levels in cereals and coffee, while biological approaches involving Trichoderma, Bacillus, and Aspergillus strains demonstrate effective biodegradation in vitro. Enzymatic detoxification and microbial biotransformation are particularly promising, but more application-specific studies and regulatory approvals are needed. Future focus should be on integrating these technologies with food processing systems and establishing standardised efficacy assessments. The review highlights the need for practical, scalable, and safe OTA detoxification methods to protect public health and ensure global food security. Graphical Abstract Graphical Abstract

Food additive zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement in the food and agriculture industries. However, ZnO NPs are directly added to complex food-matrices and orally taken through the gastrointestinal (GI) tract where diverse matrices are present. Hence, the dissolution properties, interactions with bio- or food-matrices, and the ionic/particle fates of ZnO NPs in foods and under physiological conditions can be critical factors to understand and predict the biological responses and oral toxicity of ZnO NPs. In this review, the solubility of ZnO NPs associated with their fate in foods and the GI fluids, the qualitative and quantitative determination on the interactions between ZnO NPs and bio- or food-matrices, the approaches for the fate determination of ZnO NPs, and the interaction effects on the cytotoxicity and oral toxicity of ZnO NPs are discussed. This information will be useful for a wide range of ZnO applications in the food industry at safe levels.

Background Engineered nanomaterials (ENM) are used extensively in food products to fulfill a number of roles, including enhancement of color and texture, for nutritional fortification, enhanced bioavailability, improved barrier properties of packaging, and enhanced food preservation. Safety assessment of ingested engineered nanomaterials (iENM) has gained interest in the nanotoxicology community in recent years. A variety of test systems and approaches have been used for such evaluations, with in vitro monoculture cell models being the most common test systems, owing to their low cost and ease-of-use. The goal of this review is to systematically assess the current state of science in toxicological testing of iENM, with particular emphasis on model test systems, their physiological relevance, methodological strengths and challenges, realistic doses (ranges and rates), and then to identify future research needs and priorities based on these assessments. Methods Extensive searches were conducted in Google Scholar, PubMed and Web of Science to identify peer-reviewed literature on safety assessment of iENM over the last decade, using keywords such as “nanoparticle”, “food”, “toxicity”, and combinations thereof. Relevant literature was assessed based on a set of criteria that included the relevance of nanomaterials tested; ENM physicochemical and morphological characterization; dispersion and dosimetry in an in vitro system; dose ranges employed, the rationale and dose realism; dissolution behavior of iENM; endpoints tested, and the main findings of each study. Observations were entered into an excel spreadsheet, transferred to Origin, from where summary statistics were calculated to assess patterns, trends, and research gaps. Results A total of 650 peer-reviewed publications were identified from 2007 to 2017, of which 39 were deemed relevant. Only 21% of the studies used food grade nanomaterials for testing; adequate physicochemical and morphological characterization was performed in 53% of the studies. All in vitro studies lacked dosimetry and 60% of them did not provide a rationale for the doses tested and their relevance. Only 12% of the studies attempted to consider the dissolution kinetics of nanomaterials. Moreover, only 1 study attempted to prepare and characterize standardized nanoparticle dispersions. Conclusion We identified 5 clusters of factors deemed relevant to nanotoxicology of food-grade iENM: (i) using food-grade nanomaterials for toxicity testing; (ii) performing comprehensive physicochemical and morphological characterization of iENM in the dry state, (iii) establishing standard NP dispersions and their characterization in cell culture medium, (iv) employing realistic dose ranges and standardized in vitro dosimetry models, and (v) investigating dissolution kinetics and biotransformation behavior of iENM in synthetic media representative of the gastrointestinal (GI) tract fluids, including analyses in a fasted state and in the presence of a food matrix. We discussed how these factors, when not considered thoughtfully, could influence the results and generalizability of in vitro and in vivo testing. We conclude with a set of recommendations to guide future iENM toxicity studies and to develop/adopt more relevant in vitro model systems representative of in vivo animal and human iENM exposure scenarios.

Cyclodextrins (CDs) are cyclic oligomers broadly used in food manufacturing as food additives for different purposes, e.g., to improve sensorial qualities, shelf life, and sequestration of components. In this review, the latest advancements of their applications along with the characteristics of the uses of the different CDs (α, β, γ and their derivatives) were reviewed. Their beneficial effects can be achieved by mixing small amounts of CDs with the target material to be stabilized. Essentially, they have the capacity to form stable inclusion complexes with sensitive lipophilic nutrients and constituents of flavor and taste. Their toxicity has been also studied, showing that CDs are innocuous in oral administration. A review of the current legislation was also carried out, showing a general trend towards a wider acceptance of CDs as food additives. Suitable and cost-effective procedures for the manufacture of CDs have progressed, and nowadays it is possible to obtain realistic prices and used them in foods. Therefore, CDs have a promising future due to consumer demand for healthy and functional products.

Polymeric anthocyanins are biologically active, pH-sensitive natural compounds and pigments with beneficial functional, pharmacological and therapeutic properties for consumer health. More recently, they have been used for the manufacture of active and pH-sensitive (“intelligent”) food nanopackaging, due to their bathochromic effect. Nevertheless, in order for polymeric anthocyanins to be included either as a functional food or as a pharmacological additive (medicinal food), they inevitably need to be stabilized, as they are highly susceptible to environmental conditions. In this regard, nanopackaging has become a tool to overcome the limitations of polymeric anthocyanins. The objective of this study was to evaluate their structural, thermal, morphological, physicochemical, antioxidant and antimicrobial properties, as well as their responses to pH changes, and the cytotoxicity of blends made from polymeric anthocyanins extracted from Jamaica flowers (Hibiscus sabdariffa) and natural or organo-modified montmorillonite (Mt), as active and pH-sensitive nanopackaging. This study allowed us to conclude that organo-modified Mts are efficient pH-sensitive and antioxidant nanopackaging systems that contain and stabilize polymeric anthocyanins compared to natural Mt nanopackaging and stabilizing polymeric anthocyanins. However, the use of these polymeric anthocyanin-stabilizing organo-modified Mt-based nanopackaging systems are limited for food applications by their toxicity.

Nano-sized nickel magnesium copper zircon silicate (1MgO: 2CuO: 4SiO 2 : 2.3ZrO 2 :0.7 NiO) nanocomposite was prepared using sol-gel alkoxide precursors and calcined at 700 °C. The characterization for the prepared nano-sized by various analytical techniques confirmed the biphasic nature with the tetragonal zirconium silicate (ZrSiO 4 ) dominant phase and a homogeneous inter-dispersion for the obtained nanocrystallites. The UV-Vis optical analysis in the range of 200–2500 nm was operated to check the optical energy gap (E g ), optical constants (n and k), optical density (OD), skin depth (δ), optical conductivity (σ), and the optical electronegativity (η) of the 1MgO: 2CuO: 4SiO 2 : 2.3 ZrO 2 :0.7 NiOnanocomposite. The magnetic behavior for the nanocomposite sample was investigated. The antibacterial potential of 1MgO: 2CuO: 4SiO 2 : 2.3 ZrO 2 :0.7 NiOagainst four foodborne bacterial pathogens was appraised. Results revealed that the inhibitory consequences of tested 1MgO: 2CuO: 4SiO 2 : 2.3 ZrO 2 :0.7 NiO were greater in Gram-negative species than Gram-positive species. Results unveiled that the toxicity assay of the tested nanocomposite is biocompatible and safe for food security application. Thus, the prepared1MgO: 2CuO: 4SiO 2 : 2.3 ZrO 2 :0.7 NiOis recommended to be applied in food packaging and processing due to their high thermal stability, biocompatible and potent antimicrobial agents, and can suppress the dissemination of foodborne pathogens during food manufacturing.