This study aims to evaluate the prenatal developmental toxicity potential of D-allulose produced by genetically engineered Escherichia coli in rats. Given the increasing use of D-allulose in food products, a thorough toxicological assessment is essential to ensure its safety. A prenatal developmental toxicity test in Sprague-Dawley rats was conducted in accordance with the OECD Guidelines Test No. 414 (prenatal developmental toxicity study) and GB 15193.14-2015 (National food safety standards teratogenicity test of the People's Republic of China). Pregnant female rats received repeated doses of 1250, 2500, and 5000 mg/kg bw D-allulose by gavage on Gestation Days (GD) 6-15. A vehicle control (distilled water) and a positive control (cyclophosphamide) were also included. On GD 20, pregnant rats were euthanized, and fetuses were examined for external, soft tissue and skeletal abnormalities. No treatment-related anomalies were observed, indicating that D-allulose did not exhibit prenatal developmental toxic effects. The No-Observed-Adverse-Effect-Level (NOAEL) was determined to be 5000 mg/kg/day.
D-Allulose is a rare monosaccharide structurally similar to D-fructose, characterized by low caloric content and relatively high sweetness. This study aimed to conduct a 90-day oral toxicity test to systemically evaluate the potential toxicological effects of D-allulose produced via a novel one-step fermentation process using genetically engineered Escherichia coli AS10 strain, which was genetically modified to express enzymes involved in the biosynthesis of D-allulose from D-glucose. The objectives were to determine its NOAEL, provide scientific evidence for the safety evaluation of this innovative food ingredient, and meet the regulatory requirements for the safety assessment of a novel process-derived food product. A total of 96 SD rats were randomly divided into four groups (24 rats per group, with equal numbers of males and females): a control group (basal feed) and three treatment groups fed with feed containing 2.5%, 5.0%, and 10.0% D-allulose (corresponding to estimated dietary intakes of 2000, 4000, and 8000 mg/kg body weight per day, respectively, based on an assumed daily feed intake of 8% of body weight) for 90 consecutive days. A comprehensive battery of toxicological assessments was performed on each animal, including measurements on body weight, food consumption, feed efficiency ratios, hematological metrics, serum biochemical profiles, organ weights, and histopathological examinations. No treatment-related mortality or overt toxic symptoms were observed in any group during the study period. Statistically significant differences were noted in partial metrics (e.g., body weight, feed consumption, HCT%, PLT, ALP, TC, and absolute/relative weight of kidney) between treatment groups and control group, but these changes were deemed nontoxicologically significant due to consistency with normal physiological variability (within the historical in-house reference ranges) or lack of corresponding pathological lesions. The NOAEL of D-allulose was established at 8000 mg/kg BW/day in rats, confirming its safety for use as a food ingredient.
Nanomaterials have been widely used to scavenge reactive oxygen species (ROS) and relieve mitochondria oxidative damage. However, developing nanomedicines that not only remove ROS but also accelerate the repair of dysfunctional mitochondria remains challenging. This study identifies polyvinylpyrrolidone (PVP)-modified palladium nanoparticles (PdP NPs) as mimics of cytochrome c oxidase (CcO) and superoxide dismutase (SOD), showcasing their potential as multifunctional nanoreactors to activate mitochondria for aging alleviation and neuroprotection. PdP NPs treatment enhances mitochondrial respiratory chain function, scavenges excessive ROS, thus alleviates cellular energy scarcity of aging individuals. Additionally, PdP NPs improve mitochondrial dynamics, promote biogenesis, and induce mitochondrial unfolded protein response (UPRmt), strengthening mitochondrial integrity and homeostasis for better therapeutic outcomes. In vivo evaluations reveal significant anti-aging effects, with the nanozymes notably reducing neurodegeneration and improving neuronal survival. This work highlights PdP NPs as a multifunctional nanotherapeutic platform capable of rewiring mitochondrial metabolism and homeostasis, offering a promising strategy for aging-related disease management.
Long-term safety, tolerance, and population-specific effects of innovatively fermented D-allulose are lacking in the Chinese population. This study aimed to address these gaps and support its application as a novel food ingredient in China. A 30-day randomized, double-blind, parallel-group design with pre-post comparison trial was conducted, enrolling 50 healthy Chinese adults (high-dose group: 36 g/day, 0.6 g/kg body weight, n = 26; low-dose group: 24 g/day, 0.4 g/kg body weight, n = 24). Gastrointestinal tolerance was monitored via daily questionnaires; systemic safety was evaluated using hematological tests, serum biochemical tests, urinalysis, fecal analysis, and body composition measurements. The incidence of gastrointestinal symptoms was 48.0%, which were mild, transient, and most frequent on Days 1-3, with no significant intergroup differences. All statistically significant changes in safety indicators remained within normal clinical reference ranges. Compared with baseline, the 30-day intervention resulted in reduced red blood cell count, hematocrit, and platelet count, as well as elevated mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in both groups. For serum biochemical parameters, levels of alkaline phosphatase, gamma-glutamyl transferase, uric acid, total cholesterol, and high-density lipoprotein cholesterol decreased in both groups, while fasting blood glucose was reduced only in high-dose group. Notably, high-dose D-allulose intervention decreased bone mineral density T-scores in participants aged 35 years and older. All statistically significant alterations in the measured indicators remained within normal clinical ranges and were clinically insignificant. This study provides critical safety data to support the planned approval of D-allulose as a novel food ingredient in China in 2025. Its modulation of hematological and serum biochemical parameters suggests effects on hematopoiesis and glycolipid metabolism. Given the limitations of the 30-day intervention duration, relatively modest sample size, and restriction to healthy normal-BMI adults, a provisional safe intake limit of 0.4 g/kg body weight per day is proposed for Chinese adult population, requiring validation in longer-term and larger-scale studies.
Objective To systematically analyze the domestic and international literature on exogenous risk factors associated with the yellow mealworm(Tenebrio molitor),and to comprehensively review the contamination characteristics,accumulation patterns,and health risks of exogenous risk factors during rearing,processing,and consumption.Methods A comprehensive search was conducted in domestic and international databases for studies published between 2003 and 2025 on exogenous risk factors in the yellow mealworm.After screening according to the predefined inclusion criteria,the eligible studies were included for analysis.The reported exogenous risk factors were classified into heavy metals,biotoxins,processing by-products,emerging contaminants,and so on.The contamination pathways,bioaccumulation factors,toxicological effects,and exposure risks of each category were summarized and analyzed.Results The yellow mealworm exhibited a strong bioaccumulation capacity for heavy metals such as lead,cadmium,mercury,and arsenic,with bioaccumulation factors generally≥1 and reaching as high as 34 for lead.The larvae show a certain degree of degradation and tolerance to biotoxins such as aflatoxin B ₁ and deoxynivalenol,however,residual from biotoxin metabolites remained as potential risks.Processing procedures,such as high-temperature roasting and frying,may generate harmful substances including acrylamide and polycyclic aromatic hydrocarbons.Emerging contaminants,such as microplastics and polychlorinated biphenyls,may also be retained in or accumulated by the yellow mealworm.Conclusion As a novel animal-derived food resource,the yellow mealworm is susceptible to various exogenous risk factors.Strengthening control at the source and optimizing processing procedures are essential for risk prevention and control.Future research should focus on establishing whole-chain risk prediction models and investigating the synergistic effects of combined risk factors,thereby providing a scientific basis for the safe application of novel animal-derived food resources.
L-theanine, a non-protein amino acid naturally occurring in tea leaves, is recognized for its antioxidant, anti-inflammatory, and neuroprotective properties. Despite its known benefits, the mechanisms by which L-theanine influences lifespan extension remain poorly understood. This study investigated the effects of L-theanine on the lifespan of Caenorhabditis elegans and explored the underlying mechanisms. Our findings indicate that L-theanine significantly diminishes the accumulation of advanced glycation end products (AGEs), which are biomarkers closely linked to aging and age-related diseases. Through an AGE-level analysis, we observed that L-theanine, when administered during early adulthood, notably extended the lifespan of Caenorhabditis elegans under both normal and high-glucose-induced stress conditions. L-theanine enhanced the lifespan under typical conditions and provided protective effects against high-glucose-induced stress. A further analysis demonstrated that L-theanine extends the lifespan of Caenorhabditis elegans by modulating the DAF-2/DAF-16 insulin-like signaling pathway and reducing the accumulation of advanced glycation end products (AGEs). In summary, this study identified L-theanine as a potential anti-aging intervention that extends the lifespan by reducing AGE accumulation and regulating insulin-like signaling pathways. These findings provide new insights for developing anti-aging strategies and lay the groundwork for further research on the potential benefits of L-theanine in mammals. Future studies could explore the molecular mechanisms, test L-theanine in mammalian models, and assess the long-term side effects.
Anthraquinones, both naturally occurring and synthetic, are widely distributed in the environment. Recent years, human exposure to 9,10-anthraquinone (9,10-AQ) through contaminated food has been raising significant health concerns due to its potential toxicity upon chronic exposure. Among these, 9,10-AQ has been studied in traditional toxicology, with few of established Points of Departure (PoDs) and Health-Based Guidance Values (HBGV). However, toxicological data for other anthraquinones remain severely limited. Traditional animal experiments are resource-intensive and time-consuming, restricting the feasibility of deriving PoDs and HBGVs for a larger set of compounds and exposures, especially for risk assessment purposes. To address these challenges, New Approach Methodologies (NAMs) were employed and validated by using 9,10-AQ as a reference and representative compound in current study. Hepatocyte hypertrophy via lipid metabolism pathway induced by 9,10-AQ was predicted with applying network toxicology, which was validated using HepG2 cell (0.625-10 μM, for 48 h) combined with high-content imaging showing lipid accumulation induced by 9,10-AQ. The physiologically based toxicokinetic (PBTK) model for rat of 9,10-AQ was developed using in vitro and in silicodata, which was further extrapolated to humans PBTK model, enabling the translation of in vitro concentration–response relationships into in vivo dose–response predictions through PBTK modeling-based reverse dosimetry. From this, a PoD value was derived and converted to a HBGV of 0.0105 mg/kg BW, accounting for uncertainty factors of 100. The NAMs-based HBGV of 9,10-AQ matched well with values derived from animal studies, providing a proof-of-principle of using in vitro-in silicoapproach to predict hepatic lipid metabolic disorder in humans and indicating a good performance of the NAMs. This approach has the potential to be extended to other anthraquinones and derivatives, offering more accurate and reliable human-relevant value (i.e. PoDs, HBGVs), to support Next Generation Risk Assessment (NGRA) of 9,10-AQ and related compounds.
Aging, a universal biological process in complex organisms, is increasingly recognized to be driven by progressive loss of epigenetic information, as proposed in the Information Theory of Aging (ITOA). However, research on anti-aging peptides remains scarce, with most existing efforts confined to derivatives of natural proteins, while systematic design attempts are virtually absent. This limitation not only restricts discovery within the evolutionary sequence space but also hampers the identification of candidates with novel mechanisms and improved efficacy. Here, we present ElixirSeeker2, the first computational framework for de novo design of anti-aging peptides. By integrating modeling of known anti-aging peptides, activity scoring from the IC50 database, and penalty constraints from toxic peptides, ElixirSeeker2 enables large-scale virtual screening and identification of novel peptide candidates. Several lead peptides demonstrated significant effects in delaying cellular senescence, restoring cellular functions in vitro and in enhancing locomotor activity of aged Caenorhabditis elegans . This study not only validates the feasibility of de novo design in anti-aging interventions but also establishes a strategy for the development of next-generation biologics. ### Competing Interest Statement The authors have declared no competing interest. Science and Technology Program of Bei-jing, China, Z231100004523001 Construction Project - Health Toxicology Discipline “Academic Leader”, 02-08 2021 Research Start-up Fund—Fresh Wave, Y030212059003033
Despite the growing interest in developing anti-aging drugs, high costs and low success rates of traditional drug discovery methods pose significant challenges. Aging is a complex biological process associated with numerous diseases, making the identification of compounds that can modulate aging mechanisms critically important. Accelerating the discovery of potential anti-aging compounds is essential to overcome these barriers and enhance lifespan and healthspan. Here, we present ElixirSeeker, a machine learning framework designed to maximize feature capture of lifespan-extending compounds through multi-fingerprint fusion mechanisms. Utilizing this approach, we identified several promising candidate drugs from external compound databases. We tested the top six hits in Caenorhabditis elegans and found that four of these compounds-including Praeruptorin C, Polyphyllin VI, Thymoquinone, and Medrysone-extended the organism's lifespan. This study demonstrates that ElixirSeeker effectively accelerates the identification of viable anti-aging compounds, potentially reducing costs and increasing the success rate of drug development in this field.
The identification of hazardous chemicals is critical for mitigating environmental and health risks, yet existing methods often lack efficiency and accuracy. This study presents HazChemNet, a deep learning model integrating attention-based autoencoders and mixture-of-experts architectures, designed to predict chemical hazardousness from molecular structures. The study utilized a dataset of 2428 hazardous compounds from China’s 2015 hazardous chemical list. Features were derived from molecular fingerprints and physicochemical descriptors, with external validation on 52 unseen chemicals achieving 92.3% accuracy for hazardous and 84.6% for non-hazardous classifications. Experimental validation using C. elegans assays confirmed model predictions for critical compounds. Ablation studies confirmed hydrogen bonding features as pivotal predictors, alongside molecular fingerprints. This work bridges the gap between AI-driven innovation and chemical safety, offering a transformative tool for sustainable industrial practices and proactive risk management in a rapidly evolving global landscape.
BACKGROUND: Caenorhabditis elegans is a widely used model animal. Chemotaxis assay is one of the experiments that study the effects of different chemicals on nematodes. It is mainly used to study the effects of different chemicals on the perception behavior of nematodes. By conducting this experiment, not only can the neurotoxicity of chemicals be reflected, but also the impact of chemicals on physiological functions regulated by the nervous system, such as nematode feeding behavior and basic motor ability. OBJECTIVE: The experiment of detecting the response of nematode to chemicals is also a common method of chemical toxicity testing based on nematode models. In the analysis of worm tendency behavior, manual operations are generally used. Manually processing a large number of worms under a microscope is very time-consuming and labor-intensive. The current quantitative methods for nematode chemotaxis experiments are not only time-consuming and labor-intensive, but also biased in experimental results due to differences in judgment standards among experimenters. The automatic and efficient quantification method for nematode chemotaxis experiments is a very important technical difficulty in the field of nematode experiments. METHODS: Here, we have designed an automatic quantification method for nematode chemotaxis experiments by incorporating image acquisition and processing techniques into the nematode experiment. RESULTS: The experimental results show that the Pearson correlation coefficient between manual and automatic counting results is 0.978. CONCLUSION: This proves the effectiveness of our method. Applying the automatic measurement method to replace manual counting by the experimenter can improve work efficiency, and reduce errors in human counting operations.
Despite the growing interest in anti-aging drug development, high cost and low success rate pose a significant challenge. We present ElixirSeeker, a new machine-learning framework designed to help speed up the discovery of potential anti-aging compounds by utilizing the attention-driven fusion of molecular fingerprints. Our approach integrates molecular fingerprints generated by different algorithms and utilizes XGBoost to select optimal fingerprint lengths. Subsequently, we assign weights to the molecular fingerprints and employ Kernel Principal Component Analysis (KPCA) to reduce dimensionality, integrating different attention-driven methods. We trained the algorithm using DrugAge database. Our comprehensive analyses demonstrate that 64-bit Attention-ElixirFP maintains high predictive accuracy and F1 score while minimizing computational cost. Using ElixirSeeker to screen external compound databases, we identified a number of promising candidate anti-aging drugs. We tested top 6 hits and found that 4 of these compounds extend the lifespan of Caenorhabditis elegans , including Polyphyllin Ⅵ, Medrysone, Thymoquinone and Medrysone. This study illustrates that attention-driven fusion of fingerprints maximizes the learning of molecular activity features, providing a novel approach for high-throughput machine learning discovery of anti-aging molecules. ### Competing Interest Statement The authors have declared no competing interest.
Sodium dehydroacetate (DHA-S) is a food additive and preservative. The present study was conducted to investigate the potential toxicity of repeated oral doses of DHA-S. DHA-S was administered orally by gavage to Wistar rats at doses of 0, 50, 100, or 200 mg/kg BW/day for 28 days, after which growth indicators, clinical pathology, organ weights, and histopathology were determined. Body weight and food consumption were significantly reduced at doses of 100 or 200 mg/kg BW, and some hematological indexes and organ weight were significantly affected, particularly in female rats. At a dose of 200 mg/kg BW, the blood coagulation activities were significantly reduced in female rats. At a dose of 100 or 200 mg/kg BW, the main blood biochemical parameters of both sexes were obviously affected. Similar histological changes in the hepatic and renal tissues were observed in both the treated (200 mg/kg BW DHA-S) and control animals. Female rats were more susceptible to most of the toxic effects caused by DHA-S, which further indicating a gender difference in the toxic phenotype profile of rats. Based on these results, the no observed adverse effect level (NOAEL) of DHA-S was determined to be 50 mg/kg BW/day in rats.
BACKGROUND: The survival rate of experimental animals is a very important index in chemical toxicity evaluation experiments. The calculation of nematode survival rate is used in many experiments. OBJECTIVE: Traditional survival rate quantification methods require manual counting. This is a time-consuming and laborious work when using 384-well plate for high-throughput chemical toxicity assessment experiments. At present, there is a great need for an automatic method to identify the survival rate of nematodes in the experiment of chemical toxicity evaluation. METHODS: We designed an automatic nematode survival rate recognition method by combining the bright field experimental image of nematodes and the dark field image of nematodes which is captured after adding Propidium Iodide dye, and used it to calculate the nematode survival rate in different chemical environments. Experiment results show that the survival rate obtained by our automatic counting method is very similar to the survival rate obtained by manual counting. RESULTS: Through several different chemical experiments, we can see that chemicals with different toxicity have different effects on the survival rate of nematodes. And the survival rate of nematodes under different chemical concentrations has an obvious gradient trend from high concentration to low concentration. In addition, our method can quantify the motility of nematodes. There are also significant differences in the motility of nematodes cultured in different chemical environments. Moreover, the nematode motility under different chemical concentrations showed an obvious gradient change trend from high concentration to low concentration. CONCLUSION: Our study provides an accurate and efficient nematode survival rate recognition method for chemical toxicology research.
Introduction Exposure to fine particulate matter (PM), especially PM 2.5 , can induce various adverse health effects in populations, including diseases and premature death, but the mechanism of its toxicity is largely unknown. Methods Water-soluble components of PM 2.5 (WS-PM 2.5 ) were collected in the north of China in winter, and combined in two groups with the final concentrations of 94 μg/mL (C L group, AQI ≤ 100) and 119 μg/mL (C H group, 100 < AQI ≤ 200), respectively. The acute and long-term toxic effects of WS-PM 2.5 samples were evaluated in several aspects such as development, lifespan, healthspan (locomotion behavior, heat stress tolerance, lipofucin). DAF mutants and genes were applied to verify the action of IIS pathway in WS-PM 2.5 induced-effects. RNA-Sequencing was performed to elucidate the molecular mechanisms, as well as ROS production and Oil red O staining were also served as means of mechanism exploration. Results Body length and lifespan were shortened by exposure to WS-PM 2.5 . Healthspan of nematodes revealed adverse effects evaluated by head thrash, body bend, pharyngeal pump, as well as intestinal lipofuscin accumulation and survival time under heat stress. The abbreviated lifespan of daf-2(e1370) strain and reduced expression level of daf-16 and hsp-16.2 indicated that IIS pathway might be involved in the mechanism. Thirty-five abnormally expressed genes screened out by RNA-Sequencing techniques, were functionally enriched in lipid/lipid metabolism and transport, and may contribute substantially to the regulation of PM 2.5 induced adverse effects in nematodes. Conclusion WS-PM 2.5 exposure induce varying degrees of toxic effects, such as body development, shorten lifespan and healthspan. The IIS pathway and lipid metabolism/transport were disturbed by WS-PM 2.5 during WS-PM 2.5 exposure, suggesting their regulatory role in lifespan determination.
Background: Recent studies have raised concerns about genotoxic effects associated with titanium dioxide nanoparticles (TiO2 NPs), which are commonly used. This meta-analysis aims to investigate the potential genotoxicity of TiO2 NPs and explore influencing factors. Methods: This study systematically searched Chinese and English literature. The literature underwent quality evaluation, including reliability evaluation using the toxicological data reliability assessment method and relevance evaluation using routine evaluation forms. Meta-analysis and subgroup analyses were performed using R software, with the standardized mean difference (SMD) as the combined effect value. Results: A total of 26 studies met the inclusion criteria and passed the quality assessment. Meta-analysis results indicated that the SMD for each genotoxic endpoint was greater than 0. This finding implies a significant association between TiO2 NP treatment and DNA damage and chromosome damage both in vivo and in vitro and gene mutation in vitro. Subgroup analysis revealed that short-term exposure to TiO2 NPs increased DNA damage. Rats and cancer cells exhibited heightened susceptibility to DNA damage triggered by TiO2 NPs (p < 0.05). Conclusions: TiO2 NPs could induce genotoxicity, including DNA damage, chromosomal damage, and in vitro gene mutations. The mechanism of DNA damage response plays a key role in the genotoxicity induced by TiO2 NPs.
To explore the potential the adverse outcome pathway of Gardenia Yellow (GY)-induced sensitive endpoint for nephrotoxicity, an integrated strategy was applied in the present study. Using bioinformatic analysis, based on the constructed Protein-protein interaction networks, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the core target network were performed to illustrate the potential gene targets and signal pathways. Then, the most enriched pathway was validated with Cell counting kit-8 assays and Western blot analysis in embryonic kidney epithelial 293 cell models. According to the findings, GY may interact with 321 targets related to the endpoint. The five targets on the top ranking in the PPI network were STAT3, SRC, HRAS, AKT1, EP300. Among them, PI3K/Akt was the most enriched pathway. In vitro testing showed that GY exerted a proliferative effect on the cell variability in a dose-dependent manner. GY at concentration of 1000 μg/ml and stimulation for 30 min can significantly enhance the expression of phosphorylated Akt. Thus, after the quantitative weight of evidence evaluation, Akt phosphorylation induced PI3K/Akt activation was speculated as a molecular initiating event leading to a proliferative and inflammatory response in renal tubular epithelial cells.
As widely used synthetic chemicals, perfluorooctane sulfonic acid (PFOS) and perfluorooctanic acid (PFOA) are ubiquitous in the environment and the human body. Due to the extensive toxic effects and bioaccumulation of PFOS/PFOA,their impact on human health has attracted more and more attention. The absorption, distribution, metabolism, excretion and toxic effects of PFOS/PFOA in mammals are systematically summarized in this paper. Moreover,the safety limits of PFOS/PFOA are summarizes herein as well as the internal exposure levels of PFOS/PFOA in Chinese general population based on published literature in order to provide a scientific basis for PFOS/PFOA risk assessment and risk management.
全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)是应用广泛的人工合成化学物,在环境和人体内广泛存在,PFOS/PFOA毒性作用广泛且具有生物蓄积性,因为对人体健康有影响受到越来越多的关注.本文系统总结了PFOS/PFOA在哺乳动物体内的吸收、分布、代谢、排泄和毒性作用,以及目前国际上针对PFOS/PFOA提出的安全限量,并基于现有数据概述了我国普通人群PFOS/PFOA内暴露情况,以期为PFOS/PFOA的风险评估及风险管理提供科学基础.
ObjectiveTo calculate the lower limit of 95% confidence interval of benchmark dose (BMDL) of 3-monochloro-1,2-propanediol (3-MCPD) and its esters for renal tubular hyperplasia effect based on benchmark dose (BMD) method.MethodsThe data of the most sensitive endpoint of renal tubular hyperplasia in the 2-year chronic toxicity and carcinogenicity study of 3-MCPD were analyzed. BMD model and analysis were used by methods of frequentist, frequentist model averaging and Bayesian model averaging, respectively. Smooth dose response curve was obtained by fitting the nine conventional models, and then the optimal fitting model and BMDL10 estimation value were obtained.ResultsThe best data set was selected by comparing the conservative degree of results across different data sets. Under the same data set, the selection of restricted or non-restricted model parameters, and the selection of single model or model averaging, were key factors to affect the BMDL results of 3-MCPD and its esters. According to model fitting degree and conservative degree, BMDL10 of the most sensitive endpoint of renal tubular hyperplasia of 3-MCPD and its esters was 0.87 mg/kg·BW. The health based guidance value (HBGV) needs to be further determined by the BMDL10 with uncertainty factor.ConclusionThe results of this research could be applied for the risk assessment of 3-MCPD and its esters in key foods of China, and further provide scientific advice on the supervision and control of key foods based on the assessment results.