Potential of 6'­hydroxy justicidin B from Justicia procumbens as a therapeutic agent against coronavirus disease 2019.

BACKGROUND: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6'-Hydroxy justicidin B (6'-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties. HYPOTHESIS/PURPOSE: The aim of the present study was to assess the effectiveness and safety of 6'-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. METHODS: The efficacy of 6'-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. RESULTS: The anti-SARS-CoV-2 efficacy of 6'-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6'-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6'-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6'-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6'-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6'-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. CONCLUSION: This research highlights both the antiviral efficacy and safety profile of 6'-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6'-HJB was demonstrated using modern scientific methodologies and standards.

Aging of drinking water transmission pipes during long-term operation as a potential source of nano- and microplastics.

Microplastics (MPs) and nanoplastics (NPs) released into drinking water from transmission pipes can pose a potential health risk to consumers. This paper presents the results of a comprehensive study of PE and PVC pipes after long-term operation in drinking water distribution networks, which confirmed that degradable polymers can be a significant source of MPs. Both plastics age relatively quickly, and the degree of damage to the pipe surface depends on the time and operating conditions. During aging, polymer chains deteriorate, leading to a weakening of the structure and increased amorphousness of the plastics. As a result, the surfaces of PE and PVC crack and peel, resulting in the formation of particles with sizes corresponding to NP and MP with high potential for release into water. The magnitude of the phenomenon increases as the diameter of the pipes decreases, indicating that the most vulnerable customers are those at the ends of the network to which drinking water is supplied through small-diameter pipes. Aging PE and PVC pipes should be considered a real and very important source of MPs and NPs in drinking water, and water quality in this aspect should be monitored by manufacturers.

An industry perspective on the FDA modernization act 2.0/3.0: Potential next steps for sponsors to reduce animal use in drug development.

Pharmaceutical developers are encouraged to adopt the best practices of being purposefully thoughtful about the use of animals, seeking alternatives wherever possible. They should engage with health authorities to increase their familiarity with the methods, study designs, data outputs and the context of use for new approach methodologies (NAMs). Although current state of technology does not yet provide adequate models to fully replace in vivo studies, many models are sufficiently good for an augmented approach that will enhance our understanding of in vitro to in vivo correlations and advance the long-term goal of reducing animal use through innovative NAMs. The goal of future nonclinical safety packages is to advance the utilization of such enabling technologies towards appropriate human risk characterization. Establishing confidence in NAMs is a critical first step. For example, sponsors may include both "traditional" and NAM-based nonclinical safety data in regulatory submissions to establish confidence with health authorities. In addition, regulators should create a "safe-harbor" for hybrid nonclinical data packages to facilitate iterative learning, refinement, and implementation of NAM-based safety assessment strategies. Sponsors are urged to contribute to NAMs evolution through consortia participation, peer-reviewed publications, and documenting animal reduction in studies/programs, accelerating the eventual elimination of animal use in pharmaceutical development, as envisioned in the FDA Modernization Act 3.0.

[Progress and prospects of safety assessment methods of medicinal and food homologous substances].

Food and medicinal substances(FAMS) with both edible and medicinal uses have a long history in China, being an important part of China's excellent traditional culture and traditional Chinese medicine(TCM). The legal management of FAMS is in the form of catalogue, which has a history of nearly 40 years. More than 100 substances have been included in the China's FAMS catalogue. According to the Regulation of Food and Medicinal Substances Catalogue, safety assessment is a basis for substances to be included in the catalogue. The safety assessment of FAMS should follow the principles and requirements of food safety risk assessment. However, FAMS is a complex mixture, and the nature and data adequacy of the assessed substance should be comprehensively considered. Different eva-luation models and methods should be selected according to the principle of case analysis. With the development of next-generation technologies such as big data, artificial intelligence, high-throughput and high-content in vitro testing, and computational toxicology and the trend of increasing edible substances with medicinal effects applying for the inclusion in the China's FAMS catalogue, the methods of risk assessment are applied in the management of FAMS, novel food products, and local characteristic food products, playing a scientific role. This paper systematically reviews the methods, challenges, and prospects of safety assessment of FAMS.

Advances in the preparation and application of cyclodextrin derivatives in food and the related fields.

Cyclodextrin (CD) derivatives have recently gained worldwide attention, which have versatile advantages and restrained the defects of parent CDs. The superior properties of CD derivatives in encapsulation, stabilization, and solubilization facilitate their application in food, biomedicine, daily chemicals, and textiles. In this review, the preparation, classification, and main benefits of CD derivatives are systematically introduced. By introducing targeted groups into the parent CD molecule, they exhibit significant improvement in their required characteristic. Besides, the important point closely related to application, the safety assessment, has also been highlighted. Most tested CD derivatives have been verified to be relatively safe in a limited dosage. Then, the applications of CD derivatives have been described in detail from the food to its related field. In food field, CD derivatives play an important role in the stability and bioavailability of bioactive compounds, control flavor release, and improve the antimicrobial and antioxidant properties of packaging materials. These advantages can also be expanded to the related field, offering innovative solutions that enhance product quality, human health, and environmental sustainability. This review highlights the broad applications and potential of CD derivatives, underscoring their role in driving advancements across multiple industries.

Enhancing mixed traffic safety assessment: A novel safety metric combined with a comprehensive behavioral modeling framework.

In the context of future traffic systems, where automated vehicles (AVs) coexist with human-driven vehicles (HVs), ensuring road safety is of utmost importance. Existing safety assessment methods, however, are inadequate for the complex scenarios presented by mixed traffic conditions. These methods often fail to distinguish sufficiently between AVs and HVs, leading to inaccuracies in safety evaluations. To address these issues, this paper highlights the shortcomings of current surrogate safety measures (SSMs) in mixed traffic contexts and introduces a novel SSM, the Weighted Combination of Spacing and Speed Difference Rates (WS2DR). We propose a comparative analysis method to validate the effectiveness of WS2DR and to establish its safety threshold. Experiment results reveal that WS2DR outperforms traditional metrics such as time-to-collision and deceleration rate to avoid crashes, in terms of adaptability to both homogeneous and heterogeneous traffic environments and the detection of risk levels across a wider range of traffic conditions. Additionally, the paper presents a sophisticated mixed traffic modeling approach that accounts for different characteristics of AVs and HVs, incorporating factors such as errors of estimating the motion of other vehicles and the extended reaction time of HVs, as well as the perceptual and cooperative-active control capabilities of AVs. The results of the comparison analysis underscore the critical importance of considering the differences between AVs and HVs in modeling for accurate safety evaluations of mixed traffic. Simulation experiments confirm the positive impact on safety with increased AV penetration rates, emphasizing the necessity of employing refined modeling and safety assessment metrics to capture the full benefits of AV integration.

Molecular protocol to develop ß-carotene-biofortified rice events via molecular optimization.

Providing food with nutrition and functionality is crucial for sustaining human life. Rice (Oryza sativa L.) is a representative staple crop with high carbohydrate content but low amounts of essential amino acids, micronutrients, and carotenoids such as provitamin A. To improve the nutritional quality, rice endosperm was biofortified to accumulate carotenoids such as ß-carotene through genetic engineering (i.e., using synthetic carotenoid biosynthetic genes, a nonmammalian viral polycistronic sequence, and an optimized promoter and transit peptide) and high-throughput rice transformation (approximately 300 transgenic plants per construct). To facilitate the safety assessment of genetically modified food, molecular characterization was performed to select elite lines equipped with a single intergenic insertion of T-DNA, high transgene expression, in this case leading to high carotenoid content, and with phenotypic and compositional substantial equivalence. In this study, we present ß-carotene-biofortified rice event candidate lines eligible for commercial use and a disclosed molecular protocol for the development of biotech rice crops.

Safety assessment of the process Lietpak, based on the EREMA MPR technology, used to recycle post-consumer PET into food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Lietpak (EU register number RECYC327), which uses the EREMA MPR technology. The input material is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated in a ■■■■■ reactor under vacuum. Having examined the challenge test provided, the Panel concluded that the ■■■■■ decontamination (step 2), for which a challenge test was provided, is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migration of 0.1 µg/kg food, derived from the exposure scenario for infants, when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature or below, with or without hotfill. Articles made of this recycled PET are not intended to be used in microwave or conventional ovens and such uses are not covered by this evaluation.

Safety assessment of coronary arteries during left bundle branch area pacing.

BACKGROUND: This study aimed to assess the safety of left bundle branch area pacing (LBBAP) by measuring the distance from the tip of the electrode to the nearby coronary artery with a nine-partition grid method. METHODS: From January 2019 to October 2020, patients who underwent LBBAP and postoperative coronary angiography in the Second Affiliated Hospital of Nanchang University were included in the study. The patients' fluoroscopic images of LBBAP and coronary angiography were collected and analyzed. Changes in the ST­T segment in the electrocardiogram (ECG), serum troponin, and myocardial enzyme profiles were observed before and after the LBBAP procedure. RESULTS: A total of 50 patients were included in this study, of whom 46 patients underwent implantation with a pacemaker and 4 patients received an implantable cardioverter defibrillator (ICD). The pacing electrodes were confined to the posterior-middle (PM), median (M), Posterior inferior (PI), and middle inferior (MI) positions of the two-dimensional nine-square grid or in the junction area of the above positions, and were concentrated in the rectangle formed by the line of the center points of the four positions. The average vertical distances from the electrode tip to the left anterior descending branch artery (LAD), posterior descending branches (PD) and the left posterior ventricular branches (PL) were 19.69 ± 8.72 mm, 26.09 ± 8.02 mm, and 21.11 ± 7.86 mm, respectively; the minimum was 5.28 mm, 9.51 mm, and 8.69 mm, respectively. Coronary angiography in all patients showed no significant injury to the ventricular septal branch; however, we observed elevated serum troponin and changes in ST­T segment in ECG. CONCLUSION: The study demonstrates that pacing electrodes in LBBAP can be safely implanted over a wide range. Coronary arteries are likely to be safe when the pacing electrodes are located within the rectangle formed by the line connecting the PM, M, PI, and MI zone centroids. The left bundle branch can be quickly captured and the safety of the coronary artery can be improved by locating the electrode in the posterior-mid zone. The potential risk of injury to the LAD from the electrode is greater compared with the PD.

Toxicity and safety of rosemary (Rosmarinus officinalis): a comprehensive review.

BACKGROUND: Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms. METHODS: Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024. RESULTS: The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation. CONCLUSION: While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.

Nutritional and anti-nutritional compositional analysis of transgenic potatoes with late blight resistance.

Late blight, caused by the pathogen Phytophthora infestans, is a devastating disease affecting potato production globally, with adverse effects in Africa where limited access to fungicides exacerbates its impact. Outbreaks of late blight lead to reduced yields and substantial economic losses to potato farmers and agricultural systems. The development of resistant potato varieties, tailored to African agroecological conditions, offers a viable solution in mitigating the devastating effects of late blight on potato cultivation. Leading to this study, two consumer-preferred varieties, Victoria and Shangi, with high susceptibility to late blight were targeted for conferring late blight resistance through genetic engineering. This was achieved by inserting R genes from wild relatives of potato displaying resistance to the disease. The intended effect of conferring resistance to the late blight disease has been consistently observed over twenty experimental field trials spanning 8 years at three locations in Uganda and Kenya. In this study, we assessed whether the genetic transformation has led to any significant unintended effects on the nutritional and anti-nutritional composition of potato tubers compared to the non-transgenic controls grown under the same agroecological conditions. The compositional assessments were conducted on commercial-size potato tubers harvested from regulatory trials at three locations in Uganda and Kenya. Statistical analysis was conducted using two-way analysis of variance comparing transgenic and non-transgenic samples. Overall, the results showed that the transgenic and non-transgenic samples exhibited similar levels of nutritional and antinutritional components. Variations detected in the levels of the analysed components fell within the expected ranges as documented in existing literature and potato composition databases. Thus, we conclude that there are no biologically significant differences in the nutritional and anti-nutritional composition of transgenic and non-transgenic potato tubers engineered for resistance to late blight.

Safety assessment of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt' for use in food contact materials.

The EFSA Panel on Food Contact Materials (FCM) assessed the safety of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt', used as additives up to 0.3% in polyethylene terephthalate (PET), polyamide (PA), thermoplastic polyurethane (TPU), polylactic acid (PLA) and poly(vinyl chloride) (PVC) in contact with all food types for long-term storage at room temperature and below, after hot-fill and/or heating. The substances consist of the chemical classes wax esters, carboxylic acids, alcohols and calcium salts of acids, along with an unidentified organic fraction up to ■■■■■ w/w. Migration into 10% ethanol and 4% acetic acid was below 0.012 mg/kg for each chemical class, and about 0.001 mg/kg for the unidentified fraction. In isooctane, migration was up to 0.297 mg/kg food for wax esters, below 0.01 mg/kg food for the other chemical classes and about 0.02 mg/kg food for the unidentified fraction. The contact with dry food and food simulated by 20% ethanol were considered covered by the migration tests with aqueous simulants. Based on genotoxicity assays and compositional analyses, the constituents of the chemical classes did not raise a concern for genotoxicity. The potential migration of individual constituents or groups of chemically-related compounds of the unidentified fraction would result in exposures below (for aqueous food) and above (for fatty food) the threshold of toxicological concern for genotoxic carcinogens. Therefore, the FCM Panel concluded that the substances are not of safety concern for the consumer, if used as additives up to 0.3% w/w in PET, PLA and rigid PVC materials and articles intended for contact with all food types except for fatty foods, for long-term storage at room temperature and below, including hot-fill and/or heating up to 100°C for up to 2 h.

Anti-Inflammatory, Cytotoxic, and Genotoxic Effects of Soybean Oligopeptides Conjugated with Mannose.

Soy protein is considered to be a high-quality protein with a range of important biological functions. However, the applications of soy protein are limited due to its poor solubility and high level of allergenicity. Its peptides have been of interest because they exert the same biological functions as soy protein, but are easier to absorb, more stable and soluble, and have a lower allergenicity. Moreover, recent research found that an attachment of chemical moieties to peptides could improve their properties including their biodistribution, pharmacokinetic, and biological activities with lower toxicity. This study therefore aimed to acquire scientific evidence to support the further application and safe use of the soybean oligopeptide (OT) conjugated with allulose (OT-AL) or D-mannose (OT-Man). The anti-inflammation, cytotoxicity, and genotoxicity of OT, OT-AL, and OT-Man were investigated. The results showed that OT, AL, Man, OT-AL, and OT-Man at doses of up to 1000 µg/mL were not toxic to HepG2 (liver cancer cells), HEK293 (kidney cells), LX-2 (hepatic stellate cells), and pre- and mature-3T3-L1 (fibroblasts and adipocytes, respectively), while slightly delaying the proliferation of RAW 264.7 cells (macrophages) at high doses. In addition, the oligopeptides at up to 800 µg/mL were not toxic to isolated human peripheral blood mononuclear cells (PBMCs) and did not induce hemolysis in human red blood cells (RBCs). OT-Man (200 and 400 µg/mL), but not OT, AL, Man, and OT-AL, significantly reduced the production of NO and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, suggesting that the mannose conjugation of soy peptide had an inhibitory effect against LPS-stimulated inflammation. In addition, the secretion of interleukin-6 (IL-6) stimulated by LPS was significantly reduced by OT-AL (200 and 400 µg/mL) and OT-Man (400 µg/mL). The tumor necrosis factor-α (TNF-α) level was significantly decreased by OT (400 µg/mL), AL (400 µg/mL), OT-AL (200 µg/mL), and OT-Man (200 and 400 µg/mL) in the LPS-stimulated cells. The conjugation of the peptides with either AL or Man is likely to be enhance the anti-inflammation ability to inhibit the secretion of cytokines. As OT-Man exhibited a high potential to inhibit LPS-induced inflammation in macrophages, its mutagenicity ability was then assessed in bacteria and Drosophila. These findings showed that OT-Man did not trigger DNA mutations and was genome-safe. This study provides possible insights into the health advantages and safe use of conjugated soybean peptides.

Novel Flowable Hemostatic Agent ActiClot: Efficacy and Safety Assessment in Rat and Porcine Models.

Background/Objectives: This study evaluated the hemostatic performance and safety of ActiClot (ATC), a new flowable hemostatic agent, through in vivo tests. Methods: ATC was compared with the commercially available FLOSEAL®. ATC consists of carboxymethyl starch, thrombin, and sorbitol powders in Syringe I, and a calcium chloride solution in Syringe II. In vivo evaluation used rat liver bleeding and porcine heart bleeding models. Safety was assessed using a rat subcutaneous implantation model. Results: ATC significantly reduced hemostasis time (70.00 ± 7.35 s) compared to gauze control (240.63 ± 32.31 s) in the rat liver model, showing a 70% reduction. There was no significant difference between ATC and FLOSEAL® (58.75 ± 13.42 s). In the porcine heart model, both agents achieved 100% hemostasis within 3 min, with no significant difference in success rates within 2 min (ATC 87.5%, FLOSEAL® 75%). The gauze control group failed in all tests. The rat subcutaneous implantation model showed no visual ATC observation after 48 h, indicating biocompatibility, with no inflammation observed. Conclusions: ATC demonstrated effective hemostatic performance similar to FLOSEAL® in two in vivo models, with faster hemostasis in the rat liver model. It also showed excellent safety and biocompatibility, indicating its potential for surgical and emergency bleeding control.

Safety assessment of the process KGL, based on the EREMA Basic technology, used to recycle post-consumer PET into food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process KGL (EU register number RECYC326), which uses the EREMA Basic technology. The input material is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated in a ■■■■■ reactor under vacuum before being extruded. Having examined the challenge test provided, the Panel concluded that the ■■■■■ decontamination (step 2), for which a challenge test was provided, is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migrations of 0.1 and 0.15 µg/kg food, derived from the exposure scenarios for infants and toddlers, when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature or below, with or without hotfill. Articles made of this recycled PET are not intended to be used in microwave or conventional ovens and such uses are not covered by this evaluation.

Safety assessment of the process Palamidis, based on the EREMA Basic technology, used to recycle post-consumer PET into food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Palamidis (EU register number RECYC325), which uses the EREMA Basic technology. The input material is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated in a ■■■■■ reactor under vacuum before being extruded. Having examined the challenge test provided, the Panel concluded that the ■■■■■ decontamination (step 2), for which a challenge test was provided, is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migrations of 0.1 and 0.15 µg/kg food, derived from the exposure scenarios for infants and toddlers, when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature or below, with or without hotfill. Articles made of this recycled PET are not intended to be used in microwave or conventional ovens and such uses are not covered by this evaluation.

Safety assessment of the process Ecopacking, based on the EREMA Basic technology, used to recycle post-consumer PET into food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Ecopacking (EU register number RECYC324), which uses the EREMA Basic technology. The input material is ■■■■■ washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated in a ■■■■■ reactor ■■■■■ before being extruded. Having examined the challenge test provided, the Panel concluded that the ■■■■■ decontamination (step 2), for which a challenge test was provided, is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migrations of 0.1 and 0.15 µg/kg food, derived from the exposure scenarios for infants and toddlers, when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature or below, with or without hotfill. Articles made of this recycled PET are not intended to be used in microwave or conventional ovens and such uses are not covered by this evaluation.

Evaluation of the Safety of Cosmetic Ingredients and Their Skin Compatibility through In Silico and In Vivo Assessments of a Newly Developed Eye Serum.

The term "risk assessment" is often substituted with "safety assessment", to demonstrate the safe properties of cosmetic ingredients and formulations. With respect to the actual legislative framework, the proper use of in silico evaluation could offer a representative non-animal substitute for the toxicity evaluation of cosmetic ingredients. The in silico assessment needs to be integrated with other lines of proof (in vitro and/or in vivo data) in the form of a complex methodology in order to demonstrate the safety evaluation of cosmetic ingredients/products. The present study aimed to develop and characterize a new cosmetic formulation, designed for the skin care of the periorbital area. Quality control comprising stability, physicochemical, and microbiological evaluation was performed. Another objective of this study was to present a screening model for the safety evaluation of the cosmetic formulation by identifying individual ingredients, and to confirm the skin compatibility based on in vivo evaluation. The results demonstrated the in silico and in vivo safety profile of the cosmetic ingredients used in the present formulation. In silico evaluation, using a novel, specific software applicable for the risk evaluation of ingredients and formulations, showed that the incorporated ingredients were non-mutagenic and non-sensitizing, and considering the margin of safety (MoS), the cosmetic raw materials could be considered safe. Skin compatibility was confirmed by the patch test performed under dermatological control, evidencing the "non-irritating" potential of the developed cosmetic formulation.

Genome- and Toxicology-Based Safety Assessment of Probiotic Akkermansia muciniphila ONE Isolated from Humans.

In this study, the genome of Akkermansia muciniphila ONE (designated AKK ONE) was sequenced, assembled, and analyzed. In addition, the safety of this strain was further evaluated by toxicological studies. The results showed that the AKK ONE genome is contained on a single chromosome with a total length of 2,817,524 bp and an average GC content of 55.48%. In total, 2411, 1131, 1168, 1745, and 1402 genes were annotated to the NR, GO, KEGG, COG, and SwissProt database, respectively. Potential resistance genes, adeF, tetW, ANT(3″)-IIa, and aadA1 were detected. AKK ONE was sensitive to ampicillin, ceftriaxone, cefotaxime, meropenem, tetracycline, and chloramphenicol and resistant to moxifloxacin. No potential virulence-related genes were detected. The PathogenFinder database analysis showed that AKK ONE was a non-potential human pathogen. This strain had good gastroenteric fluid tolerance and a weak ability to colonize the gut. No test item-related adverse effects were observed in the acute and subchronic toxicity test. AKK ONE did not display mutagenic activity either. This strain did not change the hematological and clinical biochemical parameters of mice. The weights of the organs were not affected by AKK ONE treatment. These results support that AKK ONE is safe for use as a probiotic at a dose of 8.28 × 109 CFU/kg bw/day.