Background/Objectives: Providing an appropriate diet to older adults with dysphagia can prevent aspiration, choking, and nutritional deficiencies and help preserve their quality of life. Therefore, assessments for determining the appropriateness of food types are required. This multicenter study aimed to determine the reliability and validity of the Meal Rounds Observation Form (MROF), which was developed to identify food forms that can be safely consumed by older adults with dysphagia. Methods: We analyzed 532 food-texture observations obtained from 155 participants (114 men and 41 women). The reliability and validity of the MROF were compared with those of videofluoroscopic (VF) or videoendoscopic (VE) examinations of swallowing. Results: The food-form categories were water (108 pairs), 0j (54 pairs), 0t (118 pairs), 1j (20 pairs), 2-1 (28 pairs), 2-2 (37 pairs), 3 (68 pairs), 4 (67 pairs), and normal food (32 pairs) based on JDD 2021 codes. The AUC was lowest for the water (0.568) category and highest for food forms requiring chewing, such as those of the 4 and normal food (0.678) categories. The sensitivity and specificity of the Gugging Swallowing Screen were 60.1% and 69.1%, respectively (p < 0.001). The agreement between the Gugging Swallowing Screen and the MROF evaluation for food types requiring mastication was 73.2%. Logistic regression analysis revealed asymmetric movement of the corners of the mouth and coughing as important indicators when evaluating food types requiring mastication. Conclusions: The MROF is useful for determining food intake safety when VF or VE tests cannot be performed in medical and nursing care settings and can guide clinical decision-making. However, caution is required in applying it clinically because of its relatively low specificity.
Human physiological and psychological states may influence work performance and safety. This study explored the relationships between couriers' work-related musculoskeletal disorders (MSDs), psychological distress, work errors and traffic safety. A total of 252 food delivery and 239 package delivery couriers were surveyed. The work-related MSDs and psychological distress were self-reported using an MSD Likert questionnaire and the Symptom Checklist-90 (SCL-90). Companies provided records of work errors and traffic accidents. Compared with the package delivery couriers, the food delivery couriers had significantly higher MSD levels in the legs, feet and ankles, higher anxiety, more work errors, and more traffic accidents. The couriers with more severe MSDs showed significantly higher psychological distress. For food delivery couriers, higher psychological distress correlated with more work errors and traffic accidents. These findings highlight the importance of MSD prevention and psychological distress management, particularly among food delivery couriers, to improve occupational health, work performance, and traffic safety. Couriers with more severe MSDs reported higher psychological distress; among food delivery couriers, psychological distress was associated with more work errors and traffic accidents. Managers should reduce their lower-limb and handling loads through rest breaks, route optimisation, ergonomic training, and handling aids. Delivery platforms should set realistic delivery times, avoid speed-based penalties, and integrate stress support with order-verification and traffic-safety training.
Ochratoxin A (OTA) is a naturally occurring mycotoxin produced by Aspergillus and Penicillium fungi that can contaminate a range of agricultural commodities and products, such as cereal grains, dried fruit, and coffee beans. While some OTA contamination in foods may be unavoidable, there are steps that can be taken to help prevent fungal growth and control the presence of OTA in foods. The U.S. Food and Drug Administration (FDA) has established a regulatory mycotoxin compliance program to sample and analyze human foods for mycotoxins. Each year, under this compliance program, samples of foods susceptible to mycotoxin contamination are collected and analyzed for various mycotoxins, including OTA. In this study, we present and discuss data on OTA levels for over 3,700 food samples collected between fiscal years (FY) 2008 and 2022. OTA levels ranged from non-detect to 116 µg/kg, with the highest findings seen in green coffee beans, dried fruits, grain products, and spices. The vast majority of samples (96.5%) had OTA levels below the levels of quantification (LOQs) of 0.21 to 24.9 µg/kg. The findings were similar to detection rates, levels, and affected foods seen in other surveys of OTA. Our findings support continued monitoring of OTA in susceptible foods and may be useful in future work to determine whether it is appropriate to establish regulatory levels for OTA in the United States.
Staphylococcus aureus is a major cause of foodborne intoxication through the production of heat-stable enterotoxins (SEs) and is also an important opportunistic pathogen of humans and livestock. Meat and meat products are major vehicles for this pathogen because their protein-rich composition supports bacterial growth and toxin production. However, the combined effects of temperature and nutrient composition on S. aureus growth and virulence expression under food-relevant conditions remain unclear. In this study, we investigated the interactive effects of temperature and nutritional context on the growth and virulence-associated phenotypes under model food-relevant environments with the reference strain S. aureus FRI-S6. Bacterial growth, biofilm formation, staphylococcal enterotoxins A and B (SEA, SEB), and hemolytic activity were evaluated at 25 °C and 37 °C in brain heart infusion (BHI) medium supplemented with NaCl, glucose, or tryptone to simulate diverse food-relevant conditions. Growth was generally faster at 37 °C, whereas glucose-supplemented cultures at 25 °C reached higher cell densities during prolonged incubation. Biofilm formation increased at 37 °C in BHI and glucose conditions. SEA production was enhanced at 37 °C under NaCl and tryptone, but at 25 °C in glucose-rich conditions. In contrast, SEB production and hemolytic activity were consistently higher at 37 °C, particularly in the presence of tryptone and glucose. These findings demonstrate the strong interaction between temperature and nutrient composition in shaping S. aureus virulence in food environments and provide important insights for food safety risk assessment and highlight practical implications for controlling enterotoxin production in meat products and other foods during storage and processing.
Inadequate food preservation has become a serious public health and environmental challenge. Foodborne illnesses caused by microbial contamination, chemical spoilage, and improper storage pose serious threats to human health and place additional pressure on the sustainability of the food supply chain. To address environmental pollution and food spoilage, it is essential to develop multi-functional intelligent food packaging materials. Herein, a novel multifunctional bio-composite film (BC-La2O3/Cur/CD) was fabricated by incorporating curcumin-β-cyclodextrin inclusion complex (Cur-β-CD) and lanthanum oxide (La2O3) into a bacterial cellulose (BC) matrix for intelligent food packaging. Compared with pure BC, the composite film exhibits integrated antimicrobial, antioxidant, barrier, and mechanical properties. Specifically, the composite film achieved 100% inhibition rates against both E. coli and S. aureus, and showed DPPH and ABTS radical scavenging rates of 76% and 97%, respectively. Consequently, the film effectively inhibited spoilage microorganisms and extended the shelf life of basa fish. Moreover, its color changed in response to alkaline volatile amines accumulated during storage, offering visual freshness monitoring. Biocompatibility tests confirmed that the film did not increase plant or cell mortality, supporting its safety as an active food packaging material. This work offers a viable strategy for the design of rare earth-containing bio-composite films with integrated antioxidant, antibacterial and intelligent freshness-monitoring functions.
Listeria monocytogenes is a major foodborne pathogen capable of persisting and growing under refrigerated storage, raising food safety concerns for ready-to-eat (RTE) foods. This study investigated the occurrence, genetic and invasion characteristics of L. monocytogenes in five categories of RTE seafood products distributed in Japan: cod roe, seasoned cod roe, salmon roe, smoked salmon, and minced tuna. A total of 500 retail samples, comprising 100 samples per category, were examined in 2023. L. monocytogenes was detected most frequently in minced tuna (23%), followed by salmon roe (9%), seasoned cod roe (4%), cod roe (2%), and smoked salmon (2%). Quantification using a three-tube MPN method indicated generally low contamination levels, with most positive samples containing <10 MPN/g. However, physicochemical analyses of pH and water activity suggested that most products were capable of supporting the growth of L. monocytogenes during storage. Whole-genome sequencing of 40 isolates revealed substantial genomic diversity, classifying isolates into 14 clonal complexes and 27 cgMLST types, with no marked bias toward either BIGSdb-defined Lineage I or II. Gene content analysis identified stress survival islets, disinfectant tolerance-associated determinants, and virulence-associated loci, including LIPI-3 and LIPI-4, in specific clonal backgrounds. Epithelial invasion assays revealed wide variation in invasion phenotypes, with higher invasion among Lineage I isolates and near-zero invasion in isolates carrying premature stop codons in inlA. Overall, these findings highlight heterogeneous risk profiles among L. monocytogenes contaminating RTE seafood products in Japan.
The global rise in allergic and autoimmune diseases since the 1960s has been associated with environmental disruptions of epithelial barriers, particularly in the gastrointestinal tract. Among the implicated factors are food emulsifiers, which have become increasingly prevalent in processed foods such as peanut butter. This study investigates the biological effects of two commonly used food emulsifiers in peanut butter, soy lecithin and diacetyl tartaric acid esters of mono- and diglycerides (DATEM), on gastrointestinal tissue responses and immune responses using advanced in vitro gut-on-a-chip models, human adult stem cell-derived colon organoids-on-a-chip, and murine models. Both emulsifiers induced dose-dependent cytotoxicity and disrupted epithelial barriers, as demonstrated by reduced transepithelial electrical resistance and disorganization of zona occludens-1 at daily-exposure doses. Transcriptomic and proteomic analyses revealed activation of pro-inflammatory pathways including TNF, NF-κB, the unfolded protein response, and cell death by apoptosis. Soy lecithin additionally induced oxidative stress. Systemic responses were confirmed by increased pro-inflammatory cytokines in serum and immune activation in peripheral blood mononuclear cells (PBMCs). Notably, both emulsifiers stimulated serum total IgG, soy lecithin induced IgE in mice upon feeding, and DATEM enhanced IL-4-induced IgE production in human PBMCs, suggesting a role in allergy development. These findings challenge the presumed safety of soy lecithin and DATEM and highlight their potential contribution to immune dysregulation and epithelial barrier dysfunction, which may initiate or exacerbate food allergy and gastrointestinal inflammatory diseases.
Food safety surveillance for fresh produce requires analytical tools that operate directly on wet, curved plant and fruit surfaces, yet gold-standard methods and flexible surface-enhanced Raman scattering (SERS) substrates are often destructive or unsuitable for in vivo use. Here, we present a bottom-up absorptive ultrathin plasmonic tape-SERS-active functional elastomeric (SAFE) tape-that conforms to wet surfaces and absorbs/transports analytes to plasmonic hotspots for quantitative, multiplex in vivo SERS readouts without substrate inversion. SAFE tape swells within seconds and achieves detection limits of 1 nM for pesticides and 1 μM for plant hormones, while maintaining high signal uniformity, mechanical durability, and long-term stability. Predictive models accurately quantify mixtures across a broad range (1 μM to 1 mM). The tape also detects Penicillium spp. up to two days before visible symptoms and enables real-time monitoring of pesticide and preservative degradation during growth and storage, providing a low-cost, field-deployable platform for food safety monitoring.
Heat-killed Lactobacillus helveticus MCC1848 is a postbiotic, which potentially aids in maintaining a positive mood. Daily intake of heat-killed L. helveticus MCC1848 for 4 weeks by healthy adults is known to be safe. However, the safety of long-term L. helveticus MCC1848 intake has not been investigated. This study aimed to evaluate the safety of long-term intake of 25 billion heat-killed L. helveticus MCC1848 in healthy adults through a randomized controlled trial involving 40 participants. The study participants were randomly assigned to either the MCC1848 group (n = 20) or placebo group (n = 20). During a 12-week period, the MCC1848 group received the test powder containing 25 billion cells of heat-killed L. helveticus MCC1848, which is five times the minimum effective dose suggested for maintaining a positive mood. The placebo group received dextrin powder without any detectable heat-killed L. helveticus MCC1848. Safety evaluations included anthropometric and blood pressure measurements, hematological and biochemical tests, urinalysis, and adverse event monitoring. No clinical issues were observed in either of the biochemical evaluations. Furthermore, no adverse events were reported due to the intake of heat-killed L. helveticus MCC1848. The results of this study suggest that 25 billion heat-killed L. helveticus MCC1848 for 12 weeks is safe for intake in healthy adults. The clinical trial was registered as UMIN000055233 (Registration Date: August 13, 2024) in the Clinical Trials Registry of the University Hospital Medical Information Network.
The optimal dosing strategy for valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection in pediatric patients after kidney transplantation (KT) remains uncertain because of the narrow therapeutic window between antiviral efficacy and safety. This study included pediatric patients who received VGCV prophylaxis after KT at a single center between December 2023 and December 2024. VGCV was administered once daily for 200 days using a reduced-dose regimen. Approximately 50% of the U.S. Food and Drug Administration-recommended dose was used for high-risk patients defined as donor-positive and recipient-negative, and 33% for intermediate-risk patients defined as recipient-positive. The incidence of CMV infection within 200 days after KT and VGCV-related adverse events (AEs) were evaluated. Nine patients with a median age of 8 years were included, with a median observational period of 431 days after KT. CMV infection within 200 days occurred in four patients, all of whom were high-risk patients. No CMV disease occurred during the observational period. Neutropenia occurred in six patients, including five high-risk patients and one intermediate-risk patient. Three high-risk patients developed febrile neutropenia. VGCV dose reduction and/or discontinuation due to hematologic AEs was required in four patients. The reduced-dose VGCV prophylaxis regimen was associated with a high incidence of CMV infection and AEs in high-risk patients, indicating a suboptimal balance between efficacy and safety. In intermediate-risk patients, the regimen appeared effective and tolerable. Further optimization of prophylactic strategies is required, particularly for high-risk pediatric recipients.
BICSTaR (BICtegravir Single Tablet Regimen) is a multinational observational study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV). Previously, the 12-month analysis of the Japan cohort of BICSTaR showed high levels of virologic effectiveness and tolerability with B/F/TAF. Data for 84 treatment-experienced (TE) or 116 treatment-naïve (TN) participants aged ≥20 years receiving B/F/TAF as part of routine clinical care in Japan were collected retrospectively and prospectively. Outcomes analyzed at 24 months included HIV-1 RNA <50 copies/mL, treatment persistence, drug-related adverse events (DRAEs), and patient-reported outcomes (prospective cohort only). At 24 months, 97% of TN and TE participants had HIV-1 RNA <50 copies/mL (missing-equals-excluded analysis), and 96% of participants remained in the study and were receiving B/F/TAF. DRAEs were reported by 14% of participants (TN: 16%; TE: 10%), with diarrhea (TN: 3%; TE: 2%) and weight gain (TN: 4%; TE: 0%) being the most common; the majority of DRAEs occurred in the first 12 months. Participants enrolled prospectively reported stable or improved quality of life through 24 months. Treatment with B/F/TAF in routine HIV clinical care in Japan was associated with high persistence, virologic effectiveness, and was well tolerated through 24 months.
The decision by the co-Editor-in-Chief of Regulatory Toxicology and Pharmacology, Prof. Martin van den Berg, to retract the 2000 review article by Williams, Kroes, and Munro has elicited widespread criticism within the scientific community. Issued in late 2025, the retraction decision cites procedural concerns including potential ghostwriting, undisclosed conflicts of interest, and omission of certain unpublished studies, invoking Committee on Publication Ethics guidelines despite lacking evidence of fraud or scientific flaws. This editorial argues that the retraction decision involves editorial overreach and misapplication of the guidelines. The alleged omissions stemmed from proprietary data access limitations that were disclosed in the original paper. Subsequent reviews by several independent expert panels and regulatory authorities with access to all glyphosate data, including the studies cited by the retracting editor, reached similar conclusions. Claims of ghostwriting were previously investigated and found lacking, including a declaration by EFSA as to the clarity of the conflict disclosures. The retraction's timing, reliance on litigation documents, and apparent biases that were not disclosed in the retraction notice raise questions of ideological interference. Absent substantive rebuttals based on scientific merit rather than speculative claims of inappropriate authorship and data access, this retraction decision sets a dangerous precedent for retroactive censorship, potentially chilling beneficial industry-academic collaborations and eroding trust in the integrity of scientific publishing. With the strongest conviction, we assert that retracting a paper without scientific flaws isn't protection-it is censorship. We therefore call for the immediate reversal of this flawed and unjustified retraction to preserve trust in peer-reviewed literature.
To summarize current advances in risk-based management of unintended food allergen presence, with a particular focus on Japan's unique 10-ppm labeling threshold and precautionary allergen labeling (PAL) prohibition, and to contextualize these within emerging international frameworks based on eliciting doses (EDs) and reference doses (RfDs). Quantitative risk assessment has shown that the aforementioned threshold offers a wide safety margin for most consumers allergic to egg, milk, and wheat, with estimated inadvertent exposures below the FAO/WHO RfDs. However, this threshold is associated with overly stringent requirements and a substantial management burden for some allergens, such as crustaceans. The FAO/WHO guidelines, Voluntary Incidental Trace Allergen Labeling (VITAL) 4.0, Codex, and regional initiatives are converging on ED-based RfDs alongside HACCP-based allergen management. In Japan, rapid shifts in nut consumption have altered allergy prevalence and ED distributions, highlighting the need for periodic threshold updates. Future allergen policy should integrate robust thresholds with realistic, HACCP-based allergen management in packaged foods and food-service settings, anticipate shifting dietary patterns, and support internationally harmonized, evidence-based PAL that enhances the safety and quality of life of food-allergic individuals.
Aerobic spore-forming bacteria cause food poisoning and spoilage and can be distinguished from other bacteria based on colony size and shape when grown on a sheet medium (MC-Media Pad™ ACplus). We developed a classifier that can distinguish between these two types of colonies and automatically count them using the deep learning algorithm, YOLO. This YOLO-based classifier was trained using Bacillus subtilis subsp. spizizenii NBRC 3134 as a spore-forming bacterium and Escherichia coli NBRC 3301 as a non-spore-forming bacterium. When classifier performance was evaluated using 60 images, including 4549 colonies, the accuracy exceeded 0.98. When versatility was investigated using 46 strains of 34 species in 24 genera, the method achieved a mean accuracy greater than 0.94 and thus demonstrated a discrimination power equivalent to that of visual inspection. We assessed the practical feasibility of the developed classifier using 66 ready-to-eat foods in six categories. Comparison of classifier-based predictions with 16S rDNA sequence-based identifications of the isolated strains revealed that the classifier had a precision approaching 0.91; thus, there was a very high possibility that the colonies predicted to be spore-forming bacteria were actual spore-forming bacteria. Regarding speed, the classifier took only ∼133 msec per sheet medium to enumerate colonies. The practical application of this novel classifier should enable users of various skill levels to quickly quantify spore-forming bacteria, to help ensure food safety and facilitate the management of food quality.
The global use of real-world data (RWD) for drug approval and post-marketing surveillance has increased significantly. During 2023 and 2024, the US Food and Drug Administration issued industry guidance, and the European Medicines Agency released real-world evidence framework reports to support regulatory decision making. In Japan, the Pharmaceuticals and Medical Devices Agency promotes the use of RWD, with collective efforts from the government and related industries. This report focuses on electronic health record (EHR) databases in Japan, aiming to (1) organize the characteristics of data generated from such databases, and (2) identify the challenges when using EHR databases for regulatory decision making. This report conducted an internet-based Google search using the keywords 'electronic medical record database' with the condition that the results include any of the keywords 'Japan' or 'real-world data'. Online interviews were conducted with representatives from eight EHR database companies identified as being utilized in Japan, focusing on the characteristics of each EHR database, challenges in their utilization, and future perspectives. The characteristics and limitations of current EHR databases were summarized; they offer broad coverage in terms of patient backgrounds and easier access to clinical laboratory values but are unable to track patients who transfer between hospitals due to lack of data linkage, and there may be loss of information during data abstraction. Data collection methods were mostly retrospective. Critically, there is no overall standardization between the EHR databases. Currently, EHR studies are primarily observational to verify efficacy and safety in real clinical practice and are gradually being used for post-marketing surveillance to support regulatory decision making in Japan. Addressing operational, technical, and methodological challenges in using EHR databases for regulatory approval applications requires efforts from multiple stakeholders, including industry, academia, and government. Real-world data (RWD) are information collected from everyday medical care, not from clinical trials. Around the world, RWD are increasingly being used to verify the effectiveness and safety of medicines. In 2023 and 2024, the US and Europe published regulations to guide this process. In Japan, the government and industry are also working to utilize RWD for drug approval and safety monitoring. This topic matters to the general public because better use of RWD can lead to safer medicines, faster access to new treatments, and healthcare decisions that more accurately reflect everyday patient care, not just clinical trials. This report examines electronic health record (EHR) databases in Japan. These databases store patient information from hospitals. The report explains what these databases can do and what challenges exist. The study used online searches and interviews with database companies. EHR databases have some strengths. They include many types of patients and laboratory test results. But there are challenges. Patients cannot be tracked if they move to another hospital. Some information may be lost when data are processed. Most data are collected after care, not in real time. Also, there is no common standard across databases. Today, EHR data in Japan are mostly used to confirm drug safety and effectiveness after approval. To use these data for new drug approvals, many issues need to be resolved through collaboration between industry, universities, and government.
Several countries and regions have established regulations or guidelines specifying permissible limits for elemental impurities in cosmetic products. Surveys of commercially available cosmetics have shown that lipsticks often contain significant amounts of elemental impurities, which are of particular concern due to the high risk of oral exposure. In this study, the elemental impurities in eight commonly used cosmetic ingredients were analyzed, namely silicon dioxide, titanium oxide, iron oxide, synthetic mica, natural mica, beeswax, Ricinus communis (castor) seed oil, and Lithol Rubine B. Total dissolution of the samples was achieved via microwave digestion, employing an ammonium fluoride solution as a safer alternative to highly toxic hydrofluoric acid (HF). Subsequently, 14 elements-chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, cadmium, tin, antimony, mercury, and lead-were quantified by inductively coupled plasma mass spectrometry. The limits of detection and quantification, as well as the accuracy and precision of the analytical method, were validated, confirming its suitability for the reliable determination of total elemental impurities in cosmetic ingredients. The inorganic ingredients contained relatively higher concentrations of elemental impurities than the organic ingredients. Se, Cd, and Hg were not detected in any samples. The developed analytical method eliminates the requirement for HF, thereby enhancing analyst safety. Accurate determination and control of elemental impurity levels-particularly in inorganic cosmetic ingredients-are essential for minimizing contamination and ensuring product safety. By avoiding the use of highly toxic HF, the analytical method presented in this study enhances analyst safety while maintaining high accuracy, rendering it a practical tool for cosmetic quality control and research and development.
Anisakis allergy (AA) is a major cause of adult food allergy in Japan. We evaluated the safety of seafood broth, cooked fish, and thawed frozen fish in AA, and the diagnostic value of early Anisakis-specific IgE (Ani sIgE) dynamics. We conducted a single-center retrospective cohort study of 44 AA outpatients. Based on clinical tolerability to cooked fish and broth, patients were classified as gastroallergic anisakiasis-like type (GAA-type; asymptomatic with cooked fish/broth; clinically tolerant) or classical anisakis allergy-like type (classical AA-type; symptomatic). Classical AA-type underwent stepwise Oral Fish Clinical Challenge (OFCC) followed by oral tolerability induction (OTI). Ani sIgE was measured in paired serum samples ≤7 days and 1-24 months after onset. Forty-four patients were analyzed; cooked-fish tolerability was 86.4% (38/44), broth tolerability 95.5% (42/44). Among GAA-type (n = 38), all 30/30 who attempted thawed frozen fish clinically tolerated it. Classical AA-type accounted for 6/44 (13.6%); all reactions were Grade 1-2. Stepwise OFCC/OTI enabled symptom-free ingestion under protocol conditions in 5/6 (83.3%); no Grade ≥3 events occurred during OTI. Paired Ani sIgE (n = 26) rose from 1 week to 4 months (peak), then declined; all 10/10 with initial <7.9 kUA/L reached ≥7.9 kUA/L. Mean fold-increase from the initial (∼1 week) to the 1-month sample was 6.50 × . Most AA patients can reintroduce cooked fish, and classical AA-type may achieve clinical tolerability to cooked fish/broth with stepwise OTI under cofactor avoidance. A two-stage Ani sIgE strategy (early and 1-4 months) may serve as a diagnostic adjunct supporting case definition and clinical decision-making.
Regulatory science (RS) is a field dedicated to developing and applying scientific methods, tools, standards, and evidence-based frameworks to improve regulatory policies and decision-making related to medical and device products. The acceleration of cardiovascular innovations over the past two decades has underscored the need for efficient evidence generation and streamlined regulatory pathways for new drugs and devices. RS seeks to address these challenges by strengthening the evidence base that informs policy and guidance, enhancing transparency, expediting approval processes, and enabling more agile responses to emerging public health needs. By evaluating innovative trial designs and employing advanced statistical methods, RS can reduce resource demands of clinical trials while preserving scientific integrity. RS also facilitates the standardization of biomarker evaluations and surrogate endpoints, supporting advancements in precision medicine. In addition to clinical evaluation, RS can enhance post-marketing surveillance by utilizing real-world evidence and advanced analytics to promptly identify safety signals, ensuring patient safety and continuous product monitoring. RS also supports global regulatory harmonization efforts, reducing redundancies and accelerating access to therapies across regions. RS aims to guide the development of regulatory policies, refine communication strategies to optimize the use of medical products, and maintain efficient, transparent, and scientifically rigorous regulatory frameworks. Continued investment in RS is essential for improving patient outcomes in cardiovascular medicine by safeguarding safety while accelerating innovation and access to therapies.
Paltusotine is a novel, nonpeptide, once-daily oral, selective somatostatin 2 receptor (SST2) agonist. We evaluated the pharmacokinetics, pharmacodynamics, and safety of oral paltusotine in healthy Japanese adults in single‑dose (20, 40, 60, 80 mg) and repeated‑dose (40 mg once daily for 7 days in a two-sequence, two‑period crossover design) studies. In addition, the effects of food intake and pharmacodynamics were examined in the repeated-dose study. Eight participants were enrolled in each dose of the single-dose study, and 12 participants were enrolled in the repeated-dose study. In both studies, there were no deaths, serious adverse events, or severe adverse events. In the single-dose study, plasma paltusotine exposures increased in a dose-dependent manner for the dose range of 20 to 80 mg (based on Cmax and AUC0-∞), and the elimination half-life (t1/2) was 24-28 h. In the repeated-dose study, similar reductions from baseline in serum insulin-like growth factor-1 (IGF-I) were observed for 1-h pre-prandial (-60.1 ± 26.0 ng/mL) and 3-h post-prandial administration (-61.6 ± 17.7 ng/mL) on Day 7. Overall, this study establishes the pharmacokinetics, pharmacodynamics, and safety in healthy Japanese adults to support the development of paltusotine as a treatment for acromegaly and pituitary gigantism.
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of oxolinic acid (CAS No. 14698-29-4), an antimicrobial agent with a quinoline structure, based on results from submitted documents. For the fifth edition, additional residue data for crops (including taro and broccoli) were submitted by the Consumer Affairs Agency. The data used in the assessment include fate in animals (including rats) and humans, fate in plants (including paddy rice and napa cabbage), residues in crops, residues in livestock products (including cattle and pigs), subacute toxicity (rats, mice, and dogs), chronic toxicity (dogs), combined chronic toxicity/carcinogenicity (rats), carcinogenicity (mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), and genotoxicity. Major adverse effects of oxolinic acid were observed in the body weight (suppressed weight gain), the testes (interstitial cell hyperplasia in rats), the ovaries (organ weight increase in rats), excitatory neurological symptoms, and behavioral changes (Table 1). No adverse effects were observed on either fertility, teratogenicity, or biologically significant genotoxicity. The lowest NOAEL for potential adverse effects after a single oral administration of oxolinic acid was 6 mg/kg bw from the results of the acute neurotoxicity study in rats (Table 2). FSCJ established an acute reference dose (ARfD) of 0.06 mg/kg bw by applying a safety factor of 100 to this NOAEL.