To ensure food safety, hazards that may threaten food safety are identified, and risk assessment is conducted to evaluate the effect on human health. In addition, risk management measures are implemented to reduce human health risks from these hazards. Risk communication is used to exchange information and opinions about risks among producers, consumers, governments, and others. A risk analysis policy to ensure food safety consists of the three components of risk assessment, risk management, and risk communication. The science that supports this risk analysis is called regulatory science, which is extremely important when considering food safety. The risk analysis is used to ensure the safety of pesticide residues in national food products. In this present issue, five articles written by experts in this field focus on the trends in risk analysis of residual pesticides by regulatory science in Japan. Through this special issue, it is hoped that correct understanding and knowledge of Japan's regulations on pesticide residues and the risk analysis system will be disseminated.

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Pesticides are widely used to protect crops from pests, diseases, and weeds, but their effectiveness can vary depending on various factors such as the type of pesticide used, the timing of application, and environmental conditions. To assess the efficacy of pesticides, several methods can be used. During the development stage of pesticides, laboratory tests are conducted to assess the effectiveness of insecticides under controlled conditions. Bioassays can be used to determine the toxicity of the pesticide to specific pests, pathogens, or weeds. Laboratory testing can provide precise data on the efficacy of the pesticide, but it may not accurately represent real-world conditions. Therefore, another approach is to conduct field trials where a pesticide is applied to a crop and its effectiveness is measured by comparing the degree of pest and disease occurrence between pesticide-treated plots and an untreated control plot. In addition, the yield and quality of pesticide-treated crops can be monitored. In Japan, the details and procedures of field tests related to the effectiveness of pesticides are conducted in accordance with the "Agricultural Chemicals Regulation Act", "Regulations for Enforcement of the Agricultural Chemicals Regulation Act", and "Data Requirements for Registration of Agricultural Chemicals" issued by the Ministry of Agriculture, Forestry and Fisheries (MAFF). Submitted data for registration of an agricultural chemical are evaluated by the Food and Agricultural Materials Inspection Center (FAMIC) under the guidelines mentioned above.

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Agricultural chemicals play a crucial role in safeguarding crops, enhancing the production of high-quality agricultural products, and maintaining a steady market supply. Despite these benefits, agricultural chemicals hold the potential for adverse impacts on both human health and the environment. Thus, a precise understanding of their toxicity, persistence, and assurance of safety during usage, including the safety assessment of residues, is of paramount significance.
In the context of agricultural chemicals registration, collaboration among the Ministry of Agriculture, Forestry and Fisheries (MAFF), the Ministry of the Environment (MOE), and the Ministry of Health, Labour and Welfare (MHLW) occurs in cooperation with the Food Safety Commission (FSC). This collaboration involves inspections and evaluations conducted in compliance with regulations such as the Agricultural Chemicals Regulation Act and the Food Sanitation Act. Specifically, the MAFF assesses pesticide efficacy and impact on users based on the Agricultural Chemicals Regulation Act, while the MOE evaluates their influence on ecosystems, flora, fauna, and water quality. The FSC conducts assessments of food safety impacts under the Food Safety Basic Act to determine the Acceptable Daily Intake (ADI) and Acute Reference Dose (ARfD). These assessments draw from a diverse pool of toxicity data derived from studies using various animal species, encompassing acute, subchronic, and chronic toxicity, genotoxicity, carcinogenicity, and reproductive and developmental toxicity, to estimate ARfD, ADI, and potential risks.
Operating under the purview of the Food Sanitation Act, the MHLW establishes residue limits for pesticides in food, grounded in food health impact assessments and residue data derived from usage practices, thereby ensuring that health risks from agricultural chemicals remain minimal. Moreover, exposure assessment is conducted by comparing residue limits, estimated food intake, and the food health impact assessment conducted by the FSC to verify that intake remains below ADI and ARfD thresholds. The MOE then establishes usage guidelines based on these assessment outcomes, taking into account ADI and ARfD considerations.
The safety assessment of agricultural chemicals confronts challenges such as evaluating simultaneous exposure to multiple pesticides and identifying links between pesticides and specific conditions like developmental disorders or cancer. To address these challenges and enhance the efficiency of safety assessments, the development of novel assessment methods is warranted.

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For registration of agricultural chemicals in Japan, submission of a data set for safety assessment is required by Notification No.30-Shouan-6278 (Ministry of Agriculture, Forestry and Fisheries). Residue chemistry studies needed for assessment of maximum residue limits (MRLs) include "Metabolism in plants" followed by "Residues in crops" for agricultural crops and "Metabolism in livestock" followed by "Residues in livestock" for livestock products. These studies are required to clarify the nature and magnitude of residues originating from agrochemical use under possible critical Good Agriculture Practice (cGAP) conditions. Metabolism studies also provide important information regarding the analytical method for the corresponding residue studies, especially for extraction procedures, by using radiolabel-incurred samples. All these studies are needed to follow OECD guidelines for the testing of chemicals and must be conducted under Good Laboratory Practice (GLP) standards, thereby producing internationally interoperable test results with high reliability and reproducibility. Based on such strictly obtained scientific evidence, residue definitions for both enforcement and dietary risk assessment purposes, as well as MRLs, can be established to ensure food safety for consumers.

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Understanding the extent of human exposure to chemicals such as pesticides, veterinary drugs, and feed additives in our daily diet is indispensable for ensuring food safety. The current methods used for exposure assessment lack detailed consideration of those chemicals consumed from mixed foods. To estimate the exposure from consumed foods, including mixed ones, a refined method was developed. This method incorporates food consumption data obtained from a nationwide dietary survey conducted in Japan, a reverse-yield factor that disaggregates mixed foods into raw primary commodity ingredients, and a processing factor that considers changes in the chemical residue concentration during processing. The short-term exposure was estimated based on the veterinary drug concentration detected in salmon, and the hazard quotient (HQ) was calculated by dividing the estimated exposure amount by the Acute Reference Dose. In the case of salmon consumption within the Japanese diet, the calculated HQs were found to be well below one, suggesting that there would be no unacceptable acute health risks associated with the detected residues in salmon.

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Pesticide residues refer to residues of pesticides used in the production process of agricultural products for the purpose of weed and pest control in crops. Even when used as a pesticide, residues remain in agricultural products, processed foods, and the environment in trace amounts, making it difficult to completely eliminate these chemicals. Therefore, it is necessary to analyze pesticide residues in foods and use these data for regulation and evaluation.
This paper first presents the current status of pesticide residue analysis in foods. The four main steps (sample preparation, extraction, purification, and quantification) are explained, and points of caution are presented. The listed as notified test methods by the MHLW (Ministry of Health, Labour and Welfare) and the specific analytical methods (QuEChERS [a dispersed solid-phase extraction method] and QuPPe method [for polar pesticides]) are discussed. The choice of analysis method according to the purpose of analysis (for risk management or risk assessment) is described. Finally, findings on future issues and expected measurement techniques (μ-SPE, LPGC, APGC, etc.) in pesticide residues analysis of foods are discussed.
It is hoped that further development of pesticide residue analysis methods will ensure food safety in the future.

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Under the Food Sanitation Law, the Nagasaki Prefectural Institute of Environment and Public Health conducts standardized inspections of food products distributed in the prefecture, inspects standards for the use of food additives, and conducts research and studies that contribute to food safety and security. This paper introduces the efforts and recent results of administrative inspections and research on marine products and processed marine products in Nagasaki Prefecture, which is surrounded by the sea on three sides and boasts abundant marine resources.
The inspections conducted on fish paste products regarding ingredient standards and the use of food additives have not found any violations of ingredient standards for coliforms or violations of standards for the use of sorbic acid over the past three years. However, in 2020, two cases were confirmed where sorbic acid was detected in samples without proper labeling indicating its use.
In the tests for veterinary drug residues in cultured fish, paralytic shellfish poisoning, and toxicity in puffer fish (Takifugu vermicularis), no samples exceeding the standard values have been found in recent years. Additionally, food allergen tests for shrimp and crab were conducted on a total of 111 samples from 2013 to 2019, out of which 9 samples were found to violate labeling regulations (potentially mislabeled products).
The Physical Chemistry Department in Nagasaki Prefecture handled 40 cases of confirmed or suspected food poisoning from 2004 to 2022, of which 37 cases were caused by marine products, which accounted for over 90% of the total cases. Particularly, food poisoning caused by tetrodotoxin (TTX), a puffer fish toxin, accounted for the majority of the 27 cases, while one case was caused by ingestion of gastropods, which are non-puffer fish organisms. In this research study, we addressed health crises caused by marine natural toxins (marine biotoxins) and developed a rapid analysis method for detecting TTX in patients' biological samples (serum and urine), and summarized the quantitative results of TTX concentrations in leftover food and biological samples of food poisoning cases caused by puffer fish and gastropod consumption in Nagasaki Prefecture from 2011 to 2017, and their correlation with symptoms. We have also initiated a research study on seafood allergy in adults. Furthermore, as a prefectural research institute, the center collaborates with other research institutes in the prefecture to evaluate the quality of marine products and conduct safety research.
As the scientific and technical core of hygiene administration in Nagasaki Prefecture, we will continue to respond to social conditions, citizens' needs, etc., and strive to ensure food safety in cooperation with government agencies.

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Overnutrition and physical inactivity lead to obesity, which is associated with adipocyte hypertrophy and hyperplasia. The body stores lipid primarily in white adipocytes, but beige adipocytes are also present in white adipose tissue. Beige adipocytes are heat-producing cells that convert energy obtained from lipid consumption into heat through mitochondrial uncoupled protein 1 (UCP-1), and this heat-producing capacity is considered to be anti-obesity. However, heat production is inhibited by the chronic inflammation induced in obese adipose tissue by macrophage infiltration. Chronic inflammation also suppresses the expression of UCP-1 and reduces thermogenesis. Therefore, food compounds with anti-inflammatory properties are expected to exert anti-obesity effects by restoring UCP-1 expression and increasing fat consumption in beige adipocytes.
Food-derived compounds have been reported to increase UCP-1 expression when administered directly to animals. When an obesity model is used to evaluate the function of food-derived compounds, some of the increased expression of UCP-1 could be attributed to its anti-inflammatory effects. It is also possible that food-derived compounds that were not found to increase UCP-1 expression could restore UCP-1 expression in the obese state due to their anti-inflammatory effects. To elucidate the mechanism of how food-derived compounds increase UCP-1 expression at the cellular level, it is necessary to perform independent experiments on adipocytes and macrophages. Therefore, we established an evaluation system to study the effects of food compounds with anti-inflammatory effects on beige adipocytes under reproduced inflammatory conditions induced by macrophages. Using this system, we analyzed 6-shogaol, which has already been reported to increase UCP-1 expression and have anti-inflammatory effects. The results showed that the expression of UCP-1 was restored by the anti-inflammatory effect of 6-shogaol. The newly developed evaluation system using macrophage culture supernatant is a useful system for evaluating food-derived compounds with anti-inflammatory effects.

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The eastern 200〜1,000 m altitude area of the Central Andes in Peru is said to be the Alkaloid region. The region is a treasury of herbs, and especially the herbs including alkaloids is high. They are classified as poisonous, psychotropic and medical herbs by functionality. The poisonous herbs, Curare, Sandbox tree, Amasisa colorada and Toe are introduced in this article. Curare is especially famous as one of four major arrow poisons of the world. Curare is a common name for the extract from alkaloid herbs originating from indigenous peoples in South America. The main source herbs for curare are Chondrodendron tomentosum that contains d-tubocurarine and Strychnos toxifera that contains toxiferine. Used as a poison for hunting, fishing and therapeutic purposes, curare only becomes active on direct wound contamination by a poison dart or arrow. But curare has no oral toxicity. The poison functions by competitively and reversibly inhibiting the nicotinic acetylcholine receptor, which is a subtype of acetylcholine receptor found at the neuromuscular junction. This causes relaxation of the skeletal muscles and, when administered in a sufficient dose, eventual death by asphyxiation due to relaxation of respiratory muscles. After the discovery of this function, curare became a widely used relaxant during medical and surgical procedures used in combination with a ventilator. In medicine, curare has been superseded by a number of curare-like agents, such as pancuronium and hexamethonium which have a similar pharmacodynamic profile, but fewer side effects.

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