Food safety and security is a very important relationship and should not be underestimated. There are many hazardous substances such as enterohemorrhagic Escherichia coli (O-157) which causes a verotoxin shigalike dysentery while diseases caused by other microorganisms include campylobacter infections, listeria monocytogenes infections, salmonella infections, and norovirus infections. In our living environment there are many chemicals which can be toxins and toxicants. A toxin is a poisonous substance produced either within living cells or organisms or by synthetic processes. When present in food, these chemicals may be hazardous, causing acute or chronic disease.
When we conduct risk assessments, we cannot always get all the information needed. In such cases, we obtain information from toxicity testing using experimental animals. In considering risk assessment of hazardous chemicals, all chemicals could have a toxic effect on the living body at high levels of exposure. Even “safe foods” may not be 100% free of potential toxic chemicals. However, this concept is difficult to explain to ordinary people as they expect absolutely(100%) safe food. However, safety is not absolute.
According to the principles of toxicological science, the safety of chemicals, including hazardous chemical substances, depends on the dose administered, the route of exposure, and the amount absorbed. Almost any substance or food can represent a hazardous factor if the amount of exposure is excessive. As another example, vitamin A is necessary for health maintenance, but a large amount of intake of this chemical, called hypervitaminosis A, causes skin aging, rash, and a feeling of fatigue. Similarly, a tiny amount of iron is necessary for a healthy body, but access intake may lead to symptoms of nausea and diarrhea as a hazardous response. Using still another example, it is said that a large amount of salt intake may cause illness with hypertension, arteriosclerosis, and gastric cancer. However, people do not feel at risk for hazardous factors that they well understand are familiar things in their environment.
During the early years of carcinogenesis studies, the food additive “Butter Yellow”, which is p-dimethylaminoazobenzene, was reported as a carcinogen. Subsequently, saccharin was found to cause bladder cancer in rodents. However, saccharin is not a human carcinogen but reacts with alkaline rat urine to form urinary tract stones with ultimate urothelial irritation leading to development of bladder cancer in rats. The news about saccharin and rat bladder cancer was highly publicized worldwide leading to ordinary folks believing “food additive = harmful” and “additive-free food = safe”.
Food additives were originally used for the purpose of keeping food quality good and safe and many food additives come from human experience. In ancient ages, human beings found ways to make the food last longer. Ancient people took wild nuts and fish in a hunting and gathering society and they process meat and fish by drying in the sun or fumigating in smoke. Also they knew that fish could be preserved with salt from the sea. Food additives were born in such circumstances. In Japan we have used natural products as food additive dyes. For example, ‘Umeboshi’ pickled plum was used for dyeing using the leaves of Perilla frutescens crispa. In Western countries, they knew how to preserve meat with rock salt to preservative quality and increase storage life. After that artificial food additives were established, including, for example, adding sodium nitrite to meat to preserve color and taste.
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In the 20 century, we had two sad stories related heavy metal poisoning in Japan. The first was Itai-itai disease caused by cadmium (Cd) poisoning from mining in Toyama Prefecture. The wastewater containing Cd was released from the mines into the Jinzu River and the residents downstream of the river were poisoned by ingesting contaminated water and rice. The victims were mostly postmenopausal older women and they showed characteristic symptoms including severe spinal and leg pain associated with bone weakness/fracture, possibly secondary to kidney failure. The second case was Minamata disease caused by methylmercury poisoning that occurred in Kumamoto Prefecture. This poisoning was due to the release of industrial wastewater containing methylmercury into Minamata Bay from a chemical factory. The methylmercury released into the bay bioaccumulated in shellfish and fish throughout the food chain. The residents around the bay daily ingested the contaminated fish and shellfish, resulting in methylmercury poisoning. The victims exhibited various neurological signs and symptoms including ataxia, numbness in the hands and feet, general muscle weakness, loss of peripheral vision, and hearing and speaking disorders. When pregnant women were involved in Minamata disease, methylmercury was transferred to the fetus through the placenta and affected the central nervous system much more severely than adults. In the most severe cases, the victims showed insanity, paralysis, and coma and eventually died within weeks of the onset of symptoms. Both Itai-itai and Minamata diseases were demonstrated to be due to the environmental contamination with heavy metals, but it took a long time to identify the actual causes after the first onset of these diseases. Our experience with these two cases indicates that environmental control is extremely important for our lives on this planet. It should be emphasized that once the environment is contaminated with pollutants, it takes a long time for recovery from the damage.

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In recent years, there has been an overflowing of information reflecting increasing public interest in safety and security of food as well as interest in dietary education. “Food additives⁠” that are regarded as bad for the body, and “functional foods⁠” or ⁠“so-called health foods” that are regarded as good for the body are at the center of food topics of interest. This article deals with poisonous and deleterious substances associated with food. In general, poisonous and deleterious substances are not deliberately included in food, but, when present in sufficient amounts, toxicity can occur. Whether or not there is toxicity is largely dependent on ⁠“dose⁠”. Understanding this is generally difficult and often misunderstood. The Poisonous and Deleterious Substances Control Law is a law to categorize chemicals depending on the strength of their toxicity (Classification and Labeling). Those specified as poisonous and deleterious are identified by the “dose” causing acute toxicity, and specifically causing death. The toxicity of the chemicals that lead to death based on a small amount of intake is strong; on the other hand, toxicity is considered weak if a large amount of compound is necessary to cause death. The acute toxicity test evaluates the dead dose as the ultimate in toxicity. Acute toxicity testing, however, has been the subject of criticism from the viewpoint of animal welfare. For that reason, the use of animal testing alternatives are being promoted. Based on these circumstances, the standard for poisonous and deleterious substances was revised so that the results of alternative methods can be used as a basis for judgement. The in vitro test has great restrictions on physical properties and predictability of chemicals, with accuracy varying depending on each test. It is necessary to understand the guidelines, their limitations, and to understand that an alternative method may not completely replace animal experiments. The use of alternative methods contributes to acceleration of the evaluation process and promotes efficiency. It is important that researchers should understand how to correctly utilize alternative methods.

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Toxicologic pathology is a biomedical specialty that integrates the science of investigation of toxicity and pathology. Toxicologic pathology is a critical component of the safety assessment process used in predicting human responses to foreign substances such as new candidate drugs, chemicals, and food additives, including identifying the potential of these agents to cause injury or cancer. The practice of toxicologic pathology involves microscopic examination of animal tissues by a trained pathologist and documenting pathological findings using specific terminology. There has been a long-standing effort to unify the descriptive and diagnostic terminology and their diagnostic criteria. An international effort called the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) was established for this purpose. The INHAND project is a joint project of the societies of toxicologic pathology from Japan (Japanese Society of Toxicologic Pathology [JSTP]), Europe (European Society of Toxicologic Pathology [ESTP]), Great Britain (British Society of Toxicological Pathologists [BSTP]), and North America (Society of Toxicologic Pathology [STP]) to establish internationally recognized diagnostic criteria and nomenclature for proliferative and nonproliferative lesions in experimental animals. This activity was started by the STP in collaboration with the ESTP, which had worked with the Registry of Industrial Toxicology Animal-data (RITA) in Europe. In 2006, with BSTP and JSTP joining this initiative, the project became a global project involving pathologists around the world. INHAND is managed by the Global Editorial and Steering Committee (GESC), which is composed of representatives selected from participating societies of toxicologic pathology in different countries including Japan. GESC manages and guides the activities of the Organ Systems Working Groups (OWG), which are the committees composed expert toxicologic pathologists from each participating society who are responsible for producing the preferred nomenclature and diagnostic criteria for each organ system. The INHAND papers of the 15 organ systems in the rat and mouse have already been completed, with only the lymph-hematopoietic system remaining. Currently, INHAND formed Non-Rodent Species Working Groups (NOWG) that are working on t h e nomenclature for non-human primates, rabbits, and minipigs. Recently, in the United States of America, applications for approval of new drugs requires digitization of toxicologic pathology nomenclature in the non-clinical safety evaluation data. The terms used for this electronic approval application is controlled, and basically has adopted INHAND nomenclature. A future goal is to establish a glossary that is consistent with INHAND and that is compatible with electronic regulatory applications worldwide.

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Pathological examination is conducted to investigate the macroscopic and microscopic findings of each organ or tissue and determination of the pathogenesis of any observed disease by an expert pathologist. Pathological examinations are conducted not only for human disease, but also for safety studies of food additives and/or toxicity studies of chemicals using laboratory animals. The pathological examination in these safety studies is one important indicator in the toxicity assessment when the NOEL (No Observed Effect Level) or NOAEL (No Observed Adverse Effect Level) will be determined. Consequently, the macroscopic and microscopic findings in these studies must be done carefully with adequate recording of pathological findings/diagnosis. If an induced lesion by a test substance is found during the pathological examination of dosed group animals, interpretation of the mechanisms of pathogenesis is required. Further, to ensure the pathological findings/ diagnosis during the histopathological examination, a second usually more experienced pathologist may recheck the same tissue specimens observed by study pathologist. This confirmative action in toxicity studies is called “pathology peer review”. In the safety studies of food additives and the toxicity test of chemicals, quality assurance of data is carried out to ensure the reliability of the test results. The pathology peer review is very important to ensure the quality of pathological examination.

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Pesticides for crop protection should be used under the four versions for safety; (1) crops, (2) users, (3) consumers, and (4) environment. The Food Safety Committee contributes risk assessment for human health to determine ADI (Acceptable daily intake) and ARfD (Acute reference dose) calculated from the minimal NOAELs (No observable adverse effect levels) obtained from toxicity studies and subsequent application of safety factors. The Ministry of Health, Labor and Welfare establishes MRL (Maximum residue limit) for each crop in order to prevent adverse human health from food. The Ministry of Environment conducts risk assessment on environmental preservation. Under the Agricultural Chemicals Control Act, the Ministry of Agriculture, Forestry and Fisheries approves the registration of pesticides for safety use and all pesticide users are required to comply with prescribed usage standards. Local governments regularly monitor the level of pesticide residues by market and environmental surveys. The members of the Japan Crop Protection Association cooperate as lecturers on Agro-chemical Safety Training Seminars for pesticide users held by local governments. Food safety and environmental preservation are guaranteed within the risk analysis framework consisting of risk assessment, risk management, and risk communication. Introducing this system brings peace of mind to consumers.

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Examining the internal structure of foods is an insatiable desire and thereby represents a challenging task in food science. However, due to imaging difficulties caused by light scattering on opaque surfaces of foods, little is known about their internal structure. Thus, we developed an optical clearing reagent that allows viewing of the internal structure of foods by fluorescence imaging. We then demonstrated images of the three-dimensional (3D) structure of whole noodles at a submicron resolution. Our method elucidated how the 3D gluten-protein structure dramatically changed from a honeycomb-shaped network to large clumps as sodium chloride was added in the process of noodle-making. The decrease in the linkage between the protein networks resulted in a reduction of the stress required for compression. In addition, the clearing method enabled us to obtain high-resolution images at high speed and in large quantities for the internal structure, and opened the way to use artificial intelligence (AI) for structural analysis. Moreover, we found interesting information on structures that humans have not noticed before by analyzing the learning content of AI. In this paper, we will explain what we have been studying on the visualization of the three-dimensional structure inside the noodle and the prediction of the texture based on its structure using AI.

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In recent years, it has been recognized that various ingredients in food play an important role in maintaining human health, and various methods have been developed in order to evaluate the antioxidant properties of food-derived components to support health maintenance. Recently, laboratory test reagents for analyzing oxidative stress of biological components such as urine, serum, cerebrospinal fluid, cells, and tissues have also become available, and several lines of research have revealed that oxidative stress is related to the onset of various diseases. However, the redox reactions involved include a wide variety of biological and food-derived components that occur in the living body; and so, the problem has become complicated as research proceeds. Therefore, a rational evaluation method for assessing antioxidant properties is strongly desired.
In this article various methods for evaluating the antioxidant property are reviewed from the viewpoint of evaluating the effects of the antioxidant substance on health maintenance. These methods are classified into four groups according to the difference in reaction mechanisms. A wide variety of food-derived components are found to be effective antioxidants by these methods. The correlation of the results, however, as measured with different methods, is not clear at present; and, thus, research on how to correlate and interpret the results obtained by different methods should remain one of the important research subjects. Further, the relationship between the results of the antioxidant evaluation by the various methods and the oxidative stress alleviation effect in the living body is not clear. Development of an in vitro assay to evaluate the effects of food-derived components to reduce oxidative stress should be an important topic in the future. It is considered effective to use not only fluorescent probes but also other biological components such as proteins as probes. It is also possible to develop antioxidants for specific targets, such as cells, proteins, lipids, nucleic acids, etc., and such specific antioxidants are expected to significantly improve preservation of not only processed food but also serum, plasma and cells for regenerative medicine.

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Glycemic index (GI) is a widely used measure of the glycemic response to food intake. The method to calculate GI values, however, has several drawbacks: it requires blood collection, which is stressful to volunteers and costly, and it fluctuates depending on the mental or physical condition of volunteers. The carbohydrate research group of the ILSI Japan discussed the problems involved in the GI method and concluded that an alternative easy-to-operate method should be considered. After a feasibility study on an assessment system for predicting postprandial glycemic responses, the research group proposed an outline of the GR (glucose-releasing rate) method, which includes in vitro reactions that simulate digestions by oral mastication and enzymatic reactions in splanchnic organs. It measures glucose released during the simulated digestion process to predict the glycemic response to individual foods or meals. The group started development of this method and completed the prototype system. Further steps of development aiming for practical application are currently underway.

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Herbal tea is a kind of self-treatment method which has passed from parents to their children and their grandchildren. The ingredients of herbal tea are derived from the plants around us and some of them are edible plants as daily foods. The point is that most of ingredients are easily accessible.
Human culture has evolved over time leading to many improvements. Herbal tea has also gradually developed through tradition from one generation to the next and has been preserved with improvements. Original herbal tea culture reached a turning point regarding change following the notification, “Regulatory control of unapproved/unpermitted drugs (1 June 1971, PAB Notification No.476)” issued from the Pharmaceutical Affairs Bureau, Ministry of Health and Welfare. The value of healthy herbal tea is reacknowledged now and will be popular among folks for long time in the future.

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Formerly, Mugi Mesi (boiled rice with barley) was the staple food for poor people.
The staple food changed from Mugi Mesi to boiled rice owing to the economic development of our country in the 1960's. Furthermore, dietary life changed to an affluent style with more economic development, resulting in various problems such as an increase in nutritionally unbalanced diets as well as irregular and high energy meals carrying many risk factors associated with metabolic syndrome, diabetes and cardiovascular disease. Recent clinical studies have suggested that the consumption of barley might reduce these risks. Now, Mugi Mesi and barley dishes are becoming healthy foods for the population. It has been shown that functionality attributed to β-glucan are present in the soluble dietary fiber of barley. The Food and Drug Administration and European Food Safety Authority have allowed the health claim of β-glucan in barley. At present, the cultivation and breeding of the varieties of high β-glucan barley are proceeding. Further, a technique for preparing barley grain in granular and powdery forms by polishing and milling with a modification of the machinery used to polish brewers' rice has been developed in order to gain wider use of barley as a healthy food.

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