The effects of food coloring on the stability of water soluble vitamins were studied as a function of time under room temperature to obtain basic data concerning the interactions between them in solutions such as beverages. In the present experiment, four colorings (Food Red No. 3, No. 40 and No. 102 as synthetic food colorings, and Cotinil as a natural one) and four vitamin Bs (B₁, B₂, B₆ and niacinamide) were chosen for the experiment, respectively.
The HPLC method was used for the simulteanous determination of these vitamins following the clean-up of food colorings.
Vitamin B₁ rapidly degraded in the presence of Food Red No. 3, but not in the control or any other food colorings. Vitamin B₂ was found to be stabilized in the presence of any of the food colorings, but degraded in the control solution. Vitamin B₆ degraded due to time in the control and Food Red No. 3 solution. Niacinamide had an acceleration in its degradation when natural food coloring, Cotinil coexisted in the solution.
Especially, in the presence of Food Red No. 40 and No. 102, there was no or only a slight degree of degradation of these vitamins. It seemed that these two colorings have properties for the prevention of the degradation of vitamin Bs.
Since Food Red No. 3 and Cotinil are known to be unstable but Food Red No. 40 and No. 102 are stable, it is highly possible that degration of the vitamins is due to the food colorings.

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乾燥和種薄荷の葉身部を粉末化したものをそのまま食品に添加すると，食品は茶褐色へと変色してしまい，薄荷本来の色である緑色にはならない．本研究では，和種薄荷粉末で“緑色”に着色することを目的として，薄荷粉末への温水処理効果について解析した．20〜100℃ の温水に15分以上浸漬すると，薄荷粉末に含まれる水溶性ポリフェノールが溶出した．これにより残存するクロロフィルの色が際立つようになり，食品を薄い緑色に着色できるようになった．さらに緑色の鮮やかさは，ポリフェノール溶出量及びクロロフィル残存量と相関性があった．実際，クロロフィル残存率の増加に伴い緑色の鮮やかさは増大する傾向にあったが，ある一定値を超える範囲では，クロロフィル残存率が高い場合よりポリフェノール溶出量が大きい条件において鮮やかさは大きくなった．またポリフェノールの溶出に伴い和種薄荷粉末が有する抗酸化機能は大幅に低減してしまった．しかるに，和種薄荷粉末独特の匂いや清涼感は十分に残っていた．温水処理した和種薄荷粉末は食用の機能性緑色着色料として十分に応用が可能であり，さらにその性能及び機能は，ポリフェノールやクロロフィルなどの成分分析を組み合わせることで予想できることが示唆された．

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国内で製造された漬物から指定外色素のオレンジII (O-II) を検出した. O-IIには, オレンジI (O-I) 及びオレンジRN (O-RN) と呼ばれる異性体が存在し, その化学的性質が酷似していることから, 確実な同定法として, 一般的な方法であるTLCに加えて, TLC/FABMS, PDA-HPLCを適用した. 漬物中の不明色素について, TLCのRf値からO-Iが否定され, TLC/FABMSのFABマススペクトルからO-IIあるいはO-RNの明確な分子イオン種を検出したが, 異性体である両者を区別することはできなかった. そこで, PDA-HPLCの保持時間及び紫外可視部吸収スペクトルを得て総合的にO-IIと同定した. なお, 後日当該漬物は, 聞き取り調査からもO-IIが混入した輸入原材料を使用していたことが判明した.

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目的
食品には数多くの添加物が使用されている。それらのなかには添加濃度により毒性を発現するものも知られており,これらについては厳しい規制が必要である。食品添加物として広く使用されている保存料もその濃度によっては有害となるためその使用については厳しい規制が設けられている。保存料の使用は食品の変質,腐敗防止などの添加物本来の目的のみならず,食品流通の拡大,価格安定などの面において大きな役割を果たしている。現在食品添加物の安全性の指標としてはADI(一日許容摂取量)が使用されている。ADIは動物による慢性毒性実験をもとに決められており,細胞レベルでの影響についてはほとんど報告されていない。著者らはこれまで種々の環境化学物質についてウサギ血小板を用いそれらの日常摂取レベルが細胞に及ぼす影響について検討し報告してきた。また,食品添加物に関してもADIレベルや現行の添加濃度レベルで血小板機能に影響を与える化合物があることを報告してきた。今回は保存料についてそのADIレベルがウサギ血小板機能に及ぼす影響についてin vitroならびにex vivoで検討した。
実験方法
保存料として,安息香酸ナトリウム,ソルビン酸カリウム,パラオキシ安息香酸ブチル,およびデヒドロ酢酸ナトリウムを用いた。トロンボキサンB₂(TXB₂)抗体は米国ケンタッキー大学薬学部H.-H.Tai教授より供与いただいた。被験化合物は10^-5～10^-8Mの濃度でDMSOあるいはTyrode液(pH7.4)に溶解して使用した。ウサギ洗浄血小板の調整は既報に準じて行ない,最終的にMg²⁺, Ca²⁺を含まないTyrode液(pH7.4)に懸濁して実験に用いた。血小板の活性化は反応溶液(Tyrode)1ml中の血小板が2x10⁷個になるように調整し,A-23187(1μM)あるいはトロンビン(1U)をそれぞれ単独あるいは種々の濃度の被験化合物とともに37℃で5分間インキュベートすることにより行った。また,血小板を上述のアゴニストを添加しないでインキュベートしたものをコントロールとした。反応液を氷冷下反応停止し直ちに遠心分離を行い,その上澄み液についてEnzyme immunoassayによりTXB₂を測定した。血小板を各種化合物で前処置する実験においては,血小板を化合物とともに37℃で5分間インキュベートした後,上記アゴニストを添加し活性化した。また,前処置後遠心分離により化合物を含む溶液と血小板を分離後,新しい反応液に血小板を験だくしアゴニストを添加して活性化した。各種添加物添加職によるex vivo実験においては通常飼育のウサギに,各化合物のADI相当量(デヒドロ酢酸については慢性毒性実験における使用量の1/100)を連続5日間摂取させ,6日目に血小板サンプルを調整し前述の方法によりその活性化の程度を測定した。
結果
1. in vitro実験結果
血小板を,種々の濃度の各添加物共存下でA-23187にあるいはトロンビンで刺激した場合,A-23187刺激に対しては使用した化合物のうちソルビン酸カリウムおよびパラヒドロキシ安息香酸ブチルが10^-6M以上でTXB₂産生を有意に抑制した。一方,トロンビン刺激によるTXB₂産生に対しては使用した全ての化合物が抑制作用を示し特に,ソルビン酸カリウム,パラヒドロキシ安息香酸ブチルならびにデヒドロ酢酸ナトリウムは実験に使用した全添加濃度で産生の有意な抑制が観察された。各添加物による前処置実験ではA-23187刺激に対してはすべての添加物が抑制効果を示した。また,A-23187およびトロンビン刺激に対するパラオキシ安息香酸ならびに,トロンビン刺激に対する安息香酸ナトリウムの抑制作用は当該化合物を洗浄除去後も消失しなかった。
2. ex vivo実験結果
各種添加物のADI相当量を,食餌とともに連続5日間摂取させたウサギから調整した血小板では,安息香酸ナトリウムおよびパラオキシ安息香酸ブチル添加食群においてトロンビン刺激に対する有意なTXB₂産生の抑制が観察された。

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Silver zeolites were developed from an invention titled "Methods of producing hard water-softening agents with germicidal action" patented in 1938. The purpose of the invention was to decrease the hardness of drinking water, and to obtain aseptic water. Using natural or synthetic zeolites as carriers, anti-bacterial zeolites are prepared by the ion exchange reaction of metal ions having an anti-bacterial effect such as silver, zinc, and copper ions. Compared with organic anti-bacterial agents which are alcohol, quaternary ammonium salt, thiabendazole, and ortho-phenylphenol, the inorganic anti-bacterial agents have excellent properties such as wide anti-bacterial spectrums, a high safety, long effective duration, and high heat-resistance. Zeolite and silver have been registered as food additives, and among the anti-bacterial zeolites, the zeolite A-silver, zinc, and ammonium compound zeolite was registered as an indirect food additive by the United States FDA in June 2000. Silver is a common metal, which has been used for tableware, spoons, costume accessories, and coins. With regard to the anti-bacterial effect of metals, Nepli discovered in 1893 that 0.1 ppm silver ions killed spirogyra, and it has been reported that silver, mercury, zinc, copper, tin, lead, bismuth, cadmium, and chromium are also anti-bacterial metals. Although the characteristics of the anti-bacterial zeolites significantly depend on the combination of the types of zeolites and those of the anti-bacterial metals, the specific combination has been determined based on experience. In this study, the combination types were investigated by preparing anti-bacterial zeolites using the zeolite A, which is a typical zeolite, and using silver, zinc, and copper, which are comparatively safe metals, and then comparing their anti-bacterial effects. It was found that the anti-bacterial effects of silver ion were quite high, showing that silver is an essential metal for anti-bacterial zeolites. Furthermore, the anti-bacterial effects of the zeolite A increased with the concentration of silver. To investigate the influence of the pore size of the zeolites on the anti-bacterial effects, silver zeolites were prepared using zeolite Y as carriers, and natural zeolite produced in Miyagi prefecture, which is directly used for water purification equipment, and then comparing the anti-bacterial effect of each zeolite with that of zeolite A. No differences in the anti-bacterial effects were observed regarding these types of zeolites.

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Light emitting diodes (LEDs) are widely used in lighting applications. In this study, we examined the differences in the degree of the color change of various medicines between LED lighting and fluorescent lighting. The degree of the color change of the medicines was evaluated subjectively, by the observation of the evaluator, as well as objectively, using a colorimeter. Noticeable color changes were observed in the Lasix^® 20-mg Tablet(Tab), Fluitran^® 2-mg Tab, and Phenobal^® powder after exposure to either LED lighting or fluorescent lighting. Interestingly, the color change of the Lasix^® 20-mg Tab was smaller for the LED lighting than for the fluorescent lighting.

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Photostability of Food Red No. 40, a synthetic food coloring not approved in Japan, was compared to those of other synthetic and natural Food Reds commonly used in Japan.
In a short-term (10 days) experiment, an ultraviolet light was irradiated onto solutions of 6 synthetic Food Reds containing ascorbic acid at a pH of either 3.0 or 6.5. Food Reds No. 3 and No. 104 rapidly faded even in the absence of the ascorbic acid. Fading of Food Reds No. 2 and No. 102 was accelerated by the ascorbic acid, the effect of which was more significant at pH 3.0 Food Reds No. 40 and No. 106 were fairly stable and over 50% of the color remained after 10 days in the presence of the ascorbic acid.
In a long-term (24 weeks) experiment, solutions of 6 synthetic and 7 natural Food Reds were placed under mid-summer sunlight, ultraviolet light, indoors or in the dark. All natural Food Reds became unstable, and lost their color even in the dark. On the contrary, all synthetic Food Reds including No. 3 and No. 104 were stable in the dark and remained unchanged after 24 weeks. Under sunlight, Food Reds No. 3 and No. 104 lost their color completely within 1 week, No. 102 gradually fading at its lower concentration. Food Reds No. 2, No. 40 and No. 106 were quite stable with no fading occurring.
A long-term experiment with 4% acetic acid-, 20% ethanol-, and 4% sodium carbonate-solutions of Food Reds, also proved the stability of No. 40 and No. 106.

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CO₂ is a food additive that has been listed in "THE JAPANESE STANDARDS FOR FOOD ADDITIVES" since its first edition. According to the questionnaire research conducted by the Ministry of Health and Welfare regarding domestic and imported CO₂, a total of 120,000 tons of food grade CO₂ from 25 companies was shipped in Japan during 1993. Based on this figure, I think it is necessary to examine how muchCO₂ is currently used and to calculate the per capita and per diem Japanese intake, as one of the basic food additives. The atmosphere is composed of 0.035% CO₂. Also, various alcohlic beverages such as beer and foamy liqueurs contain CO₂, which is produced during the fermentation and manufacturing process. It is a basic component of food and drink. Therefore, we must inspect the various aspects of CO₂ when we examine its daily intake. In studying the use of additives which are regarded as company confidential know-how, it is a general procedure to conduct a hearing to determine the production statistics of the food in question. From these studies, we obtained the following estimated breakdown of CO₂ that was shipped as food additive: 70,000 to 75,000 tons for airtight rooms and pouches to prevent the oxidation of foods. In the aforementioned types of use, CO₂ dissipates immediately after it serves its purpose and is irrelevant to human intake. Also, the quality of food grade CO₂ is high and it is often used in other fields such as medicine, research, and foam plastics. The total for these uses is estimated to be approximately 10,000 tons. The human intake of CO₂ is mainly attributed to carbonated drinks. According to a industry source, 18,115 tons of CO₂ is used in carbonated drinks and 20% of the gas dissipates when the containers are opened. In order to estimate the accumulated amount of CO₂ in food, we assumed the following figures for the calculation purpose: 1,200 tons for the CO₂ content of beer; 876 tons of CO₂ content of canned "chuhai" (Japanese distilled spirit) and foamy liqueurs; and the 20% CO₂ loss when the containers are opened. Based on the above assumption, we estimated the per capita and per diem intake of CO₂ as food additive in Japan to be 373mg based on Japan's 1993 population. We used only those 20 years of age and older because of prohibition of minors from drinking. As for CO₂ as a food component, beer is the largest contribution. Based on the amount of beer and the shipped CO₂ content, we estimated the per diem and per capita figure of 943mg. The daily consumption of CO₂ is 12,040mg, which is more than ten times larger than the aforementioned intake from foods. This is because we ihnale air that contains 0.035% CO₂. As for the respiratory amount, we assumed the per diem and per capita figure of 17.5m³ as an average of man and woman. From this viewpoint, we found that the per capita and per diem CO₂ intake of a Japanese is 13,356mg in total. However, this figure is extremely small in comparison to approximately 900g of CO₂ that is contained in human expiration. For your reference, 456 tons of sodium dicarbonate, 88.5 tons of magnesium carbonate, and 38.6 tons of calcium carbonate were shipped in 1990 in Japan as medical and pharmaceutical products. They are used as antacid and produce CO₂ in human bodies. The produced amounts of CO₂ are 238, 22.3, and 17 tons respectively with the total of 277 tons. If we assume that about 70% of the prescribed doses are taken, it amounts to 194 tons and we can obtain the per capita and per diem figure of 4.3mg.

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Silver-containing zeolite, which is natural or synthesized zeolite processed by ion exchange with silver, has an antimicrobial nature. Because of its long-lasting antibacterial activity, this substance is widely used as a plastic additive for structural parts of kitchen utensils, household electrical appliances, toilet seats and telephone handsets. With its antibacterial activity and character of filter medium, this substance is also suitable for use in simple water purification systems, and its practical use in this field is now being expected. Although silver-containing zeolite is non-carcinogenic, it has chronic toxicity, with the acceptable daily intake being calculated as 11 mg/kg・day for type A zeolite processed by silver-zinc-ammonium complex substitution. When used in water-purifying devices, silver-containing zeolite comes in direct contact with water. Therfore, serious attention from the viewpoint of public health should be paid to the possibility of elution of silver or other substituent factors and zeolite components. In this connection, we carried out elution tests of silver-containing zeolite itself, plastic products containing this type of zeolite as an additive and silver utensils. The amounts of cations of silver and other factors eluted from silver mordenite (Table 3), silver-ammonium mordenite (Table 4) and silver-zinc-ammonium type A zeolite (Table 5) immersed in 1L of water for 24 hours were determined. The types of water tested were purified water and tap water supplied in Tokyo, Osaka and Nagoya. The tap water varied in cation content according to the location (Table 2), with the total cation level being highest, 2.95 meq/L in Tokyo (Table 9). Elution of silver was always under the detection limit of 0.01 ppm, except that a trace amount of silver was detected with silver-containing mordenites immersed in the tap water of Tokyo. Zinc and ammonium were eluted increasingly, to a maximum concentration of 0.59 ppm and 5.2 ppm, respectively, as the total cation level in water increased. The mechanism of their elution was considered to be substitution by other cations present in tap water. There was not even any trace amout of eluted silver when zinc coexisted, suggesting that substiturion by inhibited the elution of silver. Concentrations of silica, aluminum and sodium in eluate were the same as those in original tap water, indicating that zeolite itself was not eluted. The allowable concentration of silver in tap water was set at 0.05 mg/L in the former Soviet Union. The corresponding standard for zinc is 1 mg/L in Japan. Elution of silver from plastic products with silver-containing zeolite and silver utensils was under the detection limit of 0.01 mg/L (Tables 6 and 7). There was also no elution of silver in tap water on flow tests (2L/min) (Table 8). Thus, silver was found to be firmly bound to zeolite in the silver-containing zeolite examined. Elution of silver was very slight if any, and was suggested to be related to the order of selectivity in ion exchange. The coexistence of harmless substituent cations which are at lower ranks in selectivity than silver seems to be effective for securely inhibiting the elution of silver.

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The authors reviewed the development of flavor regulations in Japan. Promulgated in 1900, the first flavor regulations in Japan only prohibited the use of "harmful flavoring substances" in soft drinks. However, since flavors were not widely used at the time and since no specific substances were identified in the regulations, flavors were effectively unregulated. The Food Sanitation Law was passed after World War II. Under this law, only those synthetic chemicals designated by the Minister of Health and Welfare can be manufactured, sold, imported, or used as food additives. The Enforcement Regulations of the Food Sanitation Law were promulgated on 1948. The regulations pioneered the use of positive list for synthetic food additives in the world. Flavors were listed primarily by chemical groups, such as aliphatic alcohols, aromatic aldehydes, ethers. That list was the first positive list of flavors in the world. Since 1959 the specifications and use restrictions have been developed for certain commonly used flavors. The specifications and use restrictions were complied in the First Edition of Japanese Standards for Food Additives (JSFA). Since the Food Chemicals Codex and JECFA Specifications had not yet been published, the JSFA was the first set of food additive specifications to be published in the world. The preparation of specifications for additional frequently used flavors has continued since 1959. The current editions of the JSFA contains specifications for 78 flavors. Government officials worked closely with industry to prepare them. New labeling regulations for food additives have been in force since 1991. The amended labeling regulations require that all additives used in foods be identified on food labels as a rule. However in case of flavors, collective term "flavor" is used. The safety of food flavors has been virtually unquestioned, since the amount of flavor added to foods is so small. Today, the evaluation of safety of flavors and other food additives have been continued in Japanese government agencies and in international organizations, such as JECFA. The current edition of the JSFA, the sixth edition, reflects the fact that this set of specifications has been revised five times since its initial publication. Since passage of the Food Sanitation Law, there have not been any serious violations or safety problems. When considering international harmonization, the government agencies and the flavor industry should work together.

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The first coloring known to have been used deliberately in Japan is the red of red-ocher rouge. This red is also the color of the sun and blood, so it seems natural that people in ancient times would have ascribed to it the magical properties of conferring long life and reviving the dead. In the Kofun period, which corresponds to the 3rd century A.D., many colors began to be used. The theory of Yin and Yang and the five elements, said to have been transmitted to Japan from China in the latter half of the 7th century, had a strong influence on color aesthetics in Japan. According to this theory, the five colors of blue, red, yellow, white and black are the primary colors, and are also imbued with symbolic meanings. Documentary evidence of the use of coloring in food is extremely scarce before the Edo period.The Shosoin text of the Nara period (8th century) contains references to soybean cakes and adzuki-bean cakes, so it is known that colored processed foodstuffs were eaten in some social strata such as the Imperial Court. In the Heian period (8-12th century), ceremonies became increasingly formal, and the rice, rice cakes, rice gruel and other foods eaten during them were colored with vegetable substances such as soy beans, adzuki beans, sesame and chestnuts. In the feudal society of medieval Japan (12-16th century), menus at samurai houses featured food coloring in foods eaten at ceremonies and formal meals. Records indicate that dishes colored with the five primary colors were served plated on turtle shells. Rice with red beans was also served in the Imperial Court during seasonal festivals on March 3rd, May 5th and September 9th. An anthology of old Chinese herbals -books describing the medicinal properties of plants- was compiled by Li Shi Zhen in Ben Cao Gang Mu. This work included mention of many plants such as madder, safflower, and gardenia, which are used not only as medicines, but for coloring as well. Therefore, it seems reasonable to assume that they were used to color food. Old Chinese herbals contain a good deal of information relating to the use of coloring. From the Edo period onwards, people began to enjoy the appearance of artificially colored food, as well as using it for symbolic, ceremonial purposes. Many books were written about cookery, and many of these mention adding coloring to a wide variety of foods including arum root, cakes, rice, rice gruel, dumplings and rice cakes. The pigments of madder, gardenia, turmeric, sappanwood, grapes, perilla, soy beans, adzuki beans and mugwort were used as food coloring. Many of these plants are used in processed foods today, and our study has shed light on their history as food coloring. In the latter half of the 19th century, synthetic coloring ingredients began to be used for coloring food in both Western countries and Japan, and coloring ingredient regulations began to be enforced in these countries. In 1900, the regulations for the control of harmful coloring ingredients were enacted in Japan. They listed harmful coloring not to be used for food. On January 1, 1948, the Food Sanitation Law was enacted and 22 coloring ingredients were listed as food additives. Since then, the specifications and use restrictions have been revised many times.

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神戸市立中央市民病院で使用されている医薬品集に収載されている医薬品を基に,薬物間相互作用検索システムを構築した。まず,コンピューターでの情報処理を可能にすべく,対象となる薬物の相互作用が薬物群名で記されている場合,それをコード化し,かつ単独の医薬品名のみの組み合わせで検索しなければならない場合,該当する相互作用が隠蔽されることなく網羅的に検索できるプログラムをBASICで開発した。検索効率を高めるべくランダムファイルのレコード番号を検索手段とし,薬物マスターA及びB,相互作用マスターA及びBの4種類のファイルをクロスしてアクセスし,サーチするロジックを組み立ててプログラム化した。実践的運用を重視し,臨床上の重篤度をP.Hanstenの3段階方式で入力し,臨床上の対応に供した。検索所要時間は薬物が1対1の場合は瞬時(4秒)に完了し,薬物数が増加するにつれてほぼn(n-1)の割合で検索時間も増加した。また,レコードの修正,追加等が個々のファイルに直接アクセスする簡単かつ迅速な方法で行え,更にシステム全体がフレキシブルであるので,複雑で逐次変化する薬物間相互作用の情報処理に効果的,実践的かつ経済的に対応できると思われる。

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