Recent reports on estrogenic activity and reproductive organ toxicity of alkylphenols were reviewed, citing 32 references, and the risk on human health was discussed. Alkylphenols detected environmentally are from alkylphenol-polyethoxylates, and consist of approx. 80 % para-nonylphenol and 20 % para-octylphenol. Although para-nonylphenol is a mixture of various branched para-nonylphenols and para-octylphenol is almost entirely para-tertiary octylphenol, nonylphenol and octylphenol instead of the accurate structural names are used in this article. Estrogenic Activity Nonylphenol induced growth of MCF-7 cells and transcriptional activity in estrogen receptor gene- and reporter gene-transfected MCF-7 cells and yeasts but only to the extent of one over 1,000 to 300,000 that of 17β-estradiol. Octylphenol also induced both growth and transcriptional activity, being approximately 10 to 30 fold more potent than nonylphenol. Nonylphenol showed uterotrophic activity such as an increase of uterus weight in immature and ovariectomised female rats, from as a dose as 40 mg/kg/day on 3 days oral administration. This uterotrophic activity was completely inhibited by ICI 182,780, a typical estrogen receptor antagonist. Octylphenol also showed uterotrophic activity in immature rats at 166 mg/kg/day after 3-days s.c. injections and in ovariectomised rats at 25 mg/kg/day with 14-days s.c. injections. Effects on female reproductive organs Nonylphenol given to female rats at 250 mg/kg/day by gavage for 28 days exerted no significant effects on any additional reproductive parameters with the OECD test guideline 407. Octylphenol at 100 mg/kg/day administered by s.c. injections to female rats from postnatal day 1-15 (every other day) induced earlier vaginal opening, persistent estrus after maturation and increased proliferation in the endometrial epithelium. Octylphenol at 100 mg/kg/day given by s.c. injection to adult female rats for 28 days induced increase of uterine weight and increased proliferation in the endometrial epithelium. Effects on mammary glands Nonylphenol at 0.073 mg/kg/day by implanted mini-pump for 11 days induced cell proliferation and differentiation in the mammary glands of immature female Noble rats. However, those effects were not confirmed even at a dose of 53.2 mg/kg/day by the same procedure in two additional studies using Noble and Alpk:AP rats. Nonylphenol at 100 mg/kg/day by gavage for 11 days induced only weak cell proliferation in the mammary glands of female Alpk:AP rats. Effects on male reproductive organs Histopathological changes in vas deferens and reduction of sperm counts and weights of testis and epididymis were observed in adult male rats on oral administration of nonylphenol at more than 100 mg/kg/day. The same effects in offspring male rats were shown by oral administration of nonylphenol to pregnant rats from gestation day 7 to lactation week 3 and to the offspring until week 10. A no adverse effect level (NOAEL) to male reproductive toxicity by oral administration could not be established. Furthermore, reduction of testis and accessory organ weights was observed on i.p. injections of more than 0.8 mg/kg/day to male rats on postnatal days 1 to 15. In the same system, 8.0 mg/kg/day induced cryptorchidism and lowered fertility. However, no significant effects on male reproductive organs were observed by s.c. administration of octylphenol even at a dose of 200 mg/kg/day to postnatal male rats. Toxicokinetics A study of octylphenol in rats indicated that the bioavailability by gavage ranged from 2 to 12 % and the blood concentration profile after a single administration was the same as that with 14 days consecutive administration. On the other hand, there was no detection of octylphenol in blood and tissues of rats after 28 days administration in drinking water at the maximum soluble concentration. Toxicokinetics study on volunteer using ¹³C-nonyl

(View PDF for the rest of the abstract.)

抄録全体を表示

In the analyses of pesticide residue by GC-MS (CI), it was very occasionally observed that unidentified peaks appeared from sample solutions. After preliminary investigations, these peaks were identified as phthalic acid esters (PAEs). PAEs including DBP (Di-n-butyl phthalate), DEHP (Di-2-ethylhexyl phthalate) and DEP (Diethyl phthalate) were shown to be contained in organic solvents with high purity of pesticide residue analysis grade. The highest level of total PAEs was detected in n-hexane (0.0237μg/mL), followed by acetonitrile (0.0139μg/mL), dichloromethane (0.0117μg/mL), ethyl acetate (0.0084μg/mL) and diethyl ether (0.0083μg/mL). These 3 PAEs were also detected in eluate from 11 samples of anhydrous sodium sulfate (Na₂SO₄) purified for PAEs determination grade, pesticide residue analysis grade, fluorescent analysis grade, etc., packed in glass columns with above organic solvents. As using dichloromethane for elution from different grade of Na₂SO₄, the highest level of total PAEs (4.13μg/g) was eluted from one of pesticide residue analysis grade, followed by PAEs determintation grade (1.75μg/g) and one of laboratory grade (1.51μg/g). In all of these 3 samples of Na₂SO₄, more than about 90% of total PAEs was detected in the 1st fraction (after 2 hrs, 40mL).

抄録全体を表示

1.生鮮食品を対象とした残留農薬一人一日摂取量調査を行った。2.試料はすべて兵庫県西宮市内で購入し、食品添加物調査用マーケットバスケット方式に基づいて調製した。3.分析の結果、イプロジオンがグレープフルーツ及びはくさいから検出された。また、イミダクロプリドがトマトから、さらに、テブフェンピラドがきゅうりから検出された。4.検出された農薬の残留濃度から推定農薬摂取量(mg/日)をADI×50(mg/日)と比較したところ、0.0020〜1.6%であった。

抄録全体を表示

1) An improved method of simultaneously determining imazalil (IZ) and R14821 (R1), one of its major metabolites, in citrus fruits was investigated. With this new method each detection limit was more than 10 times higher than that of the original method (US EPA): a detection level of 0.001ppm on a whole fruit basis was obtained for each compound. 2) Immediately after purchasing citrus fruits (grapefruit, orange and lemon) from the markets, concentrations of these compounds in the peels and the pulps were measured. All the samples were under regulation by the Japanese Food Sanitation Law. All peel samples were superior to the corresponding pulp in terms of concentrations and contents. When acceptable daily intake (ADI) of R1 is assumed same as that of IZ, intake of these citrus fruits in the normal diet would not be too harmful to humans, because all amounts of the compounds ingested through this route would be far lower than the ADI of IZ (0.025mg/kg of body wt./day). 3) By one-way analysis of variance and Student's t-test, IZ concentrations were reduced in the peels and the pulps of oranges stored in a refrigerator (7〜10℃, for 1 to 3 weeks). R1 concentrations increased in both portions of lemons during cold storage. The molar ratios of R1 to IZ in the peels of citrus fruits stored in a refrigerator for 3weeks were about 2 times higher than those before cold storage, compared with each average value. The same was found in the pulp: the ratios were about 1.5 to 2 times higher than those before cold storage. However, each residual concentration ratio of both compounds in the pulps against that in the peels was almost constant among the citrus fruits even after various cooling periods in a refrigerator.

抄録全体を表示

Caramel color, a food additive which is widely used as a food color for beverages, seasonings, confectionery and many food products, is obtained by heat-treating food-grade carbohydrates including starch hydrolysates, molasses, or saccharides. Caramel color is classified into Caramel I, Caramel II, Caramel III, and Caramel IV according to each manufacturing method. As part of a series of studies to evaluate the safety of caramel color A, which is made from the raw materials containing molasses and is classified into Caramel I, its mutagenicity was examined by mutagenicity studies (a reverse mutation test, a chromosome aberration test, and a micronucleus test). In the reverse mutation test, the chromosome aberration test, and the micronucleus test, the mutagenicity of caramel color A was found to be negative at the highest concentrations specified in the Guidelines for Designation of Food Additives and for Revision of Standards for Use of Food Additives. Specifically, negative results were obtained at 5000μg/plate by the method without metabolic activation and with metabolic activation in the reverse mutation test. In a cell growth inhibition test performed prior to the chromosomal aberration test, the 50% cell growth inhibition concentration (IC₅₀) of caramel color A was found to be 5000μg/mL or higher by the method with metabolic activation in the presence of S9 mix, and 3309μg/mL by the direct method. In the chromosomal aberration test, negative reactions were noted at 5000μg/mL by the method with metabolic activation and at 3500μg/mL by the direct method. Caramel color A at 4000μg/mL, a dose inducing overt cytotoxicity, caused chromosomal aberrations, but the aberration potential was weak without dose-dependency. Negative results were obtained at 2000 mg/kg, the highest dosage level, in the micronucleus test, and the maximal tolerated dose is estimated at 2000 mg/kg or higher. Based on the above results and considering the human intake, it can be concluded that there is no potentiality caramel color A causes gene mutations or chromosomal aberations in a living body.

抄録全体を表示

Caramel color, a food additive which is widely used as a food color for beverages, seasonings, confectionery and many food products, is obtained by heat-treating food-grade carbohydrates including starch hydrolysates, molasses, or saccharides. Caramel color is classified into Caramel I, Caramel II, Caramel III and Caramel IV according to each manufacturing method. As part of a series of studies to evaluate the safety of caramel color A, which is made from the raw materials containing molasses and is classified into Caramel I, repeated dose oral administration at dosage levels of 0.5, 1, and 2 mL/kg was conducted to 5 Crj: CD (SD) IGS strain rats of each sex for 28 consecutive days, and its toxicity was examined. The control group was treated with water for injection alone. 1. Neither death nor abnormal signs were noted in either sex of any group. No effects of caramel color A were disclosed in either sex by body weight measurement, food consumption measurement, urinalysis, ophthalmological examination, hematological examination, blood chemical analysis, necropsy, organ weight measurement, or histopathological examination. 2. The non-toxic dose of caramel color A is estimated at 2 mL/kg (2.66 g/kg, sp.gr. 1.33) or higher in both sexes of animals under the conditions of the present study.

抄録全体を表示

イチョウ葉エキスの循環器系に対する影響を、ラットに経口及び静脈内投与することにより検討するとともに、また、摘出心房標本に対する影響についても検討した。1.ラットの循環機能に対するイチョウ葉エキスの経口投与(3.5g/kg/day)3日間の影響を検討した。その結果、イチョウ葉エキスは投与2日目からラットの心拍数を有意に増加させた。また、収縮期血圧や末梢血管血流量を増加させる傾向を示したが有意ではなかった。さらに、ブナゾシンの血圧降下作用にも有意な影響を示さなかった。2.血圧トランスデューサーおよびレーザー血流量計を用いてラットの心拍数、血圧、末梢血管血流量に対するイチョウ葉エキス静脈内投与(25mg/kg)の影響を検討した。その結果、イチョウ葉エキスは心拍数、収縮期血圧、拡張期血圧、脈圧および末梢血管血流量を有意に増加させた。3.ラットのペースメーカー付き摘出心房標本を作成し、その心拍数および収縮力に対するイチョウ葉エキスの影響を検討した。その結果、イチョウ葉エキスは0.1mg/ml以上の濃度で直接的かつ即効的に心拍数および心収縮力を増強した。4.以上の結果から、イチョウ葉エキスは心臓機能に対し軽度の促進効果を示すが、抗高血圧薬であるブナゾシンの降圧作用には影響しないことが明らかとなった。

抄録全体を表示

コレステロール生合成律速酵素のひとつ、スクアレンエポキシダーゼ(SE)(EC1.14.99.7)は、コレステロールの生合成における最初の酸素添加反応を触媒する膜結合性のフラビンモノオキシゲナーゼである。既に我々は、大腸菌において発現させたラット組み換え酵素を用いて、天然より酵素阻害剤のスクリーニングを行った結果、緑茶由来の(-)-epigallocatechin-3-O-gallate(IC₅₀=0.69μM)など、ガロカテキン類が、強く選択的なSE酵素阻害活性を示すこと、さらにこれが緑茶のコレステロール低下作用の一因となっている可能性について言及した(Abe et al., Biochem. Biophys. Res. Commun., 268, 767, 2000)。本論文では、紅茶のポリフェノール成分であり、茶葉カテキンが醗酵過程で酵素酸化を受けることにより重合して生成した、テアフラビン類も同様に、以下のようにいずれも1-5μM程度のIC₅₀値で、強いSE酵素阻害活性を示すことを報告する。theaflavin(TF-1)(IC₅₀=5.0μM), theaflavin-3-gallate(TF-2A)(IC₅₀=1.0μM), theaflavin-3'-gallate(TF-2B)(IC₅₀=1.0μM), theaflavin-3,3'-digallate(TF-3)(IC₅₀=1.0μM)。従って、紅茶についても、緑茶の場合と同様なメカニズムで、コレステロール低下作用を期待できる可能性が示された。また、SE酵素による酸素添加反応は、酵素活性中心におけるフラビンC(4a)-O-O-Hの生成を経て進行するものと考えられており、こうした酵素阻害効果はガロイルエステルのSE酵素活性中心への特異的な結合と、ガロイル基による活性酸素種のトラッピングによるものと推測された。

抄録全体を表示

The material of polycarbonate tableware (n=20) for school lunch contained 22〜111 ppm of Total bisphenol A (T-BPA: bisphenol A, phenol and p-tert-butylphenol), but these migration were all under 0.05 ppm of T-BPA. The concentration of T-BPA in the material of new polycarbonate tableware (n=9) were lower than those of the used products (n=9). This is probably due to the conversion of the material in the used products over 4 years.

抄録全体を表示

Sucralose (4,1',6'-trichlorogalactosucrose) has been used in many countries as a sweetener, and was permitted as a food additive in Japan in July, 1999. Prior to the permission of the compound as a food additive, we studied procedures for the quantitative analysis of sucralose by a potentiometric titration method. The following method was established: weigh accurately about 1 g of the sample, transfer into a flask with a ground stopper, and add water to make exactly 100 ml. Measure accurately 10 ml of this solution into a 50-ml flask, and add 10 ml of sodium hydroxide solution (1→10), equip with a reflux condenser to the flask, and boil gently for 30 min. Cool this solution to room temperature, and neutralize it with diluted nitric acid (10%). Titrate the liberated chloride in this solution with 0.1 mol/l silver nitrate solution using potentiometer equipped with an electric indicator (Ag) and a reference electrode (Ag-AgCl). Perform a blank test, make necessary correction, and calculate on the anhydrous basis. When determination of sucralose was carried out by this method, the data were reproducible and the coefficient value was 0.4% on repeated runs. This method can be adapted for automatic potentiometric titration, and is simple, rapid and accurate. It should be useful for the deternination of sucralose.

抄録全体を表示