Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/15362
標題: 利用奈微米化技術開發多功能組合性保健食品之研究-基因毒理及食用安全性評估
Safety Evaluation for the Multi-ingredients and Functional Health Food Formulas in Genotoxicity and Animal Toxicity Tests
作者: 余雪筠
Yu, Shyuei-yuen
關鍵字: genotoxicity
基因毒理
Ames test
chromosome aberration test
micronucleus test
acute toxicity
subacute toxicity
安姆氏試驗
染色體變異試驗
微核試驗
急毒性試驗
亞急毒性試驗
出版社: 獸醫病理生物學研究所
引用: 行政院衛生署。28天餵食毒性試驗。「健康食品安全及功效評估方法」。衛署食字第8803780號。台北。1999。 行政院衛生署。基因毒性試驗(Genotoxicity study)。「健康食品安全及功效評估方法」。衛署食字第8803780號。台北。1999。 行政院衛生署。藥品非臨床試驗安全性規範。藥政處。第三版。台北。2000。 李國欽。化學物質之毒性測試原理。行政院農委會農業藥物毒物試驗所。台中。第31期。1993。 吳家駒。保健食品之安全性評估。農業生技產業季刊。台北。2005。 沈永紹。獸醫實驗診斷學提要。第五版。華香園。台北。2004。 梁鍾鼎, 張明雄, 洪昭竹, 黃坤正。建立無特定病原大小鼠之血液化學參考值。台北。中華獸醫誌。1999。 實驗動物技術人員訓練教材編輯委員會。實驗動物技術人員訓練教材。台北。第 二級。2007。 許朝凱。國內外保健食品管理制度概況。農業生技產業季刊。台北。2007。 游碧堉。姐妹子染色體交換測試法。化學物質遺傳毒性之簡易測試法。行政院農委會農業藥物毒物試驗所。台中。1987。 游碧堉。沙門菌回復突變測試法。化學物質遺傳毒性之簡易測試法。行政院農委會農業藥物毒物試驗所。台中。1987。 趙壽元、李昌生。化學誘變物的細菌檢測試驗(Ames法)。上海。1981。 Abaza L, Talorete TP, Yamada P, Kurita Y, Zarrouk M, Isoda H. Induction of growth inhibition and differentiation of human leukemia HL-60 cells by a Tunisian gerboui olive leaf extract. Biosci Biotechnol Biochem. 71(5):1306-12, 2007. Akdogan M, Ozguner M, Kocak A, Oncu M, Cicek E. Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats. Urology. 64(2):394-8, 2004a. Akdogan M, Ozguner M, Aydin G, Gokalp O. Investigation of biochemical and histopathological effects of Mentha piperita Labiatae and Mentha spicata Labiatae on liver tissue in rats. Hum Exp Toxicol. 23(1):21-8, 2004b. Alves RJ, Jotz GP, do Amaral VS, Montes TM, Menezes HS, de Andrade HH.The evaluation of maté (Ilex paraguariensis) genetic toxicity in human lymphocytes by the cytokinesis-block in the micronucleus assay. Toxicol In Vitro. 22(3):695-8, 2008. Ames BN, Mccann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res. 31(6):347-64, 1975. Ames BN, McCann J, Sawyer C. Mutagens and Carcinogens. Science. 8;194 (4261) : 132-133, 1976. Anthony JC, Merriman TN, Heimbach JT. 90-day oral (gavage) study in rats with galactooligosaccharides syrup. Food Chem Toxicol. 44(6):819-26, 2006. Aphale AA, Chhibba AD, Kumbhakarna NR, Mateenuddin M, Dahat SH. Subacute toxicity study of the combination of ginseng (Panax ginseng) and ashwagandha (Withania somnifera) in rats: a safety assessment. Indian J Physiol Pharmacol. 42(2):299-302, 1998. Bates MN, Hopenhayn C, Rey OA, Moore LE. Bladder cancer and mate consumption in Argentina: a case-control study. Cancer Lett. 246: 268-73, 2007. Bleske BE, Zineh I, Hwang HS, Welder GJ, Ghannam MM, Boluyt MO. Evaluation of hawthorn extract on immunomodulatory biomarkers in a pressure overload model of heart failure. 13(12):BR255-258, 2007. Bolkent S, Yanardag R, Karabulut-Bulan O, Yesilyaprak B. Protective role of Melissa officinalis L. extract on liver of hyperlipidemic rats: a morphological and biochemical study. J Ethnopharmacol. 14;99(3):391-8, 2005. Brewen JG, Preston RJ. Chromosome aberrations as a measure of mutagenesis: comparisons in vitro and in vivo and in somatic and germ cells. Environ Health Perspect. 6:157-66, 1973. Bushman JL. Green tea and cancer in humans: a review of the literature. Nutr Cancer. 31(3):151-9, 1998. Cariño-Cortés R, Hernández-Ceruelos A, Torres-Valencia JM, González-Avila M, Arriaga-Alba M, Madrigal-Bujaidar E. Antimutagenicity of Stevia pilosa and Stevia eupatoria evaluated with the Ames test. Toxicol In Vitro. 21(4):691-7, 2007. Chan, L.Y., Chiu, P.Y., and Lau, T.K. 2004. Embryotoxicity study of ginsenoside Rc and Re in in vitro rat whole embryo culture. Reprod Toxicol. 19: 131-4. Chen, Z.L., Gu, H., Li, Y., Su, Y., Wu, P., Jiang, Z., Ming, X., Tian, J., Pan, N., and Qu, L.J. Safety assessment for genetically modified sweet pepper and tomato. Toxicology 188: 297-307, 2003. Copplestone J.F. The development of the who recommended classification of Pesticids by hazard. Bull WHO 66:545-551, 1998. Cui T, Nakamura K, Tian S, Kayahara H, Tian YL. Polyphenolic content and physiological activities of Chinese hawthorn extracts. Biosci Biotechnol Biochem 70(12):2948-56, 2006. Daniel Reid. A Handbook of Chinese Healing Herbs. USA:Shambhala Publishing. 173-174, 1995. Dertinger SD, Bishop ME, McNamee JP, Hayashi M, Suzuki T, Asano N, Nakajima M, Saito J, Moore M, Torous DK, Macgregor JT. Flow cytometric analysis of micronuclei in peripheral blood reticulocytes: I. Intra- and interlaboratory comparison with microscopic scoring. Toxicol Sci. 94(1):83-91, 2006. de Sousa AC, Alviano DS, Blank AF, Alves PB, Alviano CS, Gattass CR. Melissa officinalis L. essential oil: antitumoral and antioxidant activities. J Pharm Pharmacol. 56(5):677-81, 2004. Diaz D, Scott A, Carmichael P, Shi W, Costales C. Evaluation of an automated in vitro micronucleus assay in CHO-K1 cells. Mutat Res. 630(1-2):1-13, 2007. Dorato MA, Engelhardt JA. The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s). Regul Toxicol Pharmacol. 42(3):265-74. 2005. Durnev AD. Mutagens and antimutagens in food products. Genetika. 33(2):165-76, 1997. Eastmond DA, Tucker JD. Kinetochore localization in micronucleated cytokinesis- blocked Chinese hamster ovary cells: a new and rapid assay for identifying aneuploidy-inducing agents. Mutat Res. 224(4):517-25, 1989. Eaton DL, Klaassen CD. Principle of toxicity. In: Casarett & Doull’s Toxicology. The Basic Science of poisons, C. D. Klaassen, Ed, 6th ed., International Edition, McGraw-Hill, New York. pp. 11-34. Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition. 22(3):321-6, 2006. EPA Health Effects Test Guidelines OPPTS 870.3050, 28-Day Oral Toxicity in Rodents, July 2000. EPA Health Effects Test Guidelines OPPTS 870.3100, 90-Day Oral Toxicity in Rodents, August 1998. EPA Health Effects Test Guidelines OPPTS 870.4100, Chronic Toxicity, August 1998. Erlund I, Marniemi J, Hakala P, Alfthan G, Meririnne E, Aro A. Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations. Eur J Clin Nutr. 57 (1):37-42, 2003. Ferramosca A., Savy V., Zara V. Olive Oil Increases the Hepatic Triacylglycerol Content in Mice by a Distinct Influence on the Synthesis and Oxidation of Fatty Acids. Biosci Biotechnol Biochem. 72(1):62-9, 2008. Fenech M. The in vitro micronucleus technique. Mutat Res. 455(1-2): 81-95, 2000. Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans Mutation Research. 428(1-2):271-83, 1999. Federal Register. Single Dose Acute Toxicity Testing for Pharmaceuticals. Federal Register 61(166):43933-43935. 1996. Fhernanda R. Smiderle, Elaine R. Carbonero, Guilherme L. Sassaki, Philip A.J. Gorin, Marcello Iacomini Characterization of a heterogalactan: Some nutritional values of the edible mushroom Flammulina velutipes. Food Chem, 108(1):329-333, 2008. Fonseca CA, Otto SS, Paumgartten FJ, Leitão AC. Nontoxic, mutagenic, and clastogenic activities of Mate-Chimarrão (Ilex paraguariensis). J Environ Pathol Toxicol Oncol. 19(4):333-46, 2000. García M, Alarcón M, Duk S, Weigert G. Induction of micronuclei in mice bone marrow cells by home made aguardientes collected in southern Chile and their incidence in gastric cancer. Bull Environ Contam Toxicol. 49(6):866-70. 1992. Goldman R, Shields PG. Food mutagens. J Nutr. 3:965-973, 2003. Goldenberg D, Golz A, Joachims H.Z. The beverage maté: a risk factor for cancer of the head and neck Head Neck. 25: 595-60, 2003. Grisolia CK. A comparison between mouse and fish micronucleus test using cyclopho- sphamide, mitomycin C and various pesticides. Mutat Res. 25;518(2):145-50, 2002. Hansteen IL. Colchicine and chromosome aberrations. Lancet. 4;2(7623):744-5, 1969. Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E. Salmonella mutagenicity test results for 250 chemicals. Environ Mutagen. 5 Suppl 1:1-142, 1983. Hayashi M, Morita T, Kodama Y, Sofuni T, Ishidate M. The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides. Mutat Res 245: 245-249, 1990. Hayashi M, MacGregor JT, Gatehouse DG, Adler ID et al. In vivo rodent erythrocyte micronucleus assay. Ⅱ. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring. Environ Mol Mutagen 35: 234-252, 2000. Health Effects Test Guidelines. In: OPPTS Harmonized Test Guidelines, Series 870.5100, 1998. Heberlein U. Ethyl methanesulfonate (E.M.S.) mutagenesis, 1988. Huang K.C. The Pharmacology of Chinese Herbs. USA: CRC Press Publishing. 255-257, 1999. Ip. Differential effect of schisandrin B and dimethyl Bicarboxylate (DDB) on hepatic mitochondrial glutathione redox status in carbon tetrachloride intoxicated mice. Mol Cell. Biochem. 205:111-4, 2000. Isbrucker RA, Bausch J, Edwards JA, Wolz E. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity. Food Chem Toxicol. 44(5):626-35, 2006. Isbrucker RA, Edwards JA, Wolz E, Davidovich A, Bausch J. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. Food Chem Toxicol. 44(5):636-50, 2006. Jemnitz K, Veres Z, Torok G, Toth E, Vereczkey L. Comparative study in the Ames test of benzo[a]pyrene and 2-aminoanthracene metabolic activation using rat hepatic S9 and hepatocytes following in vivo or in vitro induction. Mutagenesis. 19(3):245-50, 2004. Jensen D. Sister Chromatid Exchange: the induction of micronuclei. New York: 47-63, 1982. Kligler B, Chaudhary S. Peppermint oil. Am Fam Physician. 1;75(7):1027-30, 2007. Krishna G, Hayashi M. In vivo rodent microneucleus assay: protocol, conduct and data interpretation. Mutat Res 455: 155-166, 2000. Kubo S. Effect of Gomisin A(TJN-101) on liver regeneration. Planta Med. 58:489-92, 1992. Lanzetti M, Bezerra FS, Romana-Souza B, Brando-Lima AC, Koatz VL, Porto LC, Valenca SS. Mate tea reduced acute lung inflammation in mice exposed to cigarette smoke. Nutrition. 24(4):375-81, 2008. Leitão AC, Braga RS. Mutagenic and genotoxic effects of mate (Ilex paraguariensis) in prokaryotic organisms. Braz J Med Biol Res. 27(7):1517-25, 1994. Lei C, Huang SX, Chen JJ, Pu JX, Yang LB, Zhao Y, Liu JP, Gao XM, Xiao WL, Sun HD. Lignans from Schisandra propinqua var. propinqua. Chem Pharm Bull (Tokyo). 55(8):1281-3, 2007. Lemonica, I.P., Damasceno, D.C., and di-Stasi, L.C. Study of the embryotoxic effects of an extract of rosemary (Rosmarinus officinalis L.). Braz J Med Biol Res. 29: 223-7, 1996. Liang CT, Chang MH, Hong CC, Huang KJ. Establishing the blood chemistry reference values for SPF rats and mice. J. Chin. Soc. Sci. 25: 55-68, 1999. Lichstein, Herman C, Malcolm H. Soule. Studies of the Effect of Sodium Azide on Microbic Growth and Respiration. J Bacteriol. 47 (3): 221-230, 1943. Liu P, Xu Y, Yin H, Wang J, Chen K, Li Y. Developmental toxicity research of ginsenoside Rb1 using a whole mouse embryo culture model. Birth Defects Res B Dev Reprod Toxicol. 74: 207-9, 2005. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res. 113(3-4):173-215, 1983. Mary L,A Giknis, Charles B. Clifford. Clinical laboratory parametrs for Crl:CD(SD) rats. Charles river laboratories, 2006. Mathews JN, Flatt PR, Abdel-Wahab YH. Asparagus adscendens (Shweta musali) stimulates insulin secretion, insulin action and inhibits starch digestion. Br J Nutr. 95(3):576-81, 2006. Matsuoka A, Lundin C, Johansson F, Sahlin M, Fukuhara K, Sjöberg BM, Jenssen D, Onfelt A. Correlation of sister chromatid exchange formation through homologous recombination with ribonucleotide reductase inhibition. Mutat Res. 22;547(1-2): 101-7, 2004. McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res. 20(7):519-30, 2006. Molinari M, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY, Nashan B, Peltekian K. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl. 12:1892-5, 2006. Mortelmans K, Zeiger E. The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455: 29-60, 2000. Murray, M.T. The Healing Power of Herb. Prima Health. USA, 1995. Nagao M, Sugimura T, Matsushima T. Environmental mutagens and carcinogens. Annu Rev Genet 12: 117-159, 1978. National Toxicology Program (NTP). Ethyl Methanesulfonate CAS No. 62-50-0. Carcinogens. U.S. Department of Health and Human Services, Public Health Service, 1983. National Toxicology Program (NTP). Cyclophosphamide CAS No. 50-18-0. Carcinogens. U.S. Department of Health and Human Services, Public Health Service, 1980. Organization for Economic Cooperation and Development(OECD). Guidelines for the Testing of Chemicals. Section 4: Health Effects. 2002. Organization for Economic Cooperation and Development(OECD). Repeated Dose 28-day Oral Toxicity Study in Rodents. In: OECD Guideline for the Testing of Chemicals. Section 4: Health Effects, No: 407, 8, 1995. Rossner P, Boffetta P, Ceppi M, Bonassi S, Smerhovsky Z, Landa K, Juzova D, Srám RJ. Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer. Environ Health Perspect. 113(5):517-20, 2005. Savage John R K. An Introduction to Chromosomal Aberrations. March, 1999. Savage John R K. Micronuclei : Pitfalls and Problems. July, 2000. Schwartz HJ, Jones RT, Rojas AR, Squillace DL, Yunginger JW. Occupational allergic rhinoconjunctivitis and asthma due to fennel seed. Ann Allergy Asthma Immunol. 78(1):37-40, 1997. Scholliers Peter. Defining food risks and food anxieties throughout history. Appetite. 51(1):3-6, 2008. Scudiero DA, Shoemaker RH, Paull KD et al. Evaluation of a soluble tetrazolium/ formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48: 4827-4833, 1988. Sewram, V., De Stefani, E., Brennan, P., and Boffetta, P. Maté consumption and the risk of squamous cell esophageal cancer in uruguay. Cancer Epidemiol Biomarkers Prev. 12: 508-13, 2003. Seely D, Dugoua JJ, Perri D, Mills E, Koren G. Safety and efficacy of panax ginseng during pregnancy and lactation. Can J Clin Pharmacol. 15(1):e87-94, 2008. Shizuoka Laboratory Animal Center (SLA). 2003. Background data, Slc:SD rats: organ weight. Shizuoka, Japan. p. 1-17. Singh I, Mok M, Christensen AM, Turner AH, Hawley JA. The effects of olyphenols in olive leaves on platelet function. Nutr Metab Cardiovasc Dis. 18(2):127-32, 2008. Stanley JS, York JL, Benson AM. Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice. Cancer Res. 1;52(1):58-63, 1992. Stevric, B. Antimutagens and anticarcinogens in foods. Food Chem. Toxic. 32: 79-90, 1994. Stoilov L, Wojcik A, Giri AK, Obe G. SCE formation after exposure of CHO cells prelabelled with BrdU or biotin-dUTP to various DNA-damaging agents. Mutagenesis.17: 399-403, 2002. Sugimura T, Wakabayashi K. Mutagens and carcinogens in food. Prog Clin Biol Res. 347:1-18, 1990. Sugimura T, Sato S. Mutagens-carcinogens in foods. Cancer Res. 43(5 Suppl):2415s- 2421s, 1983. Pari L, Suresh A. Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats. Food Chem Toxicol. 46(5):1627-34, 2008. Pittler MH, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev. 23;(1):CD005312, 2008. Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, Peng RY. Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem. 71(9):2223-32, 2007. Proudlock R, Thompson C, Longstaff E. Examination of the potential genotoxicity of pure capsaicin in bacterial mutation, chromosome aberration, and rodent micronucleus tests. Environ Mol Mutagen. 44(5):441-7, 2004. Tabart J, Kevers C, Pincemail J, Defraigne JO, Dommes J. Antioxidant capacity of black currant varies with organ, season, and cultivar. J Agric Food Chem. 23;54(17):6271-6, 2006. Tennant RW, Margolin BH, Shelby MD, Zeiger E, Haseman JK, Spalding J, Caspary W, Resnick M, Stasiewicz S, Anderson B et al., Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science. 236(4804):933-41, 1987. Trosko JE, Chang CC. Environmental carcinogenesis: an integrative model. Q Rev Biol. 53(2):115-41, 1978. Tomasz M. Mitomycin C: small, fast and deadly (but very selective). Chem Biol. 2(9):575-9, 1995. Torous DK, Hall NE, Murante FG, Gleason SE, Tometsko CR, Dertinger SD. Comparative scoring of micronucleated reticulocytes in rat peripheral blood by flow cytometry and microscopy. Toxicol Sci. 74(2):309-14, 2003. Torous DK, Dertinger SD, Hall NE, Tometsko CR. Enumeration of micronucleated reticulocytes in rat peripheral blood: a flow cytometric study. Mutat Res. 465 (1-2):91-9, 2000. Tuomilehto J, Tikkanen MJ, Högström P, Keinänen-Kiukaanniemi S, Piironen V, Toivo J, Salonen JT, Nyyssönen K, Stenman UH, Alfthan H, Karppanen H. Safety assessment of common foods enriched with natural nonesterified plant sterols. Eur J Clin Nutr, 2008 . (in press) USEPA. In Vitro Mammalian Chromosome Aberration Test. In: Health Effects Test Guidelines, OPPTS Harmonized Test Guidelines, Series 870.5375, EPA 712-C-98- 223, p. 1-13, 1998. USEPA. Office of Pesticides & Toxic Substances. Repeated Dose 28–Day Oral Toxicity Study in Rodents. In: OPPTS Harmonized Test Guidelines, Series 870.3050, EPA712–C–00–366, Washington, DC. 10 pp, 2000. Wahab MA, Podd JV, Rapley BI, Rowland RE. Elevated sister chromatid exchange frequencies in dividing human peripheral blood lymphocytes exposed to 50 Hz magnetic fields. 28(4):281-8. Bioelectromagnetics, 2007. Weisburger JH. Antimutagenesis and anticarcinogenesis, from the past to the future. Mutation research 480-481: 23-35, 2001. Wojcik A, Sonntag Cv, Obe G. Application of the biotin-dUTP chromosome labelling technique to study the role of 5-bromo-2''-deoxyuridine in the formation of UV- induced sister chromatid exchanges in CHO cells. Photochem. Photobiol. 69:139 -144, 2003. Wuweizi. In: Chang H.M. and But P.P.H Pharmacology and Applications of Chinese Materica(Vol Ι). Singapore: World Scientific Publishing. 199-209, 1986. Yamanaka S, Hashimoto M, Tobe M, Kobayashi K, Sekizawa J, Nishimura M. A simple method for screening assessment of acute toxicity of chemicals. Arch Toxicol. 64(4):262-8, 1990. Yen GC, Chen HY, Peng HH. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants. Food Chem Toxicol. 39(11):1045-53, 2001. Young PR, Ma RI, Marfey P, Kallenbach NR. Frameshift mutagenesis of 9-aminoacridine derivatives in Salmonella typhimurium. Mutat Res. 90(1):1-10, 1981. Zaveri NT. Green tea and its polyphenolic catechins: Medicinal uses in cancer and noncancer applications. Life Sci. 27;78(18):2073-80, 2006. Zhang Lina , Yang Liqun, Ding Qiong, Chen Xianfeng. Studies on molecular weights of polysaccharides of Auricularia auricula-judae. Carbohydr Res. 270( 1):1-10, 1995. Zhu X, Zhang H, Lo R. Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities. J Agric Food Chem. 1;52(24):7272- 8, 2004.
摘要: 近年來,在發展保健食品過程,相當注重協力作用(synergy)之觀念,嘗試結合多種食材開發「組合性」的配方產品(complex formulas),即將多種明確已知活性成分資料的食材相互配合使用,結合多種保健食材和成份的生理活性和優點,達到「多功能」的目的。本群體計畫乃依此概念分別組合具預防代謝症候群相關疾病、調節免疫功能、抗氧化等多種生理功能保健食品配方,第一階段為A, B, C配方,第二階段為I及K配方,第三階段為New J 配方。唯當一個新興食品上市前,評估潛在毒性之風險與食用安全性不容忽視。依照我國衛生署訂出的健康食品安全性評估方法,分別評估基因毒理試驗與動物毒性試驗。基因毒理包括:沙門氏菌致突變性(安姆氏試驗)、中國倉鼠卵巢細胞染色體變異及小鼠紅血球微核等測試。結果顯示第一階段三種配方(A, B, C)並無基因毒性作用,同時對小鼠之口服LD50值大於5 g/kg body weight。唯配方C小鼠血清BUN及creatinine值均較對照組偏高,檢視配方C組成中含有冬青葉,可能具腎毒性,建議抽換冬青葉,再進行新組合配方之安全性評估。第二階段保健食品(I, K)進行相同基因毒理試驗,結果顯示並無基因毒性作用。第三階段最後配方(New J)進行安姆氏試驗確定並無基因毒性。在食用安全性評估之急性毒性試驗結果顯示,New J 對大鼠口服之LD50值為大於5 g/kg body weight;28天亞急毒性試驗,則分別給予低(1 g/kg)、中(3 g/kg)及高(5 g/kg)三種劑量連續餵食大鼠28天,分析體重、飼料消耗量、血液學、血液生化學、尿液學及病理學等各項檢查,結果顯示,在中、高劑量組之雄鼠與雌鼠之體重與飼料消耗量均有下降趨勢,中及高劑量組之雌鼠血清白蛋白、白蛋白/球蛋白比率、鹼性磷酸酶、澱粉酶、天門冬酸轉氨酶、氨基丙酸轉氨酶、肌酸激酶、葡萄糖、總膽紅素、總膽固醇、三酸甘油酯、鈣、磷、氯、鉀、鎂和鈉等數值與對照組雖有顯著差異(p<0.05),但仍在正常生理值範圍內,體內重要器官均無明顯肉眼及組織病理變化。綜合以上結果,配方New J 對大鼠之28天餵食無毒害作用劑量 (no-observed-adverse-effect-level, NOAEL) 為1 g/kg bw/day。
In the recent global market of functional foods, the concepts of “synergy” and “multifunctional” were popular and have driven the development of complex formulas using multi-ingredients. Several complex formulas with or without micronization treatments will be developed using different natural plants and herbal materials with the goal to prevent diseases relating to the aging, metabolism, various degenerative disorders and immunomodulatory problems. As new material come on the market, their genotoxicity and safety should be evaluated first. The aim of this study was to evaluate the possible genotoxicity of three different stages health food formulas following Ames test, chromosome aberration, and micronucleus tests and animal feeding toicity. Results revealed that all formulas (A, B, C, I, K) had no mutagenicity. Additionally, the acute oral LD50 of formula A, B and C in mice was greater than 5 g/kg body weight. However, significant increase of BUN level was noted in the formula C treated group. The of formula C contained green mate leaf (Ilex paraguariensis) that had genotoxicity and associated with the risk of renal cell carcinoma in human. For the safety, it was suggested that the green mate leaf need to exclude in the next new formulation. On second stage, no mutagenicity of I and K formulas was found. Furthermore, the final product of New J formula was evaluated by Ames and animal toxicity tests. Rat were daily administered (by gavage) at doses of 1, 3 and 5 g/kg body weight for 28 days. Results revealed that no mutagenicity of New J and the acute oral toxicity was greater than 5 g/kg bw. In the 28-day feeding toxicity, all animals survived and no clinical signs were observed. However, significant different parameters in the middle and high dose groups of male rats were noted, induding body weight, body weight gain and feed consumption. It was alo noted significant difference in the middle and high-dose of female rats in blood biochemistry values when compared with control rats. Based on the result, the no observed-adverse-effect level (NOAEL) of New J formula is 1 g/kg bw/day in the 28-day feeding toxicity in rats.
URI: http://hdl.handle.net/11455/15362
其他識別: U0005-2307200815582800
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2307200815582800
Appears in Collections:獸醫病理生物學所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.