Mutagenicity and Safety Evaluation of Ethanolic Extract of Prunus mume

ABSTRACT:  The ethanolic extract of  Prunus mume  (EPM) is a novel polyphenol preparation derived from branches (with leaves) of  Prunus mume , which could be used as a functional ingredient for antioxidant and antiobesity therapy. The purpose of this study was to evaluate the safety of EPM. An EPM was prepared and evaluated for oral acute and subacute toxicity in  Sprague–Dawley  rats, while its mutagenic potential was assessed by a reverse mutation test using  Salmonella typhimurium , by a bone marrow cell micronucleus test using ICR mice, and by a sperm abnormality test using ICR mice. The results showed no acute lethal effects at the maximal tested EPM dose of 20 g/kg bw in either rats or mice, suggesting that EPM can be regarded as virtually nontoxic. Administration at levels of 0.84, 1.67, and 3.33 g/kg bw to rats for 30 d did not induce any significant hematological, clinical, chemical, or histopathological changes. No mutagenicity evidence was detected in any of the 3 mutagenic tests. The level of "no observed adverse effect" (NOAEL) for EPM was above 3.33 g/kg bw for the subacute toxicity study.     

和辉胶囊的毒理学安全性评价

本研究了评价保健食品和辉胶囊的食用安全性。依据国家卫生和计划生育委员会《保健食品检验与评价技术规范》(2003年版)和《食品安全性毒理学评价程序》(GB 15193.1-2014),开展大鼠急性毒性试验、遗传毒性试验(小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验)和大鼠30 d喂养试验,对和辉胶囊进行毒理学研究,观察其有无毒性反应。结果表明,急性毒性实验中,雌、雄大鼠对和辉胶囊的最大耐受剂量(MTD)均大于15.0 g/kg·bw,和辉胶囊属无毒级;小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验三项结果均为阴性,和辉胶囊无遗传毒性;大鼠30 d喂养试验中,和辉胶囊试验剂量在1.20 g/kg·bw~4.80 g/kg·bw范围内(最高剂量相当于人体推荐用量的100倍),大鼠的生长发育、血液学、血液生化学及病理学方面各项相关指标的检验均未发现明显不良影响。说明和辉胶囊无急性毒性、遗传毒性和亚急性毒性,具有较高的食用安全性。     

Toxicity Study of Ethanolic Extract of Chrysanthemum morifolium in Rats

Abstract: Chrysanthemum morifolium extract (CME) has many pharmacological effects, and the effective components of CME are luteolin and apigenin which have been reported with cytotoxicity in vitro. The purpose of this study was to evaluate the safety of CME in Sprague–Dawley (S–D) rats. In the acute toxicity study, a single oral dose of 15 g/kg body weight (bw) CME was administered to rats, then the rats were observed for 14 d. No treatment-related death was observed, and the maximal tolerance dose estimated was greater than 15 g/kg bw in rats. In the long-term toxicity study, the rats were administered daily by gavage at dose levels of 320, 640, and 1280 mg/kg bw/d for consecutive 26 wk followed by 4 wk recovery period. The results showed that no toxicological changes in body weight, food, and water consumption, hematologic examination, blood biochemical examination, organ weight, and microscopic histopathologic examination were found in any treatment group. Therefore, CME is considered to be safe in general in rats at the limited dose level.     

栗树类芽孢杆菌S3胞外粘多糖毒理安全性评价

对栗树类芽孢杆菌（Paenibacillus castaneae）S3胞外粘多糖进行毒理学安全性评价,为其食用安全性提供依据。通过小鼠急性经口毒性试验、骨髓细胞染色体畸变、精子畸形及30 d喂养试验分别考察低（1.0 g/kg）、中（2.0 g/kg）、高剂量（4.0 g/kg）粘多糖的急性、致突变及亚急性等毒理性质。结果表明,小鼠的最大粘多糖耐受剂量＞12 g/kg,该粘多糖属于无毒物质;各剂量粘多糖对小鼠骨髓细胞染色体及精子无明显畸变作用;30 d喂养各剂量粘多糖组,小鼠生长发育良好,体质量增加、脏器系数、血常规及血生化等各项指标与对照组均无显著差异（P＞0.05）,未见明显的病理改变。因此,在该试验研究剂量和条件下,栗树类芽孢杆菌S3胞外粘多糖具有良好的食用安全性。     

地椒的毒理学安全性评价

为评价地椒的食用安全风险,本文研究了地椒提取物的急性毒性、遗传毒性和亚急性毒性,采用国家保健食品检验和技术评价规范标准中的急性毒性试验、Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验和经口给药30 d喂养试验。发现了分别给予昆明种小鼠、SD大鼠最大耐受剂量60 g/kg、30 g/kg BW未见中毒及死亡。TA97a、TA98、TA100、TA102和TA1535试验菌株在5000μg/皿、1581μg/皿、500μg/皿、158.1μg/皿、50μg/皿5个剂量回变突变菌落数均低于阴性对照组的2倍。各剂量组精子畸形率和阴性对照组比较,无显著性差异(p0.05);除低剂量组外,高、中剂量组微核发生率均发生显著性变化(p0.01)。中剂量组对雄性大鼠体重呈现抑制作用,而对雌性大鼠体重呈现增长作用,同时能提高动物食物利用率;血液中RBC和HGB显著升高,HCT、MCV、MCHC、RDW-CV有所升高;血生化检查指标与对照组对比,能显著降低雌鼠AST,增加雌性动物的CHO、TG水平,对雌雄动物UREA、GLU水平明显降低。除肝、肾外,其他器官未见明显组织病理学改变。表明,急性毒性试验、Ames试验无明显影响;对小鼠精子无致畸作用。受试剂量范围内,地椒对骨髓细胞微核产生有一定毒性;地椒具有潜在的降血糖活性;地椒对雄性动物性激素系统、造血系统、肌肉功能,具有潜在激活作用;高剂量地椒对大鼠肝肾有一定毒性。结果证明地椒在一定剂量范围内安全可靠,本试验为地椒安全食用提供了毒理学的安全性评价依据。     

Mutagenicity and safety evaluation of the water extract of Camellia oleifera Abel

Abstract: The purpose of this study was to evaluate the mutagenicity and safety of water extract of the fruit hull of Camellia oleifera Abel (WECO), which was prepared using hot‐reflux method. The oral maximum tolerated dose (MTD) of WECO was above 20 g/kg body weight both in rats and in mice, which can be regarded as virtually nontoxic. No mutagenicity was found in Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test. In the subacute study, the SD rats were administered orally at 0.5, 1, or 2 g/kg/BW for 30 d. There were no treatment‐related toxic effects from WECO. No significant differences were found in parameters of body weight, hematology value, clinical chemistry value, and organ/body weight ratio. The level of no observed adverse effect level (NOAEL) for WECO was 2 g/kg/BW for subacute toxicity study. Practical Application: With the gradual increase in tea oil production, it was in urgent need of dealing with Camellia fruit hull, which was always discarded because of low economic benefits. Camellia fruit hull has been shown to have significant antioxidant effects including DPPH radical‐scavenging ability and ferric‐reducing antioxidant power ( Zhang and others 2010 ). Toxicological evaluation of WECO provided a safety assurance of WECO for developing dietary supplements and functional foods.     

甲鱼肽粉安全性的初步评价研究

目的 对甲鱼肽粉的安全性进行初步评价研究。方法 采用大、小鼠急性毒性试验、Ames 试验、小 鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验和大鼠 30 d 喂养试验对甲鱼肽粉进行急性毒性、遗传毒性 和亚慢性毒性研究。结果 甲鱼肽粉对大、小鼠经口最大耐受量(MTD)均大于 20.0 g/(kg.bw); Ames 试验显示 在加与不加 S9 时各剂量组回变菌落数与自发回变对照组比较差异无统计学意义(P>0.05); 小鼠骨髓嗜多染红 细胞微核试验和精子畸形试验结果显示, 各剂量组的微核率和精子畸形率与阴性对照组比较差异均无统计学 意义(P>0.05); 30 d 喂养试验表明甲鱼肽粉未见明显毒性反应, 最大未观察到有害作用的剂量为 8.4 g/(kg.bw)。 结论 在本次实验条件下, 甲鱼肽粉经口 MTD>20.0 g/(kg.bw), 属实际无毒级, 并且未见遗传毒性, 30 d 喂养 试验未见其对受试动物有毒性损害作用。     

霍山石斛茎的食用安全性评价

本文采用动物急性毒性试验、三项遗传毒性试验、90 d喂养试验和致畸试验对霍山石斛茎(Dendrobium huoshanense stems,DHS)的食用安全性进行评价。小鼠急性经口毒性试验表明,霍山石斛茎的雌雄小鼠最大耐受剂量(MTD)均大于15.0 g/kg·bw;遗传毒性试验显示,霍山石斛茎对鼠伤寒沙门氏菌菌株TA97、TA98、TA100、TA102均未呈现遗传毒性,对小鼠骨髓嗜多染红细胞微核率及嗜多染红细胞与正染红细胞(PCE/NCE)的比值均无影响,对小鼠精子畸形发生无显著作用;90 d喂养试验表明,霍山石斛茎各剂量组与对照组相比,动物的体重变化、进食量、食物利用率、脏器重量、脏体比、血液学、血液生化及组织病理学等指标均无显著性差异;致畸试验表明,霍山石斛茎各剂量组对孕鼠体重增长、胚胎早期发育及胎鼠的生长发育、骨骼、内脏和外观发育均无明显不良影响,各项指标与对照组相比均无显著性差异。综上,霍山石斛茎在5 g/kg·bw剂量范围内食用安全。     

糙米酵素红曲酒的小鼠口服毒理学安全性评价

目的:研究糙米酵素红曲酒的引用安全性.方法:依据《保健食品检验与评价技术规范》,对糙米酵素红曲酒进行了急性毒性试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验、小鼠30d喂养试验.结果:糙米酵素红曲酒对雌雄小鼠的急性经口的最大耐受剂量(MTD)均大于20g/kg体重;小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验均为阴性;小鼠30d喂养试验中,试验动物生长情况良好,体重检查、血清检查、脏体比结果与对照组相比,均无明显差异.结论:糙米酵素红曲酒属实际无毒物质,未显示有遗传毒性,初步估计其未观察到损害作用的剂量(NOAEL)为20g/kg体重.     

纯蚂蚁粉的安全性评价

通过测试蚂蚁粉的急性毒性及致突变性,对蚂蚁粉进行安全性评价。材料与方法:采用小鼠的急性毒性试验;小鼠骨髓细胞微核试验;小鼠精子畸形试验;大鼠30d喂养试验及Ames试验等试验方法。结果:小鼠LD50>215000mg/kg,小鼠骨髓细胞微核试验和小鼠精子畸形试验测试组和对照组相比均无显著性差异,Ames试验中不同剂量组在加S9和不加S9条件下的回变菌落数均未超过空白对照组回变菌落数的2倍。大鼠30d喂养试验各剂量组动物生长发育良好,血液及生化指标均在正常范围内,各试验组与对照组比较无显著性差异,病理学检查结果肝、肾、胃、肠均正常。结论:蚂蚁粉属无毒物,致突变试验及30d喂养试验均为阴性结果。     

不同采收期红油香椿营养成分和抗氧化活性分析

以国内主要栽培品种红油香椿为研究对象,对同茬3 个不同采收期香椿嫩芽营养物质和抗氧化能力进行研究,旨在为其适时采收提供理论依据。结果表明：香椿嫩梢叶中的叶绿素、可溶性糖、可溶性蛋白及黄酮含量均在Ⅲ期达最大值,其含量分别为1.72、119.94、3.87、11.83 mg/g。叶中的叶绿素、氨基酸、可溶性蛋白、多酚及黄酮含量在所有的采收期均极显著高于茎（P＜0.01）,而可溶性糖在Ⅲ期、VC在Ⅰ期叶与茎中的含量差异不显著。不同采收期及不同部位香椿嫩芽的提取液质量浓度均与抗氧化能力呈显著量效关系（P＜0.05）。3 个采收期茎提取液清除1,1-二苯基-2-三硝基苯肼（1,1-diphenyl-2-picrylhydrazyl,DPPH）自由基能力均高于叶,而清除•OH能力叶强于茎。对不同采收期,在清除•OH能力和还原能力方面Ⅱ期香椿嫩芽提取液最强,在清除DPPH自由基能力方面Ⅰ期较强。综合考虑营养物质含量、抗氧化活性和食用性,Ⅱ期为最适宜的采收时间。     

NKA-9大孔树脂纯化香椿叶黄酮类物质工艺优化

以香椿叶提取物为原料,以吸附率和解吸率为指标,考察了9种大孔树脂对香椿叶黄酮的吸附与解吸性能,并结合静态吸附动力学,筛选出适宜纯化香椿叶黄酮的大孔树脂为NKA-9。运用静态与动态吸附、解吸实验,研究得出NKA-9纯化香椿叶黄酮的最佳工艺条件为:选取70 m L 7 mg/m L的香椿叶提取物(含Na Cl浓度为3 mol/L),上样流速2 BV/h,用80 m L 60%乙醇溶液(p H 6)为洗脱剂,以2 BV/h的流速洗脱。在该条件下,香椿叶黄酮含量由纯化前81.272 3 mg/g增加到纯化后219.970 2 mg/g。高效液相色谱结果分析表明,芦丁、金丝桃苷、异槲皮苷、槲皮苷、阿福豆苷5种黄酮类单体物质含量均提高到纯化前的3倍以上。该工艺能有效地富集纯化香椿叶黄酮类物质,槲皮苷是此香椿叶黄酮类化合物的主要组分,含量是其他4种单体总量的2倍左右。     

牡丹籽油的毒理学研究

目的：研究牡丹籽油的毒理学安全性。方法：通过小鼠急性毒性实验、小鼠精子畸形的遗传毒性实验和亚急性毒性实验进行毒理学研究,并对其做出安全性评价。结果：牡丹籽油对昆明小鼠的急性经口 LD50 大于15g/kg bw,判属无毒类;小鼠精子畸形遗传毒性实验为阴性,表明该受试物无致突变作用;在大鼠30d 喂养实验中未见动物健康状况、生化、血液学指标和器官组织形态的异常变化,据此初步估计该产品的最大无作用剂量大于 5.0g/kg bw(人体推荐摄入量的 150 倍)。结论：牡丹籽油无急性毒性、遗传毒性和亚急性毒性,具有较高的食用安全性。     

Oral Toxicity of Cold Plasma‐Treated Edible Films for Food Coating

No prior research has investigated whether the cold plasma treatment (CPT) resulted in the formation of toxic compounds. Therefore, this study carried out the experiment to check the safety of edible films treated with cold plasma by examining their acute and subacute oral toxicity in a rat model. Single‐dose acute (5000 mg/kg body weight) and 14‐d subacute (1000 mg/kg body weight/day) oral toxicity of cold plasma‐treated edible films was assessed for male and female Sprague–Dawley (SD) rats. Rats administered 5000 mg/kg of edible film did not show the signs of acute toxicity or death after 14 d of observation. Similarly, no signs of acute toxicity or death were recorded during 14 d in rats administered 1000 mg/kg/day of edible film treated with cold plasma. Although changes in the levels of several blood components (hematocrit, hemoglobin, bilirubin, creatinine, and aspartate aminotransferase) of samples were observed, the changes compared to the control were considered to be toxicologically irrelevant as their levels were within normal physiological ranges. Macroscopic analysis showed there were no changes in color or texture of representative liver sections of SD rats following the oral administration of edible films with CPT (F‐CP) or without CPT (F‐NT). The results demonstrate that the cold plasma‐treated edible film possessed very low toxicity, suggesting that CPT does not generate harmful by‐products in the edible film.     

热风与微波及其联合干燥对香椿芽品质的影响

以香椿芽为材料,比较研究热风干燥、微波干燥和热风-微波联合干燥3 种方式对香椿芽干燥特性和品质的影响。结果表明,60 ℃热风干燥和550 W微波干燥所得干制品的综合评价值较大,分别为0.890和0.884。热风-微波联合干燥的最佳干燥工艺条件为前期采用60 ℃热风干燥至转换点干基水分含量0.67 kg/kg,后期采用功率330 W进行微波干燥;在此条件下,联合干燥所得干制品的综合评价值为0.972。说明热风-微波联合干燥可以很好地保持香椿芽的品质。     

Safety Studies Conducted on a Sanitizing Agent Containing Benzalkonium Chloride

Abstract: Free N Clear is a sanitizing agent composed of United States Pharmacopeial Convention grade benzalkonium chloride (BAC), acetic acid, and methylparaben. Free N Clear is proposed for use as a sanitizing agent at a 1 : 50 dilution (2% solution), which contains approximately 100 ppm BAC. As part of a program to assess its safety, a 2% solution of Free N Clear (diluted Free N Clear) was administered by gavage to Sprague‐Dawley rats for 91 d and tested for genetic toxicity in vitro and in vivo. In the 91 d study, the no observable adverse‐effect level of diluted Free N Clear in male and female Sprague‐Dawley rats is 5000 mg/kg bw/day, the highest dose administered. Diluted Free N Clear was not mutagenic in a bacterial reverse mutation assay that tested concentrations extending into the toxic range, and did not increase the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of male or female Sprague‐Dawley rats when tested at the maximum permissible dose volume of 20 mL/kg bw. The results support safety of Free N Clear, when used at the concentration proposed for use. Practical Application: The significance of these findings will allow for the development of Free N Clear as a potential sanitizing agent for food.     

Acute and Subacute Toxicity Assessment of Lutein in Lutein‐Deficient Mice

Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein‐deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD₅₀ exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment‐related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no‐observed‐adverse‐effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested.     

蓝靛果花色苷对高脂膳食诱导肥胖大鼠脂代谢和抗氧化能力的影响

目的:研究蓝靛果果渣花色苷(Lonicera caerulea residue anthocyanin,LCRA)对高脂膳食诱导肥胖大鼠脂类代谢和抗氧化能力的影响。方法:将大鼠随机分为基础对照,肥胖模型对照和低、中、高剂量花色苷共5组,即4.0、40.0、120mg/kg bw.d的花色苷灌胃,基础对照组和肥胖模型对照组分别灌胃生理盐水(1.2g/kg bw.d);连续28d后,分别测定大鼠体质量、脂肪、肝脏质量,血清总胆固醇(TC)、总甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)含量以及肝脏脂肪酶(LPS)、肝脂酶(HL)、脂蛋白脂肪酶(LPL)、超氧化歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的活性和脂质过氧化物(MDA)含量。结果:与肥胖模型对照组相比,LCRA能显著降低肥胖模型大鼠血脂水平,使肝脏LPS、HL、LPL、SOD和GSH-Px活性明显增强,MDA的生成量显著减少。结论:LCRA对高脂膳食诱导肥胖大鼠脂代谢有明显调节作用,可有效减少肝脏过氧化损伤,预防动脉硬化的发生。     

二十八烷醇微乳液的毒理学评价

二十八烷醇微乳液是由二十八烷醇、吐温80、乙醇等配制而成的均一透明液体。通过急性毒性经口试验和28 d经口重复毒性试验,判断二十八烷醇微乳液的食品毒性。在急性毒理学试验中,对昆明小鼠一次性经口灌胃10 g/kg bw二十八烷醇微乳液,观察14 d,无中毒或死亡症状,LD50>10 g/kg bw,属于实际无毒级别。在28 d经口重复毒性试验中,设置二十八烷醇高剂量组(5.00 g/kg bw)、中剂量组(2.50 g/kg bw)、低剂量组(1.25 g/kg bw)和阴性对照组,通过临床观察、对比体质量和摄食量变化、进行血液学、血生化及病理学检查得出结论,二十八烷醇微乳液对小鼠最大无作用剂量为2.50 g/kg bw(人体推荐摄入量的100倍)。综上所述,二十八烷醇微乳液无毒。