Mutagenicity and Safety Evaluation of Water Extract of Fermented Toona Sinensis Roemor Leaves

ABSTRACT:  The purpose of this study was to evaluate the mutagenicity and safety of water extract of fermented Toona sinensis Roemor leaves (WFTS). The WFTS was prepared by fermenting Toona sinensis Roemor leaves anaerobically for 14 d, and then extracting with boiling water. The mutagenic effects of WFTS were investigated using Ames test. No mutagenicity was found toward all tester strains ( Salmonella typhimurium TA98, TA100, TA102, TA1535). In the acute oral toxicity study, a single limit dose of 2.5 or 5 g/kg body weight (bw) WFTS was given to male Sprague-Dawley (SD) rats, then the rats were observed for 14 d. No acute lethal effect at a maximal dose of 5 g/kg bw WFTS was observed in rats. In the subacute study, the male rats were administered daily by gavage at a dose of 0.5 or 1 g/kg bw/d of WFTS for 28 d. The results indicated that no significant toxic effect was found in the parameters of body and organ weight, as well as hematological, biochemical, urinary, and pathological parameters between control and the WFTS-treated rats. The level of no observed adverse effect level (NOAEL) of WFTS in male rats was 1 g/kg bw for subacute toxicity study.     

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.     

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。     

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.     

Borojo果酶解浓缩粉的毒理学安全性评价

本文通过动物实验,研究Borojo果酶解浓缩粉的食用安全性。采用急性毒性试验、小鼠骨髓微核试验、小鼠精子畸形试验及大鼠30天喂养试验对Borojoa果酶解浓缩粉进行评价。结果表明,雌雄小鼠经口急性毒性LD50〉21．5g/kg·bw,根据急陛毒性分级,受试物Borojo果酶解浓缩粉属无毒级物质;小鼠骨髓微核试验、小鼠精子畸形试验结果与对照组比较均无显著性差异;大鼠30d喂养试验表明各剂量组动物体重增重、食物利用率、脏体比、血液学检查及血液生化检查与对照组比较均无显著性差异;病理检查主要脏器未见明显中毒性病理改变,说明Borojo果酶解浓缩粉属于安全性食品。     

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.     

Subchronic and Reproductive/Developmental (Screening Level) Toxicity of Complexation Products of Iron Trichloride and Sodium Tartrate (FemTA)

A complexation/reaction product, termed FemTA, of sodium tartrate [D(–)‐ and L(+)‐tartaric acid and mesotartaric acid], sodium hydroxide, and iron trichloride may have use as an anticaking agent in salt preparations. FemTA is composed of about 4% sodium tartrate, approximately 10% mesotartaric acid, approximately 7% chloride, approximately 4% iron, approximately 7% sodium, approximately 0.3% sodium oxalate, and approximately 65% water. FemTA was tested in a 90‐d oral toxicity study, which included a screening level reproductive/developmental toxicity phase, in Harlan Wistar rats. FemTA was administered by oral gavage at 500, 1000, and 2000 mg/kg body weight/d prior to and during mating, or about 20, 40, or 80 mg of iron/kg body weight/d, such that males received 90/91 d of treatment and females 104 to 109 d. Treatment was associated with inflammatory lesions of the lower GI tract at the mid‐ and high‐dose levels, increased liver and kidney weights, increased serum bile acids and blood urea nitrogen, decreased chloride, and changes to hematological parameters consistent with inflammation. The effects were considered the result of iron overload. There were no effects on reproductive/developmental toxicity parameters. The no‐observed‐adverse‐effect level (NOAEL), based on gastrointestinal tract effects was 500 mg/kg body weight/d. The NOAEL for reproductive/developmental toxicity was 2000 mg/kg body weight/d, the highest dose tested.     

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。     

淫羊藿骨碎补联合骨营养补剂对骨质疏松大鼠的影响

目的:研究淫羊藿骨碎补鹿骨粉联合骨营养补剂对去卵巢所致骨质疏松大鼠的影响。方法:制备去卵巢大鼠,随机分为模型组、阳性药组（1.0 mg/kg·bw戊酸雌二醇片）、中药组（0.17 g/kg·bw淫羊藿骨碎补提取物,0.08 g/kg·bw鹿骨粉）、营养剂组（0.17 g/kg·bw氨基葡萄糖盐酸盐,0.08 g/kg·bw硫酸软骨素,0.17 g/kg·bw碳酸钙）、复方组（0.17 g/kg·bw淫羊藿骨碎补提取物,0.08 g/kg·bw鹿骨粉,0.17 g/kg·bw氨基葡萄糖盐酸盐,0.08 g/kg·bw硫酸软骨素,0.17 g/kg·bw碳酸钙）,另设假手术组。以上各组灌胃体积均为10 mL/kg·bw,1次/d,连续灌胃12周,每周称量体重并按体重调整灌胃量。12周之后测定各组大鼠股骨密度和骨钙含量并进行骨组织病理学检查。结果:淫羊藿骨碎补提取物中的主要功效成分为淫羊藿苷和黄酮类物质,含量分别为0.78%和4.38%。12周之后,与模型组相比,中药组、营养剂组的骨密度和骨钙含量均无显著性差异（P>0.05）,复方组骨密度和骨钙含量均显著高于模型组（P<0.05）。中药组、营养剂组具有减轻骨质疏松的趋势,但差异不显著（P>0.05）,复方组可以增加骨小梁成分,减轻骨小梁稀疏,变细、断裂的程度（P<0.01）。结论:复方组具有增加大鼠骨密度和骨钙含量的作用,可以减轻骨质疏松的程度,增加骨小梁成分,且复方组比单用中药或营养剂效果明显。     

Analysis of chemical compounds and toxicological evaluation of Forsythia suspensa leaves tea

To determine the compositions of Forsythia suspensa leaves tea (FSLT) and its safety, the chemical compounds were analysed with some methods, and the toxicity was evaluated in Kunming mice and Wistar rats. The results showed that FSLT contained rich flavonoid, lignans, triperpene acids, amino acids, and mineral elements. In the acute toxicity study, none of the mice died, and no obvious poisoning symptoms were observed after 14 days in mice at the dose of 15 mg/g·body weight (bw) FSLT; in the sub-chronic toxicity, no abnormal or dead rat was found at the dose of 1, 3, and 10 mg/g·bw during 90 days feeding administration; there was no significant difference in bw and food consumption; no significant differences were found in each hematology and serum biochemistry parameter and organ/body weight ratio comparing with the control experimental group. The results revealed that the FSLT has low or no toxicity via oral administration. Therefore, FSLT is very suitable and safe to be used as a new resource food.     

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。     

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.     

大豆异黄酮复合软胶囊的免疫增强作用及安全性评价

为观察大豆异黄酮复合软胶囊(SIC)的增强免疫力效果及安全性.按照人体推荐用量的30、20、10倍,经口给予小鼠340、670、1000 mg/kg·bw剂量的SIC干预.通过测定脏器/体重比值、细胞免疫、体液免疫、单核-巨噬细胞吞噬功能指标和NK细胞活性,评估SIC对免疫功能的影响,结果发现:高剂量SIC干预小鼠的足...     

α-酪蛋白源ACE抑制肽对高血压大鼠血压的影响

研究水解α- 酪蛋白所得水解产物对原发性高血压大鼠(SHR)血压的影响。用α- 酪蛋白水解产物以低、中、高3 个剂量(0.0245、0.1225、0.6125g/kg bw)分别灌胃SHR 大鼠,0.6125g/kg bw 灌胃正常Wistar 大鼠,测定灌胃后1～8h 尾动脉收缩压(SBP)。结果显示,单次灌胃8h 内,高剂量α - 酪蛋白水解产物对正常Wistar 大鼠的血压无影响;3 种剂量对SHR的血压升高有明显抑制作用,且高剂量组在0～6h 内降压效果最佳,SBP 维持在较低水平的时间最长,达到6h,SBP 值下降了(29.50 ± 1.0)mmHg。连续灌胃高剂量α- 酪蛋白水解产物可较长时间维持低水平SBP。     

Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in rats

Single oral dose and 13-week oral subchronic toxicity studies of fucoxanthin-containing oil extracted from microalga, Chaetoseros sp., were conducted in rats. In the single oral dose study, no mortality and no change related to the test material were observed. Thus, the 50% lethal dose of microalgal fucoxanthin oil is more than 2,000 mg/kg body weight. In the 13-week oral dose study, 0, 20 or 200 mg/kg body weight of microalgal fucoxanthin oil was administered. The fucoxanthin-administered groups, showed no mortality and no abnormalities. This result suggested that the no-observed-adverse-effect level of fucoxanthin-containing oil extracted from microalga Chaetoseros sp. was 200 mg/kg body weight under the tested subchronic dose condition.     

添加维生素E的雨生红球藻亚急性毒性评价及增强免疫作用研究

研究了添加维生素E的雨生红球藻(HPE)对大鼠亚急性毒性和增强小鼠免疫功能作用。以1670、835、418mg/kg bw (分别相当于人体推荐用量100、50、25倍)三个剂量的HPE连续给大鼠灌胃30 d进行亚急性毒性试验；以334、167、84 mg/kg bw三个剂量连续给小鼠灌胃30 d进行免疫功能试验,结果显示,亚急性毒性试验期间动物的生长发育良好,各剂量组的动物体重、增重量、进食量、食物利用率、血常规指标、血生化指标、脏器重量及脏器/体重比值与对照组比较,均无显著性差异(P>0.05)；大体解剖观察和组织病理学检查未见与添加维生素E的雨生红球藻有关的异常改变。在受试剂量范围内未见添加维生素E的雨生红球藻对大鼠各项观察指标产生毒副作用。与对照组相比,中、高剂量组显著促进小鼠的脾淋巴细胞增殖转化能力,提高小鼠的血清溶血素水平；高剂量组显著提升了迟发型变态反应能力和小鼠碳廓清吞噬指数,明显增强抗体生成细胞能力。表明添加维生素E的雨生红球藻安全性高,具有增强免疫功能。     

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。     

茶多酚急性毒性试验研究

目的对茶多酚的急性毒性进行研究,为其在保健食品中的应用提供理论依据。方法将大鼠分为6个组,大鼠灌胃剂量分别为1.00、2.15、4.64、10.0、21.5 g/kg和空白对照组。按大鼠体重20 m L/kg给予各浓度的受试液灌胃,每天灌胃2次,连续灌胃14 d。结果高剂量茶多酚灌胃大鼠后相继出现死亡,低剂量组(1.00 g/kg、2.15 g/kg)大鼠于14 d后解剖观察,未发现明显异常;与空白对照组比较,大鼠脏器重和脏体比,无显著差异(P0.05)。各剂量组大鼠体重与对照组比较,差异无统计学意义(P0.05)。结论茶多酚属低毒级,在以后的生产应用中应该注意其用量。     

大豆肽共轭亚油酸复合粉减肥作用研究

目的研究大豆肽共轭亚油酸复合粉的减肥功效。方法分别以1、2和4 g/kg·bw剂量的大豆肽共轭亚油酸复合粉对大鼠连续灌胃6周后,测定试验末体重、体内脂肪重、脂/体比等各项指标。结果受试物高剂量组(4 g/kg)的试验末体重、体内脂肪重和脂/体比均低于模型对照组;摄食量与模型对照组在试验末体重、体内脂肪重、脂/体比等各项指标方面无显著性差异。结论根据国食药监保化[2012]107号附件8《减肥功能评价方法》的结果判定,大豆肽共轭亚油酸复合粉对大鼠具有减肥功能作用。     

Comparison of PCDD/F and dl-PCB levels in Turkish foodstuffs: industrial versus rural,local versus supermarket products,and assessment of dietary intake

Polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) and dioxin-like and non-dioxin-like (indicator) polychlorinated biphenyls (PCBs) were monitored in various foodstuffs of animal origin and edible oil samples obtained from two different cities in Turkey both rural and industrial. Total dioxin+dioxin-like PCBs and indicator PCB concentrations of pooled samples ranged 0.20–4.19 pg World Health Organization-Toxic Equivalency (WHO-TEQ)₍₁₉₉₈₎/g fat and 57.2–1710 pg/g fat, respectively. The dominant congeners were 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDD and PCB126. Dietary intake of dioxin+dioxin-like PCBs and indicator PCBs from fish, dairy products, edible oil, egg and meat was 0.509 pg WHO-TEQ₁₉₉₈/kg bw (body weight)/day and 839 pg/kg bw/day in Afyon and 0.588 pg WHO-TEQ₁₉₉₈/ kg bw/day and 1070 pg/kg bw/day in Kocaeli, respectively. The major contributors to total exposure were dairy products and fish. Despite the unexplained high contamination level in an individual egg sample from Kocaeli, average concentration levels in Turkey, even in industrialized regions, were low compared to reported concentrations in Western Europe. Exposure levels were well below the tolerable daily intake (TDI) of 2 pg WHO-TEQ₁₉₉₈/kg body weight.