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.     

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.     

DL-丙氨酸的急性经口毒性和28天经口毒性研究

目的通过DL-丙氨酸的急性经口毒性和28 d经口毒性试验研究,初步判断DL-丙氨酸作为食品添加剂的安全性。方法分别按照国标的GB 15193.3-2014和GB 15193.22-2014方法来进行急性经口毒性试验和28 d经口毒性试验,然后将大鼠的各项数据进行对比分析。结果急性经口毒性试验中无毒作用表现,雌雄大鼠的经口LD5010000 mg/(kg BW)。28 d经口试验中大鼠一般状况正常,期末体重增长、进食量、食物利用率等指标未发现明显的改变;血常规、凝血、血生化及尿常规等指标均未发现有意义的异常改变;雄性高剂量组肾脏系数与对照组相比差异有统计学意义(P0.05),各剂量组间具有剂量-反应关系,其他未见异常情况;病理学检查未见与受试物有关的病理性改变。结论 DL-丙氨酸在本研究中未见毒性作用,但长期食用的安全性尚需进一步研究。     

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.     

黄芪茎叶的安全性毒理学评价

为评价黄芪茎叶的急性毒性、遗传毒性及亚慢性毒性,为黄芪茎叶安全应用提供实验依据,采用国家标准食品安全性毒理学评价程序和方法标准对黄芪茎叶进行急性经口毒性试验、三项遗传毒性试验及90 d亚慢性毒性试验研究。发现雌雄大小鼠急性经口LD50>250.00 g/kg BW,属实际无毒级。三项遗传毒性试验结果显示检测结果均为阴性,未见致突变作用。大鼠90 d经口毒性试验显示,试验期间各组动物生长发育良好,未见中毒表现和体征,大鼠眼部检查、体重、增重、进食量、食物利用率、血液学及血生化、尿常规、脏器重量及脏体比等指标均未见损害性影响,解剖及组织学观察也未见明显与试验因素有关的病理组织学变化,未观察到有害作用剂量为15.00 g/kg BW。结果表明黄芪茎叶在本条件剂量下安全无毒。     

黑果枸杞花青素提取物的初步毒性评价

该文评价了黑果枸杞花青素提取物（Anthocyanins extract of Lycium ruthenicum,AEL）的急性毒性和亚急性毒性。采用固定剂量法一次灌胃AEL 8 000 mg/kg进行经口急性毒性试验,观察小鼠毒性反应,记录14 d内一般状态。选取SD大鼠进行30 d喂养试验,记录大鼠体质量和体征变化,实验结束时进行尿液生化指标、血液学指标、血清生化指标检查,并观察脏器形态变化,计算脏体系数和脏脑系数。研究发现：急性毒性试验中,小鼠无不良反应,体质量正常增长,解剖脏器未见明显异常;连续灌胃30 d后,各组大鼠体质量正常增长,未见明显中毒反应;与对照组比较,高剂量组雌性大鼠单核细胞百分比（M%）显著升高（P<0.05）,AST/ALT的比值显著降低（P<0.05）;高剂量组雄性大鼠血清Cl-、脾脏系数高于对照组（P<0.05）。实验组大鼠其余尿液生化指标、血液学指标、血清生化指标、脏体系数和脏脑系数无明显异常。结果表明：小鼠对AEL的单次灌胃最大耐受剂量不低于8 000 mg/kg;连续灌胃30 d,大鼠未见明显中毒反应,AEL在该实验条件下无急性、亚急性毒性,具有较高的安全性。     

In vitro inhibitory effects of rosemary extracts on growth and glucosyltransferase activity of Streptococcus sobrinus

Rosemary (Rosmarinus officinalis L.) extract functions as an antioxidant and antimicrobial agent. In this study, we investigated in vitro effects of rosemary extracts on Streptococcus sobrinus growth and on its extracellular glucosyltransferase activity. The antibacterial activities of rosemary extracts were determined by the microdilution broth method. The minimum inhibitory concentrations of aqueous and methanolic rosemary extracts against S. sobrinus were 16 and 4 mg/ml, respectively. Glucosyltransferase activity was tested by incubating a crude enzyme preparation with sucrose and determining the amount of water-insoluble glucan formed. Both aqueous and methanolic extracts of rosemary markedly inhibited the formation of water-insoluble glucan. The 50% inhibitory doses of aqueous and methanolic extracts against the glucosyltransferases of S. sobrinus were 1.42 mg/ml and 0.34 mg/ml, respectively. Our results suggest that rosemary extract may prove effective for the inhibition of the growth of cariogenic oral streptococci.     

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.     

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.     

鱼油姜黄提取物急性毒性和亚急性毒性实验研究

研究鱼油姜黄提取物的急性毒性和亚急性毒性,为评价其食用安全性提供试验依据。对鱼油姜黄提取物进行大、小鼠急性经口毒性试验和大鼠30d喂养试验。试验结果表明,大、小鼠急性经口MTD值>15000mg/kg·BW,属无毒级;3个剂量组雌、雄大鼠的每周体重、每周进食量、每周食物利用率、总食物利用率、脏体比值、血液学指标及末期血生化指标检测结果与对照组比较,雌鼠高剂量组血糖显著降低(P<0.01),其它各项指标均无显著性差异(P>0.05);除动物自发病变外,受试物高剂量组未引起动物中毒性损伤。鱼油姜黄提取物在本试验条件下未显示有急性毒性或亚急性毒性。     

甜叶菊苷M的毒理学安全性评价

甜叶菊苷M是在甜叶菊中发现的糖苷类物质,已被确定为一种潜在的甜味剂。本研究依据食品安全国家标准,采用小鼠急性经口毒性试验、Ames试验、小鼠骨髓红细胞微核试验、小鼠精母细胞染色体畸变试验和28 d经口毒性试验对甜叶菊苷M进行了安全性评价。结果显示:甜叶菊苷M对雌雄小鼠急性经口MTD值均大于10000 mg/kg·bw,属实际无毒级;Ames试验、小鼠骨髓红细胞微核试验和小鼠精母细胞染色体畸变试验均为阴性;将样品以2000、1000和500 mg/kg的设计剂量掺入基础饲料中喂养大鼠28 d后,各剂量组雌雄动物的体重、摄食量、食物利用率、血液学、血生化和组织病理学等指标与对照组相比无明显异常。样品对雌、雄大鼠未观察到有害作用剂量(NOAEL)分别为2650和2421 mg/kg·bw t。研究结果表明,甜叶菊苷M未见急性毒性、遗传毒性和短期毒性,具有较高的食用安全性。     

Thermoxidative stability of soybean oil by natural extracted antioxidants from rosemary (Rosmarinus officinalis L.)

This study aimed to evaluate the effects of rosemary extract, grown in Iran, on thermoxidative stability of soybean oil. Rosemary extract was added to soybean oil at a concentration of 3000 mg/kg and then heated at 180°C for 20 h. The oxidative stability index, total polar compounds, tocopherol content, and fatty acid profile were measured at intervals of 0, 10, and 20 h. The results compared with synthetic antioxidant tert-butyl hydroquinone at a concentration of 50 mg/kg. Rosemary extract could lead to higher oxidative stability index, lower polar compounds, more retention of tocopherols and the greatest amount of polyunsaturated fatty acids in soybean oil after 20 h of thermoxidation process. The tert-butyl hydroquinone showed weaker antioxidant activity than rosemary extract and there was no synergistic effect between them.     

3种功能食品原料提取物毒性研究及安全性评价

目的 研究3种功能食品原料(红景天、五味子和蜂花粉)醇/醇水提取物毒性并评价其安全性。方法 利用小鼠急性毒性实验、遗传毒性实验(小鼠骨髓细胞微核实验、雄性小鼠精子畸形实验)和大鼠30 d喂养实验对3种提取物的毒性进行考察。结果 小鼠对红景天、五味子和蜂花粉提取物的最大耐受量都大于20 g/(kg?bw);3种提取物在遗传毒性实验均呈阴性反应;给予大鼠5.0 g/(kg?bw)红景天、五味子、蜂花粉提取物(分别相当于成人日推荐量250倍、250倍、500倍)连续灌胃30 d,大鼠生长正常,无中毒症状、异常症状和死亡,各试食组动物体重、进食量、饲料利用率、血常规指标、常见血液生化指标、脏器重量以及病理组织学等指标与阴性对照组比较,无毒性反应。结论 红景天、五味子、蜂花粉提取物属无毒物质,无遗传毒性和长期毒性。本研究为以红景天、五味子和蜂花粉提取物为原料的功能食品开发和应用提供了一定的安全性依据。     

Oral Toxicological Studies of Pueraria Flower Extract: Acute Toxicity Study in Mice and Subchronic Toxicity Study in Rats

Kudzu has been widely used as an herbal medicine in China. The root of the kudzu is also well known as an antipyretic and analgesic in treatment of the common cold, while its flower has been used to treat alcohol intoxication, alcohol abuse, and dysentery. Pueraria flower extract (PFE) is a hot water extract derived from the flower of the kudzu, Pueraria thomsonii Benth. (Fabaceae), oral intake of which exhibits anti‐obesity properties in mice and humans. In this study, we conducted acute and subchronic toxicity studies for an evaluation of safety. In the acute study, PFE (5 g/kg body weight) was orally administered to ddY mice. For 14 d after administration, no deaths or abnormal changes were observed in general signs, body weight (BW), or food consumption, and no abnormal findings were observed in the major organs and tissues of either males or females at necropsy. The oral LD₅₀ of PFE was therefore estimated to be higher than 5 g/kg BW. In the subchronic study, PFE was mixed into the diet in place of powdered CRF‐1 and administered at concentrations of 0% (control), 0.5%, 1.5%, and 5.0% to male and female Sprague–Dawley rats for 90 d. No mortality or toxicological changes were observed during the experimental period. Blood biochemical, hematological, and urinary parameters revealed no toxicologically significant changes. Furthermore, no anatomical or histopathological changes due to PFE were observed. The no‐observed adverse‐effect‐level of PFE was thus estimated to be 5.0% in the diet (male: 3.0 g/kg BW/d; female: 3.5 g/kg BW/d).     

Safety evaluation of supercritical carbon dioxide extract of Aloe vera gel

Abstract: The gel of the Aloe vera plant has been used safely for oral and external applications. Previously, we found phytosterols derived from an extract of Aloe vera gel obtained with an organic solvent to have hypoglycemic and antiobesity effects. While developing of functional foods using Aloe vera gel, we produced an active Aloe vera gel extract (AVGE) using a supercritical carbon dioxide (CO₂) extraction procedure. In this study, we tested the safety of AVGE in vitro and in vivo. In an acute oral toxicological test in which AVGE was administered to rats at a dose of 150 mg/kg body weight, there were no deaths or apparent abnormalities at necropsy. In a 90‐d toxicity test in which rats were continuously administrered AVGE at 30 or 150 mg/kg, euthanized, and subjected to pathological examinations, no abnormalities attributable to the AVGE were found. AVGE was nonmutagenic in the Ames test and a chromosomal aberration test at concentrations of up to 5000 μg/plate and 1600 μg/plate, respectively, and in an in vivo bone marrow micronucleus test at up to 150 mg/kg/d. Practical Application: AVGE can be safely used as a functional food material.     

Relationship between dietary protein level and enzymatic changes in acute poisoning of rats with chlorfenvinphos

The acute oral toxicity (LD₅₀) of chlorfenvinphos (Chl) showed no significant difference between Wistar rats (males and females) aged 42 days kept for 30 days on 4.5% or 26%-protein diet, but a twofold difference appeared after 60 days on these diets (LD₅₀ was lower in low-protein rats) showing that a longer period of protein deficiency more increases the susceptibility of rats to the lethal action of Chl. During acute poisoning produced by intragastric administration of single convulsive dose of Chl (30 mg/kg body weight) to rats kept for 30 days on low-protein or optimal-protein diet, changes were observed in the activity of some enzymes in the serum and brain. Protein deficient diet increased the Chl-produced inhibition of acetylcholinesterase (AChE) activity in the brain; the augmented activity of aspartate aminotransferase (AspAT) and alanine aminotransferase (AlaAT) and glucosephosphate isomerase (PHI) appeared only in the serum of low-protein rats - these changes were more marked in females. Other enzymatic alterations caused by Chl were similar independently of the diets and also more evident in females; for comparison the rats received also standard Murigran diet. Activity of the brain aromatic amino acids aminotransferases (AAA) showed a decreasing trend in Chl-poisoned rats, while in the liver the activity of these enzymes rose, but chiefly in the rats receiving previously the diet with 26% of protein or standard diet. In the rats surviving the acute Chl poisoning, with the evidently seen convulsions, the activity of nearly all enzymes was normal after 14 days.     

Acute and sub-acute toxicity studies using Shemamruthaa,a modified indigenous Siddha preparation,in Sprague-Dawley rats

Shemamruthaa (SM), an indigenous herbal formulation (Hibiscus rosa sinensis flowers, Phyllanthus emblica, and pure honey) in a definite ratio was analyzed using acute and sub-acute toxicity studies in Sprague-Dawley rats. The acute toxicity study for 72 h showed no adverse effects in behavior or mortality at a dosage of 75–2,000 mg/kg of BW. The sub-acute toxicity study at 50, 100, 250, and 500 mg/kg of BW for 30 days showed transient rises in the white blood cell count, and levels of hemoglobin, free fatty acids, high density lipoproteins, and cholesterol, and a significant decrease in the blood glucose, cholesterol, triglyceride, phospholipid, and LDL levels. Other parameters remained unchanged. Changes observed were significant only at the highest dosage of 500 mg/kg BW. These results proved that the drug SM is safe and not toxic.     

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。     

Untersuchungen der Pränataltoxizität von Butenylisothiocyanat an Ratten

Prenatal toxicity study of butenyl isothiocyanate in rats Butenyl isothiocyanate (BylITC), the hydrolysis product of the glucosinolate gluconapin, present in various cruciferous vegetables and in rapeseed, was administered in oral doses of 0, 50, 100 and 150 mg/kg to pregnant rats on day 12 to 19 of gestation. Maternal toxicity was indicated by reduced body weight gain and increases in the weights of liver and kidneys. BylITC doses of 100 and 150 mg/kg caused retardation of fetal growth and ossification.     

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。