过氧乙酸消毒剂的毒性试验研究

目的 对一元包装过氧乙酸消毒剂的急性和亚急性毒性进行研究,为其安全使用提供依据。方法 依据卫生部《消毒技术规范》(2002年版) 进行试验：(1)急性毒性试验：选用健康Wistar大鼠60只,随机分组,一次性经口灌胃不同剂量消毒剂,观察大鼠的中毒症状和死亡情况,计算半数致死量（LD50）。(2)亚急性毒性试验：选用健康Wistar大鼠40只,随机分为3个剂量组和阴性对照组,连续经口灌胃33-342mg/kg BW消毒剂28d,试验结束后检测大鼠体重、脏/体比值、血液学指标及血清生化指标,并进行病理组织学检查。结果 对雌性、雄性大鼠LD50分别为1470mg/kgBW、1710mg/kg BW;大鼠亚急性试验各剂量组体重、血液学指标、生化指标、脏/体比值,与阴性对照组比较,统计学上均无显著性差异;大体解剖观察未见异常,未见与受试物有关的病理组织学改变。结论 该过氧乙酸消毒剂对大鼠急性经口毒性为低毒级,且在本试验剂量范围内,未观察到明显的亚急性经口毒性。     

天麻软胶囊的毒性研究

目的研究天麻软胶囊的毒性。方法采用最大耐受剂量（MTD）试验和大鼠30d喂养试验，分别观察了麻软胶囊的急性毒性和亚急性毒性。结果天麻软胶囊对小鼠经口MTD大于15000mg／kg；大鼠30d喂养试验未观察到中毒表现，天麻软胶囊各剂量组动物体重，食物利用率，血液学和血液生化学指标值，各脏器的脏／体比值与空白对照组比较差异均无显著性（P〉0．05）。主要脏器在外观形态和组织学上均无异常变化。结论天麻软胶囊对动物的生长发育，造血功能，肝肾功能，器官组织均无明显毒性。     

中藏药新方“邦然姆散”的毒理学研究

“邦然姆散”的急性毒性：小白鼠半数致死量（LD50）为腹腔给药LD50＝9.16g/kg，灌胃给药LD50=146.6g/kg。亚急性毒性：选用大鼠分高、中、低三个剂量组，口服给药（灌胃），连续给药4周。观察指标有肝功能测定（GPT）、肾功能（BUN）、外周血细胞计数、体重增长情况及心、肝、脾、肺、肾、胃、肠等组织学镜检，并与对照组比较，结果说明“邦然姆散”毒性很小，与对照组比较无显著性差异。     

苦瓜醇提取物亚急性经口毒性研究

目的评价苦瓜醇提取物的经口亚急性毒性。方法将苦瓜醇提取物按1.25、2.50和5.00g/kg·bw剂量给大鼠连续灌胃30d,测定体重、进食量,计算食物利用率,实验末采血测定血象和血生化指标。结果苦瓜醇提取物各剂量对大鼠体重增长、总进食量及食物利用率无显著影响(P0.05)。与相应对照组比较,雄鼠1.25、2.50g/kg·bw剂量组血肌酐显著降低,雌鼠三个剂量组总蛋白均较对照组降低,其中2.50、5.00g/kg·bw剂量组总蛋白降低有显著性。各剂量对其他血液学、血生化指标、肝脏、脾脏、肾脏和雄鼠睾丸、雌鼠卵巢的脏体比值无显著影响。大体解剖和组织病理检查未见与样品有关的异常改变。结论苦瓜醇提取物给大鼠喂养30d,2.50g/kg·bw以上剂量可引起雌性大鼠总蛋白降低,高达5.00g/kg·bw的剂量未产生其它可观察到的毒副作用。     

溪黄草的亚慢性毒性研究

目的研究溪黄草的亚慢性毒性。方法选用80只健康SD大鼠随机分为4组,雌雄各半,分别经口灌胃给予0.000、0.625、1.250、1.875 g/kg剂量的溪黄草浸膏连续90 d,观察动物生长情况,试验中、末期对动物的血液学和血清生化指标进行检测,试验末计算动物主要脏器的脏体比值并进行组织病理学检查。结果试验期间动物无死亡。试验末各剂量组动物体重、增重、进食量、食物利用率、脏器绝对质量及脏体比值与对照组比较,差异无统计学意义(P0.05)。在试验的中、末期各剂量组动物血液学和血清生化检测指标均在本室正常值范围内,与对照组比较差异无统计学意义(P0.05)。大体解剖观察和病理组织学检查也未见与受试物相关的异常改变。其最大未观察到有害作用剂量为1.875 g/kg。结论在本实验室条件下,未观察到溪黄草浸膏对SD大鼠有明显的毒副作用。     

蝙蝠蛾参鹿片亚急性毒性安全性评价

目的研究蝙蝠蛾参鹿片的急性和亚急性毒性,为其食用的安全性提供试验依据。方法急性毒性试验:ICR小鼠雌雄各10只,采用最大耐受剂量法经口灌胃,观察14 d。亚急性毒性试验:Wistar大鼠雌雄各40只,随机分为低、中、高剂量组及对照组4组,每组雌雄各10只,连续喂养30 d,对各剂量组大鼠各项指标进行观察,并对数据进行统计分析。结果急性毒性试验:雌、雄性小鼠MTD 15. 2 g/(kg·BW),属无毒级。亚急性毒性试验:各剂量组与对照组大鼠在试验过程中均生长良好,各剂量组的增重、食物利用率、进食量、脏/体比、血液学指标、血液生化指标等指标与对照组比较,差异无统计学意义,主要器官未见病理改变,未观察到最大有害作用剂量。结论本试验条件下,蝙蝠蛾参鹿片具有较好的安全性。     

DEHP对子代大鼠血液学变化的影响

目的 观察DEHP对子代大鼠血液学变化的影响.方法成熟Wistar大鼠,在妊娠期7-16d,每天经口灌胃给予DEHP高(500mg/kg)、低(250mg/kg)三剂量组,对照组经口灌胃给予照物玉米油.检测子代大鼠血液学指标.结果 子代大鼠血液学中Hb、RBC、WBC及Lym、Mon、Neu、Eos、Bas指标与对照组相比,差异无统计学意义(P＞0.05).结论 在本次试验中未见到DEHP对子代大鼠血液学变化的明显影响.     

宫血净胶囊毒理学研究

目的观察宫血净胶囊的急性毒性和长期毒性。方法（1）急性毒性试验：昆明种小鼠40只,用随机数字表法分成2组,每组20只,实验组用宫血净胶囊粉,采用最大给药法灌胃给药;对照组用等体积蒸馏水灌胃观察14d,记录小鼠的体重及毒性反应;（2）长期毒性试验：Wistar种大鼠80只,用随机数字表法分成4组,每组20只,3个实验组用宫血净胶囊生药81．6、49．0、24．5g／kg连续灌胃3个月;对照组用等体积蒸馏水灌胃停药14d后分另q称量大鼠体重、计算脏器系数、血液学指标、血液生化学指标并做病理组织学检查。结果宫血净胶囊的最大给药量为生药450g／kg,未见小鼠行为异常,体重增长正常。长期毒性试验：给药期间各组大鼠毛色、活动、二便、摄食、饮水与对照组比较差异无统计学意义（P〉0．05）;但大剂量组部分大鼠体重、血液学、血液生化学指标和脏器系数有异常变化,停药后,上述异常变化指标均恢复正常。给药期和恢复期重要脏器病理组织检查均未发现明显异常变化。结论宫血净胶囊的最大给药量为生药450g／ks;长期大剂量灌胃给予宫血净胶囊对大鼠有一定毒性,但停药后均恢复正常。该药按使用剂量和疗程给药是安全的。     

芎归滴丸毒理学研究

芎归滴丸急性毒性试验，采用ICR系小鼠，ig给药LD50为1716.88mg／kg体重，ip给药LD50为526．9mg／kg体重，死亡动物的内脏肉眼未见异常改变；长期毒性试验，Wistar大鼠ig剂量为85．5、42．75、21．37mg／kg·d（人用量的50、25及12．5倍），共计给药90d，对大鼠一般情况的观察和对大鼠脏器系数、血象、肝肾功能、血糖的影响以及组织学研究（系统尸检和病理组织学）与对照组相比无显著差异，脏器系数比值正常，未发现毒性反应。     

二月桂酸二丁基锡对大鼠妊娠及对子代毒性作用

目的通过染毒观察二月桂酸二丁基锡（Dibulytin Dilaurate,简称DBTD）对子代胎鼠形态、体重、性别及骨骼发育状的影响。方法按随机分组的原则,将大鼠分为对照组和染毒组,对照组用玉米油,染毒组用DBTD玉米油溶液,浓度分别是2.5 mg/kg体重（1/72 LD50）、10 mg/kg体重（1/18 LD50）和20 mg/kg体重（1/9 LD50）,采用灌胃的方式进行染毒,6 d/周,每天同一时间进行染毒,共计染毒48 d。染毒第五周后,各组大鼠与正常雄性大鼠以1：1的比例合笼,合笼期间不染毒,每只雌鼠查到阴栓为妊娠第0天,继续染毒,于妊娠第18天处死取胎鼠。结果1/18 LD50及1/9LD50剂量组中活胎及胎儿的体重明显下降,1/18 LD50剂量组胎儿的性别开始发生明显的变化（P〈0.05）。结论DBTD染毒对大鼠每胎存活数、胎重、胎儿的形态及性别有影响,有一定的生殖毒性。     

补骨脂素、异补骨脂素和补骨脂酚急性毒性的性别差异研究

[目的] 探究补骨脂素、异补骨脂素和补骨脂酚对小鼠急性毒性的性别差异。[方法] 补骨脂素给药剂量为雌性（1 125、843、633、475、356 mg/kg）、雄性（633、475、356、267、200 mg/kg）,异补骨脂素给药剂量为雌性（404、343、292、248、210 mg/kg）、雄性（317、292、269、248、229 mg/kg）,补骨脂酚雌、雄剂量均为2 000、1 765、1 500、1 200、1 020 mg/kg。一次性灌胃给予受试药,连续观察并记录14 d小鼠的毒性反应、体质量和死亡情况,应用SPSS统计学软件,采用Probit回归法计算半数致死量（LD₅₀）和95%可信区间。[结果] 给药后小鼠毒性反应主要表现为抽搐、四肢强直,部分动物口眼周围有分泌物,剂量越高反应越明显。与对照组比较,补骨脂素、异补骨脂素给药组随给药剂量增大,小鼠体质量呈现降低趋势。补骨脂素雌性小鼠的LD₅₀为514.35mg/kg,雄性小鼠LD₅₀为421.37 mg/kg,雌性小鼠LD₅₀值比雄性高出22%。异补骨脂素雌性小鼠LD₅₀为258.02 mg/kg,雄性小鼠LD₅₀为255.26 mg/kg。补骨脂酚雌性小鼠LD₅₀超出2 000 mg/kg,雄性小鼠LD₅₀为1 679.4 mg/kg。[结论] 补骨脂素和补骨脂酚对小鼠的急性毒性存在一定性别差异,但无统计学意义。     

Effects of melatonin on changes in cognitive performances and brain malondialdehyde concentration induced by sub–chronic co–administration of chlorpyrifos and cypermethrin in male Wister rats

ObjectiveTo evaluate the ameliorative effect of melatonin on sub-chronic chlorpyrifos (CPF) and cypermethrin (CYP)-evoked cognitive changes in male Wistar rats.MethodsFifty adult male Wistar rats, divided into five groups of ten rats each, were used for the study. Groups 1 and II were given distilled water and soya oil (2 mL/kg) respectively. Group III was administered with melatonin at 0.5 mg/kg only. Group IV was administered with CPF [7.96 mg/kg (1/10th LD₅₀)] and CYP [29.6 mg/kg (1/10th LD₅₀)], and Group V was administered with CPF [7.96 mg/kg (1/10th LD₅₀)] and CYP [29.6 mg/kg (1/10th LD₅₀)] 30 min after melatonin (0.5 mg/kg). The regimens were administered by gavage once daily for 12 weeks. Thereafter, cognitive performances were determined and the brain was evaluated for malonaldehyde concentration.ResultsCPF and CYP induced cognitive deficits and increased brain malonaldehyde concentration, which were all ameliorated by melatonin.ConclusionCognitive deficits elicited by CPF and CYP was mitigated by melatonin due to its antioxidant property.     

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na) and to determine the point of departure(POD), which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome para...     

Toxicity effects of water extracts of H olothuria atra Jaeger in mice

ObjectiveTo determine lethal median dose (LD₅₀) and histopathological toxicity of water extract of Holothuria atra (H. atra) in mice.MethodsThe behavioral changes, mortality and histopathology examination on liver were assessed in mice 14 d after the administration (i.p.) of H. atra water extract. Seven doses (10, 20, 30, 50, 100, 150 and 200 mg/kg) of H. atra were used. The control group was treated with normal saline.ResultsIn the acute study in mice, the water extracts of H. atra caused dose-dependent general behavior adverse affects and mortality. The main behavioral sign of toxicity was hypoactivity, noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death. Mortality increased with increasing doses, the calculated LD₅₀ was 41 mg/kg in mice. The liver toxicity was confirmed by histopathological examination, which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups. High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining, massive cytoplasm, pyknotic, karyorhexis and karyolytic nuclei (necrosis of hepatocytes). Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei, with granular cytoplasm.ConclusionsBecause of the relatively low LD₅₀ value in the acute study in mice, it may be concluded that the H. atra water extract is toxic.     

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective: To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine(TET) in female BALB/c mice. Methods: The median lethal dose(LD_(50)) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET(30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result: LD_(50) was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET(P0.05). In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group(P0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions: The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.     

富含DHA的鱼油制剂遗传毒性和亚急性毒性研究

目的研究富含DHA的鱼油制剂对哺乳动物的遗传毒性和亚急性毒性的影响,了解富含DHA的鱼油制剂可能存在的远期危害和毒性作用。方法采用小鼠骨髓细胞微核试验和大鼠亚急性毒性试验,观察3.33g/kg.BW、1.67g/kg.BW和0.83g/kg.BW剂量的富含DHA的鱼油制剂对小鼠骨髓细胞微核率的影响及对产生亚急性毒性作用。结果通过小鼠骨髓细胞微核试验未观察到富含DHA的鱼油制剂有明显的诱导骨髓细胞形成微核的作用;通过大鼠亚急性毒性试验未观察到与受试物有关的毒性作用的最大剂量。结论实验未观察到富含DHA的鱼油制剂对哺乳动物产生遗传毒性和亚急性毒性作用,也未发现其可能存在的远期危害,有关其在其它方面的毒理学作用还有待进一步研究。     

护肝中药“五田保肝液”急性毒性实验研究

[目的]明确护肝中药"五田保肝液"的用药安全剂量范围,为临床用药安全提供实验依据。[方法]依据中药、天然药物急性毒性实验研究技术指导原则设计实验,观察小鼠急性毒性反应,并记录其死亡情况,确定急性毒性实验中五田保肝液半数致死量(LD50)或最大给药量。[结果]半数致死量实验中未测得LD50,最大给药量实验获得小鼠最大给药量折合生药228 g/(kg·d),相当于成人临床用药量的120倍。[结论]护肝中药"五田保肝液"急性毒性反应低,临床常用药物剂量安全可靠。     

细辛脑注射制剂异常毒性检查标准研究

目的测定细辛脑注射制剂静脉给药的小鼠LD50值,同时起草本品异常毒性检查标准。方法采用加权回归机率单位法(Bliss法)对小鼠静脉给药测定LD50值,同时按照《中国药典》2010年版要求确定异常毒性检查限值,起草异常毒性标准。结果测定细辛脑注射制剂的小鼠LD50为51.9-153.1 mg/kg,为标准中拟增加异常毒性检查项,异常毒性检查项的限值建议定为15 mg/kg,按此限值检查结果符合规定。结论细辛脑注射制剂毒性较大,各企业生产工艺不同毒性也差异较大,为减少本品临床使用不良反应的发生,应在其质量标准中增加异常毒性检查项。     

茶多酚急性、慢性毒性实验研究☆

ObjectiveThe study was to observe the acute and chronic toxicity of Tea Polyphenols(TP).Methodsthe mice were divided into five groups and TP was given orally for 7 days.The method of Bliss was used to determine the LD₅₀ of the TP.The rats was divided into control group,TP high dosage group,TP middle dosage group and low dosage group(0.4,0.6,0.8g/kg^.d^-1)to observe the chronic toxicity.ResultThe LD₅₀ of TP is 2.499g/kg.The rats have showed no toxicity reaction in weight,blood,the internal organs,liver and kidneys function after the using of the drug.ConclusionThe TP has low toxicity,the dosage of 0.8g/kg.d^-1 in rat is equivalent to 100 times of the dosage used in clinic for an adult.It indicates that the clinical using of TP is safe.     

脂肪酸合成酶抑制剂胖大海提取物对营养性肥胖大鼠的减肥作用

目的研究胖大海提取物对营养性肥胖大鼠的减肥作用。方法利用高脂营养饲料制备大鼠肥胖模型,观察胖大海提取物10、30和100 mg/kg 3个不同剂量对肥胖大鼠的减肥效果及对肝脏脂肪酸合成酶的影响。于实验结束时测定体质量、机体脂肪、食物消耗量、血清生物化学指标及肝脏脂肪酸合成酶活性指标,实验持续45 d。结果胖大海提取物100 mg/kg组大鼠体脂显著低于模型对照组(P<0.05);实验期间各剂量组大鼠的食物消耗量均低于模型对照组,且100 mg/kg组与模型对照组相比差异有统计学意义(P<0.05)。给予胖大海提取物组大鼠肝脏脂肪酸合成酶(fatty acid synthase,FAS)活性低于模型对照组,其中胖大海提取物30和100 mg/kg,2组与模型对照组相比差异有统计学意义(P<0.05)。结论胖大海提取物可抑制脂肪酸合成酶活性,抑制肥胖大鼠摄食量。