碳包铁纳米晶急性毒性实验及其对肝肾功能和血液系统的影响

目的 分析碳包铁纳米晶(CCIN)的急性毒性及其对肝肾功能和血液系统的影响.方法 经小鼠尾静脉分别注入不同剂量的CCIN粒子,观察小鼠14 d内的急性毒性反应;经大鼠尾静脉分别注入高、中、低剂量CCIN粒子及对照组注入生理盐水,分别于给药前1 d,给药后第1、3、7、14天检测大鼠肝肾功能及血常规.结果 小鼠静脉注射CCIN粒子的LD50=203.8mg/kg;当大鼠静脉注入CCIN 80mg/kg以内时,无动物死亡,肝肾功能、血液系统可能会有一过性轻微损害,但2周内一般可自行恢复.结论 CCIN粒子毒性较低,在一定剂量范围内对肝肾功能及血液系统影响不大.     

Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats

Objective To investigate the subchronic oral toxicity of silica nanoparticles(NPs) and silica microparticles(MPs) in rats and to compare the difference in toxicity between two particle sizes.Methods Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7,500, and 1,500 mg/(kg·bw·day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver,kidneys, and testis were determined.Results There were no toxicologically significant changes in mortality, clinical signs, body weight,food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.Conclusion Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.     

丹红注射液对Beagle犬的13周亚慢性毒性试验

目的研究Beagle犬连续静脉注射给予丹红注射液13周后所产生的亚慢性毒性作用。方法选取Beagle犬24只,分为4组,连续静脉给药13周,以体重、血液生化学、血液学、脏器重量、组织病理学检查为检测指标,综合评价丹红注射液对Beagle犬的毒性作用。结果丹红注射液494 mg/kg组Beagle犬体重增长明显延缓,肾功能指标(BUN、CR)明显增加,组织病理学检查表明肝脏枯否细胞增生。结论丹红注射液494 mg/kg剂量下连续静脉注射13周可致Beagle犬产生明显的肾脏和肝脏毒性。     

昆虫生长调节剂扑虱灵的毒性和诱变性观察

报道了新一代农药昆虫生长调节剂扑虱灵的急性、亚急性毒性和致突变性试验结果。扑虱灵SD大鼠经口急性LD_(50)雄性为6810mg/kg,雌性为5010mg/kg,经皮LD_(50)雌雄两性均>5000mg/kg。90天喂养亚慢性试验12500ppm组,动物体重增长率非常显著的降低,心、肝、肾、脾脏体比显著异常,肝肾功能和血红蛋白量有轻度改 ,2500ppm 组也出现毒性症状,据推算扑虱灵毒性阈剂量为250mg/kg,最大无作用剂量为50mg/kg。Ames和小鼠骨髓细胞微核试验结果均为阴性,提示扑虱灵无致突变性。     

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.     

Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous...     

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.     

过氧乙酸消毒剂的毒性试验

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（33～342）mg/kg体重消毒剂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/kg体重、1710mg/kg体重;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,统计学上均差异无显著性;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。     

CA-1对Baegle犬的毒性试验研究

目的 :观察经口给予CA - 1对Baegle犬所产生的毒性反应、中毒症状、毒作用靶器官和无毒性反应剂量 ,为CA - 1的开发研究提供毒理学依据 .方法 :CA - 1以 1 0、 3 0、 6 0 g/kg体重连续 90d经口给予Baegle犬 ,每周 6d ,停药恢复 30d的亚慢性毒性试验 .结果 :给药期和停药恢复期动物一般状况良好 ,体重增长 ,未见中毒反应 .骨髓象检查发现高剂量组晚幼粒细胞和浆细胞数均高于其他三个组 ,有显著性差异(P <0 0 5 ,P <0 0 1) .血液学、血清生化、心电图及病理组织学检查均未见由CA - 1所致的异常改变 .结论 :试验结果提示经口给予CA - 190d对Beagle犬未产生毒性反应 ,该试验结果可作为CA - 1新药开发研究的安全性参考依据 .     

In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

ObjectiveTo ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T. paniculata) ethanolic extract in Sprague Dawley rats.MethodsThe solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata.ResultsEthyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups.ConclusionsTogether our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.     

甘草浸膏的遗传毒性、致畸性及亚慢性毒性研究

目的 研究甘草浸膏对哺乳动物的遗传毒性、致畸性及亚慢性毒性,了解甘草浸膏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、小鼠精子畸形试验、Ames试验、大鼠致畸试验和亚慢性毒性试验,观察甘草浸膏的遗传毒性、致畸性及亚慢性毒性作用。结果2．50-10．0g／kgBW剂量的微核试验及精子畸变试验结果为阴性,8-5000ug／皿剂量组Ames试验结果为阴性;致畸试验研究结果表明,0．71-6．42g／kg BW剂量的甘草浸膏对大鼠不具母体毒性、胚胎毒性和致畸作用;通过亚慢性毒性试验观察到的甘草浸膏最大无作用剂量雌雄大鼠均为6．42s／ksBW。结论在本实验条件下,未观察到甘草浸膏对哺乳动物产生遗传毒性、致畸性和亚慢性毒性作用,未发现其可能存在的远期危害。     

三聚氰胺急性毒性实验的研究

目的用半数致死量来评价三聚氰胺的急性毒性。方法分别选用的清洁级健康成年雌雄两种性别的昆明小鼠各20只,在清洁级动物室隔夜禁食16h后,按霍恩氏法采用21500、10000、4640、2150mg/kg.bw的剂量经口给予三聚氰胺后,观察在14天内动物所产生的毒性反应。结果经口给予小鼠三聚氰胺,其LD50为5840mg/kg.bw。结论根据LD50数值,依据WHO外源化学物急性毒性分级标准,判定三聚氰胺毒性分级为微毒物质。     

甘草地上部分活性部位的急性毒性和长期毒性实验研究

[目的] 探索甘草地上部分活性部位对小鼠的急性毒性及大鼠的长期毒性,评价其安全性,为合理开发利用甘草地上部分资源以及临床应用提供可靠的理论依据。[方法] 甘草地上部分活性部位33.2 g/kg灌胃给予昆明种小鼠,24 h内两次（间隔5 h）经口灌胃给予受试物,持续观察14 d内小鼠的急性毒性反应;SD大鼠随机分为对照组和甘草地上部分低、中、高剂量组,按8.3、16.6、33.2 g/kg剂量连续灌胃甘草地上部分活性部位90 d,观察大鼠的一般状况,并分别于给药后45、90 d进行血液学指标检测与血清生化指标检测,给药后90 d进行大体解剖及病理学检查,观察甘草地上部分活性部位的长期毒性反应。[结果] 急性毒性实验中小鼠的一般状态、饮食、分泌物、排便未见异常,无小鼠死亡,肉眼尸检心、肝、脾等主要脏器组织未见明显异常;长期毒性实验中,各组大鼠与对照组比较,一般状况、血液学及血清生化指标未见明显差异;病理检查未见主要脏器组织形态学改变。[结论] 甘草地上部分活性部位无急性毒性和长期毒性,在治疗剂量范围内用药安全性高。     

不同单位生产的二氧化氯消毒剂急性经口毒性比较

目的对同一剂型不同单位生产的二氧化氯消毒剂急性经口毒性进行比较,为其安全使用提供科学依据。方法剂量设计采用霍恩氏法和一次最大限度试验,按要求对KM小鼠进行随机分组,将受试样品给各组动物一次灌胃,观察动物的中毒症状和死亡情况,根据试验结果计算LD50,并确定急性毒性分级。结果 3个单位生产的二氧化氯消毒剂急性经口毒性雌性动物分别为:3 160mg/kg.bw,>5 000 mg/kg.bw,3 690mg/kg.bw;雄性动物分别为:3 160mg/kg.bw,4 300 mg/kg.bw,3 690mg/kg.bw。结论按照《消毒技术规范》2002版毒性分级评价,A、C2种受试样品及B受试样品对雄性动物均属低毒物,B受试样品对雌性动物属实际无毒物。     

除虫脲亚慢性染毒对大鼠血液系统的影响

目的在研究除虫脲对大鼠的亚慢性经口毒性基础上,初步探讨染毒后对大鼠血液系统的影响。方法将80只SPF级SD大鼠按体重随机分成4组,每组20只,雌雄各半。分别用含0、25、500、10000 mg/kg除虫脲的饲料连续喂饲染毒3个月,观察各组大鼠的临床表现、摄食量、体重,实验结束时测定相关血液学指标、血液生化学指标、脏器重量、脏器系数及病理组织学改变。结果实验期间,各剂量组雌、雄鼠进食、活动、饮水基本正常,未见明显中毒表现。中、高剂量组大鼠血液红细胞计数(RBC)、血红蛋白浓度(HGB)和红细胞压积(HCT)降低,高剂量组大鼠血液平均红细胞体积(MCV)和红细胞分布宽度(RDW)升高,并且雄鼠血清总胆红素(TBIL)升高,与对照组比较,差异均有统计学意义(P0.01或0.05)。高剂量组大鼠脾脏重量和脏器系数均增高,雌鼠肝脏重量和脏器系数均增高,与对照组比较,差异有统计学意义(P0.01)。高剂量组全部动物及中剂量组部分动物脾脏明显肿大,质地较硬,颜色较深。病理检查结果显示其脾脏红髓髓窦高度扩张并充满大量红细胞,髓质内含铁血黄素沉积明显。结论除虫脲对大鼠血液系统有明显损害,长期接触可能会导致脾脏肿大、机体出现慢性溶血性贫血表现。     

皂荚提取物对大鼠亚慢性毒性的实验研究

目的对皂荚提取物的亚慢性毒性进行研究。方法以Wistar大鼠为实验动物,每天以皂荚提取物0.180、0.090、0.045g/kg的剂量连续灌胃12周,停药2周,分别在第12周、14周末取血及主要脏器,系统研究皂荚提取物对大鼠生长性能、组织病理变化、血常规、血液生化指标的影响。结果皂荚提取物长期灌胃给药大鼠,大鼠无严重毒性反应,仅有体重增长减慢,WBC、HGB、PT、GLU增高,ALT减低,光镜下各组织病理学观察未见异常改变。结论皂荚提取物对大鼠亚慢毒性试验仅有部分毒性反应及延迟毒性反应,停药后其毒性作用大部分可逆。     

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...     

新型多酸化合物NCW-6的毒理学安全性评价

目的：评价具有抗病毒活性的多酸化合物NCW-6的安全性,阐明NCW-6的毒性及潜在的危险。方法：依据新药临床前毒理学评价方法进行NCW-6经口急性毒性实验和致畸敏感期实验。急性毒性实验中,将健康的昆明小鼠随机分为7组,每组10只,雌雄各半;给药剂量最低为4 000.00 mg•kg^-1、最高为6 000.00 mg•kg^-1,组距为400.00 mg•kg^-1;经口灌胃1次给药,观察给药后14 d小鼠的中毒表现,记录死亡数,用Bliss法计算半数致死剂量(LD_^50);致畸敏感期实验中,孕鼠随机分为5组,每组至少20只;给药组剂量分别为91.7、366.8和1 467.5 mg•kg^-1;阴性对照组给予5 mL•kg^-1蒸馏水,于受孕后第6～15天连续给药,每天灌胃1次;阳性对照组于妊娠第10天一次灌胃给予130 mg•kg^-1的维甲酸;各组孕鼠于孕期第20天颈椎脱臼处死,检查受孕情况,记录黄体数、活胎数、死胎数和吸收胎数等,做胎鼠一般外观检查（体质量、身长、尾长和外观有无异常）,取胎鼠雌雄各半行内脏形态检查和骨骼形态检查。结果：急性毒性实验,NCW-6的LD₅₀为5 869.9 mg•kg^-1,属于无毒化合物。致畸敏感期实验,3 个给药组孕鼠的体质量和增重与阴性对照组比较差异无统计学意义( P>0.05),各给药组胎鼠的平均体质量、身长、尾长以及平均胎质量、窝质量与阴性对照组比较差异无统计学意义( P>0.05),各给药组胎鼠外观、内脏畸形率、骨骼畸形率与阴性对照组比较差异无统计学意义( P>0.05)。结论：NCW-6属于无毒化合物,且对大鼠无致畸作用,具有深入研究开发的价值。     

金粉蕨素急性毒性实验

目的　观察金粉蕨素 (Onychin)的毒性 ,为评价其毒性等级以及拟定临床安全剂量提供依据。方法　采用急性毒性实验方法 ,以一次大剂量给小白鼠灌胃金粉蕨素 ,连续观察小鼠行为活动等指标和毒性反应程度 ,并在实验结束时处死小白鼠进行剖检 ,以获得金粉蕨素初步毒性资料。结果　实验连续观察 14d ,小鼠无明显行为异常 ,也未出现死亡 ,求不出LD50 。结论　本实验设定的最高剂量 6 40mg/kg及其以下剂量对小白鼠均无明显毒性作用 ,提示在临床和药理实验上应用金粉蕨素是安全的     

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day,Repeated Dose Study in Rats

Objective

The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).