三氯异氰尿酸原药急性毒性和蓄积毒性试验

目的研究三氯异氰尿酸原药对大鼠的急性毒性和小鼠的蓄积毒性。方法选用sD大鼠40只,以三氯异氰尿酸原药混悬液按215、464、1000、2150mg／kg4个剂量组,一次性灌胃染毒。选用SD大鼠10只按2150mg／kg剂量一次性涂皮染毒。选用家兔进行急性眼刺激和皮肤刺激。另选昆明种小白鼠50只,采用剂量固定的20天蓄积法经口灌胃染毒,观察动物的死亡数。结果三氯异氰尿酸原药急性经口毒性中毒表现为少动、伏卧、呼吸困难等症状,雌性大鼠LD50为1100mg／kg,雄性大鼠LD50为794mg／kg。急性经皮毒性LD50大于2150mg／kg。眼刺激积分指数（I．A．O．L）为96,急性皮肤刺激强度分值为5．8。蓄积毒性试验小鼠低剂量组无死亡,中高剂量组死亡数有剂量反应关系。结论三氯异氰尿酸原药急性经口、经皮属于低毒级,重度眼刺激及中等皮肤刺激,于小鼠体内有中等蓄积作用。     

二甲酚草胺原药的大鼠亚慢性毒性

按GB15670—1995《农药登记毒理学试验方法》进行二甲酚草胺原药大鼠亚慢性经口毒性试验,设60、30、15 mg/kg二甲酚草胺原药剂量组和对照组。染毒14 d后60mg/kg组动物出现精神萎靡、被毛蓬松等中毒症状,雄性动物28 d后体重降低(P0.05);60 mg/kg组动物血生化中AST活性明显增高(P0.05);病理检查发现60 mg/kg组动物肝脏、肾脏、脑组织有一定程度的病理改变;30 mg/kg组动物肾、脑组织也见病理改变但程度较轻;15 mg/kg组各指标均未见明显异常。二甲酚草胺原药对雌雄性大鼠亚慢性经口毒性最大无作用剂量均为15 mg/kg。     

戊唑醇原药诱变性与亚慢性经口毒性的实验研究

目的探讨戊唑醇原药的诱变性及亚慢性毒性作用。方法按照我国GB15670-1995《农药登记毒理学试验方法》要求进行。结果 62.5~250μg/皿的Ames实验结果为阴性;染毒14.7~294 mg/kg的剂量组微核试验结果为阴性;染毒36.8~147 mg/kg的剂量组的小鼠睾丸精母细胞染色体畸变率未见增加;亚慢性经口毒性试验高剂量组(71.7mg/kg.bw/d)的雄鼠在染毒中后期出现精神不振、少动、被毛蓬松、会阴部污秽等中毒症状。结论戊唑醇原药无明显致突变作用。戊唑醇原药有一定的蓄积毒性作用,可引起潜在的慢性中毒,主要的毒作用部位是肝脏与血液系统。戊唑醇原药SD雌、雄大鼠亚慢性(90 d)经口试验未观察到有害效应的剂量水平分别为16.3、8.0 mg/kg.bw/d。     

杀虫磺原药大鼠亚慢性毒性研究

目的研究杀虫磺原药对大鼠亚慢性经口毒性,探讨其亚慢性毒性的阈作用剂量和最大无作用剂量。方法雌鼠剂量以135、67.50、22.50mg/kg,雄鼠剂量以157.5、78.752、6.25mg/kg,连续90d给予杀虫磺原药,观察动物的一般状况,体重增长及血液、生化指标并解剖进行病理检查。结果杀虫磺原药高剂量组动物,染毒8周后出现被毛蓬松、活动减少、体重减轻等症状;染毒结束后血清中谷草转氨酶（AST）升高,肝及雄鼠肾脏器系数增大,组织病理学检查显示：肝细胞明显浊肿,胞浆疏松,汇管区可见慢性炎细胞浸润。中剂量组动物染毒结束后谷草转氨酶（AST）显著升高,雄鼠肾脏器系数增大;肝细胞病变相同,但程度较轻。低剂量组动物一般行为、体重增长、尿常规、血液学、血液生化学、脏器重量、脏器系数及病理学检查均未见变化。结论本实验条件下,初步确定大鼠90d亚慢性经口最大无作用剂量,雌性为22.50mg/kg;雄性为26.25mg/kg。     

硝基胍的毒性研究

目的对硝基胍的毒性进行研究,为制订卫生标准提供依据.方法包括急性毒性试验、蓄积毒性试验及亚慢性毒性试验.结果硝基胍大鼠经口LD50为8 066 mg/kg,小鼠经口LD50为10 044 mg/kg,蓄积系数大于5.3.亚慢性毒性试验中,高剂量组雄性大鼠在染毒第3周和第8周,体重有明显的负增长(P＜0.05);高剂量组雄性大鼠睾丸脏器系数明显高于对照组(P＜0.05);红细胞免疫功能测定结果显示,中、高剂量组大鼠红细胞受体花环率分别为10.00±2.37和7.50±2.66,明显低于对照组(P＜0.05,P＜0.01).其余各项指标未见明显改变.结论硝基胍属于微毒级毒物,轻度蓄积,亚慢性毒性试验对动物有一定的影响.     

硼硒联合对大鼠的急性毒性和亚慢性毒性研究

为了解硼硒联合毒性作用 ,首先选用 12 0只成年Wistar大鼠 ,雌、雄各半 ,参照霍恩氏 (Horn)法 ,对大鼠进行了急性毒性实验 ,其亚硒酸钠与四硼酸钠配比为 :雄性大鼠 1∶10 0 ,雌性大鼠 1∶2 15。再进行亚慢性毒性实验 ,选用 12 0只Wistar大鼠 ,雌、雄各半 ,分为 4个染毒剂量组 (1 10LD50 、1 2 0LD50 、1 5 0LD50 、1 10 0LD50 )和蒸馏水对照组。各组动物经口灌胃染毒 90天。结果 :亚硒酸钠与四硼酸钠联合作用表现为拮抗作用 ,急性毒性LD50 (♂ ) =172 7 10mg kg ,LD50 (♀ ) =1717 94mg kg。在整个亚慢性实验期内 ,1 10LD50 组雌雄大鼠在实验 8周后体重开始减少 ,至实验终止减少更明显。雄性大鼠 1 10LD50 组和 1 2 0LD50 组动物血清谷丙转氨酶活性比对照组增加非常显著 (P <0 .0 1)。其它血液生化指标无明显规律性变化。组织病理学检查可见雌、雄动物 1 10LD50 组均有肝细胞水肿发生。结果表明最大无作用剂量雄性大鼠为 1 5 0LD50 ,雌性大鼠为 1 2 0LD50 。亚硒酸钠对雌、雄性大鼠最大无作用剂量分别为 397和 34 2 μg kg,四硼酸钠 (按无水四硼酸钠计 )分别为 6 1 5和 2 4 6mg kg,均大于硼硒联合使氟中毒大鼠康复效果较好的剂量 (亚硒酸钠为 40 μg kg ,四硼酸钠为 18 6mg kg)。提示硼硒联合对氟中毒大     

3-硝基-1,2,4-三唑-5-酮对大鼠亚急性毒性实验研究

目的 探讨新型含能材料3-硝基-1,2,4-三唑-5-酮(3-nitro-1,2,4-triagol-5 -one,NTO)的亚急性经口毒性效应,为亚慢性毒性或慢性毒性实验提供剂量设定依据.方法 按照《化学品毒性鉴定技术规范》,选择健康成年SD大鼠44只,雌雄各半,随机分为对照组、NTO 250、500和1 000 mg/kg染毒组.染毒组用NTO-植物油混悬液灌胃(10 ml/kg),对照组用等量植物油灌胃,经口连续灌胃28 d.观察大鼠体质量、脏/体比;分析红细胞、白细胞计数等10项血常规指标;血清天冬氨酸转氨酶(AST)、尿素氮、肌酐(Cr)水平等12项生化指标.取心、肝、脾等7种脏器进行病理组织学检查.结果 中、高剂量组雄性大鼠体质量增长缓慢,睾丸/体比值低于对照组.高剂量组雄性大鼠平均红细胞体积升高,雌性大鼠淋巴细胞百分比降低,低、中、高剂量组血清AST活力明显升高,高剂量组血清Cr升高,与对照组比较差异均有统计学意义(P＜0.05).与对照组比较,中、高剂量组大鼠肝脏、肾脏和睾丸病理组织学检查显示发生病变.结论 NTO对大鼠肝脏、肾脏和睾丸有一定的损伤作用.     

2,4-二氯苯氧乙酸亚慢性毒性实验研究

目的 探讨2,4-二氯苯氧乙酸(2,4-D)的亚慢性毒性.方法 选择无特定病原体级健康成年SD大鼠80只,雌雄各半,随机均分为对照组和61.50、20.50、10.25 mg/kg 3个2,4-D染毒组.连续经口灌胃染毒90 d,实验期间观察动物一般情况,记录每周体质量,结束时检测血、尿常规,血生化,脏器系数及病理变化.结果 ①61.50 mg/kg组动物出现明显中毒症状,染毒14、18 d时雌性动物体质量增长缓慢;血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶活力升高(P＜0.05),且雄性动物尿素氮亦升高(P＜0.05),尿中蛋白和红细胞阳性;肝组织出现明显的病理改变;②20.50mg/kg组动物出现中毒症状,染毒14 d时雌性动物体质量增长缓慢,尿蛋白和红细胞阳性;③10.25 mg/kg组各项检测指标均未见明显异常.结论 2,4-D大鼠经口毒性效应主要表现为对肝脏和肾脏的毒性作用.本实验条件下,供参考的经口慢性毒性实验适宜剂量范围为0.21 ～ 10.25 mg·kg-1·d-1.     

环丙唑醇的急性和亚慢性毒性研究

为探讨环丙唑醇对大鼠的急性和亚慢性经口毒性，在急性试验中设低（215 mg/kg）、中（464 mg/kg）、次高（1 000 mg/kg）和高（2 150 mg/kg）4个剂量染毒组；在亚慢性试验中设对照组和低、中、高剂量染毒组，雌/雄性大鼠实际染毒剂量分别为1.38/1.18、7.93/7.18、47.70/48.60 mg/kg。结果显示，大鼠环丙唑醇急性经口半数致死剂量（LD50）为316 mg/kg，亚慢性经口染毒大鼠部分血液指标和肝组织病理发生改变。环丙唑醇最大无作用剂量（NOAEL）分别为1.38/7.18 mg/kg（雌/雄），长期暴露对动物肝脏具有毒性作用。     

溴虫腈亚慢性毒性研究

按照GBl5670-1995<农药登记毒理学试验方法>,以25、50、125 me/kg剂量的溴虫腈染毒大鼠,以观察其亚慢性毒性.结果 125 mg/kg剂量组动物出现明显中毒症状,丙氨酸氨基转移酶(ALT)及白细胞总数(WBC)升高,肝脏脏器系数增大,肝脏病理组织学检查可见明显的组织形态学改变.提示溴虫腈可引起大鼠肝脏损伤,大鼠经口亚慢性最大无作用剂量为25 mg/(kg·d).     

Antimony toxicity

Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.     

Zinc toxicity

Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.     

Lead toxicity

Lead is one of the oldest known and most widely studied occupational and environmental toxins. Despite intensive study, there is still vigorous debate about the toxic effects of lead, both from low-level exposure in the general population owing to environmental pollution and historic use of lead in paint and plumbing and from exposure in the occupational setting. The majority of industries historically associated with high lead exposure have made dramatic advances in their control of occupational exposure. However, cases of unacceptably high exposure and even of frank lead poisoning are still seen, predominantly in the demolition and tank cleaning industries. Nevertheless, in most industries blood lead levels have declined below levels at which signs or symptoms are seen and the current focus of attention is on the subclinical effects of exposure. The significance of some of these effects for the overt health of the workers is often the subject of debate. Inevitably there is pressure to reduce lead exposure in the general population and in working environments, but any legislation must be based on a genuine scientific evaluation of the available evidence.     

Digitalis toxicity

Digitalis toxicity is a frequently encountered clinical problem. Drug interactions leading to digitalis toxicity are very common. Within this group, the interaction of digitalis and verapamil is increasingly recognized as an important cause of digitalis toxicity. The use of digoxin-binding antibodies represents a significant advance in the treatment of this problem and can be lifesaving in the setting of massive overdose. A case report of digitalis toxicity and a review of this problem and its treatment are presented.     

蒜氨酸口服液的毒性试验研究

[目的]对蒜氨酸口服液的毒性进行了试验研究。[方法]采用小鼠急性毒性试验、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30d喂养试验。[结果]该口服液对雌雄小鼠LD50均大于20g／kg，属无毒物质；Ames试验、微核试验和精子畸形试验结果均为阴性；对大鼠30d喂养试验各项指标均未产生明显影响。[结论]在本次试验条件下，该口服液安全无毒。     

芽孢菌肽的急性毒性和遗传毒性研究

目的研究芽孢菌肽的急性毒性和遗传毒性。方法以急性毒性试验、骨髓细胞微核试验和睾丸染色体畸变试验评估芽孢菌肽的急性毒性和遗传毒性。结果芽孢菌肽雌、雄小鼠急性经口LD50值及95%CI分别为5 010(3 080~8 140)mg/kg BW和7 940(4 670~13 500)mg/kg BW。骨髓细胞微核率为(2.2±0.4)‰~(2.6±0.6)‰,睾丸染色体畸变率为(0.20±0.45)%~(0.40±0.55)%,与溶剂对照相比,差异均无统计学意义(P值均0.05),结果均为阴性。结论在试验条件下,芽孢菌肽属实际无毒级,未见遗传毒性。