乙酰甲胺磷毒性与代谢研究

一、毒性研究1.急性毒性试验: 用Wistar大鼠,按流动平均数法测得98％乙酰甲胺磷经口LD_(50)为825mg/kg(雌雄混合),雄鼠经皮LD_(50)为4,640mg/kg,65％原粉对雄或雌大鼠经口LD_(50)均为1,470mg/kg。根据三部会议对农药急性毒性的分级标准,乙酞甲胺磷属低毒类。从有效成分65％的乙酞甲胺磷LD_(50)比较,说明工业品中杂质的急性毒性低于乙酞甲胺磷本身,与国外报道一致。     

间苯二甲酰丙烯亚胺致突变作用的研究

本文报道间苯二甲酰丙烯亚胺对小鼠和大鼠的急性经口毒性、对家兔皮肤和眼结膜的毒性,及其致突变作用。结果小鼠LD_(50)为694.2mg/kg(雌)、593mg/kg(雄);大鼠LD_(50)为1230.3mg/kg。对家兔眼结膜有严重的刺激作用,但对皮肤无反应。Ames试验阳性,染色体畸变率和微核率明显增高,表明该品有致突变作用。     

骆驼蓬有效成分两种给药途径的毒性比较研究

目的:开展骆驼蓬有效成分骆驼蓬碱、去氢骆驼蓬碱两种给药途径的小鼠急性毒性比较研究。方法:采用Bliss法测定小鼠经口灌胃和静脉注射给药骆驼蓬碱、去氢骆驼蓬碱的LD_(50),同时观察小鼠中毒症状及中毒反应的起止时间。结果:骆驼蓬碱经口灌胃的LD_(50)及其95%可信区间为118.9 mg/kg(105.8~133.9 mg/kg),静脉注射的LD_(50)及其95%可信区间为80.3 mg/kg(60.6~146.1 mg/kg);去氢骆驼蓬碱经口灌胃的LD_(50)及其95%可信区间为250.3 mg/kg(210.0~293.3 mg/kg),静脉注射的LD_(50)及其95%可信区间为74.1 mg/kg(67.2~83.1 mg/kg)。小鼠经口灌胃给药时,骆驼蓬碱小鼠死亡时间早于去氢骆驼蓬碱小鼠死亡时间;小鼠静脉注射给药时,去氢骆驼蓬碱小鼠死亡时间早于骆驼蓬碱小鼠死亡时间。结论:小鼠经口灌胃给药骆驼蓬碱毒性去氢骆驼蓬碱毒性,小鼠静脉注射给药去氢骆驼蓬碱毒性骆驼蓬碱毒性。     

数种荧光素衍生物的小鼠急性毒性实验半数致死量的测定

本文报道8种荧光素的衍生物的半数致死量:2,7——二氯荧光素LD_(50)为207.8mg/kg;二氯荧光素二乙酸酯LD_(50)为466.5mg/kg;荧光素二丙烯酸酯LD_(50)为489.9mg/kg;四碘荧光素LD_(50)为500.2mg/kg;二溴荧光素二乙酸酯LD_(50)为608.7mg/kg;荧光素顺丁烯二乙酸酯LD_(50)为979.4mg/kg;二溴二硝基荧光素二乙酸酯LD_(50)为1463.5mg/kg;四溴四氯荧光素二乙酸酯LD_(50)为1496.5mg/kg。     

40％病虫净乳剂的急性毒性研究

40％病虫净(30％甲胺磷、10％异稻瘟净和50％乳油助剂配比)是一种新型的杀虫、杀菌剂。本文观察了该农药对大白鼠、小白鼠经口及皮肤染毒的急性毒性。同时也观察了鲤鱼的回避率。雌、雄大白鼠经口LD_(50)分别为86.86mg/kg和104.5mg/kg;雌、雄小白鼠经口LD_(50)分别为40.22mg/kg和42.45mg/kg;大白鼠(雌、雄各半)经皮肤LD_(50)为90.45mg/kg;鲤鱼回避率为0％～41.8％(浓度为0.75～9.0mg/L)。该农药均较甲胺磷、异稻瘟净毒性低,属于中等毒性物质。正常农田用量对水体鱼类生存不会有危害。     

3—乙酰乌头碱的半合成及其镇痛作用

以乌头碱为原料半合成3—乙酰乌头碱,其对小鼠镇痛效果较吗啡、高乌甲素强;经实验结果证明化学结构及药理作用与天然产物一致。用热板法及0.7％醋酸扭体法(SC)测得其镇痛ED_(50)分别为0.0766mg/kg和0.162mg/kg,LD_(50)为0.77±0.0317mg/kg。     

膦甲酸钠的毒性研究

膦甲酸钠为新型抗病毒药,其毒性试验结果表明:KM小鼠经静脉注射,LD_(50)为395.7mg/kg,大鼠经腹腔注射,LD_(50)为1050.5mg/kg。大鼠腹腔注射和犬静脉注射3个月长期毒性试验中,毒性反应剂量分别为300mg/kg、120mg/kg,主要中毒表现为肝肾功能异常、中毒性肾病及肾小管坏死等。Ames试验及NIH小鼠微核试验结果均呈阴性。     

临床新药介绍

一、药理试验及临床验证本品对6种DNA病毒及10种RHA病毒有效,毒性小,小鼠口服LD_(50)为2000mg/kg,腹腔注射LD_(50)为1200～1300mg/kg。大鼠口服,LD_(50)为5300mg/kg。     

亚硒酸钠对艾氏腹水癌(实体型)生长的抑制作用

本文用“肿瘤抑制率”为指标,观察亚硒酸钠对艾氏腹水癌(实体型)生长的抑制作用。3个实验组小鼠腹腔注射亚硒酸钠,剂量分别为1/7LD_(50)(3.50mg/kg体重)、1/10LD_(50)(2.45mg/kg体重)和1/30LD_(50)(0.82mg/kg体重)每日给药1次,共7天。结果以1/10LD_(50)组的“肿瘤抑制率”为最高,经体重校正瘤重后,“肿瘤抑制率”仍高达35.59％。     

贵州省沙蚕毒系新农药——多噻烷毒性研究

对多噻烷进行毒性研究,以评价沙蚕毒系新农药的安全性。结果:大鼠纯品经口 LD_(50)雄303mg/kg,雌274mg/kg;乳油经口 LD_(50)雄253mg/kg,雌235mg/kg;经皮 LD_(50)1217mg/kg;鲤鱼 TLm_(48)为1.42ppm;1%以上浓度对家兔皮肤、眼粘膜有轻度刺激作用。蓄积系数 6.0,属轻度蓄积。亚慢性毒性实验大鼠进食含本品40、80、240、480ppm 的饲料3个月,最大无作用剂量为80ppm。以 Ames 试验、微核试验、精子畸形试验等对多噻烷进行致突变性检测,均为阴性。     

Observations of cattle, goats and pigs after administration of synthetic interferon inducers and subsequent exposure to foot and mouth disease virus

Polyriboinosinic-polyribocytidylic acid (poly [rI.rC]) was administered intravenously to 11 cattle and 13 goats in doses of 0.25 to 4.0, and 1.0 to 5.0 mg/kg, respectively. Subsequent exposure of these and untreated control animals to foot and mouth disease virus (FMDV) failed to demonstrate any differences in either the course or severity of the disease. Serum interferon was detected in cattle one hour after the intravenous administration of poly (rI.rC).Six pigs given 4, 20, or 100 mg/kg of itaconic-acrylic acid copolymer (IAA, HMW) intraperitoneally reacted clinically the same as six untreated control pigs after contact exposure to FMDV.Three pigs given 50, 100, or 200 mg/kg of divinyl ether-maleic anhydride copolymer (DVE/MA, pyran) intraperitoneally similarly failed to show any difference in clinical reaction from three untreated control pigs after intranasal instillation of FMDV. Three pigs given 100, 200 or 400 mg/kg of DVE/MA intraperitoneally developed rapid diffuse peritonitis causing the death of one in 48 hours.     

Beneficial Effects of Nicorandil on Lidocaine Intoxicity

It was demonstrated that nicorandil 50 and 100 mg/kg intravenously orintraperitoneally could prevent the intoxication of lidocaine and decrease itsmortality rate,furthermore nicorandil 50mg/kg,if combined with 5 mg/kgdiazepam,had a synergetic prophylactic effect against lidocaine toxicity,and thistoxicity could be effectively antagonized by 100 mg/kg of nicorandil in mice.Itwas found that the tolerant dose of lidocaine was elevated by nicorandil 100mg/kg intraperitoneally in rats.     

烟浪丁对利多卡因毒性的影响

经小鼠静脉或腹腔注射烟浪丁50mg/kg及100mg/kg,均可预防利多卡因的毒性作用,降低其死亡率;烟浪丁50mg/kg与安定5mg/kg伍用,对利多卡因中毒,有协同的拮抗作用;烟浪丁100mg/kg对此毒性,尚有治疗效果,且可增加大鼠对利多卡因的耐受量。     

左旋多巴对帕金森病大鼠神经行为学影响的动态研究

目的:探讨50 mg/kg剂量左旋多巴(L-dihydroxy-phenylalanine,L-dopa)对帕金森病(Parkinson disease,PD)大鼠神经行为学影响的动态变化.方法:采用经典的6-OHDA脑立体定向注射术建立大鼠PD模型,并将成功PD模型随机分成2组:PD模型组和L-dopa组,其中L-d...     

氯化镧拮抗内毒素效应的小鼠体内研究

目的　探讨氯化镧对内毒素 (LPS)体内效应的拮抗作用 ,寻找新的有效内毒素拮抗剂 ,为防治内毒素血症提供实验依据。方法　 (1)观察不同方式给予氯化镧处理对半数致死量LPS(17 5mg/kg)攻击小鼠的死亡率的影响。 (2 )观察氯化镧对LPS(12 5mg/kg)攻击后小鼠血浆肿瘤坏死因α(TNFα)及肝脏TNFαmRNA表达水平的变化、胸腺细胞凋亡状况、肝肺的病理损伤状况的影响。结果　 (1)经 5、10、2 0mg/kg氯化镧处理的半数致死量LPS攻击小鼠的死亡率分别为 0、0和 8% ,明显低于对照组的死亡率 (6 7% ) (P <0 0 1)。 10mg/kg氯化镧预防性给药 ,半数致死量LPS攻击小鼠后死亡率为 2 0 % ,明显低于对照组死亡率 (5 5 % ) (P <0 0 5 )。 (2 )经氯化镧处理的内毒素血症小鼠血浆TNFα含量为 0 4 4± 0 2 15ng/ml,肝组织TNF αmRNA表达量为 (3 9± 0 6 )× 10 5拷贝 / μgRNA ,明显低于内毒素血症小鼠 [0 99± 0 2 4ng/ml,(1 9± 0 3)× 10 7拷贝 / μgRNA],P <0 0 0 1;经氯化镧处理的内毒素血症小鼠胸腺细胞DNA片段百分率为 30 35 %± 6 4 2 % ,明显低于未处理小鼠(5 5 38%± 3 88% ) (P <0 0 0 1) ;内毒素血症小鼠胸腺细胞凋亡百分率为 15 5 6 %± 0 5 9% ,明显高于氯化镧处理小鼠 (6 0 5 %± 0 71% ) (P <     

新抗肿瘤药氨三肼的药理研究

氨三肼(Nitrazine)灌胃及腹腔注射对大鼠W-256及小鼠L615白血病均有明显疗效,对腹水型W-256仅灌胃给药法有效;对小鼠ECS、HCS,脑瘤B22等亦有抗肿瘤作用,对S37及ARS则无疗效。维生素B6可取消氨三肼的抗W-256作用,维生素B6拮抗剂去氧吡哆醛(DOP)则可加强其作用。氨三肼对W-256的疗效与给药方案有关,一次给予维生素B6及去氧吡哆醛对氨三肼的LD_so没有明显影响。氨三肼的主要毒性反应表现在胃肠道,对体液免疫和细胞免疫无抑制作用。     

Effect of Pre-treatment of α-Ketoglutarate on Cyanide-induced Toxicity and Alterations in Various Physiological Variables in Rodents

Objective To investigate the effects of pre-treatment of α-ketoglutarate (α-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of α-KG (protected animals) and LD50 of KCN in the absence of α-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) α-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po). Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of α-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of α-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of α-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of α-KG. Conclusions Cyanide antagonism by α-KG is best exhibited when both α-KG and KCN are given by po route. The protective effect of α-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of α-KG as an alternative cyanide antidote.     

序贯法测定原位凝胶材料OALA的LD50

目的：测定小鼠静脉注射给予原位凝胶材料OALA的半数致死量（LD50）,从而对该材料的生物毒性进行评价。方法：采用KM种雄性小鼠,运用急性毒性实验中的序贯法分别测定原位凝胶材料OALA不同浓度相同给药体积和相同浓度不同给药体积的LD50。结果：根据实验方法提供的计算公式得出不同浓度相同给药体积的LD50=（7．53±0．576）mg／mL（给药体积为0．4mL／20g体重,相当于150．6mg/kg）,相同浓度下不同给药体积的LD50=（0．31±0．113）mL（浓度为7．53mg／mL,相当于116．7mg／kg）;组织病理学检查显示死亡动物肺脏各级静脉中OALA凝胶材料广泛分布,导致血管阻塞。结论：OALA静脉注射KM小鼠。不同浓度相同给药体积的LD50为150．6mg／kg,相同浓度不同给药体积的LD50为116．7mg／kg。其死亡原因主要是弥散性肺栓塞。     

喷洒过敌枯双农药的稻谷对大鼠致畸作用的研究

敌枯双农药属中等毒性,雌性大鼠和小鼠分别经口及腹腔注射的LD_(50)为253和501.5mg/kg。该药对大鼠和小鼠的致畸作用呈剂量效应关系,在高剂量的阳性对照组,即于妊娠第10d给小鼠和大鼠的剂量分别为50和2.5mg/kg,对母鼠的体重出现抑制,有大量的胚胎吸收,其吸收率分别为39.8和46.7％,仔鼠的畸胎发生率分别为56.3和6.8％。1ppm仅见母鼠的体重增长及仔鼠生长发育受抑制,未见仔鼠畸形。0.1ppm组和喷洒三次敌枯双农药的稻谷组的大鼠和小鼠的母鼠和仔鼠均无不良影响。     

云芝多糖的实验药理研究

本文对云芝菌体多糖(PV-1)及滤液多糖(PV-4)作了抗肿瘤及对免疫功能的影响等实验研究。结果,两种多糖均使小鼠胸腺缩小,脾重增加,并有提高巨噬细胞吞噬的作用。但抑瘤作用较弱。PV-1能增强戊巴比妥钠的作用,使小鼠睡眠时间延长。两种多糖毒性均很小,小鼠腹腔注射 LD50 PV-1为2750mg/kg,PV-4为2883mg/kg。