应用型本科院校“食品毒理学”课程教学改革与实践

以培养应用型人才为目标,结合食品质量与安全专业的实际情况,探索“食品毒理学”课程教学改革的必要性,并从教学内容、教学方法等方面对“食品毒理学”课程的教学改革效果进行了分析,为应用型人才的培养打下基础。     

精制竹醋液的安全性毒理学评价

以精制竹醋液为材料,按食品安全性毒理学评价程序和方法(GB15193-94)进行了急性毒性、小鼠微核、小鼠精子畸形和Ames试验。结果表明,精制竹醋液对大、小鼠经口LD50雌雄均大于10.0 g.kg-1BW,属实际无毒,小鼠骨髓嗜多染红细胞微核、精子畸形和Ames试验检测均为阴性。证实了精制竹醋液接触人和动物皮肤及经口、鼻使用是安全可靠的。     

《动物药理与毒理》项目化教学设计及实施效果分析

根据《动物药理与毒理》课程的特点和高职生物技术及应用专业学生就业的技能需求,通过企业调研,建立了一套项目化教学设计方案,在2009级学生中进行应用,并对该方案的实施效果进行了分析。     

利用家蚕蛹生物反应器生产的人粒细胞/巨噬细胞集落刺激因子口服给药的临床前安全性评价

开发了用家蚕蛹表达的人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)的口服药物。试验评价了猕猴、大鼠和小鼠口服rhGM-CSF毒性情况,包括遗传毒性、单剂量和重复剂量的全身毒性以及生殖毒性。毒理学试验显示:静脉给药在NIH小鼠中最大耐受剂量为3 300μg/kg,LD50为2 020μg/kg,在SD大鼠中LD50为3 660μg/kg。在猕猴和大鼠的重复剂量毒性试验结果中显示:口服rhGM-CSF后,除了雌性SD大鼠的血糖含量外,其余各项指标包括白细胞、红细胞、血红蛋白含量、血小板数量以及血细胞凝集等都正常。雌性大鼠每天口服剂量为1 250μg/kg时,给药后血糖浓度显著增加(P<0.001),但在恢复期间可恢复到正常水平。微核实验、CHL染色体畸变试验和埃姆斯测验法都表明无论是在体内还是体外服用rhGM-CSF均未见遗传毒性,普通的生殖毒性试验和围产期及致畸敏感期的毒性试验均未见异常现象,表明口服rhGM-CSF无明显生殖毒性。临床前毒性试验表明口服超过临床剂量10倍的rhGM-CSF与严重的慢性中毒没有联系,其在药理学有效剂量的范围内是很安全的。     

Comparative metabolism of six ethoxychlor analogs and DDT in DDT-resistant and susceptible strains of the house fly Musca domestica L

The metabolic fate of six ³H-ring-substituted ethoxychlor analogs with altered aliphatic moieties and [¹⁴C]p,p′-DDT was investigated in susceptible and DDT-resistant strains of the house fly Musca domestica Linnaeus. The chloroalkane analogs, dichloroethane, chloropropane, and dichloropropane were primarily metabolized to the corresponding dehydrochlorinated products. This pathway was relatively more prominent in the resistant strain than in the susceptible strain. Biotransformation and detoxication of the isobutane, nitropropane, and neopentane derivatives was through microsomal oxidation (O-deethylation) of aryl ethoxy degradophores, and oxidation of the aliphatic moieties to produce the corresponding benzophenones, with no substantial differences between the resistant and susceptible strain. There was a strong correlation between the Taft ($\text{σ}{}^1$) values for the altered aliphatic moieties of chloroalkane analogs and their rate of dehydrochlorination in both the strains. These results suggest the importance of altered aliphatic moieties in developing resistance-proof DDT derivatives.     

In vitro metabolism and interaction of profenofos by human, mouse and rat liver preparations

Biotransformations of profenofos were studied in vitro. Two metabolites, desthiopropylprofenofos and hydroxyprofenofos, were detected by LC-MS after incubation of profenofos with human liver homogenates and different mammalian liver microsomes. The rank order of desthiopropylprofenofos formation in liver microsomes based on intrinsic clearance (V_max/K_m) was mouse > human > rat, while for profenofos hydroxylation it was mouse > rat > human. In view of the ratio between desthiopropylation and hydroxylation intrinsic clearance rates, human liver microsomes were most active in profenofos bioactivation. The interspecies differences and interindividual variation were within range of the default uncertainty/safety factors for chemical risk assessment. CYP3A4, CYP2B6 and CYP2C19 were identified as profenofos-oxidizing enzymes in human liver on the basis of recombinant expressed enzymes and correlation with CYP model activities. The rank order of CYPs in profenofos activation was CYP3A4 > CYP2B6 > CYP2C19, whereas it was the contrary for profenofos hydroxylation. Profenofos inhibited relatively potently several human liver microsomal activities: the lowest IC₅₀ values were about 3 μM for CYP1A1/2 and CYP2B-associated activities. Profenofos is extensively metabolized by liver microsomal CYP enzymes and its interaction potential with several CYP activities is considerable.     

50％竹焦油乳油的安全性毒理学评价

为了解50%竹焦油乳油作为农药使用的安全性,按GB 15670-1995农药登记毒理学试验方法进行了安全性评价。结果表明,50%竹焦油乳油对雌雄大鼠经口LD50分别为:雌性3690 mg.kg-1,雄性大于4640 mg.kg-1,均属低毒。对雌雄大鼠经皮LD50均大于2000 mg.kg-1,均属低毒。对兔眼的刺激强度为中度刺激性,洗眼试验结果有轻度刺激性。对家兔急性皮肤刺激反应均值积分为0,即对皮肤无刺激性。对豚鼠致敏试验,致敏率为0%,属级弱致敏。证实50%竹焦油乳油为低毒性、无刺激性、无致敏的安全生物农药。     

大豆胰蛋白酶抑制剂的研究进展

从结构、毒理学分析和灭活方法3个方面对国内外近年来对大豆胰蛋白酶抑制剂的研究进展进行了综述。     

镉对绵羊的毒理学研究

本文按每日１ｍｇＣｄ／ｋｇ体重剂量对绵羊口服氯化镉溶液，成功复制出了镉中毒的动物模型。结果表明：（１）实验第２０天左右即出现粘膜苍白、消瘦、血液稀薄、水肿等临诊中毒症状，并且上述症状呈渐进性发展；（２）在试验第２０天或４０天时ＲＢＣ、Ｈｂ、ＰＣＶ、ＭＣＨＣ均显著或极显著低于对照组（Ｐ＜０．０５，Ｐ＜０．０１），红细胞发生了明显的棘形改变，呈一种典型的正细胞低色素性贫血，血清ＢＵＮ、ＴＰ、Ａ１ｂ和Ｔ＿３含量与对照组相比均出现显著差异（Ｐ＜０．０５，Ｐ＜０．０１）；（３）所测生物样品Ｃｄ含量极显著高于对照组，而Ｆｅ含量则明显降低（Ｐ＜０．０１）；（４）病理组织学变化以肝、肾等实质性器官的损害为主。