急性经口毒性试验替代测试方法进展

急性经口毒性试验是毒理学安全性评价最基础的试验,主要研究24 h内单次或多次经口染毒后动物所产生的毒性反应和死亡情况。其主要目的是求出受试物对试验动物的半数致死剂量(LD50);初步估测毒作用的靶器官和可能的毒作用机制,为亚慢性、慢性和其他毒性试验的剂量水平设计提供参     

巯基乙酸的毒性

巯基乙酸的毒性张黎，综述甘卉芳审校巯基乙酸（Ｔｈｉｏｇｌｙｃｏｌｉｃａｃｉｄ以下简称ＴＧＡ）又名硫代乙醇酸，为微黄或几乎无色液体，有强烈的难闻气味，能与水、醇、醚、氯仿、苯及其他有机溶剂混合，不溶于石油醚。在空气中迅速氧化为二硫撑二乙酸〔１〕。自１９...     

对二氯苯毒性研究的概况

对二氯苯毒性研究的概况上海医科大学劳动卫生学教研室（上海２０００３２）陆荣柱，金锡鹏，顾学箕对二氯苯（１，４－Ｄｉｃｈｌｏｒｏｂｅｎｚｅｎｅ·ｐ－Ｄｉｃｈｌｏｒｏｂｅｎｚｅｎｅ，Ｄｉｃｈｌｏｒｏｃｉｄｅ，ｐ－ＤＣＢ），又名１．４－二氯苯．是一种氯代芳...     

甲基汞生殖毒性的研究

生殖毒理学的研究发现环境化学物、金属、激素、抗癌药物等可影响雄性动物生殖过程。甲基汞是一种重要的重金属污染物,研究证实它可通过胎盘产生胎儿性水误病[1,2]。为了解甲基汞对雄性动物的生殖毒性,我们采用不同剂量甲基汞对雄性小鼠经口慢性染毒,然后同正常处女鼠进行交配,观察其交配能力、受孕能力及胎鼠的发育情况。     

三氯乙醛的毒性和致突变研究

【目的】了解三氯乙醛的毒性和致突变作用。[方法]对三氯乙醛进行急性毒性试验、致突变试验、单细胞凝胶电泳试验。【结果】雄性大鼠急性经口LD50为1000mg／kg，雌性大鼠为681mg／kg。雄性大鼠急性经皮LD50为1470mg／kg，雌性大鼠为1210mg／kg。对皮肤具中等刺激性，对眼具中度至重度刺激性。Ames试验1mg／皿为阳性。小鼠骨髓细胞身长核试验160mg／kg时为阳性。小鼠与人淋巴细胞单细胞凝胶电泳试验为阳性。【结论】三氯乙醛属低毒级化学药物，致突变试验阳性。     

酒花浸膏的毒性研究

本文对食品添加剂酒花浸膏进行了急性毒性和蓄积毒性的毒理学试验，酒花浸膏LD50为270mg／kg，95％可信限198～370mg／kg．大鼠经口LD50为370mg／kg，95％可信限310～459mg／kg，均属中等毒级．蓄积系数K=4．3，属中等蓄积性．急性中毒表现，先兴奋，继呆滞嗜睡，最后麻痹衰竭而死亡．尸解检查发现有不同程度的肝脏瘀血现象．初步认为，有必要对酒花浸膏进行全面的毒理学安全评价，为制定其卫生标准提供依据．     

氯化镍对小鼠生殖毒性的影响

对探讨氯化镍（NiCl2)对雌性小鼠（F0及F1）生殖能力的影响,采用两代生殖毒性实验,依NiCl2注射剂量将雌性小鼠分为5mg/kg和10mg/kg两组,腹腔注射10天后使其交配。结果显示F0、F1染毒组小鼠的生殖能力明显低于对照组。说明NiCl2不仅影响F0代雌性小鼠的生殖能力,还对F1代雌性小鼠有性腺毒作用的远期效应。     

氯化铝毒性的初步研究

本文对混凝净水剂氯化铝毒性进行了初步研究。急性毒性试验结晶氯化铝小白鼠经口LD_(50)为3033mg/kg,属低毒;蓄积试验蓄积系数为1.45,属明显或强蓄积物质;Ames试验、微核试验结果均为阴性,骨髓细胞染色体畸变试验阳性,但属弱阳性;骨髓细胞分裂指数试验存在剂量-反应关系;SCE试验阴性,但氯化铝对人外周血淋巴细胞生长有轻度抑制作用;小鼠精子畸形试验阳性,且随着氯化铝剂量的增加,小鼠精子畸形构成比也发生改变。     

有机锡的生殖毒性和遗传毒性研究进展

本文对有机锡化合物的生殖毒性和遗传毒性研究成果进行综述。有机锡化合物可使海洋动物性成熟和繁殖推迟,引起贝类和腹足纲动物性畸变;也可干扰哺乳动物的内分泌,导致生育力下降、胚胎畸形、生长发育迟缓;还可诱发基因突变、染色体畸变和DNA损伤等遗传毒性问题;但有机锡化合物对人体的生殖健康危害方面研究尚不全面,有待进行全面系统地研究和探讨。     

急性经口毒性替代方法在化学品检验中的应用研究

目的 探讨3种急性经口毒性替代法(固定剂量法、急性毒性分级法和上下法)在化学品急性毒性评价中的应用价值.方法 健康雌性SD大鼠,8～12周龄,体重160～200 g.分别选取10种化妆品原料和12种日化品原料共22种化学品作为受试物,参照经济合作与发展组织(OECD)3个急性经口毒性试验替代方法进行检测,依据全球化学品统一分类及标签制度(GHS)急性经口毒性分级原则获得各受试物毒性分级,分析各替代方法结果与传统试验方法之间的相关性和一致性.结果 与传统试验方法结果相比较,各替代方法判断化妆品原料急性毒性分级的一致率均为80%(8/10),固定剂量法、急性毒性分级法和上下法判断日化品原料的一致率分别为91.7%(11/12)、75.0%(9/12)和83.0%(10/12).各替代方法消耗动物数量均少于传统试验方法,差异有统计学意义(P<0.05),但所需实验时间长于传统试验方法,差异亦有统计学意义(P<0.05).结论 在化妆品和日化品原料急性经口毒性分析检测中,3种替代方法结果与传统试验方法具有较高的一致性和相关性,其中固定剂量法在日化品原料毒性检测中更具应用潜力.

Abstract：

Objective To evaluate three alternative methods for LD50 test-Fixed Dose Procedure (FDP),the Acute Toxic Class Method (ATC) and Up and Down Procedure (UDP).Methods Female SD rats (8～12 weeks of age,160~200 g) were used.Three alternative methods from OECD were applied to assess 22 chemicals (10 cosmetic raw materials and 12 raw materials of personal and home care products).The toxicity ranking for tested chemicals was established according to Globally Harmonized System(GSH).The results LD50 test were compared for the consistency and correlation between alternative methods and traditional test.Results For cosmetic raw materials,the concordance rate of the three alternative methods was 80%(8/10);for raw material of personal and home care products,the concordance rates of FDP,ATC and UDP was 91.7%(11/12),75.0%(9/12) and 83.0%(10/12),respectively.The number of animals required in three alternative methods was significantly lower than that in traditional test (P<0.05),but the time required in three alternative methods was significantly higher than that in traditional test (P<0.05 ).Conclusions High consistency and correlation were found between each alternative method and LD50 test.FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.     

高内涵筛选技术在毒理学研究中的应用进展

随着各种新、老化学物质健康风险评价的需求急剧增长,基于动物实验的测试方法难以满足当前健康风险评价的需求,迫切需要研发新型的、高通量、灵敏的毒性测试方法,整合基于体外替代模型的高通量筛选技术、计算方法和信息技术的毒性测试策略。其中,高内涵筛选（HCS）利用自动化显微镜和图像分析平台,以可视化和定量的方式对体外模型进行多参...     

3种替代方法在急性经口毒性实验中应用研究

目的评价3种替代法(固定剂量法、急性毒性分级法和上下法)在急性经口毒性检测中的应用价值。方法分别选取7种消毒剂原料和6种农药原药共13种化学品作为受试物,参照经济合作与发展组织3种急性毒性实验替代方法进行实验,依据全球化学品统一分类及标签制度(GHS)急性经口毒性分级原则获得各受试物毒性分级,分析各替代方法结果与传统实验方法之间的相关性和一致性。结果 3种替代方法判断GHS毒性分级与传统实验方法间具有较高一致率、相关性和一致性。各替代方法消耗动物数量均少于传统实验方法,但所需实验时间长于传统实验方法(P<0.05)。结论 3种替代方法结果与传统实验方法间具有较高一致性和相关性,可认为这3种方法具有取代传统检测方法的潜力。     

Species extrapolation for the 21st century

Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment. More accurate extrapolation of species responses is important. Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and, in part, an explanation for the variability in whole organism responses to toxicants. We highlight potential short- and medium-term development goals to meet our long-term aspiration of truly predictive in silico extrapolation across wildlife species' response to toxicants. A conceptual approach for considering cross-species extrapolation is presented. Critical information is required to establish evidence-based species extrapolation, including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species' homologies. A case study is presented that examines steroidogenesis inhibition in fish after exposure to fadrozole or prochloraz. Similar effects for each compound among fathead minnow, medaka, and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2). Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes, for example, CYP19 aromatase, which would eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species. Eventually, predictive models will be developed to extrapolate across species, although substantial research is still required. Knowledge gaps requiring research include defining differences in life histories (e.g., reproductive strategies), understanding tissue-specific gene expression, and defining the role of metabolism on toxic responses and how these collectively affect the power of interspecies extrapolation methods.     

Physician leadership for the 21st century

This article examines how rapidly evolving health care delivery structures are radically altering the traditional clinical and organizational autonomy enjoyed by physicians. These changes may render maintenance of prior levels of physician autonomy virtually impossible. The author calls for the emergence of a new breed of physician leaders who will preserve the best of traditional medical practice culture but also effectively implement a nascent form of integrated health care practice.