克菌丹的亚慢性经口毒性研究

目的 研究克茵丹的亚慢性经口毒性,确定克茵丹亚慢性经口的最大无作用剂量并初步确定毒作用靶器官.方法 96只SD大鼠分为4组,每组24只,分别为空白对照组,受试物低、中、高剂量组,共4个实验组,分别用含0、333、1 105和3 333 ng/kg克茵丹的饲料给无特定病原体级大鼠喂饲90 d(动物实际摄食克茵丹的量在雌性分别为0、36.0、124.4、371.3 mg.kg-1·d-1,在雄性分别为O、30.9.94.2.323.6 mg-1·d-1).以一般状态、体质量、血常规9项,血生化12项,尿液常规,部分脏器系数和病理检查为观察指标.结果 中、高剂量组雌性和雄性动物试验期间体质量较对照组明显降低;高剂量组雌性动物血小板(Plt)降低,高剂量组雄性动物的白细胞(WBC)降低和血清尿素氮(BUN)升高.中、高剂量组动物部分脏器体比升高.中、高剂量的部分动物肾脏有不同程度病理改变.结论 克茵丹在SD大鼠亚慢性经口试验中最大无作用剂量为:雌性36.0 mg·kg-1·d-1,雄性30.9 mg·kg-1·d-1.肾脏可能是克茵丹的靶器官.     

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。     

甲氨基阿维菌素苯甲酸盐原药的致突变性及亚慢性毒性

目的 探讨甲氨基阿维菌素苯甲酸盐原药的致突变性及亚慢性毒性作用。方法 按照GB15670—1995《农药登记毒理学试验方法》进行Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠睾丸精母细胞染色体畸变试验及大鼠亚慢性毒性试验。结果 （1）50～200μg/皿剂量组的Ames试验结果为阴性。（2）染毒6.25～50.00 mg/kg剂量组的微核率与阴性对照组比较差异无统计学意义（P〉0.05）,甲氨基阿维菌素苯甲酸盐原药不引起小鼠骨髓多染红细胞染色体断裂或整条染色体丢失。（3）染毒12.5～50.0 mg/kg剂量组的小鼠睾丸初级精母细胞染色体畸变率未见增加。（4）亚慢性毒性试验高剂量组部分动物在染毒后期出现全身震颤、精神不振、被毛蓬松、体重增长缓慢等中毒症状。实验结束时,高剂量组雌鼠淋巴细胞比例降低、中间细胞比例增高,肝脏脏器系数明显增高;雄鼠肾脏和脑的脏器系数增高。中、高剂量组雄鼠淋巴细胞比例降低、中间细胞比例增高,心脏脏器系数增高。结论 甲氨基阿维菌素苯甲酸盐原药无明显致突变作用。该药可引起动物出现神经系统症状,影响动物的生长发育及免疫功能。本实验提示,SD大鼠口服甲氨基阿维菌素苯甲酸盐原药90 d的最大无作用剂量为0.89 mg.kg-1.d-1。     

苯氧菌酯90天亚慢性毒性研究

[目的] 通过90 d亚慢性喂饲试验,提出农药杀菌剂-苯氧菌酯对大鼠的亚慢性无作用剂量,并探讨其毒作用特点.[方法] 苯氧菌酯对雄、雌大鼠的LD50均大于5 000 mg/kg体重.用清洁级Wistar大鼠,雄、雌各40只,体重为130～160 g.两种性别大鼠分别分为对照组和低、中、高3个剂量组.喂饲饲料中苯氧菌酯的含量雄、雌大鼠分别为0、560、1 110、2 770 mg/kg和0、625、1 249、3 117 mg/kg.相应的雄、雌大鼠每日染毒剂量分别为0、34.56、68.62、211.90 mg/kg和0、44.42、88.84、225.10 mg/kg.观察指标有日摄食量、体重、行为表现、血常规、血清生化、尿常规、脏器系数及病理学检查等.血清指标丙氨酸氨基转移酶活性(ALT)、天门冬氨酸氨基转移酶活性(AST)、碱性磷酸酶活性(ALP)、尿素氮含量(BUN)、肌酐含量(Cre)、胆固醇含量(CHO)、血糖含量(GLU)、总蛋白含量(TP)、白蛋白含量(ALB)、总胆红素含量(BIL)等.各项检测数据用OFFICE 97软件EXCEL中单因素方差分析检验各组间的差异.[结果] 动物的日平均摄食量各组大体一致,每只动物的日平均摄食量雄鼠为22.5～26.6 g,雌鼠为16～18.2 g.试验中,雄性大鼠高剂量组的体重增长在第4周和第6周开始出现明显降低,8周后体重持续到试验结束;而雌性高剂量组大鼠的体重增长则从染毒第2周即开始明显降低并直至试验结束(P＜0.01),雌性中剂量组从第6周后体重增长一直减少(P＜0.05或0.01).血常规检查未见有意义的改变.血清生化检测见雄性大鼠中、高剂量组的BUN、TP、ALB和BIL增加(P＜0.01);雌性大鼠高剂量组的GLU(P＜0.01)和ALB降低(P＜0.05).这些变化中,BUN的增加提示肾脏功能可能受到损害.尿常规检查各组未见有意义的改变.解剖检查各脏器未见异常改变.脏器系数测定结果表明雄性大鼠高剂量组心脏、肺脏、肝脏、肾脏、肾上腺和睾丸的脏器系数比对照组增高(P＜0.01);雄性大鼠高剂量组的心脏、肝脏、肾脏的脏器系数明显增高(P＜0.01).光镜病理检查见高剂量组雄鼠有1例脾窦扩张充血,雌鼠2例肝细胞浊肿.其他各组和其他脏器未见有毒理学意义的改变.[结论] 苯氧菌酯在达到中毒剂量时可影响多数脏器的血液循环而导致其脏器系数增大.雄鼠血中BUN含量增高与肾脏增重相联系,提示苯氧菌酯的毒作用靶点可能是肾脏.苯氧菌酯对雄、雌大鼠的无作用剂量分别为34.6和44.4 mg/kg*d-1.     

孕期大鼠全氟辛烷磺酸染毒对子代发育状况的影响研究

目的:评价孕期大鼠全氟辛烷磺酸(PFOS)染毒后对子代大鼠体重、脏器系数、睁眼和张耳等发育状况的影响。方法:将120只雌鼠、40只雄鼠分别按体重随机各分为4组,分别为对照组、低剂量组、中剂量组和高剂量组。适应性喂养1周后雌雄鼠合笼,1周后处死雄鼠。合笼第1天开始到整个孕期结束分别对低剂量组、中剂量组和高剂量组用不同剂量的PFOS每天灌胃染毒大鼠,剂量依次为PFOS 0.4 mg·kg-1·d-1、0.8 mg·kg-1·d-1和1.6 mg·kg-1·d-1,对照组不给予。哺乳期停止染毒,哺乳结束时(哺乳1个月)髂静脉取血后处死所有亲代大鼠及2只子代大鼠。处死后取肝脏、胸腺、睾丸、卵巢和子宫,称上述组织的重量并计算脏器系数。喂养过程中记录哺乳期子代大鼠1、4、7、14、21、28天时的体重,观察大鼠的睁眼和张耳时间。1个月后每周记录剩余大鼠的体重。结果:出生前7天各组的平均体重无差异,而7天后对照组的平均体重低于3个实验组。对照组睁眼时间及张耳时间分别主要集中在出生后的第14天与第16天,较3个实验组的睁眼及张耳时间早,差异有统计学意义(P<0.025 0)。雌鼠的各脏器系数无差异,对照组雄鼠睾丸的脏器系数低于中剂量组及高剂量组,差异有统计学意义(P<0.05)。而其他脏器系数无差异。结论:孕期PFOS染毒会对子代大鼠的体重、脏器系数、睁眼和张耳等发育状况造成一定的影响。     

粉唑醇原药的亚慢性经口毒性研究

目的研究粉唑醇原药亚慢性经口毒性作用,初步分析染毒后对大鼠血液、肝和肾功能的影响。方法按照GB15670-1995《农药登记毒理学试验方法》的要求进行实验,将80只清洁级SD大鼠按体重随机分成4组,每组20只,雌雄各半。分别用含37.5、150和600 mg/kg粉唑醇的饲料连续喂饲染毒90 d。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。结果雌鼠各组实际染毒剂量分别为2.8、12.2、47.2 mg/kg,雄鼠各组实际染毒剂量分别为2.8、11.3、47.1 mg/kg。试验期间,各剂量组雌、雄鼠活动、进食、饮水基本正常,未见明显中毒表现。与相应对照组相比,高剂量组雄鼠白细胞计数(WBC)显著降低。中、高剂量组大鼠尿素氮(BUN)和肌酐(CREA)显著升高,高剂量组雌鼠总胆红素(TBIL)升高;中、高剂量组雌鼠天冬氨酸氨基转换酶(AST)和乳酸脱氢酶(LDH)显著升高;各剂量组雌、雄鼠各脏器重量和脏器系数与对照组相比差异均无统计学意义(P0.05)或无生物学意义。大体解剖未见明显异常,粉唑醇原药未引起SD大鼠各脏器病理性改变。结论粉唑醇原药长期暴露对大鼠的血液、肝、肾具有毒性作用和潜在的致病风险。其对雌、雄SD大鼠亚慢性经口毒性试验的最大无作用剂量均为2.8 mg/(kg bw·d)。     

乳氟禾草灵原药的亚慢性经口毒性

根据《农药登记毒理学试验方法》(GB 15670—1995)进行乳氟禾草灵原药亚慢性经口毒性试验。结果显示，高剂量染毒组大鼠血WBC计数降低，血清天门冬氨酸氨基转移酶和丙氨酸氨基转移酶升高，雄鼠中性粒细胞比例升高，肾脏器系数偏高；中、高剂量染毒组大鼠单核细胞比例、血清尿素氮和肌酐升高，肝脏质量及脏器系数均偏高，雌鼠淋巴细胞比例降低。雌、雄大鼠亚慢性经口最大无作用剂量分别为3.81 mg/kg和3.50 mg/kg。     

单甲脒盐酸盐原药的亚慢性毒性研究

目的研究85%单甲脒盐酸盐原药对大鼠的亚慢性经口毒性。方法分别用含625、125、25、0 mg/kg 85%单甲脒盐酸盐原药的饲料,给大鼠连续喂饲染毒3个月,观察一般表现、体重、进食量,实验结束时测定血常规7项、血生化11项、尿常规及生化8项,取脏器称重计算脏器质量系数并进行病理组织学检查。结果实验期间,对照组和低剂量组动物无异常发现;高、中剂量组动物活动减少,烦躁,眼鼻血性分泌物,会阴部污秽,皮肤破损或溃烂,体重、进食量下降,体重增长缓慢。实验结束时,高剂量组雌雄动物尿素氮(BUN)、碱性磷酸酶(ALP)升高,胆碱酯酶(ChE)降低;雄性动物天门冬氨酸氨基转移酶(AST)升高,总蛋白(TP)、白蛋白(ALB)、血糖(GLU)降低。中剂量组雌雄动物总蛋白(TP)、血糖(GLU)降低。高、中剂量组部分动物尿蛋白呈阳性。高剂量组动物脑、心、肝、肾、肾上腺及雄性睾丸脏器质量系数均高于对照组;中剂量组雌性动物脑、肾及雄性动物脑、肝及睾丸脏器重量系数均高于对照组。病理检查显示高剂量组部分动物可见肝细胞肿胀,细胞内有小圆形空泡,肝窦结构受压,中剂量组部分雌性动物周边性肝细胞内小圆形空泡。结论85%单甲脒盐酸盐原药影响动物食量、营养状况,引起行为改变、抗感染能力减低,体重和食物利用率下降,部分生化指标(TP、ALB、GLU、BUN、ALP、ChE)及部分脏器质量系数改变,且能造成部分动物肝脏损害。该药喂饲染毒最大无作用剂量,雌性大鼠为2.34 mg/kg,雄性大鼠为1.59 mg/kg。     

幼鼠重复吸入氯氟醚菊酯蚊香28d亚急性毒性研究

目的 通过幼鼠重复吸入氯氟醚菊酯蚊香28 d的亚急性毒性研究了解该蚊香对幼鼠可能存在的毒性.方法 对SD雌雄刚断乳大鼠静式染毒28 d,进行血液学、血清生化学及组织病理学检查和脏器系数等指标的测定.结果 雄鼠中高剂量组ALT指标明显高于对照组;雄鼠3个剂量组肝脏器系数高于对照组;雌鼠高剂量组肝脏湿重明显高于对照组,且上述差异均有统计学意义(P＜0.05);雌雄高剂量组动物肝细胞不同程度胞质疏松,空泡状,部分肝细胞肿胀,噬碱性小体减少,肝索排列紊乱等;雄鼠中高剂量组及雌鼠中剂量组CHO指标明显高于对照组,差异均有统计学意义(P＜0.05).结论 氯氟醚菊酯蚊香主要作用的靶器官是肝脏,具有一定的肝脏毒性.     

β-烟酰胺单核苷酸的急性及亚急性经口毒性

β-烟酰胺单核苷酸(NMN)急性经口毒性试验采用最大限量法,将大、小鼠分别设置对照组和5000mg/kg剂量组,每组10只动物,雌雄各半,进行一次性经口灌胃染毒。28d重复剂量亚急性经口毒性试验,将大鼠分为对照组和1000mg/kg剂量组,每组10只大鼠,雌雄各半,连续灌胃染毒28d,记录动物摄食和体质量变化,染毒后检测动物血常规和血清生化指标。取大鼠主要脏器,计算脏器系数并制作病理组织切片。结果显示,急性经口毒性试验未见动物明显异常。亚急性经口毒性试验1000mg/kg剂量染毒组大鼠体质量、摄食量、食物利用率、血常规及生化指标与对照组相比差异均无统计学意义(P>0.05),肝、肾脏器质量和脾脏器系数与对照组相比,差异有统计学意义(P<0.05)。组织学检查未见病理性损伤。NMN急性经口毒性试验半数致死剂量(LD₅₀)>5000mg/kg,亚急性经口毒性试验最大无作用剂量(NOAEL)>1000mg/kg。     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.