复合生物杀菌剂F6-11的安全性毒理学研究

目的：为研究复合生物杀菌剂F6．11毒性,采用动物实验法进行毒理学评价。方法：对复合生物杀菌剂F6-11进行小鼠急性毒性试验、小鼠骨髓嗜多染红细胞微核试验、亚急性毒性试验、家兔多次完整皮肤刺激试验、急性眼刺激试验、豚鼠皮肤变态反应试验、鱼类延长毒性14天试验。结果：复合生物杀菌剂F6—11对小鼠急性毒性LD50〉5000mg／kg．bw,属于实际无毒级物质;小鼠微核试验该杀菌剂各剂量组与阴性对照组比较,微核率无显著性差异（P〉0．05）;亚急性毒性试验动物血常规、生化指标及各脏器均未发现异常;对家兔多次完整皮肤及眼刺激反应积分均为0,均属无刺激性;对豚鼠皮肤变态反应试验组动物与阴性对照组无可见不同．试验组动物皮肤致敏反应积分为0,无致敏作用;鱼类延长毒性14天试验无异常。结论：毒理学研究表明,复合生物杀菌剂F6．11具有良好的使用安全性。     

Silver speciation during chronic toxicity tests with the mysid,Americamysis bahia

A 28-day chronic toxicity test and two 7-day chronic estimation toxicity tests were conducted with silver nitrate (AgNO(3)) and the marine invertebrate, Americamysis bahia, in 20 per thousand (parts-per thousand) salinity seawater. One 7-day test was initiated with 7-day-old mysids and the second was initiated with <24-h-old mysids. There was very good agreement between the three toxicity tests. The no-observed-effect concentration (NOEC) values from the 28-day test, the 7-day test initiated with 7-day-old mysids, and the 7-day test initiated with <24-h-old mysids were 34, 65 and 38 microg/l silver, respectively. The 96-h LC50 values from the 28-day toxicity test and the 7-day toxicity test initiated with 7-day old mysids were 260 microg/l, and the 96-h LC50 value from the 7-day toxicity test initiated with <24-h-old mysids was 280 microg/l. Free ionic silver, Ag(+), concentrations measured with a silver electrode were in good agreement with concentrations calculated using total dissolved silver and chloride concentrations. Mean measured concentrations of Ag(+) in the test solutions ranged from 0.99 to 25 ng/l for the dissolved silver concentrations that ranged from 34 to 410 microg/l silver, indicating that free ionic silver varied from 0.003 to 0.006% of the silver dissolved in the 20 per thousand salinity seawater. Understanding the relationship of salinity and silver speciation, and the effect of this relationship on chronic invertebrate toxicity, will be useful for development of a marine biotic ligand model (BLM) and a water quality criterion for silver. This model could provide an important tool for improving the relationship of laboratory toxicity test results and predicted effects in natural environments, where variations in salinity may act to modify the toxicity of silver and other metals.     

令肤适洗液皮肤和阴道局部毒性研究

目的评价令肤适皮肤和阴道局部使用的安全性。方法采用皮肤急性毒性、皮肤刺激、皮肤过敏、阴道急性毒性和阴道刺激等试验方法。结果未见令肤适具有皮肤毒性、皮肤刺激作用和明显的阴道急性毒性反应;在阴道刺激试验中低剂量未引起阴道明显的刺激反应,高剂量可引起阴道粘膜炎细胞浸润、淤血、出血及溃疡等病理变化。结论令肤适皮肤使用较安全,阴道使用浓度不宜过高。     

嗜酸乳杆菌LA-G80的毒理学研究

目的对嗜酸乳杆菌的毒性进行研究。方法采用大、小鼠急性毒性试验、Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验和大鼠30 d喂养等对嗜酸乳杆菌进行安全性试验研究。结果急性经口毒性试验表明,大、小鼠灌胃给予嗜酸乳杆菌,最大耐受剂量雌雄两性别均大于20.0 g/kg体重,Ames试验、微核试验和精子畸形试验结果均为阴性。大鼠30 d喂养试验结果表明各项指标均未见明显毒性反应。结论在本次实验条件下,嗜酸乳杆菌未见遗传毒性。由此可初步判定,使用嗜酸乳杆菌是安全可靠的。     

Evaluation and application of aquatic toxicity tests: use of the Microtox test for the prediction of toxicity based upon concentrations of contaminants in soil

The quality control for the reuse of cleaned soil from a contaminated site consisted in the determination of the main contaminants by analytical chemical methods such as GC and HPLC. Since it is not possible to analyze for all contaminants a toxicity test should be used to detect large concentrations of not routinely analyzed chemicals. The aim of the study was to develop a system for toxicity testing, which should be able to predict the toxicity of soil samples based on the concentration of chemicals in the soil and to detect toxic chemicals not analyzed by the routinely conducted soil analysis.Based upon the relative sensitivity to various contaminants as well as practical aspects such as test duration and costs the Microtox® test was favoured over the bioassays with Daphnia magna and Scenedesmus subspicatus. The Microtox® test was used to measure the toxicity of various pesticides and their major metabolites. The toxicity data of the pure compounds were used to predict the toxicity (EC₅₀ and % inhibition of the bioluminescence reaction) of defined mixtures of chemicals in water by applying two different mathematical appriaches which are based on the additivity of the effects of the single chemicals. The predicted values were compared with the experimental data and showed good agreement.In order to be able to predict the toxicity of soil samples using the Microtox® test the soil/water partition coefficient (K _d) was measured for the main contaminants. The toxicity of soil samples was predicted by calculating the concentration of the contaminants in the leachate by using the corresponding concentration in the soil and applying the K _d values determined. From the calculated composition of the leachate the expected toxicity was estimated. This value was compared with the toxicity experimentally determined in the Microtox® test.     

On-line microbial biosensing and fingerprinting of water pollutants

The potential for biosensors to contribute to on-line toxicity testing for monitoring of water quality is currently constrained both by the relevance of the biosensors available and the technology for biosensor delivery. This paper reports the use of novel slow release biosensor delivery for on-line monitoring instrumentation, with environmentally relevant bacteria for both simple toxicity testing and more complex toxicity fingerprinting of industrial effluents. The on-line toxicity test, using bioluminescence-based biosensors, proved to be as sensitive and reliable as the corresponding batch test, with comparable contaminant EC(50) values from both methods. Toxicity fingerprinting through the investigation of the kinetics (dose-response) and the dynamics (response with time) of the biosensor test response proved to be diagnostic of both effluent type and composition. Furthermore, the slow release of biosensors immobilised in a polyvinyl alcohol (PVA) matrix greatly improved biosensor delivery, did not affect the sensitivity of toxicity testing, and demonstrated great potential for inclusion in on-line monitoring instrumentation.     

A novel continuous toxicity test system using a luminously modified freshwater bacterium

An automated continuous toxicity test system was developed using a recombinant bioluminescent freshwater bacterium. The groundwater-borne bacterium, Janthinobacterium lividum YH9-RC, was modified with luxAB and optimized for toxicity tests using different kinds of organic carbon compounds and heavy metals. luxAB-marked YH9-RC cells were much more sensitive (average 7.3-8.6 times) to chemicals used for toxicity detection than marine Vibrio fischeri cells used in the Microtox assay. Toxicity tests for wastewater samples using the YH9-RC-based toxicity assay showed that EC50-5 min values in an untreated raw wastewater sample (23.9 +/- 12.8%) were the lowest, while those in an effluent sample (76.7 +/- 14.9%) were the highest. Lyophilization conditions were optimized in 384-multiwell plates containing bioluminescent bacteria that were pre-incubated for 15 min in 0.16 M of trehalose prior to freeze-drying, increasing the recovery of bioluminescence and viability by 50%. Luminously modified cells exposed to continuous phenol or wastewater stream showed a rapid decrease in bioluminescence, which fell below detectable range within 1 min. An advanced toxicity test system, featuring automated real-time toxicity monitoring and alerting functions, was designed and finely tuned. This novel continuous toxicity test system can be used for real-time biomonitoring of water toxicity, and can potentially be used as a biological early warning system.     

一株白腐菌的食用安全性初步评价

本研究选取了一株白腐菌模式菌株进行了小鼠急性毒性试验、小鼠骨髓嗜多染红细胞微核试验以及小鼠精子畸形试验,以分析该白腐菌的食用安全性,为进一步应用白腐菌开发功能性食品提供数据支持。结果显示,小鼠经灌胃白腐菌,其LD50为6.76 g/kg(以白腐菌菌丝干重计)。微核试验和精子畸形试验结果均为阴性(P0.05)。试验结果表明,本次实验条件下,白腐菌对小鼠表现出一定的急性毒性,但未见遗传毒性,由此推断,在一定剂量范围内使用白腐菌作为食用材料是相对安全的,安全的剂量范围需要进一步扩大浓度梯度来确定。     

Toxicity analysis of freshwater and marine sediments with meio- and macrobenthic organisms: a review

Benthic metazoans play a key role as test organisms in toxicity analyses of aquatic ecosystems. This report gives an overview of the species of benthic metazoans used for the assessment of toxicity in freshwater and marine sediments, as well as of the criteria relevant to the choice between test species and procedures. The main applications of these organisms are mono-species bioassays, test-batteries, analyses of benthic communities and bioaccumulation studies. Sediment toxicity assays, including acute and chronic exposures, have been developed for nematodes, insects, oligochaetes, polychaetes, crustaceans, molluscs and echinoderms. At least 30 species of freshwater and 71 species of marine and estuarine benthic metazoans have thus far been used in sediment toxicity bioassays. Although aquatic pollution is a world-wide problem, most sediment toxicity bioassays have been developed for organisms native to Europe and North America. The most common bioassay endpoints are mortality, development, growth and behavioural responses. The value of genetic, biochemical, physiological and pathological responses as toxicity endpoints is currently being investigated. The quest for additional test species and protocols is still a worthwhile endeavour in sediment ecotoxicology.     

Development of pertussis vaccine production and control in the National Institute of Public Health in the Netherlands during the years 1950–1962

The development of the pertussis vaccine production in the National Institute of Public Health in the Netherlands since 1953, and the results with the consecutive lots of vaccine in the mouse protection test and the U.S.A. toxicity test are described. The results in the latter test are compared with the results of a locally developed guinea pig toxicity test. Special attention is given to the difficulties encountered when the U.S.A. toxicity test is used for adsorbed DPT vaccines. The potency data of all lots of DPT vaccines produced since 1958 fall within the limits of the potency test as prescribed in the U.S.A. Minimum Requirements. There are indications that the increased potency of the vaccine may have led to a lower mortality rate of pertussis.     

A need for careful evaluation of endotoxin contents in acellular pertussis-based combination vaccines

Two batches each of diphtheria-tetanus-acellular pertussis vaccine (DTaP) and that combined with inactivated polio vaccine purchased from foreign markets were tested by mouse body weight decreasing (BWD) toxicity test and Limulus amaebocyte lysate (LAL) test. Three out of the four imported vaccine batches showed the levels of BWD toxicity even comparable to that of DT-whole cell pertussis vaccine. BWD toxicity test is based on endotoxin dose-dependent weight loss of mice and has been used for controlling endotoxin in DTaP. Although of the strong BWD toxicity of the imported vaccines, there was no marked difference in LAL test results between the imported vaccines and Japanese DTaP. However, one imported DTaP batch showed very strong interference with LAL activity of spiked lipopolysaccharide (LPS). The batch interfered not only with LAL activity but also with pyrogenicity and prostaglandin E₂ induction activity. However, the pyrogenicity of the spiked LPS could be recovered from the precipitated fraction of the batch by treating with phosphate buffer to suggest the possibility of recovering in vivo toxicity. As an adequate in vitro test method could not be identified for controlling the safety of the interfering batch, an appropriate in vivo test would be required for testing such vaccines.     

中草药烟熏对空气消毒及预防呼吸道传染病作用的研究

为了空气消毒和预防呼吸道传染病,生产了中草药烟熏剂"寿而康空气消毒保健香"。经中国人民解放军第二军医大学等单位检测,杀灭空气中细菌有效率99.95%。急性经口毒性试验LD50>5000mg/kg,慢性毒理试验观察未发现中毒和蓄积中毒,属于实际无毒类。现场试验自然菌杀灭率90%以上,对预防呼吸道传染病流感、流脑等效果显著。     

Use of a rapid bioluminescence assay for detecting cyanobacterial microcystin toxicity

The recent rise in the awareness of the occurrence of toxic cyanobacterial blooms in aquatic environments, with associated human health problems and animal deaths, has increased the need for rapid, reliable and sensitive methods of determining cyanobacterial toxicity. A luminescent bacterial toxicity test was assessed as a complement to the established mouse bioassay. Seventeen samples including pure cyanobacterial microcystin-LR hepatotoxin, laboratory isolates and natural blooms of cyanobacteria were tested and toxicity data compared with mouse LD50 values. Microcystin-LR and all five microcystin-containing cyanobacterial samples, hepatotoxic by mouse test gave EC50 values of less than 0.46 mg/ml in bioluminescence-based Microtox assays. Of 11 samples non-toxic by mouse bioassay, only two gave an EC50 of less than 0.98 mg/ml by bioluminescence assay. It is suggested that the Microtox bioluminescence assay may prove useful in the preliminary screening of cyanobacterial blooms for microcystin-based toxicity.     

斑马鱼胚胎发育技术在毒性评价中的应用

对斑马鱼（Brachydanio rerio)胚胎发育技术在环境科学领域的应用作一综述,斑马鱼胚胎毒性技术是各国际标准组织认可的标准毒性测定方法之一,属于致畸效应检验,该项技术成本低、易操作、灵敏度高,特别是具有可记录多项毒性指标的特点,并可以此判断污染物的致毒机理,斑马鱼胚胎发育过程受重金属影响较大,其中Cu的毒性最强,Hg次之,Cr最弱,有机农药中三苯基锡类（TPTA）的毒性最强,林丹次之;有机试剂中含卤素取代基和苯胺类毒性最大,这与其它毒性测定方法的结果完全一致,并表现出较高的灵敏度,特别是选用非致死性的指标,可以初步认定这对测定复合污染物毒性并分析毒物的致畸效应方面有很好的发展前景。     

中药异位康冲剂治疗子宫内膜异位症小鼠的研究

目的：探讨中药异位康冲剂对小鼠子宫内膜异位症的作用及可能机理。方法：通过对小鼠一般情况、血常规、肝肾功及各主要脏器的组织学观察,观察中药异位康冲剂急性和长期毒副作用。通过一般情况、阴道脱落细胞观察、激素检测、病理组织学检查及血液流变学的改变,了解中药异位康冲剂对小鼠子宫内膜异位症模型的药理作用。结果：急性和长期毒性实验表明,中药异位康冲剂无明显毒性反应。异位康冲剂能抑制大鼠子宫内膜异位模型,降低血清雌二醇水平（P〈0.01）。病理学观察显示异位子宫的内膜腺体及腺上皮明显萎缩,其作用与丹那唑相似。结论：中药异位康冲剂无明显毒副作用,可促进子宫内膜异位组织细胞凋亡、抑制子宫内膜异位组织增殖,为临床用药提供了实验依据。     

BACTOX, a Rapid Bioassay That Uses Protozoa To Assess the Toxicity of Bacteria

A new type of toxicity test based on the protozoan Tetrahymena pyriformis has been developed to assess the overall toxicity of bacterial strains given as prey. This simple and rapid test is able to detect toxicant-producing bacteria, which may present a biohazard. It can also be used for the risk assessment of microbes designed for deliberate release.     

东湖茶港排污口底泥对稀有鮈鲫的毒性

以东湖茶港排污口底泥复溶水为试验相,采用96h急性毒性试验和胚胎—卵黄囊吸收阶段毒性试验方法,研究了东湖茶港排污口底泥对稀有的鮈鲫毒性。结果显示,高浓度的复溶水对稀有鮈鲫胚胎、仔鱼和幼鱼具有明显的毒性效应,而胚胎—卵黄囊吸收阶段更为敏感。随着复溶水浓度的增加,稀有鮈鲫受精卵孵化率降低,仔鱼畸形率增高、成活率降低、生长减慢;对胚胎—卵黄囊吸收阶段的NOEC、LOEC和MATC分别为12.5%、25%和17.68%;对幼鱼96h LC50为69.1%。本文的研究还表明,底泥经晾晒后毒性大幅降低,暗示恢复东湖通江状态并让水位自然涨落,可能有助于缓解污染、恢复生态环境。     

基于多种微生物的毒性检测MTOXPlate冻干板制备及优化

[目的]制备基于多种微生物的生物毒性检测MTOXPlate冻干板,从而简化操作程序,使其能更灵敏、方便、快速地进行生物毒性测试.[方法]采用真空冷冻干燥法将指示微生物固定在微孔板中.以存活率为指标,利用荧光分光光度法确定冻干保护剂的组成.通过分析毒性响应灵敏度对检测条件进行优化.[结果]MTOXPlate的冻干保护剂组成为8％海藻糖、2％葡萄糖、2％甘露醇、1％谷氨酸钠.在此组成下,11株菌株的平均存活率最高,可达89.41％.复活介质与测试样品同时加入,在缩短了测试时间的同时也提高了检测灵敏度.该冻干板具有良好的灵敏度和重现性,能较好地满足污染物生物毒性测试的需要.[结论]MTOXPlate冻干板可作为一种新型的生物毒性测试技术,在生态毒理检测领域推广应用.     

Chinese Hamster Ovary (CHO) Cell Clustering Does Not Correlate With In Vivo Histamine-Sensitization When Measuring Residual Activity of Aldehyde-Treated Pertussis Toxin (PT)

CHO cell clustering test failed to detect a reversion to PT toxicity of a commercial DTaP vaccine batch that failed to pass the test for reversion to histamine sensitizing (HS) activity. Efficacy of CHO cell clustering assay was, accordingly, evaluated using purified PT treated with graded concentrations of formaldehyde at 37 degrees C for 24h. The formaldehyde-treated PT was shown to lose CHO cell clustering activity to the level of 0.01% by the mild treatment while retaining 3.7-20.3% of HS activity which were far over the levels of commercial vaccines. When a reversion to toxicity of the aldehyde-detoxified PT was examined by incubating at 37 degrees C for three weeks, CHO cell clustering test again failed to detect the reversion to toxicity of the PT which showed a remarkable reversion to HS activity. These findings suggested that CHO cell clustering test might have an efficacy limitation in predicting in vivo activity of aldehyde-treated PT.