Effect of malathion on reproductive system of male rats

The pesticides are one of the most potentially harmful chemicals liberated in the environment in an unplanned manner Malathion is widely used as a potent pesticide in many countries and has been shown to produce some adverse health effects. A study was conducted to asses the effects of malathion on the male reproductive system of wistar rats. The pesticide was administered to rats orally at dose levels of 50, 150 and 250 mg/kg/body wt/day for 60 days. In comparison to the control rats, there was a significant reduction in the weight of testes, epididymis, seminal vesicle and ventral prostate. Testicular and epididymal sperm density were decreased in the animals treated with malathion. Pre and post fertility test showed 80% negative results after treatment Biochemical profile of the testis revealed a significant decline in the contents of sialic acid and glycogen. Whereas a significant increase in the protein content of testis and testicular cholesterol was observed. The activity of testicular enzyme acid phosphatase increased significantly while decreased alkaline phosphatase activity was found. Malathion also suppressed the level of testosterone significantly Results of the present study clearly suggest that malathion induce toxic effects on the male reproductive system of rats.     

环境化学物对雄(男)性生殖损伤的评价指标及检测技术

随着工业的迅速发展,迄今为止,已有大约10万种化学物进入人们的日常生活.人们在生产和生活中接触的许多种环境化学物都会影响人类的生殖功能,使人类的生育能力特别是精子的质量和数量发生显著改变.环境化学物所造成的生殖损伤日益受到人们的重视,检测方法和检测技术日益成熟和完善.但大多数环境化学物对生殖的损害目前尚未得到全面地研究和认识,某些毒物的生殖毒性也需要重新认识与评价,生殖毒理学的研究任务迫切而艰巨.动物实验是生殖毒性评价中最主要的方法.在总结近年来国内外相关研究基础上综述了环境化学物动物实验中雄(男)性生殖损伤评价指标及检测技术,以期对环境化学物生殖毒性评价提供借鉴和参考.     

Östrogene Wirkung von Xenobiotika

A number of xenobiotic organic substances are known which, in cases of prenatal exposition, may produce an estrogenic effect leading subsequently to serious reproductive disorders in the male progeny. Damage of this kind which is seen to occur in wildlife populations leads to the assumption that environmental chemicals exerting such estrogenic effects may be responsible for these disorders. Listed here are environmental chemicals which are known to date to exert an estrogenic effect. The article provides a review of papers and hypotheses on the estrogenic effects of xenobiotic substances. This is followed by a discussion concerning the significance of chemical estrogenicity on environmental and chemical policies as well as on the possibilities and limitations of test systems for the verification of estrogenicity.     

Organophosphorous compounds and oxidative stress: a review

Organophosphorous compounds (OP) have largely been used as pesticides globally. These chemicals induce oxidative stress as a possible mechanism of action, which has been a focus of toxicological research for the last decade. This review evaluated the presence of oxidative stress, balance between total antioxidant capacity, and oxygen free radicals associated with OP compound exposure. Oxidative stress induced by OP leads to disturbances in function of different organs and tissues. Evidence indicates that stimulation of free radical production, induction of lipid peroxidation, and disturbance of the total antioxidant capacity are mechanisms of toxicity induced by most OP. Thus, use of antioxidants may be beneficial in treatment of OP poisoning, which remains to be elucidated with further clinical trials.     

Adult respiratory distress syndrome in human organophosphate poisoning cases

Adult respiratory distress syndrome (ARDS) is a clinical syndrome which occurs due to various direct or indirect noxious agents and pyhsical mechanisms. One of the etiological factors is ingested chemicals (e.g. paraquat, ethylene glycol). The organophosphorous (OP) insecticides are the most toxic and frequently encountered chemicals that produce poisoning in humans. Studies were undertaken to investigate whether OP insecticides may produce ARDS. Fifteen autopsy cases due to suicidal OP insecticide poisoning were investigated. Toxicological analyses were performed with a gas chromatography-nitrogen phosphorous detector (GC-NPD). Methamidophos, dimefox and dichlorvos were the detected OP. Lungs were examined macroscopically. Two cases showed features compatible with ARDS in which the only cause of death was OP poisoning. Due to the severity of ARDS it is important to assess insecticidal exposure in an attempt to enhance survival patterns following OP poisoning in patients in order to initiate therapy.     

有机氯农药硫丹的生殖毒性及其机制研究进展

硫丹作为一种广谱有机氯农药,在农业区域周边的土壤和水体中都存在较高残留,2011年被斯德哥尔摩公约列入持久性有机污染物(POPs)名单。硫丹已被证实对神经系统、心血管系统、肝、肾等具有毒性作用,关于其生殖毒性的研究很多,但潜在机制尚不完全清楚。本文总结了硫丹导致的不同动物的生殖毒性,并从生殖器官和生殖细胞损伤、氧化应激以及DNA损伤、生殖细胞周期阻滞及细胞凋亡等方面,对近年来硫丹生殖毒性及其作用机制研究进展进行综述,并对其中存在的问题进行讨论,以期有助于深入了解硫丹的毒性效应。     

Toxicology of perfluorinated compounds

Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds).     

基于模式生物秀丽隐杆线虫的环境污染物生殖毒性研究进展

由于人类社会的发展,环境污染也越来越严重,研究环境污染物对生态及人类健康的影响极为重要。生殖系统是人和动物繁衍后代的重要系统,常见环境污染物对生殖系统的影响正引起研究人员的广泛关注。秀丽隐杆线虫具有身体透明、品系丰富和遗传背景清楚等优点,为生殖毒理学研究提供了一个便利的平台。以秀丽隐杆线虫为模型已对多种环境污染物的生殖毒性进行了评价。本文重点叙述了重金属、纳米材料、有机物等化学污染,辐射、磁场等物理污染,以及病毒等生物污染对秀丽线虫生殖系统的影响,并归纳讨论了环境污染物造成生殖功能障碍的几种主要机制,如氧化应激、DNA损伤、内质网应激以及神经损伤等,但不同类型污染物的毒性效应与其自身的物化性质紧密相关。环境污染物诱导的生殖毒性中不同响应机制之间的关联性、不同发育阶段的敏感性差异、污染物的传代效应以及有效的缓解方式的筛选等都有待进一步的开展。     

硝基甲苯对小鼠睾丸生殖细胞DNA的损伤作用

为提供硝基甲苯的环境遗传毒理学依据和建立鱼类生殖细胞的培养方法,采用昆明小鼠睾丸支持细胞/生殖细胞共培养法以及彗星实验,研究了2,4-二硝基甲苯(2,4-DNT)、2,6-二硝基甲苯(2,6-DNT)、对硝基甲苯(4-NT)对小鼠睾丸生殖细胞DNA的损伤作用.结果表明,3种受试硝基甲苯化合物均能够诱导小鼠睾丸生殖细胞DNA单链断裂,而且其受损率与剂量对数具有明显的剂量-效应关系.2,4-DNT、2,6-DNT以及4-NT的各个剂量浓度引起细胞DNA损伤的程度,与对照组相比,均具有显着性差异(p<0.01,p<0.05).受试化合物的毒性顺序为2,6-DNT>2,4-DNT>4-NT,DNA的损伤作用二硝基甲苯大于单硝基甲苯.提示在体外条件下,2,4-DNT、2,6-DNT和4-NT具有生殖毒性,可以引起小鼠睾丸生殖细胞DNA损伤.     

Medaka (Oryzias latipes) for use in evaluating developmental effects of endocrine active chemicals with special reference to gonadal intersex (testis-ova).

Japanese medaka (Oryzias latipes) has been widely used for the evaluation of the toxicity of endocrine active chemicals (EACs) and other chemicals as well as for monitoring the adverse effects of effluent discharges in relation to sexual development and function. It is useful for these evaluations for many reasons including the following: 1) it has a short life cycle facilitating studies extending over long phases of development and over multigenerations, 2) it is easy to rear, 3) male and female phenotypes can easily be distinguished on the basis of secondary sex characteristics, and 4) a genetic marker (DMY) is available for identifying the true genotypic sex. Several biomarkers have been found to be useful for identifying the effects of exposure to estrogenic and androgenic chemicals in medaka and they include increased levels of hepatic vitellogenin (VTG) and testis-ova induction in males for exposure to estrogenic chemicals, and decreased levels of hepatic VTG in females and an altered morphology of dorsal and anal fins and formation of papillae for androgenic chemicals. In this paper, we present a critical analysis of the use of medaka as a test species for studies of endocrine disruption and report on the use of sex-related genetic markers and alterations in gonadal development, including the induction of testis-ova formation, for assessing the disruptive effects of EACs. In this paper, we focus on some of the more recent studies and findings.     

Hormonaktive Xenobiotika

Developmental and reproductive processes are most sensitive to the toxic effects of environmental chemicals. Especially alarming is the fact that many groups of industrial chemicals and pesticides are capable of disrupting the endocrine system in man and animals. Of great concern is the reduction in the sperm count in Europe, but also the worldwide increase in a great number of reproductive and developmental disturbances observed in both man and wildlife. A correlation to a high chemical burden has been demonstrated for many different animal species as well as for women. An important consideration in assessing the potential effects of environmental chemicals on the endocrine system is the time at which such an exposure occurs. In the adult organism, hormones initiate functional processes; these effects are usually transient. In early life, hormones control developmental processes and are capable of producing permanent changes in organ structure and function (organizational effects). Therefore, chemical disruption of hormonal functions during development can result in permanent functional changes of the afflicted organ.     

有害结局路径(AOP)框架在水体复合污染监测研究中的应用

由于包含复杂的毒害化学污染物质,水体复合污染一直威胁着人类健康和水生生态安全。对复合污染水体进行监测、评估和治理是水环境管理的重点之一。监测并识别水体关键毒害污染因子是进行水质管理的前提,也是复合污染研究的难点。目前国内外在水复合污染毒性监测研究上主要基于动物活体试验或者生物体外测试。由于受限于毒理学测试方法,常见的应用通常仅关注于某方面的毒性效应或者少数的分子指标,因而受到质疑和挑战。有害结局路径(Adverse outcome pathway, AOP)的概念将化学污染物的结构、致毒的分子启动事件和生物毒性的有害结局建立关联,为污染物的毒性测试、预测和评估提供了新的模式。本文旨在论述有害结局路径在复合污染毒性评估和关键毒害物质鉴别中的指导性价值和意义。在有害结局路径的指导框架下,借助于生物体外高通量测试技术、化学分析的靶向和非靶向分析技术、和生物信息学技术,可以系统地分析化学混合物在分子、细胞水平上健康相关指标的响应水平,评估水体中复杂结构污染物,与不同生态和健康有害结局之间的关联,为水环境评价和优先污染物的筛选管理提供有效支撑。本文通过综述AOP框架在复合水体中毒害物质风险研究的现状和优势,对AOP在水环境环境管理上的应用前景提出展望。     

有害结局路径(AOP)框架在水体复合污染监测研究中的应用

水体复合污染包含低浓度、种类复杂的毒害化学污染物,威胁人类健康和生态安全。监测并识别水体关键毒害污染因子是进行水质管理的前提,也是复合污染研究的难点。目前国内外在水复合污染毒性监测研究上主要基于动物活体试验或者生物体外测试。由于受限于毒理学测试方法,常见的应用通常仅关注于某方面的毒性效应或者少数的分子指标,因而受到质疑和挑战。有害结局路径(Adverse outcome pathway,AOP)的概念将化学污染物的结构、致毒的分子启动事件和生物毒性的有害结局建立关联,为污染物的毒性测试、预测和评估提供了新的模式。本文旨在论述有害结局路径在复合污染毒性评估和关键毒害物质鉴别中的指导性价值和意义。在有害结局路径的指导框架下,借助于生物体外高通量测试技术、化学分析的靶向和非靶向分析技术和生物信息学技术,可以系统地分析化学混合物在分子、细胞水平上健康相关指标的响应水平,评估水体中复杂结构污染物,与不同生态和健康有害结局之间的关联,为水环境评价和优先污染物的筛选管理提供有效支撑。本文通过综述AOP框架在复合水体中毒害物质风险研究的现状和优势,对AOP在水环境环境管理上的应用前景提出展望。     

邻苯二甲酸二(异)丁酯及其替代品的内分泌干扰效应研究进展

邻苯二甲酸二丁酯(di-n-butyl phthalate,DnBP)和邻苯二甲酸二异丁酯(diisobutyl phthalate,DiBP)是广泛用于塑料、树脂和橡胶制品中的邻苯二甲酸酯类增塑剂,曾在各种环境介质中频繁检出.现有研究表明,DnBP和DiBP对人类和其他动物具有显著的内分泌干扰效应以及生殖发育毒性等不...     

Comparative effects of five chelating agents on testicular toxicity in mice induced by acute exposure to cadmium

The aim of this study was to develop new antidotes for cadmium (Cd) since this metal is known to produce mammalian toxicity. N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), diethyldithiocarbamate (DDTC), 2,3-dimercaptopropanol (BAL), and ethylenediamine-tetraacetic acid (EDTA) were studied for their ability to inhibit the adverse effects induced by Cd on mouse testes. The parameters examined included concentrations of Cd, calcium (Ca), iron (Fe), and zinc (Zn) in testes, lipid peroxidation (LPO) levels in testes, lactate dehydrogenase (LDH) activity in serum and reproductive ability of male mice. Mice injected intraperitoneally (ip) with CdCl₂ (2.5?mgCd?kg^?1) after 30?min or 24?h, were then injected ip with chelating agents (400?µmol?kg^?1). Cd increased the concentrations of testicular Ca, Cd, Fe, Zn, and LPO levels as well as the activity of LDH in serum. HBGD and BGD effectively prevented the increase in above indices, and improved the reproductive ability weakened by exposure to Cd. The results suggested that HBGD and BGD are more effective detoxificants in the case of testicular toxicity in mice induced by acute exposure to Cd.     

Comparative Toxicity of PCBs and PBDEs Using Human Cancer Cell Lines and Zebrafish Embryos

研究了6种多氯联苯(PCBs)3,3′,4,4′-四氯联苯(PCB77)、2,3,3′,4,4′-五氯联苯(PCB105)、2,3′,4,4′,5-五氯联苯(PCB118)、3,3′,4,4′,5-五氯联苯(PCB126)、2,3,3',4,4',5-六氯联苯(PCB156)和商业型混合多氯联苯Aroclor1254,两种多溴联苯醚(PBDEs)2,2′,4,4′-四溴二苯醚(PBDE47)、十溴二苯醚(PBDE209)对人类癌细胞生长和斑马鱼脱膜与不脱膜胚胎发育的影响.8种化合物均使用0.01、0.1、1.0、10μmol·L-14个浓度进行1~6d的暴露实验.结果表明,PBDE209在最高浓度10μmol·L-1下对结肠癌细胞HCT116(暴露3d后)和RKO(暴露5d后)具有显著的生长抑制作用,所有化合物均对乳腺癌细胞没有显著影响.相比之下,化合物对受精后5~6h(5~6hpf)的斑马鱼胚胎的毒性效应显得比较明显,而各化合物对胚胎的致畸和致死效应又不相同,其毒性强弱依次为PCB126≈PCB156>PCB1254(Aroclor1254)>PBDE47>PCB77>PCB105≈PCB118≈PBDE209.其中PBDE209在未脱膜暴毒后均无致畸与致死现象,脱膜暴毒后最高浓度才表现出显著意义的致畸作用,而PBDE47在最高浓度下可产生高达80%的致畸率,这说明胚胎绒毛膜具有有效阻挡大分子物质如PBDE209进入的作用.PCBs的毒性效应与其空间结构密切相关.如PCB126和PCB105具有相同的分子式,前者在1μmol·L-1下就引起了显著的致死和致畸效应,而后者即使在10μmol·L-1下也没有显著的效应.实验结果也说明不同类型的实验对象所展示的毒性效应并不相同,化合物对体外培养的细胞和发育中的胚胎具有不同的影响.     

有机紫外防晒剂内分泌干扰效应研究进展

有机紫外防晒剂是一类新兴环境污染物,大量研究表明,部分有机紫外防晒剂能模拟生物体内多种激素的作用,干扰动物和人体正常的内分泌功能,造成严重的健康威胁.本文在大量文献调研的基础上,从个体水平、器官水平、细胞水平和分子水平4个层次,就有机紫外防晒剂对生殖系统、青春期发育、成活率、pS2蛋白、卵黄蛋白原及激素受体等多方面的影响进行了综述,以加深对紫外防晒剂的认识,也为紫外防晒剂的正确使用及相关部门对其进行科学管理提供参考.     

紫外吸收剂在湖泊中的分布及其对底栖动物的毒性效应

紫外吸收剂大量用于工业材料和个人护理品中,近年来在水体中不断被检出,同时由于其高度亲脂性,易在底泥和水生生物体内富集,产生潜在的毒性效应,已成为一类新型污染物。本文综述了紫外吸收剂在湖泊环境中的分布和生物富集效应,重点分析了二苯甲酮类等典型紫外吸收剂对底栖动物的药物代谢系统、抗氧化系统及其生长发育的影响及其毒性作用机制,并对未来该领域的研究进行了展望。     

Systemic risks of genetically modified crops: the need for new approaches to risk assessment

Background

European chemicals legislation (registration, evaluation, authorisation and restriction of chemical substances (REACH)) requires a broad assessment of chemicals with respect to, inter alia, their health-relevant properties. Due to the extreme number of substances to be assessed and the limited current toxicological knowledge on their respective properties, REACH implicitly requires a paradigm change: away from knowledge generated mainly from costly animal experiments towards the use of mechanistic findings. Moreover, effect mechanisms at the biochemical or cellular level are essential when conclusions shall be drawn about "new" endpoints and mixtures of xenobiotics. This study (funded by the German Federal Environment Agency) describes examples of biochemical processes in the mammalian organism and how xenobiotics interfere with them. Interference with physiological processes expected to lead to adverse health effects is characterised as "toxicity pathway". The study describes toxicological endpoints not usually covered in routine animal testing and the respective toxicity pathways.

Results and conclusions

Screening for chemicals which exert effects via common toxicity pathways and subsequently conducting targeted short-term tests may generate new information about the toxicity of chemicals without performing extensive substance-by-substance animal experiments. Information on common toxicity pathways may also provide input for the assessment of mixture effects. The U.S. Environmental Protection Agency is working intensely on this concept. It involves the use of enormous amounts of data on relevant biochemical and cellular processes, which are generated by "high-throughput screening" methods, and then are combined with substance-specific kinetic data, experimental apical test outcomes and modelling. Current limitations in the regulatory use of this integrated approach on risk assessment will be outlined.     

纳米材料对鼠科动物的生殖毒性及致毒机理

纳米材料是近几年应用越来越多的一种新型材料,因此国内外科研单位对其毒性的研究也逐年增加。但是目前对鼠科动物生殖毒性及其机理的了解还相对较少,亟需大量研究填补此领域的空白。本文主要从亲代和子代2个方面阐述了纳米材料对鼠科动物的生殖毒性,从不同生物水平等方面概述了纳米材料对亲子两代鼠科动物的损伤效应及可能的机制。最后,试探性地提出了今后在纳米材料领域对鼠科动物生殖毒性的研究重点。