美国NRC支持将苯乙烯列为致癌物

<正>2014年7月29日美国国家研究委员会(NRC)支持国家毒理学计划在其第12份《致癌物报告》中将苯乙烯列为"有理由预期是一种人类致癌物"的物质。美国国会在2012年授权NRC审查苯乙烯的该列入。NRC负责进行这项审查的委员会对上述《致癌物报告》列入进行了一项同行评议,并对苯乙烯研究文献进行了一项独立评估后得出结论:该列人基于人类研究中"有限但可信的"致癌性证据、充分的动物研究证据以及苯乙烯暴露对人类细胞DNA损害机制研究中的"具有说服力的相关信息"。同时,NRC研究了该文件中引用的主要文献以及在2011年6月10日以后发表的其他研究,发现《致癌     

环境致癌物与肿瘤发生

癌症已成为严重威胁人类生命与健康的疾病之一，所以，有关恶性肿瘤的病因、发病机理及预防措施等的研究一直受到世界各国的重视；而在肿瘤的病因学研究中发现，由环境因素导致的肿瘤占９０％以上，因此，环境致癌物的致癌机理研究一直是人们研究的热点，本文对环境致癌物的种类、致癌作用及机理等进行了综合评述。     

拉萨市垃圾填埋场地下水水质的居民健康风险评价

对拉萨市垃圾填埋场地区地下水6个监测井中的Cr~(6+)、As、Cd、Pb、NO~-_3-N、F~-、Cl~-指标采用美国环保局USEPA推荐的健康风险评价模型,按照不同人群进行健康风险评价.评价结果表明,通过暴露剂量计算,在饮水途径和皮肤接触途径下非致癌物暴露剂量一般高于致癌物暴露剂量;饮水途径暴露剂量高于皮肤接触途径下的暴露剂量.致癌污染物在饮水途径下风险值大于皮肤接触途径下的风险值,其中饮水途径下风险贡献为Cr~(6+)AsCd,Cr~(6+)风险值超过USEPA的最大可接受水平1×10~(-4);在皮肤接触途径下贡献为Cr~(6+)AsCd,Cr~(6+)的风险值超过瑞典环保局、荷兰建设环保局、英国皇家协会和IAEA最大可接受风险水平;非致癌风险的污染物贡献最大的是Cl~-,其通过饮水暴露途径在成人中风险值高于瑞典环保局(1×10~(-6))、荷兰建设环保局(1×10~(-6))、英国皇家协会(1×10~(-6))和IAEA(5×10~(-7))最大可接受水平.因此,致癌物中Cr~(6+)成为主要的致癌物,人们在饮水中要将其去除,起到预防癌症和减少患癌的几率.     

西南某矿区家庭灰尘中重金属的暴露及其健康风险评价

家庭灰尘是人群居住场所的重要环境介质,人群可通过吸入、摄食及皮肤接触等途径摄入灰尘中的污染物,对健康造成一定的损伤。为探索我国西南某矿区周边村庄室内重金属的污染对人群健康的潜在风险,采用2014年3月对我国西南某矿区周边村庄室内灰尘中重金属污染水平调查的数据,结合美国EPA健康风险评价模型对人群健康风险进行分析。结果表明:人群非致癌风险和致癌风险暴露剂量均表现为儿童>成人男性>成人女性,呈现手-口摄食途径>皮肤接触途径>吸入途径,其中儿童、成人男性和成人女性手-口摄食暴露途径占总暴露剂量的98.16%、55.61%和51.5%;儿童以Pb、Cr的暴露为主,成人以Cr的暴露为主;家庭灰尘中单种重金属元素和多途径叠加的非致癌风险在8.81E-03~1.24E-02之间,均小于1,其中儿童以Pb的非致癌风险为主,经手-口摄食暴露占总风险的40%;致癌风险在4.19E-05~3.35E-04之间;A、B、C村儿童的致癌风险均高于US EPA所推荐的可接受水平10-4,其暴露剂量和健康风险均为成人男性和成人女性的5~6倍,且以Cr通过手-口摄食暴露产生的风险最大,占总风险的93%左右。     

N-亚硝基二甲胺(NDMA)的环境过程和毒理效应

N-亚硝基二甲胺(NDMA)是一种工业和环境污染物,具有强烈的致癌、致畸和致突变毒性;实验证明它可导致动物很多器官包括肝脏、肺和肾脏的癌症;它几乎无处不在,广泛分布于人类的生活环境中,已引起了人们的高度重视。在综合了大量文献的基础上,充分总结了NDMA的物理和化学性质、来源、毒理学信息和暴露途径等,并就研究中尚未解决的问题作了讨论,以期为NDMA的人类毒理效应研究以及各类标准的制定提供科学依据。     

专家质疑评估混合物的不确定性系数

2013年7月11日来源:环境卫生权威混合物毒理学专家认为,不能假定在评估对单独化学物质的暴露构成的健康风险时通常使用的缺省不确定性系数,以免遭受化学混合物的潜在有害影响。不确定性系数长久以来被用于将毒理学结果由实验动物研究外推到人类。由Andreas Kortenkamp领     

镉致癌的分子机制研究进展

镉是一种无处不在的重金属环境污染物,广泛用于工业环境中。普通人主要通过摄食、吸烟及饮水等方式摄入镉。1993年国际肿瘤研究机构(IARC)就已将镉及其化合物列为第1类人致癌物,镉的致癌性被广泛研究,大量研究发现镉会提高肺癌、前列腺癌、乳腺癌、消化道肿瘤等肿瘤的患病风险。但至目前为止,镉的致癌分子机制尚不清楚。大量研究认为镉通过以下几方面致癌:氧化应激、抑制DNA损伤修复、DNA异常甲基化、抑制细胞凋亡、影响细胞周期调控、致多种基因异常表达、雌激素样效应、促进肿瘤干细胞生长、慢性炎症刺激。     

室内环境中全（多）氟烷基化合物的分布特征和暴露风险

全（多）氟烷基化合物（PFAS）是一类人工合成、应用广泛、高度氟化的化合物,由于数量众多及其持久性、生物累积性和潜在毒性,其暴露风险受到越来越多关注。人体可能通过食物、饮水、室内空气和灰尘等多种介质暴露于PFAS,当前研究多集中于饮水和食品暴露途径,较少针对室内空气和灰尘的人体暴露进行评估。然而人类通过室内环境介质对PFAS的暴露不可忽视,尤其对婴儿而言。该文综述了室内环境中释放PFAS的各类产品,PFAS在不同介质中的分布特征以及人体暴露于PFAS的途径,重点分析了不同人群的暴露特点和PFAS生物有效性的研究进展,提出了降低室内PFAS浓度的有效措施。发现皮肤接触暴露途径的研究数据较少,室内环境中PFAS从产品到室内的迁移转化机制尚不清楚,此外,目前的研究大多是通过检测膳食、饮水、灰尘、空气等环境介质中的PFAS浓度,然后通过风险评估模型去计算外暴露水平,或者通过尿液、血液、头发等检测PFAS的内暴露水平,外暴露和内暴露研究是相对独立的,二者之间的关联并不明确。众多研究已经表明,很多PFAS类型在各种暴露源中均有高水平检出,仅通过已有的体外暴露风险评估模型对外暴露风险的评估可能高估了...     

有机磷阻燃剂的环境暴露与动物毒性效应

有机磷阻燃剂(OPFRs)逐渐替代了危害较大的多溴联苯醚(PBDEs),因此使得人类及其他生物更易暴露于这种有机物中。有研究表明,部分有机磷酸酯具有致癌性,因而使人们对其毒性的问题也日益关注。本文概述了有机磷阻燃剂的环境暴露水平,总结了近年来从体外与体内实验2个方面动物毒性效应的研究。目前研究发现诸多地区的大气、土壤和水体中的有机磷阻燃剂总含量水平相对较低;仅高浓度暴露才会对不同动物体造成一定程度的损伤,而远大于环境浓度的低浓度暴露几乎无损伤效应。最后,对有机磷阻燃剂毒性效应的未来研究重点进行了展望。     

打印机使用过程中颗粒物等有害因素释放及其毒理学效应研究进展

打印机的应用日趋广泛,其释放的颗粒物质尤其是纳米颗粒引起人们的高度关注。现有研究已经证明纳米级颗粒物更容易进入呼吸系统,穿越气血屏障,随之引起机体的氧化损伤、炎症反应和遗传毒性等。打印机释放颗粒的暴露水平评价及其毒理学效应识别是评估打印机健康风险的基础。本文综述了打印机工作场所颗粒暴露水平的监测结果、实验室模拟研究进展、人体采样评价、流行病学调查、体外细胞或整体动物水平毒理学效应评价方法及结果,并提出了打印机危害评估过程的标准化方案建议,以利于不同研究间的比较和总结。     

Characteristics of heavy metal absorption of river bed sludge components

Chronic inhalation of aerosols of different Cd compounds by rats gave sufficient evidence that inhaled Cd is a lung carcinogen in rats. In contrast, the evidence in humans has been termed limited that inhaled Cd causes lung cancer in occupationally exposed humans. In order to assess the carcinogenic potential of ambient air concentrations of Cd, the accumulated dose of Cd in lung tissue from a rat inhalation study was modelled taking into account deposition and retention of Cd in the lung. A lung Cd—cancer incidence relationship could then be established, and an equivalent human exposure could be calculated using man specific pulmonary Cd retention and deposition data for Cd containing particle sizes in the ambient air. Linear interpolation to low doses showed that the pulmonary carcinogenic risk from inhalation of environmental airborne Cd is generally very low, but may reach about 1 × 10^‐4 in polluted industrialized areas. Combined exposures to Cd plus other carcinogens or air pollutants may increase the risk considerably. Cd in cigarette mainstream smoke was estimated to contribute less than 5 % of the total lung cancer risk from smoking cigarettes. However, the influence of co‐exposure to other compounds in cigarette smoke is not known and should be taken into account.     

Is using nanosilver mattresses/pillows safe? A review of potential health implications of silver nanoparticles on human health

Human exposure to engineered nanoparticles has become inevitable in today’s extensive commercial use and large-scale production of engineered nanoparticles. Even though several studies have characterised the exposure to nanomaterials during wakeful state (related to occupational exposures and exposures from commercially available particles), very few studies on human exposure during sleep exist. As the study of exposure to all possible nanomaterials during sleep is extensive, this study focuses on exposure to specifically silver nanoparticles which are present in beddings and mattresses. The reasoning behind the use of silver nanoparticles in bedding and related materials, possible routes of entry to various population groups in several sleep positions, exposure characterisation and toxicity potential of such silver nanoparticles are reviewed in this study. The toxicity potential of silver nanoparticles in vivo tests with relation to mammals and in vitro tests on human cells has been tabulated to understand the risks associated during oral, dermal and inhalation exposure to silver nanoparticles. The exposure to humans with regard to dermal absorption and oral intake has been summarised. Although potential inhalation exposure to silver nanoparticles is increasing, only a few studies address the possible toxic effect of inhaled silver particles. Determination of exposure to silver nanoparticles in beddings is a topic that has been less researched, and this review aims to provide background information for future research and help establish a comprehensive risk assessment during sleep in the times of increasing usage of nanoparticles in our daily activities. Despite the current limitations of our understanding, risk assessments must utilise the available data and apply extrapolation procedures in the face of uncertainty, in order to address the needs of regulatory programs. This would enable safe use of the antimicrobial properties of silver nanoparticles without negatively impacting human health. Until then, it would be better to adopt a conservative approach on the usage of silver nanoparticles in daily used commercial items.

     

Human carcinogenesis by arsenic

Arsenic is one of the few human carcinogens for which there is not yet a reliable animal cancer model. As such, the classification of arsenic as a carcinogen is based upon data derived from human epidemiologic studies. Although the mechanisms of action of arsenic as a toxic agent have been known for many years, the inability to produce cancer with arsenic in laboratory animals has confounded the operational characterisation of arsenic as initiator, promoter, complete carcinogen, or cocarcinogen for humans. Arsenic is clearly a genotoxic agent that induces chromosomal aberrations, micronuclei and sister chromatid exchange in mammalian cells as well as neoplastically transforms Syrian hamster embryo cells; however, it is not a classical point mutagen. This paper reviews some of the scientifically based issues relating to arsenic and risk assessment.     

Feasibility of metabolic parameter estimation in pharmacokinetic models of carbon tetrachloride exposure in rats1

Carbon tetrachloride (CCl₄) is a toxic chemical that was once used in degreasers and detergents, and some remnants of the chemical may be present in the water supply. Physiologically-based pharmacokinetic (PBPK) modeling can assist in understanding resulting internal doses of CCl₄ after exposure, but the pharmacokinetic parameters describing the metabolism of CCl₄ are not well characterized. The goal of this study was to provide insights into how to more accurately estimate these values in rats using PBPK modeling and data from previous studies. Three different PBPK models were constructed to describe CCl₄ exposure in rats via inhalation, oral ingestion, and venous injection. Each of these models was compared to data, and sensitivity analysis was performed for each model to determine whether the available data could be used to accurately determine the metabolic parameters of interest. These parameter sensitivities were so low that optimization to the available data yielded physiologically unrealistic results. Model sensitivities were analyzed for different doses and routes of exposure in order to find experimental conditions that would allow for greater identifiability of the metabolic parameters. Data were simulated from these models at optimal conditions with varying levels of noise from a normal distribution. Optimizations were then performed to confirm that the original values could be obtained. The experiments developed are left as suggestions for investigators who wish to further pursue estimating these metabolic parameters.     

Susceptibility of male and female Japanese medaka (Oryzias latipes) to 2,4,6-trichlorophenol-induced micronuclei in peripheral erythrocytes

2,4,6-trichlorophenol (2,4,6-TCP) is a widespread probable human carcinogen and has been proven to have genotoxicity in in vitro assays. However, little genotoxicity information and no micronuclei induction data for 2,4,6-TCP is available from in vivo tests, especially for sex-specific differences. Following a preliminary test, a piscine peripheral erythrocyte micronucleus assay was conducted on medaka (Oryzias latipes) after a 28-day exposure to 2,4,6-TCP. In the present study, the mean micronuclei (MNC) frequencies of all of the groups increased in a dose-dependent manner, which indicated the potential genotoxicity of 2,4,6-TCP. Moreover, males were found to be more susceptible compared with females after a 28-day exposure to 2,4,6-TCP in all of the dosed groups above 10 μg·L^?1. This is the first report on the potential of micronuclei induction and a sex-susceptible effect in the peripheral erythrocytes of mature fish after 2,4,6-TCP in vivo exposure.     

Oral bioaccessibility of inorganic contaminants in waste dusts generated by laterite Ni ore smelting

The laterite Ni ore smelting operations in Niquelândia and Barro Alto (Goiás State, Brazil) have produced large amounts of fine-grained smelting wastes, which have been stockpiled on dumps and in settling ponds. We investigated granulated slag dusts (n = 5) and fly ash samples (n = 4) with a special focus on their leaching behaviour in deionised water and on the in vitro bioaccessibility in a simulated gastric fluid, to assess the potential exposure risk for humans. Bulk chemical analyses indicated that both wastes contained significant amounts of contaminants: up to 2.6 wt% Ni, 7580 mg/kg Cr, and 508 mg/kg Co. In only one fly ash sample, after 24 h of leaching in deionised water, the concentrations of leached Ni exceeded the limit for hazardous waste according to EU legislation, whereas the other dusts were classified as inert wastes. Bioaccessible fractions (BAF) of the major contaminants (Ni, Co, and Cr) were quite low for the slag dusts and accounted for less than 2 % of total concentrations. In contrast, BAF values were significantly higher for fly ash materials, which reached 13 % for Ni and 19 % for Co. Daily intakes via oral exposure, calculated for an adult (70 kg, dust ingestion rate of 50 mg/day), exceeded neither the tolerable daily intake (TDI) nor the background exposure limits for all of the studied contaminants. Only if a higher ingestion rate is assumed (e.g. 100 mg dust per day for workers in the smelter), the TDI limit for Ni recently defined by European Food Safety Authority (196 µg/day) was exceeded (324 µg/day) for one fly ash sample. Our data indicate that there is only a limited risk to human health related to the ingestion of dust materials generated by laterite Ni ore smelting operations if appropriate safety measures are adopted at the waste disposal sites and within the smelter facility.     

Indium tin oxide nanoparticles-mediated DNA fragmentation and cell death by apoptosis in human lung epithelial cells

Indium tin oxide (ITO) nanoparticles (NP) have extensive applications in industrial fields, and concerns regarding their potential toxicity in humans and environmental impact have increased. Since exposure to ITO NP is mainly via skin and inhalation, this study was conducted utilizing human lung epithelial (A549) cell line. Cells were exposed to different concentrations of the ITO NP for 24 and 48 hr. A severe cytotoxic response of ITO NP was observed as evident by the (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red uptake assays after 48 hr exposure. ITO NP significantly reduced glutathione levels with a concomitant increase in lipid hydroperoxide levels, superoxide activity, and reactive oxygen species (ROS) generation after exposure. A significant induction in caspase activity and formation of condensed chromosomal bodies was also observed after ITO NP (10 or 25 µg/ml) exposure. Furthermore, a significant induction in DNA damage was observed by the Comet assay in cells exposed to ITO NP. Our data demonstrate that ITO NP display cytotoxic and genotoxic potential. However, increase in ROS levels and oxidative stress leading to oxidative DNA damage and condensed chromosomal bodies formation, suggests involvement of apotosis. Thus, ITO NP-mediated effects on cell viability indicate cytotoxicity, and therefore, exposures need to be carefully monitored in the industrial sector.     

Dioxins: Sources of environmental load and human exposure

Polychlorinated dibenzo‐p‐dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) represent a class of tricylic, almost planar, aromatic ethers with 1 to 8 chlorine atoms. Congeners with substituents in the positions 2, 3, 7, and 8 are of special concern due to their toxicity, stability, and persistence. These compounds have been identified in almost all environmental compartments and humans.

Dioxins are a potent carcinogen for animals and—at the moment—considered a probable carcinogen for humans. Actual toxicological risk assessment for humans are based on 2,3,7,8‐Cl4DD carcinogenicity studies on rodents. Tumorigenic effects were found for 2 strains of rats and 2 strains of mice. All dioxins and furans elicit common toxic and biological responses, starting with a specific binding to a protein receptor, but existing epidemiologic data do not provide definitive data on human health effects.

Toxicity equivalency factors (TEFs) have been developed by several agencies as a provisional method of risk assessment for complex mixtures of PCDD/PCDF.

Dioxins have never been produced intentionally and have never served any useful purpose. They are formed in trace amounts as by‐products in industrial processes; for instance within the chemical industry, of the pulp and paper industry, metallurgical processes, processes for reactivation of granular carbon, dry cleaning, and the manufacture of flame‐retarded plastics.

The main pathway for dioxins to enter the environment is via combustion processes. Incineration is of special importance since PCDD/PCDF are directly released to the atmosphere from either stationary sources, such as municipal, hazardous and hospital waste incinerators, the combustion of sewage sludge, and scrap metal recycling, or diffuse sources, e.g. automobile exhausts, private home heating with fossil fuels, forest fires, and cigarette smoking. Furthermore, fires with PCB and PVC have additionally contributed to the total dioxin load. The emission gases can undergo long‐range transport, so that dioxins have been found even in remote areas.

Besides the two primary sources (industrial processes and combustion processes) the release of dioxins from contaminated areas and waste dumps via the leachate and the application of sewage sludge for fertilization represents a third source of PCDD/PCDF.

After more than 10 years of dioxin research the most important sources of PCDD/PCDF have been identified and analytical methods have been developed for their quantification in trace levels and in complex matrices.

Various efforts have been undertaken to reduce the emission of dioxins: for example, optimization of combustion processes for municipal waste incineration, use of unleaded gasoline, ban of chemicals, such as polychlorinated biphenyls (PCBs) and pentachlorophenol (PCP). More detail is provided in the pulp and paper section where changes have been initiated to significantly reduce the sources of PCDD/PCDF.

However, relatively little is known about transport and transformation processes, so only rough estimates can be made. Photodegradation has been found to be the primary process for 2,3,7,8‐Cl4DD breakdown. A half‐life of 3–4 days has been estimated for photochemical degradation under oxidative conditions. Field studies on the fate of 2,3,7,8‐Cl4DD in soil gave a half‐life of 9.1 (Seveso) and 12 years (under special conditions: sand, erosion), respectively. Biodegradation seems to be negligible. Transfer factors soil‐plants for PCDD/PCDF have been determined—with a high degree of uncertainty—to be less than 0.1.

Human exposure primarily occurs via ingestion whereas inhalation is a minor pathway. Dermal absorption can be neglected although skin contact to polluted surfaces may occur. Due to the lipophilicity of PCDD/PCDF and their potential for accumulation, foods such as meat and especially dairy products contribute most to the dioxin body burden of humans.

Both national agencies and international organizations have recognized the significance of this problem and as a result have initiated regulations, recommendations and research programmes (1) to understand where and how PCDD/PCDF are formed, (2) to reduce their impact on the environment and to humans, and (3) to start remedial action on contaminated areas.     

Risk assessment for ingested inorganic arsenic: A review and status report

Arsenic presents several unique problems in risk assessment. First, there is no good animal model for arsenic as a carcinogen, although in humans arsenic exposure through inhalation is judged to cause lung cancer and ingested inorganic arsenic is judged to cause skin cancer. Second, detoxification of arsenic through methylation is believed to be important, but the mechanisms and the quantitative relationships are not yet understood.EPA provided a risk assessment for ingested inorganic arsenic in its 1984 Health Assessment Document and a revised version in 1988. In both cases EPA calculated a cancer potency or slope factor using epidemiological data from Taiwan. EPA's standard or default risk assessment procedure is to use the linear coefficient from the multistage model in order to calculate cancer risk. This procedure was challenged by the EPA Science Advisory Board (SAB) in a report to the Administrator in September of 1989. The SAB recommended that EPA (1) develop a revised risk assessment based on estimates of the delivered dose of non-detoxified arsenic to target tissues, and (2) consider the potential reduction in cancer risk due to detoxification in establishing an MCL for arsenic.This paper will draw upon the author's experience with the SAB to summarise major issues in arsenic risk assessment and to examine how these issues might be resolved through further research.     

Trace analysis of airborne toluene diisocyanate as a pentafluorobenzyl derivative by gas chromatography with electron capture detection

Trace analysis of airborne toluene diisocyanate (TDI) vapor was accomplished by measuring the derivative using gas chromatography with electron‐capture detector after collecting gas samples with a microimpinger containing 2 ml toluene, 1 μl pentafluorobenzyl alcohol, and 1 μl triethylamine. The sampling efficiency was determined to be 99.4% for short‐term exposure level of TDI and the 2,4‐ and 2,6‐isomers of TDI were well separated. The derivative was identified to be a new compound with a molecular weight of 570 by mass spectrometry in fast atomic bombardment mode and nuclear magnetic resonance spectrometry. This method is convenient and can be applied in the field where airborne TDI is in vapor form.