Hazard Identification

危险源辨识
  • 文章类型: Journal Article
    几个世纪以来,牛奶一直是全球公认的全面和重要的食物来源。然而,牛奶中重金属和类金属(类金属)的存在是一个全球性问题。由于自然地质和各种人为活动,土壤中存在金属(类),这些金属被生物转移到动物饲料中,由于生物转移/积累,这进一步导致牛奶中存在金属(类)。本系统综述整理了2000年至2021年间已发表文献中的信息。它专注于全球牛奶中的金属(loid)问题,带来潜在的健康风险。这些污染物通过从土壤到动物饲料再到牛奶的生物转移/积累过程进入食物链。检查的关键金属(类)是砷(As),汞(Hg),铅(Pb),镉(Cd)。对66篇论文的荟萃分析揭示了这些污染物在全球牛奶样品中的广泛存在,铅是研究最多的(43%)。这项研究估计金属(类)的水平或浓度为12.71(95%置信区间(CI)=0.16-25.26),16.09(95%CI=4.31-27.70),197.04(95%CI=75.28-318.18),砷31.67(95%CI=20.14-43.20)μg/kg(ppb),Hg,Pb,还有Cd,分别使用Stata™。牛奶中的金属(类)浓度在Pb和Cd以外的阈值范围内。在美国的一些研究,非洲,亚洲报告铅和镉浓度升高,引发健康担忧。模拟风险商(RQ)和综合风险商(IRQ)值通常保持在1以上,表明潜在的人类健康风险。值得注意的是,IRQ值随着更多金属(类)的考虑而增加。亚组分析表明低脂牛奶中含有较高的金属(类)浓度。虽然牛奶中的金属浓度在很大程度上符合安全限制,一些地区表现出有关浓度。因此,为了确保乳制品的安全,有必要继续进行监测,以解决与牛奶中金属(类)相关的潜在健康风险。
    Milk has been globally recognised as a comprehensive and vital food source for centuries. However, the presence of heavy metals and metalloids (metal(loid)s) in milk is a global problem. As metal(loid)s are present in the soil due to natural geogenic and various anthropogenic activities, these metal(loid)s are bio-transferred into animal feed, which further results in the presence of metal(loid)s in milk due to bio transfer/accumulation. This systematic review collated information from published literature between 2000 and 2021. It focused on the global issue of metal(loid)s in milk, posing potential health risks. These contaminants enter the food chain through the bio-transfer/accumulation process from soil to animal feed to milk. The key metal(loid)s examined are arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A meta-analysis of 66 selected papers revealed the widespread presence of these contaminants in milk samples globally, with Pb being the most studied (43 %). This research estimated metal(loid)s levels or concentrations as 12.71 (95 % Confidence Interval (CI) = 0.16-25.26), 16.09 (95 % CI = 4.31-27.70), 197.04 (95 % CI = 75.28-318.18), 31.67 (95 % CI = 20.14-43.20) μg/kg (ppb) for As, Hg, Pb, and Cd, respectively using Stata™. The metal(loid) concentrations in milk were within the threshold limits other than Pb and Cd. Some studies in America, Africa, and Asia reported elevated Pb and Cd concentrations, raising health concerns. The simulated Risk Quotients (RQ) and Integrated Risk Quotient (IRQ) values generally remain above one, indicating potential human health risks. Notably, the IRQ value increases with more metal(loid)s consideration. Subgroup analysis indicates low-fat milk contains higher metal(loid)s concentrations. While metal(loid)s concentrations in milk largely comply with safety limits, some regions exhibit concerning concentrations. Therefore, continued surveillance to address potential health risks associated with metal(loid)s in milk is necessary to ensure dairy products\' safety.
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  • 文章类型: Journal Article
    几十年来,内分泌干扰化学物质或致癌物因其内分泌信号干扰而闻名。内分泌干扰化学品是一个严重问题,它们已被列入最优先的毒物和持久性有机污染物。因此,研究人员长期以来一直致力于了解它们在不同人体器官中的相互作用机制。关于这些化学品的致癌性有几份报告。本综述旨在了解与人体有关的内分泌干扰致癌物的危害识别。本文讨论了主要的内分泌干扰致癌物及其致癌作用。它讨论了人类暴露,进入路线,致癌性和机制。此外,本文讨论了与研究相关的研究差距和瓶颈。此外,它讨论了与检测内分泌干扰致癌物的分析技术相关的局限性。
    Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.
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  • 文章类型: Journal Article
    气候变化对全球沿海地区构成重大威胁。本研究提出并应用修改后的沿海脆弱性指数(CVI)来评估村庄一级的沿海脆弱性,专注于Canacona,一个在南果阿的taluka,印度。它通过合并其他变量来调整现有的CVI方法,以更好地表示脆弱性的各个层面,导致21个变量分为物理脆弱性指数(PVI)和社会脆弱性指数(SoVI)。结果表明,在研究的村庄中,沿海脆弱性的空间变异性,Agonda和Nagercem-Chaudi被发现非常脆弱,而Loliem是最不脆弱的。还使用了水文建模方法来比较每个村庄的CVI与海平面上升对淹没的敏感性。结果表明,当地因素对脆弱性的影响,考虑到适应通常发生的规模,对以前的taluka级别评估提出了挑战。
    Climate change poses a significant threat to coastal regions worldwide. This study presents and applies a modified Coastal Vulnerability Index (CVI) to assess coastal vulnerability at the village level, focusing on Canacona, a taluka in South Goa, India. It adapts the existing CVI methodology by incorporating additional variables to better represent the various dimensions of vulnerability, resulting in 21 variables split into a Physical Vulnerability Index (PVI) and a Social Vulnerability Index (SoVI). The results show spatial variability in coastal vulnerability across the studied villages, with Agonda and Nagercem-Chaudi found to be highly vulnerable and Loliem to be the least vulnerable. A hydrological modeling approach is also used to compare the CVI of every village with their susceptibility to inundation due to rising sea levels. The results demonstrate the influence of local factors on vulnerability, challenging previous taluka-level assessments given the scale upon which adaptation typically takes place.
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  • 文章类型: Journal Article
    随着环境空气质量恶化,呼吸道健康伤害和疾病增加,提高我们开发更好的方法来识别潜在危险的能力至关重要。新兴毒理学中的一种有希望的方法涉及利用肺表面活性剂作为模型,该模型通过结合吸入的生物物理方面来解决常规体外毒理学方法的局限性。这项研究使用了一种受限的液滴表面流量计来评估20种化学物质对潜在的表面活性剂抑制作用。其中,八种被鉴定为抑制肺表面活性物质功能:1-氨基乙醇,牛血清白蛋白,马来酸酐,丙二醇,甘胆酸钠,牛磺胆酸钠,牛磺脱氧胆酸钠,和TritonX-100.这些结果与先前报道的体内化学诱导的急性肺功能障碍一致。该研究提供了有关每种化学品的最小和最大表面张力条件以及相应的相对面积和接触角值的信息。报告了不同剂量的选定化学品的等温线和箱线图,和矢量图用于简要总结和比较结果。这种肺表面活性物质生物测定是一种有前途的非动物模型的危害识别,对开发预测建模和决策工具具有更广泛的意义。
    As environmental air quality worsens and respiratory health injuries and diseases increase, it is essential to enhance our ability to develop better methods to identify potential hazards. One promising approach in emerging toxicology involves the utilization of lung surfactant as a model that addresses the limitations of conventional in vitro toxicology methods by incorporating the biophysical aspect of inhalation. This study employed a constrained drop surfactometer to assess 20 chemicals for potential surfactant inhibition. Of these, eight were identified as inhibiting lung surfactant function: 1-aminoethanol, bovine serum albumin, maleic anhydride, propylene glycol, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate, and Triton X-100. These results are consistent with previously reported chemical-induced acute lung dysfunction in vivo. The study provides information on each chemical\'s minimum and maximum surface tension conditions and corresponding relative area and contact angle values. Isotherms and box plots are reported for selected chemicals across doses, and vector plots are used to summarize and compare the results concisely. This lung surfactant bioassay is a promising non-animal model for hazard identification, with broader implications for developing predictive modeling and decision-making tools.
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  • 文章类型: Journal Article
    三氯蔗糖,1991年首次批准使用的一种糖替代品,是一种无热量的甜味剂,作为食品添加剂受到全球监管。基于许多实验动物研究(可追溯到1980年代)和人类流行病学研究,国际卫生机构已经确定,三氯半乳蔗糖在按预期消费时是安全的。Ramazzini研究所(RI)进行的一项终生啮齿动物致癌性生物测定报告说,饲喂含有三氯半乳蔗糖的饮食的小鼠会发生造血肿瘤,但是关于这些数据预测人类健康影响的有效性和相关性的争议仍在继续。本文通过提供经验丰富的病理学家对三氯蔗糖相关动物毒性和致癌性数据的总体观点来解决这一争议,特别是RI致癌性生物测定结果,使用公开文件和国际监管机构决定的结果。在作者看来,设计中的缺陷,方法论,数据评估,三氯半乳蔗糖RI致癌性生物测定的报告降低了数据的价值,证明该药物对人类具有致癌危害。这种限制将一直存在,直到在良好实验室规范和设计下重复RI生物测定,数据,由具有评估潜在化学诱发致癌危害经验的合格病理学家审查的病理学诊断和解释的准确性。
    Sucralose, a sugar substitute first approved for use in 1991, is a non-caloric sweetener regulated globally as a food additive. Based on numerous experimental animal studies (dating to the 1980s) and human epidemiology studies, international health agencies have determined that sucralose is safe when consumed as intended. A single lifetime rodent carcinogenicity bioassay conducted by the Ramazzini Institute (RI) reported that mice fed diets containing sucralose develop hematopoietic neoplasia, but controversy continues regarding the validity and relevance of these data for predicting health effects in humans. The present paper addresses the controversy by providing the perspective of experienced pathologists on sucralose-related animal toxicity and carcinogenicity data generally, and the RI carcinogenicity bioassay findings specifically, using results from publicly available papers and international regulatory authority decisions. In the authors\' view, flaws in the design, methodology, data evaluation, and reporting of the RI carcinogenicity bioassay for sucralose diminish the value of the data as evidence that this agent represents a carcinogenic hazard to humans. This limitation will remain until the RI bioassay is repeated under Good Laboratory Practices and the design, data, and accuracy of the pathology diagnoses and interpretations are reviewed by qualified pathologists with experience in evaluating potential chemically-induced carcinogenic hazards.
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  • 文章类型: Journal Article
    健康与环境科学研究所发育与生殖毒理学(HESI-DART)小组在华盛顿举行了一次面对面和虚拟的混合研讨会,DC,2022年。研讨会的标题是,“在监管环境和框架中解释DART。在9个国家/地区有154名参与者(37人,117人)。研讨会的目的是在确定非临床发现时,获取用于评估与化学产品暴露相关的DART风险的关键共识方法。确定DART终点是否被认为是不利的决策过程至关重要,因为结果可能具有下游影响(例如,增加动物的使用,修改生殖分类和妊娠标签,对临床试验和价值链注册的影响)。研讨会包括一系列网络研讨会模块,用于培训和参与与联邦和国际监管机构的讨论,临床医生,学术研究人员,非政府组织,合同研究组织科学家,和私营部门的科学家在监管要求和流程的背景下解释DART和新方法方法的最佳做法和原则。尽管化学和制药行业之间的监管框架存在差异,数据解释应采用相同的基本原则。讨论导致了原则的分类,为数据的系统解释提供了指导。步骤1需要通过密切分析研究终点水平的数据来识别任何危险,而步骤2涉及使用证据权重评估风险。这些指导原则源自讲习班审议的集体成果。
    The Health and Environmental Sciences Institute Developmental and Reproductive Toxicology (HESI-DART) group held a hybrid in-person and virtual workshop in Washington, DC, in 2022. The workshop was entitled, \"Interpretation of DART in Regulatory Contexts and Frameworks.\" There were 154 participants (37 in person and 117 virtual) across 9 countries. The purpose of the workshop was to capture key consensus approaches used to assess DART risks associated with chemical product exposure when a nonclinical finding is identified. The decision-making process for determining whether a DART endpoint is considered adverse is critical because the outcome may have downstream implications (e.g., increased animal usage, modifications to reproductive classification and pregnancy labeling, impact on enrollment in clinical trials and value chains). The workshop included a series of webinar modules to train and engage in discussions with federal and international regulators, clinicians, academic investigators, nongovernmental organizations, contract research organization scientists, and private sector scientists on the best practices and principles of interpreting DART and new approach methodologies in the context of regulatory requirements and processes. Despite the differences in regulatory frameworks between the chemical and pharmaceutical sectors, the same foundational principles for data interpretation should be applied. The discussions led to the categorization of principles, which offer guidance for the systematic interpretation of data. Step 1 entails identifying any hazard by closely analyzing the data at the study endpoint level, while Step 2 involves assessing risk using weight of evidence. These guiding principles were derived from the collective outcomes of the workshop deliberations.
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  • 文章类型: Journal Article
    Can的聚酯涂料旨在取代环氧酚醛涂料,因为在增加的法规和消费者压力下,有关双酚A潜在释放的安全问题日益增加。在这项研究中,已经研究了与非有意添加的物质从单个聚酯涂层的锡板(5批)迁移到罐头食品的危险。使用乙腈(ACN)和乙醇(EtOH)95%进行迁移测试。通过液相色谱-高分辨率质谱法进行的非针对性分析显示,存在四种被归类为CramerIII类物质的环状低聚酯,其估计暴露量(仅针对法国人群计算)低于毒理学关注值的阈值1.5μg/kgb.w./天,暗示没有安全问题。此外,使用直接掺入(TA100,TA98,TA102,TA1537)和预孵育(TA100,TA98)方法,对不同菌株的鼠伤寒沙门氏菌进行了体外遗传毒性DNA损伤反应(DDR)测试和微型诱变性测试(MMT)。样品在两种生物测定中均为阴性,表明混合物不存在遗传毒性/致突变性。为了验证由于基体效应引起的任何假阴性反应,在MMT和DDR试验的同时,将迁移物加入相应的阳性对照.在这些实验条件下没有观察到基体效应。
    Can\'s polyester coatings are intended to replace epoxy-phenolic ones due to rising safety concern regarding the potential release of bisphenol A under increased regulations and consumer pressure. In this study, hazard linked to the migration of non-intentionally added substances from a single polyester-coated tin plate (5 batches) to canned food has been studied. Migration tests were performed using acetonitrile (ACN) and ethanol (EtOH) 95 %. Non-targeted analyses by liquid chromatography-high-resolution mass spectrometry revealed the presence of four cyclic oligoesters classified as Cramer class III substances with an estimated exposure (calculated for French population only) below the threshold of toxicological concern value of 1.5 μg/kg b.w./day, suggesting a no safety concern. Moreover, migrates were tested using in vitro genotoxicity DNA damage response (DDR) test and mini mutagenicity test (MMT) with different strains of S. Typhimurium using direct incorporation (TA100, TA98, TA102, TA1537) and pre-incubation (TA100, TA98) methods. Samples were negative in both bioassays suggesting the absence of genotoxicity/mutagenicity of the mixtures. To verify any false negative response due to matrix effect, migrates were spiked with corresponding positive controls in parallel with the MMT and the DDR test. No matrix effect was observed in these experimental conditions.
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  • 文章类型: Journal Article
    目的:本综述的目的是通过评估文献中最新的流行病学和实验室研究,评估工作场所原油蒸气(COV)暴露的毒理学后果。
    结果:原油是碳氢化合物沉积物的天然混合物,无机和有机化合物。从事石油开采上游过程的工人面临许多风险和危害,包括将原油涂在皮肤上或吸入原油蒸气。有几份报告称,工人因吸入在储油罐顶部打开小偷舱口而释放的高水平COV而死亡。尽管已经对下游油加工过程中吸入特定碳氢化合物的毒性进行了许多研究,关于COV暴露本身的潜在毒性的信息很少。这篇综述评估了当前对工作场所暴露于COV的毒理学后果的了解。
    The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature.
    Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace.
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  • 文章类型: Journal Article
    为了帮助为普通人群设定安全接触限值,已经实施了各种技术来对化学品和其他环境压力源进行风险评估;然而,这些工具都不能帮助识别可能有害并引起不利生物学影响的全新化学物质。这里,我们在计算机上详述了一部小说,深度学习框架,旨在系统地生成预测为化学危害的新化合物的结构。为了评估框架的效用,我们将该工具应用于与环境毒物及其对人类和动物健康的影响相关的四个端点:(i)对蜜蜂的毒性,(ii)免疫毒性,(iii)通过ER-α拮抗作用引起的内分泌干扰,和(iv)致突变性。此外,我们表征了这些化合物的预测效力,并检查了它们与现有关注的化学物质的结构关系。作为一系列新兴的新方法方法(NAM)的一部分,我们预计,在规划和预测时,这种框架将成为风险评估人员和其他环境科学家的重要资产。虽然不在本研究的范围内,我们希望此处详述的方法也可以用于更环保的工业化学品的从头设计。
    With the aim of helping to set safe exposure limits for the general population, various techniques have been implemented to conduct risk assessments for chemicals and other environmental stressors; however, none of these tools facilitate the identification of completely new chemicals that are likely hazardous and elicit an adverse biological effect. Here, we detail a novel in silico, deep-learning framework that is designed to systematically generate structures for new chemical compounds that are predicted to be chemical hazards. To assess the utility of the framework, we applied the tool to four endpoints related to environmental toxicants and their impacts on human and animal health: (i) toxicity to honeybees, (ii) immunotoxicity, (iii) endocrine disruption via ER-α antagonism, and (iv) mutagenicity. In addition, we characterized the predicted potency of these compounds and examined their structural relationship to existing chemicals of concern. As part of the array of emerging new approach methodologies (NAMs), we anticipate that such a framework will be a significant asset to risk assessors and other environmental scientists when planning and forecasting. Though not in the scope of the present study, we expect that the methodology detailed here could also be useful in the de novo design of more environmentally-friendly industrial chemicals.
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  • 文章类型: Journal Article
    二氧化钛(TiO2)纳米材料用于几个项目(植入材料,药丸成分,化妆品,等。).虽然TiO2不再被认为是安全的食品添加剂,普通民众每天通过不同的路线暴露,缺乏有关动物和人类健康的某些方面的信息。这项研究评估了食品级TiO2纳米颗粒(NP)(主要尺寸<25nm)在雄性和雌性大鼠中的肝和肾毒性,这些大鼠每天口服暴露于0、1和2mg/kg体重5天(与每日E171消耗相当)。选定的肝和肾毒性终点包括血清生物标志物,组织病理学分析和骨桥蛋白(SPP1)的表达,血管内皮生长因子(VEGF),白细胞介素6(IL-6),和神经肽Y(NPY)。尽管已知TiO2NP会影响胃粘膜,短期暴露引起的性别特异性效应:一般毒性参数在雌性大鼠中主要改变,而雄性大鼠的肝脏似乎比肾脏受到的影响更大,其还显示NPY和SPP1的过表达。在肾脏,两种性别的TiO2NP效应在数量上相似,但在质量上不同。总之,应仔细考虑其他可能导致人类暴露的项目中是否存在TiO2NPs。
    Titanium dioxide (TiO2) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO2 is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO2 nanoparticles (NPs) (primary size < 25 nm) in male and female rats that were orally exposed for 5 days to 0, 1, and 2 mg/kg body weight per day (comparable with daily E171 consumption). Selected liver and kidney toxicity endpoints included serum biomarkers, histopathological analysis and expression of osteopontin (SPP1), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and neuropeptide Y (NPY). Although TiO2 NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO2 NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO2 NPs in other items that can lead to human exposure.
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