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A critical review of talc and ovarian cancer. 滑石粉与卵巢癌的研究综述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-07-03 Epub Date: 2020-05-13 DOI: 10.1080/10937404.2020.1755402
Julie E Goodman, Laura E Kerper, Robyn L Prueitt, Charlotte M Marsh

The association between perineal talc use and ovarian cancer has been evaluated in several epidemiology studies. Some case-control studies reported weak positive associations, while other case-control and three large prospective cohort investigations found this association to be null. A weight-of-evidence evaluation was conducted of the epidemiology, toxicity, exposure, transport, in vitro, and mechanistic evidence to determine whether, collectively, these data support a causal association. Our review of the literature indicated that, while both case-control and cohort studies may be impacted by bias, the possibility of recall and other biases from the low participation rates and retrospective self-reporting of talc exposure cannot be ruled out for any of the case-control studies. The hypothesis that talc exposure induces ovarian cancer is only supported if one discounts the null results of the cohort studies and the fact that significant bias and/or confounding are likely reasons for the associations reported in some case-control investigations. In addition, one would need to ignore the evidence from animal experiments that show no marked association with cancer, in vitro and genotoxicity studies that did not indicate a carcinogenic mechanism of action for talc, and mechanistic and transport investigations that did not support the retrograde transport of talc to the ovaries. An alternative hypothesis that talc does not produce ovarian cancer, and that bias and confounding contribute the reported positive associations in case-control studies, is better supported by the evidence across all scientific disciplines. It is concluded that the evidence does not support a causal association between perineal talc use and ovarian cancer.

会阴使用滑石粉与卵巢癌之间的关系已在几项流行病学研究中得到评估。一些病例对照研究报告了弱正相关,而其他病例对照和三个大型前瞻性队列调查发现这种关联为零。对流行病学、毒性、暴露、运输、体外和机理证据进行了证据权重评估,以确定这些数据是否支持因果关系。我们对文献的回顾表明,虽然病例对照和队列研究都可能受到偏倚的影响,但对于任何病例对照研究,都不能排除由于低参与率和回顾性自我报告滑石粉暴露而引起的回忆和其他偏倚的可能性。滑石粉暴露诱发卵巢癌的假设只有在不考虑队列研究的无效结果以及某些病例对照调查中报告的关联可能存在显著偏倚和/或混杂的事实时才得到支持。此外,人们需要忽略来自动物实验的证据,这些证据表明滑石粉与癌症没有明显的联系,体外和遗传毒性研究没有表明滑石粉的致癌机制,以及不支持滑石粉向卵巢逆行运输的机制和运输研究。另一种假设是,滑石粉不会导致卵巢癌,偏倚和混淆促成了病例对照研究中报告的正相关性,所有科学学科的证据都更好地支持了这一假设。结论是,证据不支持会阴使用滑石粉与卵巢癌之间的因果关系。
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引用次数: 5
A review of hepatic nanotoxicology - summation of recent findings and considerations for the next generation of study designs. 回顾肝脏纳米毒理学-总结最近的发现和下一代研究设计的考虑。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-05-18 Epub Date: 2020-04-23 DOI: 10.1080/10937404.2020.1751756
Ali Kermanizadeh, Leagh G Powell, Vicki Stone

The liver is one of the most important multi-functional organs in the human body. Amongst various crucial functions, it is the main detoxification center and predominantly implicated in the clearance of xenobiotics potentially including particulates that reach this organ. It is now well established that a significant quantity of injected, ingested or inhaled nanomaterials (NMs) translocate from primary exposure sites and accumulate in liver. This review aimed to summarize and discuss the progress made in the field of hepatic nanotoxicology, and crucially highlight knowledge gaps that still exist.Key considerations include In vivo studies clearly demonstrate that low-solubility NMs predominantly accumulate in the liver macrophages the Kupffer cells (KC), rather than hepatocytes.KCs lining the liver sinusoids are the first cell type that comes in contact with NMs in vivo. Further, these macrophages govern overall inflammatory responses in a healthy liver. Therefore, interaction with of NM with KCs in vitro appears to be very important.Many acute in vivo studies demonstrated signs of toxicity induced by a variety of NMs. However, acute studies may not be that meaningful due to liver's unique and unparalleled ability to regenerate. In almost all investigations where a recovery period was included, the healthy liver was able to recover from NM challenge. This organ's ability to regenerate cannot be reproduced in vitro. However, recommendations and evidence is offered for the design of more physiologically relevant in vitro models.Models of hepatic disease enhance the NM-induced hepatotoxicity.The review offers a number of important suggestions for the future of hepatic nanotoxicology study design. This is of great significance as its findings are highly relevant due to the development of more advanced in vitro, and in silico models aiming to improve physiologically relevant toxicological testing strategies and bridging the gap between in vitro and in vivo experimentation.

肝脏是人体最重要的多功能器官之一。在各种关键功能中,它是主要的解毒中心,主要涉及清除可能包括到达该器官的颗粒的外来生物。现在已经确定,大量注射、摄入或吸入的纳米材料(NMs)从主要暴露部位转移并在肝脏中积累。本文旨在总结和讨论肝脏纳米毒理学领域的进展,并重点强调仍然存在的知识空白。体内研究清楚地表明,低溶解度NMs主要积聚在肝巨噬细胞Kupffer细胞(KC)中,而不是肝细胞中。衬在肝窦内的KCs是体内第一个与NMs接触的细胞类型。此外,这些巨噬细胞控制着健康肝脏的整体炎症反应。因此,NM与KCs在体外的相互作用显得非常重要。许多急性体内研究证明了多种NMs诱导的毒性迹象。然而,由于肝脏独特而无与伦比的再生能力,急性研究可能没有那么有意义。在几乎所有包括恢复期的调查中,健康的肝脏能够从NM挑战中恢复。这个器官的再生能力在体外是无法复制的。然而,建议和证据提供了更多的生理相关的体外模型的设计。肝脏疾病模型增强纳米颗粒诱导的肝毒性。该综述为未来肝脏纳米毒理学研究设计提供了一些重要建议。这是非常重要的,因为它的发现是高度相关的,因为更先进的体外和计算机模型的发展,旨在改善生理学相关的毒理学测试策略和弥合体外和体内实验之间的差距。
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引用次数: 24
Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) pandemic: a timely review. 促进氯喹和羟氯喹在2019冠状病毒病(COVID-19)大流行管理中的合理使用的挑战和关注:及时回顾
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-05-18 Epub Date: 2020-04-12 DOI: 10.1080/10937404.2020.1752340
Boscolli Barbosa Pereira

As a result of the 2019 coronavirus disease pandemic (COVID-19), there has been an urgent worldwide demand for treatments. Due to factors such as history of prescription for other infectious diseases, availability, and relatively low cost, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has been tested in vivo and in vitro for the ability to inhibit the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, even though investigators noted the therapeutic potential of these drugs, it is important to consider the toxicological risks and necessary care for rational use of CQ and HCQ. This study provides information on the main toxicological and epidemiological aspects to be considered for prophylaxis or treatment of COVID-19 using CQ but mainly HCQ, which is a less toxic derivative than CQ, and was shown to produce better results in inhibiting proliferation of SARS-CoV-2 based upon preliminary tests.

由于2019年冠状病毒病大流行(COVID-19),全球对治疗的需求迫切。由于其他传染病的处方史、可获得性和相对较低的成本等因素,氯喹(CQ)和羟氯喹(HCQ)在体内和体外进行了抑制致病病毒——严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的能力测试。然而,即使研究人员注意到这些药物的治疗潜力,重要的是要考虑毒理学风险和合理使用CQ和HCQ的必要护理。本研究提供了使用CQ预防或治疗COVID-19时应考虑的主要毒理学和流行病学方面的信息,但主要是HCQ,它是一种毒性较小的衍生物,根据初步试验显示,HCQ在抑制SARS-CoV-2增殖方面具有更好的效果。
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引用次数: 47
A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro. 一种男性生殖细胞试验及其辅助体细胞:在体外基因毒素相特异性检测中的应用。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-04-02 Epub Date: 2020-02-11 DOI: 10.1080/10937404.2020.1724577
Khaled Habas, Martin H Brinkworth, Diana Anderson

Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable in vivo studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on in vivo studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis in vitro, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity in vivo. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known in vivo phase specificities used during this test system development.

男性生殖干细胞负责将遗传信息传递给下一代。一些化学物质对男性生殖细胞产生负面影响,或直接影响,或通过作用于体细胞间接影响。最终,这些影响可能会抑制生育能力,并可能对未来的后代产生负面影响。基因毒性抗癌药物可能与生殖细胞中的DNA相互作用,可能导致可遗传的种系突变。支持这一理论的实验信息并不总是可重复的,适合的体内研究仍然有限。因此,现在能够检测这类药物的期特异性的替代男性生殖细胞测试,可能被监管机构用来帮助评估突变的潜在风险。然而,由于该领域直到最近还依赖于体内研究,因此迫切需要这种方法来鉴定男性生殖基因毒素。许多因素推动了替代方法,包括(1)对3R原则的承诺(替换、还原和改进),(2)动物实验的耗时和高成本,以及(3)新的分子分析方法带来的新机会。在REACH倡议下,目前还没有明显合适的哺乳动物体外完整精子发生模型,因此,为评估遗传毒性和诱变性而引入的新测试需要避免对动物进行不必要的测试。因此,最近开发了一系列与高通量STAPUT重力沉淀法结合使用的测试,用于纯化男性生殖细胞,以研究生殖细胞的期特异性遗传毒性。该系统可能是有价值的阶段的检查,以前只能在哺乳动物体内进行生殖细胞遗传毒性的大规模研究。本综述的目的是关注这种替代方法及其应用,以及在该测试系统开发过程中使用的已知体内相特异性的化学物质。
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引用次数: 2
Endogenous doesn't always mean innocuous: a scoping review of iron toxicity by inhalation. 内源性并不总是意味着无害:铁吸入毒性的范围审查。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-04-02 Epub Date: 2020-02-27 DOI: 10.1080/10937404.2020.1731896
Jody Morgan, Robin Bell, Alison L Jones

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

环境空气污染是全球疾病负担的主要风险因素。颗粒物(PM)引起毒性的一个可能途径是通过大气中最丰富的金属铁(Fe)。本综述的目的是考虑吸入暴露后铁介导毒性的复杂性,重点关注铁作为过渡金属的化学和表面反应性,以及通过活性氧(ROS)产生的可能毒性途径,以及考虑PM的大小、形态和来源。对4个数据库进行了广泛的检索,确定了过去10年中2189篇通过吸入接触铁的期刊文章和报告。按标题、摘要和全文对这些数据进行顺序分析,确定了87篇发表了含铁PM吸入或滴入对呼吸系统毒性研究结果的文章。对其余87篇论文进行了审查,以总结涉及吸入或滴注含铁或氧化铁的PM的体外、体内和流行病学研究。这些调查的主要结果被总结和列成表格。流行病学研究表明,接触氧化铁与癌症、心血管疾病和几种呼吸系统疾病的发病率增加有关。研究发现,铁PM在体内和体外均可诱发炎症,并在吸入后转移到包括大脑在内的远端部位。吸入含pm铁介导的毒性的潜在途径是通过产生ROS导致脂质过氧化和DNA和蛋白质氧化。我们的建议包括扩大流行病学、体内和体外研究,整合本综述中概述的研究改进,如颗粒制备方法、细胞系类型和动物模型,以增强我们对这些颗粒复杂的生物相互作用的理解。
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引用次数: 13
Arsenic in edible macroalgae: an integrated approach 食用大型藻类中砷的综合分析
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-02 DOI: 10.1080/10937404.2019.1672364
Julieta R Camurati, Vanesa N. Salomone
ABSTRACT Arsenic is a metalloid naturally present in marine environments. Various toxic elements including arsenic (As) are bioaccumulated by macroalgae. This metalloid is subsequently incorporated as arsenate into the organism due to similarity to phosphate. In recent decades, the use of macroalgae in food has increased as a result of their numerous benefits; however, As consumption may exert potential consequences for human health. The objective of this review was to discuss the articles published up to 2019 on As in seaweed, including key topics such as speciation, toxicity of the most common species in marine macroalgae, and their effects on human health. Further, this review will emphasize the extraction methods and analysis techniques most frequently used in seaweed and the need to develop certified reference materials (CRMs) in order to support the validation of analytical methodologies for As speciation in macroalgae. Finally, this review will discuss current legislation in relation to the risk associated with consumption. The number of articles found and the different approaches, biological, analytical and toxicological, show the growing interest there has been in this field in the last few years. In addition, this review reveals aspects of As chemistry that need further study, such as transformation of organic metalloid species during digestion and cooking, which necessitates analytical improvement and toxicological experiments. Taken together our findings may contribute to revision of current legislation on As content in edible seaweed relating to human health in a growing market.
砷是一种天然存在于海洋环境中的类金属。包括砷(As)在内的各种有毒元素是由大型藻类生物积累的。由于与磷酸盐相似,这种类金属随后以砷酸盐的形式并入生物体。近几十年来,由于其众多益处,大型藻类在食品中的使用有所增加;然而,消费大麻可能对人体健康产生潜在后果。本综述的目的是讨论截至2019年发表的关于海藻中砷的文章,包括物种形成、海洋大型藻类中最常见物种的毒性及其对人类健康的影响等关键主题。此外,本文将重点介绍海藻中最常用的提取方法和分析技术,以及开发标准物质(CRMs)的必要性,以支持大型藻类中砷形成分析方法的验证。最后,本综述将讨论与消费相关风险的现行立法。发现的文章的数量和不同的方法,生物学的,分析的和毒理学的,表明在过去的几年里,人们对这个领域的兴趣越来越大。此外,本文还揭示了砷化学中有待进一步研究的方面,如有机类金属物质在消化和烹饪过程中的转化,这需要进行分析改进和毒理学实验。综上所述,我们的研究结果可能有助于在不断增长的市场中修订有关食用海藻中与人类健康有关的砷含量的现行立法。
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引用次数: 17
Potential adverse health effects of ingested micro- and nanoplastics on humans. Lessons learned from in vivo and in vitro mammalian models. 摄入微塑料和纳米塑料对人类健康的潜在不利影响。从体内和体外哺乳动物模型中获得的经验教训。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 Epub Date: 2019-12-10 DOI: 10.1080/10937404.2019.1700598
Laura Rubio, Ricard Marcos, Alba Hernández

In recent years, increasing global attention has focused on "microplastics" (MPs) and "nanoplastics" (NPs) resulting in many studies on the effects of these compounds on ecological and environmental aspects. These tiny particles (<5000 µm), predominantly derived from the degradation of plastics, pollute the marine and terrestrial ecosystems with the ability to enter into the food chain. In this manner, human consumption of food contaminated with MPs or NPs is unavoidable, but the related consequences remain to be determined. The aim of this review is to complement previous reviews on this topic by providing new studies related to exposure, absorption, and toxicity in mammalian in vivo and in vitro systems. With respect to novel information, gaps and limitations hindering attainment of firm conclusions as well as preparation of a reliable risk assessment are identified. Subsequently, recommendations for in vivo and in vitro testing methods are presented in order to perform further relevant and targeted research studies.

近年来,“微塑料”(MPs)和“纳米塑料”(NPs)越来越受到全球的关注,对这些化合物对生态和环境的影响进行了许多研究。这些微小的颗粒(体内和体外系统)。关于新资料,指出了妨碍得出确定结论和编制可靠风险评估的差距和限制。随后,提出了体内和体外测试方法的建议,以便进行进一步相关和有针对性的研究。
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引用次数: 121
The complex puzzle of dietary silver nanoparticles, mucus and microbiota in the gut. 膳食银纳米颗粒、肠道粘液和微生物群的复杂谜团。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 Epub Date: 2020-01-10 DOI: 10.1080/10937404.2019.1710914
Yuqiang Bi, Andrew K Marcus, Hervé Robert, Rosa Krajmalnik-Brown, Bruce E Rittmann, Paul Westerhoff, Marie-Hélène Ropers, Muriel Mercier-Bonin

Hundreds of consumer and commercial products containing silver nanoparticles (AgNPs) are currently used in food, personal-care products, pharmaceutical, and many other applications. Human exposure to AgNPs includes oral intake, inhalation, and dermal contact. The aim of this review was to focus on oral intake, intentional and incidental of AgNPs where well-known antimicrobial characteristics that might affect the microbiome and mucus in the gastrointestinal tract (GIT). This critical review summarizes what is known regarding the impacts of AgNPs on gut homeostasis. It is fundamental to understand the forms of AgNPs and their physicochemical characterization before and during digestion. For example, lab-synthesized AgNPs differ from "real" ingestable AgNPs used as food additives and dietary supplements. Similarly, the gut environment alters the chemical and physical state of Ag that is ingested as AgNPs. Emerging research on in vitro and in vivo rodent and human indicated complex multi-directional relationships among AgNPs, the intestinal microbiota, and the epithelial mucus. It may be necessary to go beyond today's descriptive approach to a modeling-based ecosystem approach that might quantitatively integrate spatio-temporal interactions among microbial groups, host factors (e.g., mucus), and environmental factors, including lifestyle-based stressors. It is suggested that future research (1) utilize more representative AgNPs, focus on microbe/mucus interactions, (2) assess the effects of environmental stressors for longer and longitudinal conditions, and (3) be integrated using quantitative modeling.

目前,数百种含有银纳米颗粒(AgNPs)的消费和商业产品被用于食品、个人护理产品、制药和许多其他应用。人类对AgNPs的暴露包括口服、吸入和皮肤接触。本综述的目的是关注口服AgNPs,有意的和偶然的,其中众所周知的抗菌特性可能影响胃肠道(GIT)中的微生物组和粘液。这篇重要的综述总结了已知的AgNPs对肠道稳态的影响。了解AgNPs的形式及其在消化前和消化过程中的物理化学特性是至关重要的。例如,实验室合成的AgNPs不同于用作食品添加剂和膳食补充剂的“真正的”可摄取AgNPs。同样,肠道环境也会改变作为AgNPs被摄入的银的化学和物理状态。在体外和体内啮齿类动物和人类的新研究表明,AgNPs、肠道微生物群和上皮粘液之间存在复杂的多向关系。可能有必要超越目前的描述性方法,采用基于建模的生态系统方法,定量地整合微生物群、宿主因素(如粘液)和环境因素(包括基于生活方式的压力源)之间的时空相互作用。建议未来的研究:(1)利用更具代表性的AgNPs,关注微生物/黏液的相互作用,(2)评估长期和纵向条件下环境应激源的影响,(3)利用定量模型进行整合。
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引用次数: 16
Genetic toxicity assessment using liver cell models: past, present, and future 使用肝细胞模型的遗传毒性评估:过去,现在和未来
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2019-11-20 DOI: 10.1080/10937404.2019.1692744
Xiaoqing Guo, Ji‐Eun Seo, Xilin Li, N. Mei
ABSTRACT Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.
遗传毒性化合物可能被解毒为非遗传毒性代谢物,而许多致癌物需要代谢激活才能在体内发挥其遗传毒性。标准遗传毒性测定法的开发和用于风险评估已有40多年的历史。这些试验大多是在代谢不正常的啮齿动物或人类细胞系中进行的。由于缺乏正常代谢和依赖外源性代谢激活系统,目前的体外遗传毒性检测常常产生高假阳性率,从而引发不必要的和昂贵的体内研究。代谢活跃的细胞如肝细胞已被认为是预测体内致癌物遗传毒性的一个有前途的细胞模型。近年来,组织培养和生物技术的重大进展为肝细胞在遗传毒理学中的应用提供了新的机会。本综述包括已发表的使用肝细胞进行遗传毒性评估的研究(包括体外和体内)。总结了标准遗传毒性试验和新开发的遗传毒性试验的结果。描述了用于遗传毒性评估的各种肝细胞模型,包括先进肝细胞模型的潜在应用,如3D球体,类器官和工程肝细胞。一项综合战略,包括使用具有增强生物学相关性和通量的人类细胞,以及应用数据的定量分析,可能为未来的遗传毒性风险评估提供一种方法。
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引用次数: 38
Properties, toxicity and current applications of the biolarvicide spinosad 杀虫剂spinosad的性质、毒性及应用现状
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2019-11-11 DOI: 10.1080/10937404.2019.1689878
Vanessa Santana Vieira Santos, B. B. Pereira
ABSTRACT Characterized as a highly valuable bioactive natural product, spinosad is a pesticide with a complex chemical structure, composed of spinosyn A and D, molecules synthesized by the actinomycete Saccharopolyspora spinosa. The larvicidal activity of spinosad was postulated to be a promising approach to combat crop pests and control species responsible to transmit mosquito-borne illness, including Aedes aegypti. Although initially deemed as relatively safe for non-target organisms and highly effective against insects and crop pests, recent studies focused on the toxicity profile detected the occurrence of side effects in different living species. Thus, the present review was undertaken to describe the properties and characteristics of spinosad. In addition to indicating potential adverse effects on living organisms, alternative uses of the biopesticide as a mixture with different compounds are provided.
spinosad是一种化学结构复杂的农药,具有很高的生物活性,是由放线菌Saccharopolyspora spinosa合成的spinosyn a和D分子组成。spinosad的杀幼虫活性被认为是一种很有前途的方法来对抗农作物害虫和控制负责传播蚊媒疾病的物种,包括埃及伊蚊。虽然最初被认为对非目标生物相对安全,对昆虫和作物害虫非常有效,但最近的研究集中在毒性概况上,发现在不同的生物物种中发生了副作用。因此,本文对spinosad的性质和特点进行了综述。除了表明对生物体的潜在不利影响外,还提供了生物农药与不同化合物混合的替代用途。
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引用次数: 20
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Journal of Toxicology and Environmental Health-Part B-Critical Reviews
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