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Experimental models of chemically induced Parkinson's disease in zebrafish at the embryonic larval stage: a systematic review. 斑马鱼胚胎幼体期化学诱导帕金森病的实验模型:系统综述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-05-19 DOI: 10.1080/10937404.2023.2182390
Paola Briñez-Gallego, Dennis Guilherme da Costa Silva, Marcos Freitas Cordeiro, Ana Paula Horn, Mariana Appel Hort
ABSTRACT Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that results in a decrease in dopamine levels, resulting in motor-type disturbances. Different vertebrate models, such as rodents and fish, have been used to study PD. In recent decades, Danio rerio (zebrafish) has emerged as a potential model for the investigation of neurodegenerative diseases due to its homology to the nervous system of humans. In this context, this systematic review aimed to identify publications that reported the utilization of neurotoxins as an experimental model of parkinsonism in zebrafish embryos and larvae. Ultimately, 56 articles were identified by searching three databases (PubMed, Web of Science, and Google Scholar). Seventeen studies using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 4 1-methyl-4-phenylpyridinium (MPP+), 24 6-hydroxydopamine (6-OHDA), 6 paraquat/diquat, 2 rotenone, and 6 articles using other types of unusual neurotoxins to induce PD were selected. Neurobehavioral function, such as motor activity, dopaminergic neuron markers, oxidative stress biomarkers, and other relevant parameters in the zebrafish embryo-larval model were examined. In summary, this review provides information to help researchers determine which chemical model is suitable to study experimental parkinsonism, according to the effects induced by neurotoxins in zebrafish embryos and larvae.
帕金森病(PD)是一种神经退行性疾病,其特征是黑质中多巴胺能神经元的丧失,导致多巴胺水平下降,导致运动型障碍。不同的脊椎动物模型,如啮齿动物和鱼类,已被用于研究帕金森病。近几十年来,斑马鱼因其与人类神经系统的同源性而成为研究神经退行性疾病的潜在模型。在此背景下,本系统综述旨在识别报道神经毒素作为斑马鱼胚胎和幼虫帕金森病实验模型的出版物。最终,通过搜索三个数据库(PubMed, Web of Science和Google Scholar)确定了56篇文章。选取了17篇使用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)、4篇使用1-甲基-4-苯基吡啶(MPP+)、24篇使用6-羟多巴胺(6- ohda)、6篇使用百草枯/双喹特、2篇鱼藤酮和6篇使用其他类型异常神经毒素诱导PD的研究。检测斑马鱼胚胎-幼体模型的神经行为功能,如运动活性、多巴胺能神经元标志物、氧化应激生物标志物及其他相关参数。综上所述,根据神经毒素对斑马鱼胚胎和幼虫的影响,本综述为研究人员确定适合研究实验性帕金森病的化学模型提供了信息。
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引用次数: 4
A comprehensive overview of genotoxicity and mutagenicity associated with outdoor air pollution exposure in Brazil. 巴西室外空气污染暴露的遗传毒性和致突变性的全面概述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-04-03 DOI: 10.1080/10937404.2023.2175092
Vera Maria Ferrão Vargas, Flavio Manoel Rodrigues da Silva Júnior, Tatiana da Silva Pereira, Cristiane Silva da Silva, Mariana Vieira Coronas

This review examined the mutagenicity and genotoxicity associated with exposure to outdoor air pollutants in Brazil. A search was performed on the Web of Science database using a combination of keywords that resulted in 134 articles. After applying exclusion criteria, a total of 75 articles were obtained. The articles were classified into three categories: (1) studies with plants and animals, (2) in vitro studies, and (3) human biomonitoring. The investigations were conducted in 11 of 27 Brazilian states with the highest prevalence in the southeast and south regions. Only 5 investigations focused on the effects of burning biomass on the quality of outdoor air. Plants, especially Tradescantia pallida, were the main air pollution biomonitoring tool. When available, a significant association between levels of air pollutants and genetic damage was described. Among the in vitro studies, Salmonella/microsome is the most used test to evaluate mutagenesis of outdoor air in Brazil (n = 26). Human biomonitoring studies were the least frequent category (n = 18). Most of the investigations utilized micronucleus bioassay, in oral mucosa cells (n = 15) and lymphocytes (n = 5), and the comet assay (n = 6). The analysis in this study points to the existence of gaps in genotoxicity studies and our findings indicate that future studies need to address the variety of potential sources of pollution existing in Brazil. In addition to extent of the impacts, consideration should be given to the enormous Brazilian biodiversity, as well as the determination of the role of socioeconomic inequality of the population in the observed outcomes.

本综述研究了巴西暴露于室外空气污染物的致突变性和遗传毒性。在Web of Science数据库中使用关键词组合进行了搜索,结果是134篇文章。应用排除标准后,共获得75篇文献。文章分为三类:(1)植物和动物研究;(2)体外研究;(3)人体生物监测。调查在巴西东南部和南部地区患病率最高的27个州中的11个州进行。只有5项调查关注燃烧生物质对室外空气质量的影响。植物是主要的大气污染生物监测工具,尤其是苍白草。在可用的情况下,描述了空气污染物水平与遗传损害之间的重大关联。在体外研究中,沙门氏菌/微粒体是巴西室外空气诱变评价最常用的检测方法(n = 26)。人类生物监测研究是最不常见的研究类别(n = 18)。大多数调查使用微核生物测定法,在口腔粘膜细胞(n = 15)和淋巴细胞(n = 5),以及彗星测定法(n = 6)。本研究的分析指出遗传毒性研究存在差距,我们的研究结果表明,未来的研究需要解决巴西存在的各种潜在污染源。除了影响的程度外,还应考虑到巴西巨大的生物多样性,以及确定人口的社会经济不平等在观察到的结果中的作用。
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引用次数: 2
Biomonitoring of firefighting forces: a review on biomarkers of exposure to health-relevant pollutants released from fires. 消防力量的生物监测:火灾释放的与健康有关的污染物暴露的生物标志物综述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-04-03 DOI: 10.1080/10937404.2023.2172119
Bela Barros, Marta Oliveira, Simone Morais

Occupational exposure as a firefighter has recently been classified as a carcinogen to humans by International Agency for Research on Cancer (IARC). Biomonitoring has been increasingly used to characterize exposure of firefighting forces to contaminants. However, available data are dispersed and information on the most relevant and promising biomarkers in this context of firefighting is missing. This review presents a comprehensive summary and critical appraisal of existing biomarkers of exposure including volatile organic compounds such as polycyclic aromatic hydrocarbons, several other persistent other organic pollutants as well as heavy metals and metalloids detected in biological fluids of firefighters attending different fire scenarios. Urine was the most characterized matrix, followed by blood. Firefighters exhaled breath and saliva were poorly evaluated. Overall, biological levels of compounds were predominantly increased in firefighters after participation in firefighting activities. Biomonitoring studies combining different biomarkers of exposure and of effect are currently limited but exploratory findings are of high interest. However, biomonitoring still has some unresolved major limitations since reference or recommended values are not yet established for most biomarkers. In addition, half-lives values for most of the biomarkers have thus far not been defined, which significantly hampers the design of studies. These limitations need to be tackled urgently to improve risk assessment and support implementation of better more effective preventive strategies.

最近,国际癌症研究机构(IARC)将消防员的职业暴露列为人类致癌物。生物监测已越来越多地用于表征暴露于污染物的消防部队。然而,现有的数据是分散的,在这种消防背景下,关于最相关和最有希望的生物标志物的信息是缺失的。本文综述了现有的暴露生物标志物,包括挥发性有机化合物,如多环芳烃,其他几种持久性有机污染物,以及在参加不同火灾场景的消防员的生物体液中检测到的重金属和类金属。尿液是最具特征的基质,其次是血液。消防员呼出的气体和唾液的评估很差。总的来说,参加消防活动后,消防员体内化合物的生物水平主要增加。结合不同的暴露和影响的生物标志物的生物监测研究目前是有限的,但探索性的发现是非常有趣的。然而,生物监测仍然有一些未解决的主要限制,因为大多数生物标志物的参考值或推荐值尚未建立。此外,大多数生物标志物的半衰期值迄今尚未确定,这极大地阻碍了研究的设计。迫切需要解决这些限制,以改进风险评估并支持实施更好、更有效的预防战略。
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引用次数: 5
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models. 评估空气(纳米)颗粒对人体呼吸系统的体外毒性:从基本模型到高级模型。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-02-17 DOI: 10.1080/10937404.2023.2166638
Maria João Bessa, Fátima Brandão, Fernanda Rosário, Luciana Moreira, Ana Teresa Reis, Vanessa Valdiglesias, Blanca Laffon, Sónia Fraga, João Paulo Teixeira

Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relationship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an overview of the available human respiratory models and exposure systems for in vitro testing, advantages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.

已经进行了几项研究,以解决因接触纳米级材料而造成的潜在不利健康风险。虽然体内研究是确定剂量和不良反应发生之间关系的基础,但体外模型系统在分子水平上提供了有关作用机制的重要信息。特别关注吸入(纳米)颗粒物质暴露毒性评估,本综述概述了可用的人体呼吸模型和体外测试暴露系统,优点,局限性以及使用不同复杂性模型的现有研究。简要概述了人类呼吸系统,途径和吸入(纳米)颗粒的命运。
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引用次数: 4
Trichoderma after crossing kingdoms: infections in human populations. 跨越王国后的木霉病:人群中的感染。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-02-17 DOI: 10.1080/10937404.2023.2172498
Uener Ribeiro Dos Santos, Jane Lima Dos Santos

Trichoderma is a saprophytic fungus that is used worldwide as a biocontrol and biofertilizer agent. Although considered nonpathogenic until recently, reports of human infections produced by members of the Trichoderma genus are increasing. Numerous sources of infection were proposed based upon patient data and phylogenetic analysis, including air, agriculture, and healthcare facilities, but the deficit of knowledge concerning Trichoderma infections makes patient treatment difficult. These issues are compounded by isolates that present profiles which exhibit high minimum inhibitory concentration values to available antifungal drugs. The aim of this review is to present the global distribution and sources of infections that affect both immunocompetent and immunocompromised hosts, clinical features, therapeutic strategies that are used to treat patients, as well as highlighting treatments with the best responses. In addition, the antifungal susceptibility profiles of Trichoderma isolates that have emerged in recent decades were examined and which antifungal drugs need to be further evaluated as potential candidates to treat Trichoderma infections are also indicated.

木霉是一种腐生真菌,在世界范围内被用作生物防治和生物肥料。虽然直到最近才被认为是非致病性的,但由木霉属成员引起的人类感染的报告正在增加。根据患者数据和系统发育分析,提出了许多感染源,包括空气,农业和医疗设施,但有关木霉感染的知识不足使患者治疗困难。这些问题是复杂的分离,目前的概况表现出高的最低抑菌浓度值对现有的抗真菌药物。这篇综述的目的是介绍影响免疫正常和免疫功能低下宿主的感染的全球分布和来源,临床特征,用于治疗患者的治疗策略,以及强调具有最佳反应的治疗方法。此外,对近几十年来出现的木霉分离株的抗真菌敏感性进行了研究,并指出哪些抗真菌药物需要进一步评估,作为治疗木霉感染的潜在候选药物。
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引用次数: 2
Polycyclic aromatic hydrocarbons (PAHs): Updated aspects of their determination, kinetics in the human body, and toxicity. 多环芳烃(PAHs):其测定、人体内动力学和毒性的最新方面。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-01-02 DOI: 10.1080/10937404.2022.2164390
Fernando Barbosa, Bruno A Rocha, Marília C O Souza, Mariana Z Bocato, Lara F Azevedo, Joseph A Adeyemi, Anthony Santana, Andres D Campiglia

Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants of considerable public health concern. Polycyclic aromatic hydrocarbons arise from natural and anthropogenic sources and are ubiquitously present in the environment. Several PAHs are highly toxic to humans with associated carcinogenic and mutagenic properties. Further, more severe harmful effects on human- and environmental health have been attributed to the presence of high molecular weight (HMW) PAHs, that is PAHs with molecular mass greater than 300 Da. However, more research has been conducted using low molecular weight (LMW) PAHs). In addition, no HMW PAHs are on the priority pollutants list of the United States Environmental Protection Agency (US EPA), which is limited to only 16 PAHs. However, limited analytical methodologies for separating and determining HMW PAHs and their potential isomers and lack of readily available commercial standards make research with these compounds challenging. Since most of the PAH kinetic data originate from animal studies, our understanding of the effects of PAHs on humans is still minimal. In addition, current knowledge of toxic effects after exposure to PAHs may be underrepresented since most investigations focused on exposure to a single PAH. Currently, information on PAH mixtures is limited. Thus, this review aims to critically assess the current knowledge of PAH chemical properties, their kinetic disposition, and toxicity to humans. Further, future research needs to improve and provide the missing information and minimize PAH exposure to humans.

多环芳烃(PAHs)是一种遗留污染物,具有相当大的公共卫生问题。多环芳烃来自自然和人为来源,在环境中无处不在。几种多环芳烃对人类具有高度毒性,具有相关的致癌和致突变特性。此外,对人类和环境健康造成更严重有害影响的原因是存在高分子量多环芳烃,即分子质量大于300 Da的多环芳烃。然而,对低分子量(LMW)多环芳烃的研究越来越多。此外,没有HMW多环芳烃在美国环境保护署(US EPA)的优先污染物清单上,该清单仅限于16种多环芳烃。然而,分离和测定高分子量多环芳烃及其潜在异构体的分析方法有限,而且缺乏现成的商业标准,使得对这些化合物的研究具有挑战性。由于大多数多环芳烃动力学数据来自动物研究,我们对多环芳烃对人类的影响的了解仍然很少。此外,由于大多数调查集中于接触单一多环芳烃,目前关于接触多环芳烃后毒性作用的知识可能不够充分。目前,关于多环芳烃混合物的信息有限。因此,本综述旨在批判性地评估目前对多环芳烃的化学性质、动力学处置和对人类的毒性的认识。此外,未来的研究需要改进和提供缺失的信息,并尽量减少人类对多环芳烃的暴露。
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引用次数: 18
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions. 纳米材料诱导的毒性在病理生理模型中代表了已有医疗条件的个体。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2023-01-02 DOI: 10.1080/10937404.2022.2153456
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh

The integration of nanomaterials (NMs) into an ever-expanding number of daily used products has proven to be highly desirable in numerous industries and applications. Unfortunately, the same "nano" specific physicochemical properties, which make these materials attractive, may also contribute to hazards for individuals exposed to these materials. In 2021, it was estimated that 7 out of 10 deaths globally were accredited to chronic diseases, such as chronic liver disease, asthma, and cardiovascular-related illnesses. Crucially, it is also understood that a significant proportion of global populace numbering in the billions are currently living with a range of chronic undiagnosed health conditions. Due to the significant number of individuals affected, it is important that people suffering from chronic disease also be considered and incorporated in NM hazard assessment strategies. This review examined and analyzed the literature that focused on NM-induced adverse health effects in models which are representative of individuals exhibiting pre-existing medical conditions with focus on the pulmonary, cardiovascular, hepatic, gastrointestinal, and central nervous systems. The overall objective of this review was to outline available data, highlighting the important role of pre-existing disease in NM-induced toxicity with the aim of establishing a weight of evidence approach to inform the public on the potential hazards posed by NMs in both healthy and compromised persons in general population.

将纳米材料(NMs)集成到越来越多的日常使用产品中,已被证明在许多行业和应用中是非常理想的。不幸的是,同样的“纳米”特定的物理化学性质,使这些材料具有吸引力,也可能对暴露于这些材料的个人造成危害。据估计,2021年,全球每10例死亡中就有7例被确认为慢性疾病,如慢性肝病、哮喘和心血管相关疾病。至关重要的是,人们还了解到,全球数十亿人口中有很大一部分目前患有一系列未确诊的慢性健康状况。由于受影响的个人人数众多,重要的是,慢性病患者也应被考虑并纳入纳米危害评估战略。本综述检查并分析了在模型中关注纳米颗粒诱导的不良健康影响的文献,这些模型代表了表现出既往医学状况的个体,重点是肺、心血管、肝脏、胃肠道和中枢神经系统。本综述的总体目标是概述现有数据,强调已存在疾病在纳米颗粒诱导毒性中的重要作用,目的是建立证据权重方法,告知公众纳米颗粒对普通人群中健康和受损人群构成的潜在危害。
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引用次数: 4
A comparison of fine particulate matter (PM2.5) in vivo exposure studies incorporating chemical analysis. 结合化学分析的细颗粒物(PM2.5)体内暴露研究的比较。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-11-17 DOI: 10.1080/10937404.2022.2142345
Allie Sidwell, Samuel Cole Smith, Courtney Roper

The complex, variable mixtures present in fine particulate matter (PM2.5) have been well established, and associations between chemical constituents and human health are expanding. In the past decade, there has been an increase in PM2.5 toxicology studies that include chemical analysis of samples. This investigation is a crucial component for identifying the causal constituents for observed adverse health effects following exposure to PM2.5. In this review, investigations of PM2.5 that used both in vivo models were explored and chemical analysis with a focus on respiratory, cardiovascular, central nervous system, reproductive, and developmental toxicity was examined to determine if chemical constituents were considered in the interpretation of the toxicity findings. Comparisons between model systems, PM2.5 characteristics, endpoints, and results were made. A vast majority of studies observed adverse effects in vivo following exposure to PM2.5. While limited, investigations that explored connections between chemical components and measured endpoints noted significant associations between biological measurements and a variety of PM2.5 constituents including elements, ions, and organic/elemental carbon, indicating the need for such analysis. Current limitations in available data, including relatively scarce statistical comparisons between collected toxicity and chemical datasets, are provided. Future progress in this field in combination with epidemiologic research examining chemical composition may support regulatory standards of PM2.5 to protect human health.

细颗粒物(PM2.5)中存在的复杂、可变的混合物已经得到了很好的证实,化学成分与人类健康之间的联系正在扩大。在过去的十年里,包括对样本进行化学分析在内的PM2.5毒理学研究有所增加。这项调查是确定暴露于PM2.5后观察到的不良健康影响的因果成分的关键组成部分。在这篇综述中,我们探索了PM2.5在体内模型中的研究,并对呼吸、心血管、中枢神经系统、生殖和发育毒性进行了化学分析,以确定化学成分是否在解释毒性发现时被考虑在内。模型系统、PM2.5特征、终点和结果之间进行了比较。绝大多数研究观察到暴露于PM2.5后的体内不良影响。虽然有限,但探索化学成分和测量终点之间联系的研究指出,生物测量与各种PM2.5成分(包括元素、离子和有机/元素碳)之间存在显著关联,表明需要进行此类分析。指出了现有数据的局限性,包括收集的毒性和化学数据集之间的统计比较相对较少。该领域的未来进展与检查化学成分的流行病学研究相结合,可能会支持PM2.5的监管标准,以保护人类健康。
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引用次数: 9
Ecotoxicological perspectives of microplastic pollution in amphibians. 两栖动物微塑料污染的生态毒理学观点。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-11-17 DOI: 10.1080/10937404.2022.2140372
Mario A Burgos-Aceves, Caterina Faggio, Miguel Betancourt-Lozano, Donají J González-Mille, César A Ilizaliturri-Hernández

Microplastics (MPs) are contaminants widely distributed in the environment and biota. Previously, most studies focused on identifying and characterizing microplastics in the marine environment, while their impact on freshwater ecosystems remains to be determined. This review summarizes recent findings regarding MPs physiological, immunological, and genetic effects on amphibians based upon the biological relevance of this species as indicators of freshwater pollution. Data demonstrated that MPs contamination may potentially alter various physiological processes in aquatic animals, mainly in the embryonic stages. It is worthwhile noting that adverse effects might be enhanced in synergy with other pollutants. However, amphibians might counteract the effect of MPs and other pollutants through microbiota present both in the intestine and on the skin. In addition, amphibian microbial composition might also be altered by MPs themselves in a manner that leads to unpredicted health consequences in amphibians.

微塑料(MPs)是广泛分布于环境和生物群中的污染物。以前,大多数研究都集中在识别和表征海洋环境中的微塑料,而它们对淡水生态系统的影响仍有待确定。本文综述了MPs对两栖动物生理、免疫和遗传影响的最新研究成果,并基于该物种作为淡水污染指标的生物学相关性。数据表明,MPs污染可能潜在地改变水生动物的各种生理过程,主要是在胚胎阶段。值得注意的是,与其他污染物的协同作用可能会加强不利影响。然而,两栖动物可能会通过肠道和皮肤上的微生物群来抵消MPs和其他污染物的影响。此外,两栖动物的微生物组成也可能被MPs本身以某种方式改变,从而导致两栖动物无法预测的健康后果。
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引用次数: 14
Current trends in read-across applications for chemical risk assessments and chemical registrations in the Republic of Korea. 大韩民国化学品风险评估和化学品登记的跨读应用的当前趋势。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-11-17 DOI: 10.1080/10937404.2022.2133033
Sang Hee Lee, Jongwoon Kim, Jinyong Kim, Jaehyun Park, Sanghee Park, Kyu-Bong Kim, Byung-Mu Lee, Seok Kwon

Read-across, an alternative approach for hazard assessment, has been widely adopted when in vivo data are unavailable for chemicals of interest. Read-across is enabled via in silico tools such as quantitative structure activity relationship (QSAR) modeling. In this study, the current status of structure activity relationship (SAR)-based read-across applications in the Republic of Korea (ROK) was examined considering both chemical risk assessments and chemical registrations from different sectors, including regulatory agencies, industry, and academia. From the regulatory perspective, the Ministry of Environment (MOE) established the Act on Registration and Evaluation of Chemicals (AREC) in 2019 to enable registrants to submit alternative data such as information from read-across instead of in vivo data to support hazard assessment and determine chemical-specific risks. Further, the Ministry of Food and Drug Safety (MFDS) began to consider read-across approaches for establishing acceptable intake (AI) limits of impurities occurring during pharmaceutical manufacturing processes under the ICH M7 guideline. Although read-across has its advantages, this approach also has limitations including (1) lack of standardized criteria for regulatory acceptance, (2) inconsistencies in the robustness of scientific evidence, and (3) deficiencies in the objective reliability of read-across data. The application and acceptance rate of read-across may vary among regulatory agencies. Therefore, sufficient data need to be prepared to verify the hypothesis that structural similarities might lead to similarities in properties of substances (between source and target chemicals) prior to adopting a read-across approach. In some cases, additional tests may be required during the registration process to clarify long-term effects on human health or the environment for certain substances that are data deficient. To improve the quality of read-across data for regulatory acceptance, cooperative efforts from regulatory agencies, academia, and industry are needed to minimize limitations of read-across applications.

当无法获得相关化学物质的体内数据时,一种可供选择的危害评估方法Read-across已被广泛采用。通过计算机工具,如定量结构活动关系(QSAR)建模,可以实现读取。在这项研究中,基于结构活性关系(SAR)的跨读应用在韩国(ROK)的现状进行了研究,考虑了化学品风险评估和来自不同部门的化学品注册,包括监管机构、工业和学术界。从监管的角度来看,环境部(MOE)于2019年制定了《化学品注册和评估法》(AREC),使注册人能够提交替代数据,如跨读信息,而不是体内数据,以支持危害评估和确定化学品特定风险。此外,食品和药物安全部(MFDS)开始考虑根据ICH M7指南建立药品生产过程中发生的杂质的可接受摄入量(AI)限制的解读方法。尽管跨读有其优点,但这种方法也有局限性,包括:(1)缺乏监管接受的标准化标准,(2)科学证据的稳健性不一致,(3)跨读数据的客观可靠性不足。跨读的应用和接受率在各监管机构之间可能有所不同。因此,在采用跨读方法之前,需要准备足够的数据来验证结构相似性可能导致物质(源化学品和目标化学品之间)性质相似性的假设。在某些情况下,可能需要在注册过程中进行额外测试,以澄清某些缺乏数据的物质对人类健康或环境的长期影响。为了提高监管机构接受的跨读数据的质量,需要监管机构、学术界和工业界的合作努力,以最大限度地减少跨读应用程序的限制。
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引用次数: 1
期刊
Journal of Toxicology and Environmental Health-Part B-Critical Reviews
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