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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
Pulmonary effects of e-liquid flavors: a systematic review. 电子液体香精对肺部的影响:系统综述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-10-03 DOI: 10.1080/10937404.2022.2124563
Felix Effah, Benjamin Taiwo, Deborah Baines, Alexis Bailey, Tim Marczylo

Electronic cigarettes (ECs) are purported to be tobacco harm-reduction products whose degree of harm has been highly debated. EC use is considered less hazardous than smoking but is not expected to be harmless. Following the banning of e-liquid flavors in countries such as the US, Finland, Ukraine, and Hungary, there are growing concerns regarding the safety profile of e-liquid flavors used in ECs. While these are employed extensively in the food industry and are generally regarded as safe (GRAS) when ingested, GRAS status after inhalation is unclear. The aim of this review was to assess evidence from 38 reports on the adverse effects of flavored e-liquids on the respiratory system in both in vitro and in vivo studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects in vitro with cinnamon (9 articles), strawberry (5 articles), and menthol (10 articles), flavors than other flavors. The most reported effects among these investigations were perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity. There is sufficient evidence to support the toxicological impacts of diacetyl- and cinnamaldehyde-containing e-liquids following human inhalation; however, safety profiles on other flavors are elusive. The latter may result from inconsistencies between experimental approaches and uncertainties due to the contributions from other e-liquid constituents. Further, the relevance of the concentration ranges to human exposure levels is uncertain. Evidence indicates that an adequately controlled and consistent, systematic toxicological investigation of a broad spectrum of e-liquid flavors may be required at biologically relevant concentrations to better inform public health authorities on the risk assessment following exposure to EC flavor ingredients.

电子烟(ECs)被认为是一种减少烟草危害的产品,其危害程度一直备受争议。使用欧共体被认为比吸烟危害小,但并非无害。随着美国、芬兰、乌克兰和匈牙利等国家禁止使用电子液体香料,人们越来越担心电子烟中使用的电子液体香料的安全性。虽然这些在食品工业中广泛使用,并且在摄入时通常被认为是安全的(GRAS),但吸入后的GRAS状态尚不清楚。本综述的目的是评估2006年至2021年间发表的38份关于调味电子液体对呼吸系统不利影响的体外和体内研究报告的证据。收集的数据表明,肉桂(9篇文章)、草莓(5篇文章)和薄荷醇(10篇文章)的香料比其他香料的有害影响更大。这些研究中报道最多的影响是促炎生物标志物的扰动和细胞毒性的增强。有足够的证据支持含二乙酰和肉桂醛的电子液体在人体吸入后的毒理学影响;然而,其他口味的安全概况难以捉摸。后者可能是由于实验方法之间的不一致和其他电子液体成分的不确定性造成的。此外,浓度范围与人类暴露水平的相关性是不确定的。有证据表明,可能需要在生物学相关浓度下对广泛的电子液体香料进行充分控制和一致的系统毒理学调查,以便更好地告知公共卫生当局接触EC香料成分后的风险评估。
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引用次数: 8
Idiopathic Pulmonary Fibrosis: What do we Know about the Role of Occupational and Environmental Determinants? A Systematic Literature Review and Meta-Analysis. 特发性肺纤维化:我们对职业和环境决定因素的作用了解多少?系统文献回顾与元分析。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-10-03 DOI: 10.1080/10937404.2022.2131663
A Pauchet, A Chaussavoine, J C Pairon, C Gabillon, A Didier, I Baldi, Y Esquirol

The objectives of this systematic review of original articles published up until August 2021 and meta-analyses were to identify the links between occupational and non-occupational environmental exposures, types of occupations and idiopathic pulmonary fibrosis (IPF). Sixteen selected case-control studies were qualified as good level with Newcastle-Ottawa quality assessment scale. Sensitivity analyses highlighted the role of choice of control group, tobacco adjustment and diagnostic tools. Significantly increased risks of IPF were observed (OR (95%CI): for metals (1.42(1.05-1.92)), wood (OR:1.32(1.02-1.71)), and general dust (OR:1.32(1.08-1.63)) exposures. Subgroup analyses found a significantly elevated risk for: hardwood (OR:1.75 (1.13-2.70)), organic dusts (OR:1.72 (1.20-2.46)) and pesticides (OR:2.30 (1.30-4.08)), while no significant change was noted for softwoods and solvents. Smoking adjustments: general dust (1.45 (1.04-2.03)/organic dust (2.5 (1.49-4.22)/metals (1.87 (1.16-3)/wood dust OR: 1.16 (0.86-1.61)/pesticide exposure 2.4 (0.84-6.9) were calculated. Among agricultural workers, the risk was also increased (OR:2.06 (1.02-4.16)). Few environmental data were available and no significant associations detected. Thus, these meta-analyses highlighted the role of some occupational exposures in IPF occurrence. A more accurate and thorough assessment of exposures over the entire working life as well as on the duration and intensity of exposure and complex of multi-pollutant exposure is needed in future research and clinical practice.

本系统回顾了截至2021年8月发表的原始文章,并进行了荟萃分析,目的是确定职业和非职业环境暴露、职业类型和特发性肺纤维化(IPF)之间的联系。16项选定的病例对照研究被纽卡斯尔-渥太华质量评定量表评定为良好水平。敏感性分析强调了对照组选择、烟草调整和诊断工具的作用。观察到IPF风险显著增加(OR (95%CI):金属(1.42(1.05-1.92)),木材(OR:1.32(1.02-1.71))和一般粉尘(OR:1.32(1.08-1.63))暴露。亚组分析发现,硬木(OR:1.75(1.13-2.70))、有机粉尘(OR:1.72(1.20-2.46))和农药(OR:2.30(1.30-4.08))的风险显著升高,而软木和溶剂的风险没有显著变化。吸烟调整:一般粉尘(1.45(1.04-2.03)/有机粉尘(2.5(1.49-4.22))/金属粉尘(1.87(1.16-3))/木屑OR: 1.16(0.86-1.61)/农药暴露2.4(0.84-6.9)。在农业工人中,风险也增加了(OR:2.06(1.02-4.16))。可获得的环境数据很少,也没有发现显著的关联。因此,这些荟萃分析强调了某些职业暴露在IPF发生中的作用。在未来的研究和临床实践中,需要对整个工作寿命的暴露以及暴露的持续时间和强度以及多污染物暴露的复杂性进行更准确和全面的评估。
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引用次数: 3
A comprehensive summary of disease variants implicated in metal allergy. 与金属过敏有关的疾病变异的综合总结。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-08-18 DOI: 10.1080/10937404.2022.2104981
Ka Roach, Jr Roberts

Allergic disease represents one of the most prominent global public health crises of the 21st century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy - including allergic contact dermatitis - are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed - from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described.Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet.

过敏性疾病是21世纪最突出的全球公共卫生危机之一。虽然已知有许多不同的物质会产生超敏反应,但金属是过敏原的主要类别之一,在与过敏相关的疾病总负担中占不成比例的很大一部分。一些最常见的金属过敏形式——包括过敏性接触性皮炎——是公认的;然而,据我们所知,在目前的科学文献中,还没有对人类金属过敏病例中涉及的许多独特疾病变异进行全面审查。因此,撰写这篇综述的主要目标是:(1)生成一份包含这些信息的最新参考文件,以协助实验室研究人员、临床医生、监管毒理学家、工业卫生学家和其他与金属过敏有关的科学家的工作;(2)确定与疾病相关的知识空白。因此,对科学文献进行了广泛的审查-从中确定,收集和分析了数百份描述人类患者金属特异性过敏反应病例的出版物。从这些文章中获得的信息随后被用于编制与金属过敏相关的独特皮肤/眼部、呼吸、胃肠道和全身超敏反应的详尽清单。本文简要讨论了每种疾病变异,其中确定了与每种反应类型相关的特定金属,总结了潜在的免疫机制,并描述了每种反应的主要临床表现。缩写:ACD:过敏性接触性皮炎,AHR:气道高反应性,ASIA:佐剂诱导的自身免疫/自身炎症综合征,BAL:支气管肺泡灌洗,CBD:慢性berylum病,CTCL:皮肤t细胞淋巴瘤,CTL:细胞毒性t淋巴细胞,DRESS:嗜酸性粒细胞增多和全身症状的药物反应,GERD:胃食管反流病,GI:胃肠道,GIP:巨细胞间质性肺炎,GM-CSF:粒细胞巨噬集落刺激因子,HMLD:硬金属肺病,HMW:高分子量,IBS:肠易激综合征,Ig:免疫球蛋白,IL:白细胞介素,LMW:低分子量,PAP:肺泡蛋白症,PPE:个人防护装备,PRR:病原体识别受体,SLE:系统性红斑狼疮,SNAS:系统性镍过敏综合征,Th:辅助性t细胞,UC:溃疡性结肠炎,UV:紫外线。
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引用次数: 5
Identification of effective control technologies for additive manufacturing. 增材制造有效控制技术的识别。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-07-04 DOI: 10.1080/10937404.2022.2092569
Johan du Plessis, Sonette du Preez, Aleksandr B Stefaniak

Additive manufacturing (AM) refers to several types of processes that join materials to build objects, often layer-by-layer, from a computer-aided design file. Many AM processes release potentially hazardous particles and gases during printing and associated tasks. There is limited understanding of the efficacy of controls including elimination, substitution, administrative, and personal protective technologies to reduce or remove emissions, which is an impediment to implementation of risk mitigation strategies. The Medline, Embase, Environmental Science Collection, CINAHL, Scopus, and Web of Science databases and other resources were used to identify 42 articles that met the inclusion criteria for this review. Key findings were as follows: 1) engineering controls for material extrusion-type fused filament fabrication (FFF) 3-D printers and material jetting printers that included local exhaust ventilation generally exhibited higher efficacy to decrease particle and gas levels compared with isolation alone, and 2) engineering controls for particle emissions from FFF 3-D printers displayed higher efficacy for ultrafine particles compared with fine particles and in test chambers compared with real-world settings. Critical knowledge gaps identified included a need for data: 1) on efficacy of controls for all AM process types, 2) better understanding approaches to control particles over a range of sizes and gas-phase emissions, 3) obtained using a standardized collection approach to facilitate inter-comparison of study results, 4) approaches that go beyond the inhalation exposure pathway to include controls to minimize dermal exposures, and 5) to evaluate not just the engineering tier, but also the prevention-through-design and other tiers of the hierarchy of controls.

增材制造(AM)是指从计算机辅助设计文件中,将材料一层一层地连接起来以构建物体的几种类型的工艺。许多增材制造过程在打印和相关任务中释放潜在的有害颗粒和气体。人们对包括消除、替代、行政和个人防护技术在内的控制措施在减少或消除排放方面的效力了解有限,这阻碍了风险缓解战略的实施。使用Medline、Embase、Environmental Science Collection、CINAHL、Scopus和Web of Science数据库和其他资源确定了42篇符合本综述纳入标准的文章。主要调查结果如下:1)与单独隔离相比,包含局部排气通风的材料挤出型熔丝制造(FFF) 3d打印机和材料喷射打印机的工程控制通常在降低颗粒和气体水平方面表现出更高的效果;2)与细颗粒相比,FFF 3d打印机的颗粒排放工程控制在超细颗粒和测试室中表现出更高的效果。确定的关键知识差距包括对数据的需求:1)对所有增材制造工艺类型的控制效果,2)更好地理解控制不同尺寸颗粒和气相排放的方法,3)使用标准化收集方法获得,以促进研究结果的相互比较,4)超越吸入暴露途径的方法,包括控制以最大限度地减少皮肤暴露,5)不仅评估工程层,还有通过设计进行预防和其他层次的控制。
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引用次数: 0
Regional variation in percutaneous absorption in in vitro human models: a systematic review. 体外人体模型经皮吸收的区域差异:系统综述。
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-04-03 Epub Date: 2022-01-30 DOI: 10.1080/10937404.2022.2032517
Aileen M Feschuk, Nadia Kashetsky, Chavy Chiang, Anuk Burli, Halie Burdick, Howard I Maibach

Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous penetration, including anatomical region, although little is currently known regarding this parameter. Hence, the aim of this study was to summarize existing data on regional variation in percutaneous penetration in in vitro human models. PubMed, Embase, Web of Science, and US patent literature were explored, and relevant data collected. Eight eligible articles were identified, which together, explored 15 anatomical locations. Four investigations compared percutaneous penetration between scalp and abdominal skin, and all concluded that the former was more permeable. Within those four studies, 10 penetrants of varying physical/chemical properties were tested indicating that in those particular study conditions, anatomical location exerted a greater effect on percutaneous absorption than the physicochemical properties of the penetrants. In addition, torso area was less absorptive than scrotum in both studies in which these sites were compared. In conclusion, the scrotum and scalp appear to be highly susceptible to percutaneous absorption compared to other locations such as the abdomen. This is postulated to be largely due to the high density of hair follicles in these areas, enabling greater penetration via the appendageal pathway. However, there is a paucity of conclusive data regarding the penetrability of other anatomical locations. Investigations testing and ranking the susceptibility of different anatomical regions is of vital importance given the importance of (1) transdermal drug delivery and decontamination protocols and (2) understanding the underlying mechanisms and degree of these variances might aid our pharmacologic/toxicologic judgments.

经皮吸收在局部药物、透皮药物系统和皮肤毒理学中发挥重要作用。许多因素影响经皮穿透,包括解剖区域,尽管目前对这一参数知之甚少。因此,本研究的目的是总结体外人体模型中经皮渗透的区域差异的现有数据。检索PubMed、Embase、Web of Science和美国专利文献,收集相关数据。8篇符合条件的文章被确定,它们一起探索了15个解剖位置。四项调查比较了头皮和腹部皮肤的经皮穿透性,均得出结论,头皮的渗透性更强。在这四项研究中,对10种不同物理/化学性质的渗透剂进行了测试,表明在这些特定的研究条件下,解剖位置对渗透剂的经皮吸收的影响大于渗透剂的物理/化学性质。此外,在两项研究中,躯干区域比阴囊吸收更少。总之,与腹部等其他部位相比,阴囊和头皮似乎对经皮吸收非常敏感。据推测,这主要是由于这些区域的毛囊密度高,能够通过附属物途径进行更大的渗透。然而,关于其他解剖位置的穿透性,缺乏结论性数据。考虑到(1)经皮给药和去污方案的重要性,(2)了解这些差异的潜在机制和程度可能有助于我们的药理学/毒理学判断,对不同解剖区域的易感性进行调查、测试和排序至关重要。
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引用次数: 2
Methyl-tert-butyl ether (MTBE): integration of rat and mouse carcinogenicity data with mode of action and human and rodent bioassay dosimetry and toxicokinetics indicates MTBE is not a plausible human carcinogen 甲基叔丁基醚(MTBE):综合大鼠和小鼠的致癌性数据和作用方式,以及人类和啮齿动物的生物测定剂量学和毒性动力学表明,MTBE不是一种可信的人类致癌物
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-03-15 DOI: 10.1080/10937404.2022.2041516
J. Bus, B. Gollapudi, G. Hard
ABSTRACT Methyl-tert-butyl ether (MTBE) is a fuel oxygenate used in non-United States geographies. Multiple health reviews conclude that MTBE is not a human-relevant carcinogen, and this review provides updated mode of action (MOA), exposure, dosimetry and risk perspectives supporting those conclusions. MTBE is non-genotoxic and has large margins of exposure between blood concentrations at the overall rat 400 ppm inhalation NOAEL and blood concentrations in typical workplace or general population exposures. Non-cancer and threshold cancer hazard quotients range from a high of 0.046 for fuel-pump gasoline station attendants and are 100–1,000-fold lower for general population exposures. Cancer risks conservatively assuming genotoxicity for these same scenarios are all less than 1 × 10−6. The onset of MTBE nonlinear toxicokinetics (TK) in rats at inhalation exposures less than 3,000 ppm, a dose that is also not practically achievable in fuel-use scenarios, indicates that high-dose specific male rat kidney and testes (3,000 and 8,000 ppm) and female mouse liver tumors (8000 ppm) are not quantitatively relevant to humans. Mode of action analyses also indicate MTBE male rat kidney tumors, and lesser so female mouse liver tumors, are not qualitatively relevant to humans. Thus, an integrated analysis of the toxicology, exposure/dosimetry, TK, and MOA data indicates that MTBE presents minimal human cancer and non-cancer risks.
甲基叔丁基醚(MTBE)是一种用于非美国地区的燃料含氧剂。多项健康综述得出结论,MTBE不是与人类相关的致癌物,本综述提供了支持这些结论的最新作用方式(MOA)、暴露、剂量学和风险观点。MTBE无基因毒性,在大鼠总体吸入400ppm NOAEL的血液浓度与典型工作场所或一般人群暴露的血液浓度之间有很大的暴露幅度。非癌症和阈值癌症的危害商数从燃油泵加油站服务员的0.046不等,而一般人群暴露的危害商数则低100 - 1,000倍。在相同情况下,保守地假设遗传毒性,癌症风险均小于1 × 10−6。吸入低于3,000 ppm的剂量(在燃料使用情景中也无法实际实现)时,大鼠MTBE非线性毒性动力学(TK)的发作表明,高剂量特异性雄性大鼠肾脏和睾丸(3,000和8,000 ppm)以及雌性小鼠肝脏肿瘤(8,000 ppm)与人类在数量上没有相关性。作用模式分析还表明,MTBE雄性大鼠肾脏肿瘤和较小的雌性小鼠肝脏肿瘤与人类没有定性相关性。因此,对毒理学、暴露/剂量学、TK和MOA数据的综合分析表明,MTBE对人类癌症和非癌症的风险最小。
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引用次数: 0
The wash-in effect and its significance for mass casualty decontamination 冲入效应及其对大规模伤亡净化的意义
IF 7.2 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2022-02-27 DOI: 10.1080/10937404.2022.2042443
Thomas James, Lydia Izon-Cooper, S. Collins, Haydn Cole, T. Marczylo
ABSTRACT Decontamination of skin by washing may increase dermal absorption, a phenomenon known as the wash-in effect. The wash-in effect is frequently discussed in studies investigating casualty decontamination where potentially life-saving interventions may enhance the dermal penetration of toxic chemicals, leading to an increase in incidence of morbidity and rates of mortality. However, the wash-in effect is seldom investigated within the context of mass casualty decontamination and real-life consequences are therefore poorly understood. This paper reviews the existing literature on the wash-in effect to highlight the proposed mechanisms for enhanced absorption and evaluate the wash-in effect within the context of mass casualty chemical decontamination.
摘要:通过洗涤来净化皮肤可能会增加真皮吸收,这种现象被称为洗涤效果。在调查伤员去污的研究中,经常讨论冲刷效应,其中潜在的救生干预措施可能会增强有毒化学物质的皮肤渗透,导致发病率和死亡率增加。然而,很少在大规模伤亡净化的背景下对冲刷效应进行调查,因此对现实生活中的后果了解甚少。本文回顾了现有的关于冲洗效果的文献,以强调所提出的增强吸收的机制,并在大规模伤亡化学去污的背景下评估冲洗效果。
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引用次数: 1
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Journal of Toxicology and Environmental Health-Part B-Critical Reviews
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