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In silico occupational exposure banding framework for data poor compounds in biotechnology. 生物技术中数据贫乏化合物的硅学职业接触带框架。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-06 DOI: 10.1177/07482337241289184
Andrey Massarsky, Ernest S Fung, Veneese Jb Evans, Andrew Maier

Occupational exposure limits (OELs) and occupational exposure bands (OEBs) provide quantitative benchmarks for worker health protection. If empirical toxicology data are insufficient to derive an OEL, an OEB is often assigned using partial toxicology data along with other relevant hazard information. There is no consensus methodology to assign OEBs for chemicals lacking any empirical toxicology data. Thus, this study developed an in silico framework for OEB assignment of data poor compounds. It relies upon computational tools to evaluate standard toxicological end points and to assign reliability ratings, which are then used to assign Global Harmonization System (GHS) hazard categories. Subsequently, the hazard categories are entered into the National Institute for Occupational Safety and Health (NIOSH) occupational exposure banding tool to assign bands for individual end points as well as an overall OEB. As a proof-of-concept, five compounds with established OELs (i.e., "knowns") were evaluated. The knowns were assigned to overall OEBs C, D, or E, four of which were equal to or lower than the OEBs based on actual harmonized GHS categories as well as established OELs, indicating that the OEBs assigned using this framework are likely to be protective. Subsequently, five compounds with little to no experimental data and no established OELs from any U.S. agency or consensus OEL-setting organizations were evaluated (i.e., "unknowns"). The unknowns were assigned to overall OEBs D or E. It was concluded that the proposed framework can be used to assign protective OEBs to compounds with little to no toxicology testing data. As additional data become available, the compound may be de-risked, and a precautionary OEB (or an OEL) can be assigned. The proposed framework provides an example of a practical methodology to evaluate data poor compounds and shows that the output of this framework is expected to be protective of worker health.

职业接触限值(OEL)和职业接触带(OEB)为工人健康保护提供了量化基准。如果经验毒理学数据不足以得出 OEL,则通常使用部分毒理学数据和其他相关危害信息来指定 OEB。对于缺乏任何经验性毒理学数据的化学品,目前还没有达成共识的 OEB 分配方法。因此,本研究为数据贫乏的化合物制定了一个 OEB 分配硅学框架。该框架依靠计算工具来评估标准毒理学终点并分配可靠性等级,然后利用可靠性等级来分配全球统一制度(GHS)的危害类别。然后,将危害类别输入美国国家职业安全与健康研究所(NIOSH)的职业接触带工具,为单个终点和整体 OEB 分配带。作为概念验证,评估了五种已确定 OEL 的化合物(即 "已知化合物")。已知化合物被分配到总体 OEB C、D 或 E,其中四种等于或低于基于实际协调的 GHS 类别和既定 OEL 的 OEB,表明使用此框架分配的 OEB 可能具有保护作用。随后,对五种几乎没有实验数据,也没有任何美国机构或共识 OEL 制定组织制定的 OEL 的化合物(即 "未知化合物")进行了评估。得出的结论是,建议的框架可用于为几乎没有毒理学测试数据的化合物指定保护性 OEB。随着更多数据的获得,该化合物可被降低风险,并可分配预防性 OEB(或 OEL)。建议的框架提供了一个实用方法的范例,用于评估数据贫乏的化合物,并表明该框架的结果有望保护工人的健康。
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引用次数: 0
Bis-(2-Chloroisopropyl) ether. 双(2-氯异丙基)醚。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-06-05 DOI: 10.1177/07482337241245745

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers.

双(2-氯异丙基)醚(BCIPE)曾用作脂肪、油脂、油漆和清漆去除剂的溶剂,也可用于斑点处理和清洁溶液。不过,BCIPE 已多年未投入商业生产或使用。在动物实验研究中,急性经口、皮肤和吸入途径接触 BCIPE 后会产生中度毒性。BCIPE 对眼睛有严重刺激性,但对皮肤没有刺激性,也不会引起皮肤过敏。在体外和体内试验中,BCIPE 不具有遗传毒性或诱变性;在对大鼠进行的三代生殖膳食研究中,BCIPE 没有毒性。短期、反复吸入和口服 BCIPE 会导致大鼠肝脏和肾脏重量增加和充血;兔子皮肤接触 BCIPE 不会产生任何可观察到的不良影响。在对小鼠和大鼠进行的两项为期两年的不同膳食研究中,BCIPE 不会导致肿瘤出现统计学意义上的显著增加。在小鼠中,工业级 BCIPE 会增加雌性小鼠肺泡/支气管腺瘤的发病率,增加雄性小鼠肝细胞癌的发病率,并降低森林胃增生的发病率(高剂量时雌雄小鼠均会发生)。使用工业级 BCIPE 进行的进一步调查得出结论,这些影响是物种和剂量特异性的,与人类的相关性有限(如果有的话)。雌性大鼠为期两年的膳食研究得出的无观测不良效应水平(NOAEL)为 400 ppm(15 毫克/千克/天),这被认为是推导基于健康的 WEEL 的出发点。在对接触时间、个体间差异和个体内差异进行调整后,得出 8 小时时间加权平均值 (TWA) WEEL 值为 3 ppm(21 mg/m3)。预计这一接触限值将为工人的健康提供很大的安全边际,以避免任何潜在的不良健康影响。
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引用次数: 0
Musculoskeletal disorders and visual problems among surgical versus medical physicians: A cross-sectional study. 外科医师与内科医师的肌肉骨骼疾病和视觉问题:一项横断面研究。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1177/07482337241261416
Enjy Ahmad Esmat Khorshed, Dalia A El-Shafei, Mona Fathy Zaitoun, Tarek ElHewala, Ahmed Mohamed Bahgat Awad, Raghda Ali Elshamy

The healthcare industry is one of the main industries with a high prevalence of musculoskeletal disorders (MSDs). Surgical practice mostly involves repetitive tasks with fine motor control, precise motions, high levels of mental concentration, and close visual focus. This cross-sectional study aimed to define the prevalence and risk factors of MSDs and visual problems among physicians. One hundred surgical physicians and one hundred medical physicians were involved in the study. Both groups underwent assessment of socio-demographic and occupational history, alongside evaluation for musculoskeletal and visual problems. The study revealed a significantly higher prevalence of MSDs, particularly neck and back pain, as well as blurred near vision and eye dryness, among surgical physicians compared to medical physicians. Risk factors for these conditions included long working hours (≥30 h/week) in clinics or operating rooms, as well as using endoscopes and microscopes/loupes during surgery. In conclusion, MSDs and visual problems were prevalent among physicians, particularly surgical physicians. Integrating ergonomic principles across all domains of healthcare and promoting healthcare worker awareness through training and intervention programs are crucial steps in addressing these issues.

医疗保健行业是肌肉骨骼疾病(MSDs)高发的主要行业之一。外科手术大多涉及重复性工作,需要精细的运动控制、精确的动作、高度的精神集中和近距离的视觉聚焦。这项横断面研究旨在确定内科医生中 MSDs 和视觉问题的患病率和风险因素。100 名外科医师和 100 名内科医师参与了研究。两组人员均接受了社会人口学和职业史评估,以及肌肉骨骼和视力问题评估。研究显示,与内科医生相比,外科内科医生的 MSDs 患病率明显更高,尤其是颈部和背部疼痛,以及近视模糊和眼睛干涩。这些疾病的风险因素包括在诊所或手术室工作时间长(≥30 小时/周),以及在手术过程中使用内窥镜和显微镜/放大镜。总之,内科医生,尤其是外科内科医生普遍存在 MSD 和视觉问题。将人体工程学原理融入医疗保健的各个领域,并通过培训和干预计划提高医护人员的意识,是解决这些问题的关键步骤。
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引用次数: 0
Letter re: Regulatory toxicology approaches in workplaces of Iran. 关于伊朗工作场所毒理学监管方法的信函。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-05-31 DOI: 10.1177/07482337241258664
Seyed Mohammad Ebrahimi, Mansur Rezazadeh Azari, Razzagh Rahimpoor

The objective of establishing occupational exposure limits (OELs) is to utilize them as a risk management tool, ensuring the protection of workers' health and well-being from hazardous substances present in the workplace. To regulate and develop an OEL, it is essential to conduct toxicological studies on both animals and humans, to determine the dose-response relationship for each chemical compound, and to determine whether the dose-response relationship is linear or non-linear. Because the OELs suggested by different organizations or countries are just the result of their scientific methods, knowledge, and judgment, this does not confirm the applicability in other countries. Therefore, it is not scientific and logical to imitate the permissible limits recommended in Western countries. In most Western Asian nations, there is a significant difference in the suggested OEL levels between the reference organizations, and in assessing and managing a specific situation's risk, using any of the proposed OELs can lead to contradictory results. Suggestions for the development and improvement of the basics of determining the OELs for chemical pollution in West Asian countries have been made.

制定职业接触限值(OEL)的目的是将其作为一种风险管理工具,确保工人的健康和福祉不受工作场所有害物质的影响。要规范和制定职业接触限值,必须对动物和人体进行毒理学研究,确定每种化合物的剂量-反应关系,并确定剂量-反应关系是线性关系还是非线性关系。由于不同组织或国家提出的操作限值只是其科学方法、知识和判断的结果,并不能确认是否适用于其他国家。因此,模仿西方国家建议的允许限值是不科学、不符合逻辑的。在大多数西亚国家,参考组织之间建议的 OEL 水平存在显著差异,在评估和管理特定情况的风险时,使用任何建议的 OEL 都可能导致相互矛盾的结果。对西亚国家化学污染 OEL 值的基本确定方法的发展和改进提出了建议。
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引用次数: 0
Biomarkers of occupational benzene exposure: A Systematic Review to estimate the exposure levels and individual susceptibility at low doses. 职业苯暴露的生物标志物:系统回顾:估算低剂量时的暴露水平和个体易感性。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1177/07482337241259053
Zhijuan Zhang, Wenmin Shi, Lihua Ru, Wei Lv

Benzene is associated with diverse occupational and public health hazards. It exhibits an ability to rapidly permeate the skin and contaminate water and food sources, leading to dermal and ingestion exposures. Despite numerous studies examining the associations between benzene and various indicators of harm, the findings have yielded inconsistent results. Furthermore, relying solely on air concentration as a measure of benzene exposure is limited, as it fails to account for internal exposure dose and individual susceptibility. This study aimed to conduct a comprehensive review in order to present current knowledge on benzene biomarkers and their significance in evaluating exposure levels and associated health hazards. The search methodology adhered to the PRISMA guidelines and involved the application of specific inclusion and exclusion criteria across multiple databases including PubMed, Embase, and Web of Science. Two researchers independently extracted and evaluated the relevant data based on predetermined criteria. Following the screening process, a total of 80 articles were considered eligible out of the initially retrieved 1053 articles after undergoing screening and assessment for inclusion. As the level of exposure decreased, specific biomarkers demonstrated a gradual increase in limitations, including heightened background concentrations and vulnerability to confounding factors. The advancement of sampling and analysis techniques will yield new biomarkers. Additionally, when conducting practical work, it is crucial to employ a comprehensive utilization of diverse biomarkers while excluding individual metabolic variations and combined exposure factors.

苯与各种职业和公共健康危害有关。它能够迅速渗透皮肤并污染水源和食物源,导致皮肤接触和摄入。尽管有大量研究探讨了苯与各种危害指标之间的关联,但得出的结果并不一致。此外,仅仅依靠空气浓度来衡量苯的暴露量是有限的,因为它没有考虑到内部暴露剂量和个人易感性。本研究旨在对苯类生物标志物及其在评估暴露水平和相关健康危害方面的意义进行全面综述。检索方法符合 PRISMA 准则,包括在 PubMed、Embase 和 Web of Science 等多个数据库中应用特定的纳入和排除标准。两名研究人员根据预先确定的标准独立提取和评估相关数据。经过筛选和评估,在最初检索到的 1053 篇文章中,共有 80 篇文章被认为符合纳入条件。随着暴露水平的降低,特定生物标志物的局限性逐渐增加,包括背景浓度升高和易受混杂因素影响。取样和分析技术的进步将产生新的生物标志物。此外,在开展实际工作时,关键是要综合利用各种生物标志物,同时排除个体代谢变化和综合暴露因素。
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引用次数: 0
Effect of chlorpyrifos on cypermethrin-induced dopaminergic neurotoxicity in rats. 毒死蜱对氯氰菊酯诱导的大鼠多巴胺能神经毒性的影响
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI: 10.1177/07482337241267192
Neeraj Rawat, Mahendra Pratap Singh

The study aimed to investigate the combined effects of chlorpyrifos and cypermethrin combined on dopaminergic neurotoxicity, motor behaviours and level of selected inflammatory proteins in rats compared to either alone for delineating an interaction between these two pesticides. The rotarod and grip strength tests were employed to assess neurobehavioural changes. The striatal dopamine content and expression of tyrosine hydroxylase (TH), α-synuclein, cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α) proteins in the nigrostriatal tissue were measured. Chlorpyrifos impaired the neurobehavioural indexes, reduced the striatal dopamine level, augmented the level of α-synuclein, COX-2, and TNF-α and attenuated the expression of TH similar to but a little less than cypermethrin. Half the dose of both pesticides together produced additional neurotoxicity compared with the usual (highest employed) dose of either alone. The results showed that chlorpyrifos induced moderately less dopaminergic neurotoxicity than cypermethrin. In the combination, they produced a little higher toxicity than either pesticide alone.

该研究旨在调查毒死蜱和氯氰菊酯对大鼠多巴胺能神经毒性、运动行为和特定炎症蛋白水平的综合影响,并与单独使用其中一种农药进行比较,以确定这两种农药之间的相互作用。采用转体和握力测试来评估神经行为的变化。测量了黑质组织中纹状体多巴胺的含量和酪氨酸羟化酶(TH)、α-突触核蛋白、环氧化酶-2(COX-2)和肿瘤坏死因子-α(TNF-α)蛋白的表达。毒死蜱损害了神经行为指数,降低了纹状体多巴胺水平,增加了α-突触核蛋白、COX-2和TNF-α的水平,减弱了TH的表达,与氯氰菊酯相似,但略低于氯氰菊酯。与单独使用两种杀虫剂的通常(最高使用剂量)剂量相比,两种杀虫剂同时使用一半剂量会产生额外的神经毒性。结果表明,毒死蜱引起的多巴胺能神经毒性比氯氰菊酯低一些。在混合使用的情况下,它们产生的毒性略高于单独使用其中一种杀虫剂产生的毒性。
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引用次数: 0
Global dioxin research trends and focal points: A century-long visual and bibliometric analysis (1923-2022). 全球二恶英研究趋势和焦点:百年视觉和文献计量分析(1923-2022 年)。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-10-01 Epub Date: 2024-06-05 DOI: 10.1177/07482337241257276
Sa'ed H Zyoud

Dioxin-like compounds, recognized by the World Health Organization (WHO) as among the most enduring toxic chemical substances in the environment, are linked to various occupational activities and industrial accidents worldwide. The aim of this study was to examine and present research publications on dioxins, pinpoint current research trends, identify research gaps, and highlight potential avenues for future exploration in the field. The study period for relevant research articles ranged from 1923 to December 31, 2022, and these articles were sourced from the Scopus database. The analysis involved the identification of key contributors to the field and the visualization of topics, themes, and international collaboration. VOSviewer software (version 1.6.20) was used for visualization analysis. A total of 11,620 publications on dioxins were documented in the Scopus database. The predominant category of these documents comprised 9780 original articles, which represents 84.17% of the total publications. The United States lead in the number of publications, with 3992 (34.35%), followed by Japan, with 1429 (12.3%), China, with 1005 (8.65%), and Germany, with 974 (8.38%). Before 2002, scholarly attention in this field focused primarily on the health effects, environmental fate, and mechanism of toxicity of tetrachlorodibenzo-p-dioxin (TCDD). However, a noticeable change in research focus has been observed since 2002, highlighting the emergence of a topic related to the health effects and environmental fate of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PFDFs). This study is the first to conduct a comprehensive quantitative bibliometric analysis of dioxins over time. These findings indicate a significant increase in the overall growth of the dioxin literature over the past 30 years. These findings may prove crucial in guiding and organizing subsequent investigations related to dioxins.

二恶英类化合物被世界卫生组织(WHO)认定为环境中最持久的有毒化学物质之一,与世界各地的各种职业活动和工业事故有关。本研究的目的是检查和介绍有关二恶英的研究出版物,指出当前的研究趋势,找出研究差距,并强调该领域未来探索的潜在途径。相关研究文章的研究期限为 1923 年至 2022 年 12 月 31 日,这些文章来自 Scopus 数据库。分析工作包括确定该领域的主要贡献者,以及将主题、专题和国际合作可视化。可视化分析使用了 VOSviewer 软件(1.6.20 版)。Scopus 数据库中共收录了 11,620 篇关于二恶英的出版物。这些文献的主要类别是 9780 篇原创文章,占出版物总数的 84.17%。美国的出版物数量居首位,有 3992 篇(占 34.35%),其次是日本的 1429 篇(占 12.3%)、中国的 1005 篇(占 8.65%)和德国的 974 篇(占 8.38%)。2002 年以前,该领域的学术研究主要集中在四氯二苯并对二恶英 (TCDD) 的健康影响、环境归宿和毒性机理方面。然而,自 2002 年以来,研究重点发生了明显的变化,出现了与多氯二苯并对二恶英(PCDD)和多氯二苯并呋喃(PFDF)的健康影响和环境归宿相关的课题。这项研究首次对二恶英随时间变化的情况进行了全面的定量文献计量分析。这些研究结果表明,在过去 30 年中,二恶英文献的总体增长速度明显加快。这些发现对于指导和组织与二恶英有关的后续调查至关重要。
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引用次数: 0
Effects of bisphenol A, bisphenol S, and tetramethyl bisphenol F on male fertility in Caenorhabditis elegans. 双酚 A、双酚 S 和四甲基双酚 F 对秀丽隐杆线虫雄性生殖力的影响
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-09-30 DOI: 10.1177/07482337241287967
Cole M Higley, Katelyn D Waligora, Jessica R Clore, Shannon C Timmons, Aleksandra Kuzmanov

Research has shown that exposure to bisphenol A (BPA), a widely used plasticizer, can lead to meiotic errors, resulting in poor reproductive cell quality and infertility. Health-related concerns have prompted the search for BPA alternatives; however, evidence suggests that currently used BPA analogs, such as bisphenol S (BPS), may pose similar risks to human health. While the effects of BPA on female fertility are well documented, the impact of BPA exposure on sperm quality is poorly understood. To better understand the effects of bisphenol analogs on spermatogenesis, we synthesized a less investigated BPA analog, tetramethyl bisphenol F (TMBPF), and compared its reprotoxic potential to that of widely used BPA and BPS using C. elegans-based assays. We evaluated germ cell count, spermatid size, morphology, and activation in males treated with 0.5 mM ethanol-dissolved bisphenol analogs for 48 h as well as their cross-progeny number and viability. Our results indicated that all of the evaluated bisphenol analogs-BPA, BPS, and TMBPF-adversely affect male fertility to varying degrees. Whereas all three bisphenols reduced spermatid size, only BPA exposure resulted in impaired spermatid activation and significantly reduced brood size. In addition, a decrease in embryonic viability, suggestive of an increased incidence of sperm chromosomal aberrations, was observed following exposure to all of the tested bisphenols. Further investigation is necessary to fully elucidate the underlying mechanisms and implications of BPA, BPS, and TMBPF on spermatogenesis.

研究表明,接触广泛使用的增塑剂双酚 A(BPA)会导致减数分裂错误,造成生殖细胞质量低下和不育。与健康有关的担忧促使人们寻找双酚 A 的替代品;然而,有证据表明,目前使用的双酚 A 类似物(如双酚 S (BPS))可能会对人类健康造成类似的风险。虽然双酚 A 对女性生育力的影响已得到充分证实,但人们对暴露于双酚 A 对精子质量的影响却知之甚少。为了更好地了解双酚类似物对精子发生的影响,我们合成了一种研究较少的双酚A类似物--四甲基双酚F(TMBPF),并利用基于线虫的实验将其生殖毒性潜力与广泛使用的双酚A和双酚S进行了比较。我们评估了经0.5 mM乙醇溶解的双酚类似物处理48小时的雄性动物的生殖细胞数量、精子大小、形态和活化情况,以及它们的杂交后代数量和存活率。我们的研究结果表明,所有被评估的双酚类似物--BPA、BPS 和 TMBPF 都会对雄性的生育能力产生不同程度的负面影响。虽然这三种双酚都会降低精子的大小,但只有双酚 A 暴露会导致精子活化受损,并显著降低育雏规模。此外,在接触所有受测双酚后,还观察到胚胎存活率下降,表明精子染色体畸变的发生率增加。要充分阐明双酚 A、双酚 BPS 和 TMBPF 对精子发生的潜在机制和影响,还需要进一步的调查。
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引用次数: 0
Virtual screening study for biological activity assessment and metabolism pathway of a fuel dye in airborne exposure scenario. 燃料染料在空气暴露情况下的生物活性评估和代谢途径的虚拟筛选研究。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-09-23 DOI: 10.1177/07482337241286187
Sayed Vahid Esmaeili, Ali Alboghobeish, Vafa Feyzi, Fatemeh Ravannakhjavani, Rezvan Zendehdel

The utilization of synthetic dyes increases the risk to human health. Despite the progress of information on azo dyes, very little attention has been reported on toxicity assessment of anthraquinone dyes. Solvent Blue 35 (SB35) is one of the anthraquinone dyes likely to be encountered because of its increasing use in various industries. Whereas the design of laboratory tests is very expensive, in silico screening was used to predict the metabolic profile and toxicity effect of SB35. MetaTox software was used to predict the metabolites of phase I and II in two layers. Since airborne exposure has been considered, the pathways of inhalation and dermal absorption of SB35 were investigated through the SwissADME model based on the modified Lipinski's rule of five. To predict the biological effect and toxicity of SB35 and each of the metabolites, PASS online software was used. Chemical activity was considered according to the probability of activation values (Pa) higher than the probability of inactivation values (Pi). N- dealkylation of SB35 was predicted in the first layer, while seven active compounds were obtained in the second layer from phases I and II reactions. Investigating the physicochemical properties of SB35 confirmed inhalation absorption for occupational exposure scenarios. All metabolites are absorbed from intestinal routes based on the RO5 rules. SB35 and their metabolites have an effective substrate role for the sub-type of CYP 450 enzymes. The toxicity effect of carcinogenicity for SB35 and mutagenicity for metabolites are predicted while confirmed with some biological effects. However, reproductive disorders are pointed with SB35 by probability higher than 70%. Virtual screening methods are efficient tools for creating cost-effective predictions in the hazard's evaluation of SB35. However, a perspective view is suggested before decision-making for laboratory designing tests.

合成染料的使用增加了人类健康的风险。尽管有关偶氮染料的信息取得了进展,但有关蒽醌染料毒性评估的报道却很少。溶剂蓝 35 (SB35) 是可能会遇到的蒽醌染料之一,因为它在各行各业的使用越来越多。由于实验室测试的设计成本非常高昂,因此采用了硅学筛选来预测 SB35 的代谢概况和毒性效应。MetaTox 软件用于预测第一阶段和第二阶段的两层代谢物。由于考虑了通过空气接触的情况,因此根据修改后的利宾斯基 5 规则,通过 SwissADME 模型研究了 SB35 的吸入和皮肤吸收途径。为了预测 SB35 和每种代谢物的生物效应和毒性,使用了 PASS 在线软件。化学活性是根据活化概率值(Pa)高于失活概率值(Pi)来考虑的。第一层预测了 SB35 的 N-脱烷基化反应,第二层从第一和第二阶段反应中获得了 7 种活性化合物。对 SB35 物理化学特性的研究证实,职业暴露情况下可通过吸入吸收。根据 RO5 规则,所有代谢物都会从肠道吸收。SB35 及其代谢物对 CYP 450 亚型酶具有有效的底物作用。预测了 SB35 的致癌性和代谢物的致突变性,并证实了一些生物效应。不过,SB35 会导致生殖障碍的概率高于 70%。虚拟筛选方法是在 SB35 危害评估中进行经济有效预测的有效工具。不过,在对实验室设计测试做出决策之前,建议从更广阔的视角进行分析。
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引用次数: 0
Metallic and metallic oxide nanoparticles toxicity primarily targets the mitochondria of hepatocytes and renal cells 金属和金属氧化物纳米颗粒的毒性主要针对肝细胞和肾细胞的线粒体
IF 1.9 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2024-09-17 DOI: 10.1177/07482337241282860
Bashir Jarrar, Mansour Almansour, Amin Al-Doaiss, Shiou Yih Lee, Walid Melhem, Qais Jarrar, Amal Sewelam
Nanoparticles (NPs) are utilized in various applications, posing potential risks to human health, tissues, cells, and macromolecules. This study aimed to investigate the ultrastructural alterations in hepatocytes and renal tubular cells induced by metallic and metal oxide NPs. Adult healthy male Wistar albino rats ( Rattus norvegicus) were divided into 6 ( n = 7) control and 6 treated groups ( n = 7). The rats in the treated groups exposed daily to silver NPs, gold NPs, zinc oxide NPs, silicon dioxide NPs, copper oxide NPs, and ferric oxide NPs for 35 days. The members of the control group for each corresponding NPs received the respective vehicle. Liver and kidney tissue blocks from all rats were processed for Transmission Electron Microscopy (TEM) examinations. The hepatocytes and renal tubular cells of all NPs-treated rats demonstrated mitochondrial ultrastructural alterations mainly cristolysis, swelling, membrane disruption, lucent matrices, matrices lysis, and electron-dense deposits. However, other organelles demonstrated injury but to a lesser extent in the form of shrunken nuclei, nuclear membrane indentation, endoplasmic reticulum fragmentation, cellular membranes enfolding, brush border microvilli disruption, lysosomal hyperplasia, ribosomes dropping, and peroxisome formation. One may conclude from the findings that the hepatocytes and the renal tubular cells mitochondria are the main targets for nanoparticles toxicity ending in mitochondrial disruption and cell injury. Further studies taking into account the relation of mitochondrial ultrastructural damage with a weakened antioxidant defense system induced by chronic exposure to nanomaterials are needed.
纳米粒子(NPs)被广泛应用于各种领域,对人类健康、组织、细胞和大分子构成潜在风险。本研究旨在探讨金属和金属氧化物 NPs 诱导的肝细胞和肾小管细胞的超微结构改变。将成年健康雄性 Wistar 白化大鼠(Rattus norvegicus)分为 6 个对照组(n = 7)和 6 个处理组(n = 7)。处理组的大鼠每天接触银氧化物、金氧化物、氧化锌氧化物、二氧化硅氧化物、氧化铜氧化物和氧化铁氧化物,为期 35 天。各相应 NPs 对照组的成员则接受相应的载体。对所有大鼠的肝脏和肾脏组织块进行透射电子显微镜(TEM)检查。所有经 NPs 处理的大鼠的肝细胞和肾小管细胞都出现了线粒体超微结构改变,主要是嵴溶解、肿胀、膜破坏、透明基质、基质溶解和电子致密沉积。然而,其他细胞器也表现出损伤,但程度较轻,表现为细胞核缩小、核膜凹陷、内质网破碎、细胞膜折叠、刷状缘微绒毛破坏、溶酶体增生、核糖体下降和过氧化物酶体形成。从这些发现中可以得出结论,肝细胞和肾小管细胞线粒体是纳米粒子毒性的主要目标,最终导致线粒体破坏和细胞损伤。需要进一步研究线粒体超微结构损伤与长期暴露于纳米材料导致的抗氧化防御系统减弱之间的关系。
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Toxicology and Industrial Health
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