Journal of Toxicological Sciences最新文献_第7页

Transcriptome analysis in various cell lines exposed to nitric oxide. 暴露于一氧化氮的各种细胞系的转录组分析。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.281

Tohta Mizushima, Sho Kubota, Yuta Iijima, Nobumasa Takasugi, Takashi Uehara

{"title":"Transcriptome analysis in various cell lines exposed to nitric oxide.","authors":"Tohta Mizushima, Sho Kubota, Yuta Iijima, Nobumasa Takasugi, Takashi Uehara","doi":"10.2131/jts.49.281","DOIUrl":"https://doi.org/10.2131/jts.49.281","url":null,"abstract":"Nitric oxide (NO) plays a physiological role in signal transduction and excess or chronic NO has toxic effects as an inflammatory mediator. NO reversibly forms protein S-nitrosylation and exerts toxicological functions related to disease progression. DNA methyltransferases, epigenome-related enzymes, are inhibited in enzymatic activity by S-nitrosylation. Therefore, excess or chronic NO exposure may cause disease by altering gene expression. However, the effects of chronic NO exposure on transcriptome are poorly understood. Here, we performed transcriptome analysis of A549, AGS, HEK293T, and SW48 cells exposed to NO (100 μM) for 48 hr. We showed that the differentially expressed genes were cell-specific. Gene ontology analysis showed that the functional signature of differentially expressed genes related to cell adhesion or migration was upregulated in several cell lines. Gene set enrichment analysis indicated that NO stimulated inflammation-related gene expression in various cell lines. This finding supports previous studies showing that NO is closely involved in inflammatory diseases. Overall, this study elucidates the pathogenesis of NO-associated inflammatory diseases by focusing on changes in gene expression.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 6","pages":"281-288"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DTox: A deep neural network-based in visio lens for large scale toxicogenomics data. DTox：用于大规模毒物基因组学数据的基于深度神经网络的 visio 镜头。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.105

Takeshi Hase, Samik Ghosh, Ken-Ichi Aisaki, Satoshi Kitajima, Jun Kanno, Hiroaki Kitano, Ayako Yachie

{"title":"DTox: A deep neural network-based in visio lens for large scale toxicogenomics data.","authors":"Takeshi Hase, Samik Ghosh, Ken-Ichi Aisaki, Satoshi Kitajima, Jun Kanno, Hiroaki Kitano, Ayako Yachie","doi":"10.2131/jts.49.105","DOIUrl":"10.2131/jts.49.105","url":null,"abstract":"With the advancement of large-scale omics technologies, particularly transcriptomics data sets on drug and treatment response repositories available in public domain, toxicogenomics has emerged as a key field in safety pharmacology and chemical risk assessment. Traditional statistics-based bioinformatics analysis poses challenges in its application across multidimensional toxicogenomic data, including administration time, dosage, and gene expression levels. Motivated by the visual inspection workflow of field experts to augment their efficiency of screening significant genes to derive meaningful insights, together with the ability of deep neural architectures to learn the image signals, we developed DTox, a deep neural network-based in visio approach. Using the Percellome toxicogenomics database, instead of utilizing the numerical gene expression values of the transcripts (gene probes of the microarray) for dose-time combinations, DTox learned the image representation of 3D surface plots of distinct time and dosage data points to train the classifier on the experts' labels of gene probe significance. DTox outperformed statistical threshold-based bioinformatics and machine learning approaches based on numerical expression values. This result shows the ability of image-driven neural networks to overcome the limitations of classical numeric value-based approaches. Further, by augmenting the model with explainability modules, our study showed the potential to reveal the visual analysis process of human experts in toxicogenomics through the model weights. While the current work demonstrates the application of the DTox model in toxicogenomic studies, it can be further generalized as an in visio approach for multi-dimensional numeric data with applications in various fields in medical data sciences.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 3","pages":"105-115"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MiR-98-3p alleviates lipopolysaccharide-induced pulmonary microvascular endothelial barrier dysfunction by targeting DKK3 in sepsis-induced acute lung injury. 在脓毒症诱发的急性肺损伤中，MiR-98-3p通过靶向DKK3缓解脂多糖诱发的肺微血管内皮屏障功能障碍

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.289

Dan Zhong, Cong Luo, Neng Wang, Jie Lin

{"title":"MiR-98-3p alleviates lipopolysaccharide-induced pulmonary microvascular endothelial barrier dysfunction by targeting DKK3 in sepsis-induced acute lung injury.","authors":"Dan Zhong, Cong Luo, Neng Wang, Jie Lin","doi":"10.2131/jts.49.289","DOIUrl":"10.2131/jts.49.289","url":null,"abstract":"Background: Endothelial barrier dysfunction is critical for the pathogenesis of sepsis-induced acute lung injury (ALI). Lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) are widely used as the cell model of sepsis-associated ALI for exploration of endothelial barrier dysfunction. Dickkopf (DKK) family proteins were reported to mediate endothelial functions in various diseases. The present study explored the effect of Dickkopf-3 (DKK3) on endothelial barrier permeability, angiogenesis, and tight junctions in LPS-stimulated HPMECs.Methods: RT-qPCR was required for detecting DKK3 and miR-98-3p expression. The angiogenesis of HPMECs was evaluated by tube formation assays. Monolayer permeability of HPMECs was examined by Transwell rhodamine assays. The protein expression of DKK3 and tight junctions in HPMECs was measured via western blotting. Luciferase reporter assay was used to verify the interaction between miR-98-3p and DKK3.Results: LPS treatment inhibited angiogenetic ability while increasing the permeability of HPMECs. DKK3 expression was upregulated while miR-98-3p level was reduced in LPS-treated HPMECs. DKK3 knockdown alleviated HPMEC injury triggered by LPS stimulation. MiR-98-3p targeted DKK3 in HPMECs. Overexpression of miR-98-3p protects HPMECs from the LPS-induced endothelial barrier dysfunction, and the protective effect was reversed by DKK3 overexpression.Conclusions: MiR-98-3p ameliorates LPS-evoked pulmonary microvascular endothelial barrier dysfunction in sepsis-associated ALI by targeting DKK3.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 7","pages":"289-299"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of selenium content in fetal bovine serum on ferroptosis susceptibility and selenoprotein expression in cultured cells. 胎牛血清硒含量对培养细胞中铁下垂易感性和硒蛋白表达的影响。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.555

Hayato Takashima, Takashi Toyama, Eikan Mishima, Kei Ishida, Yinuo Wang, Atsuya Ichikawa, Junya Ito, Syunsuke Yogiashi, Stephanie Siu, Mayumi Sugawara, Satoru Shiina, Kotoko Arisawa, Marcus Conrad, Yoshiro Saito

{"title":"Impact of selenium content in fetal bovine serum on ferroptosis susceptibility and selenoprotein expression in cultured cells.","authors":"Hayato Takashima, Takashi Toyama, Eikan Mishima, Kei Ishida, Yinuo Wang, Atsuya Ichikawa, Junya Ito, Syunsuke Yogiashi, Stephanie Siu, Mayumi Sugawara, Satoru Shiina, Kotoko Arisawa, Marcus Conrad, Yoshiro Saito","doi":"10.2131/jts.49.555","DOIUrl":"https://doi.org/10.2131/jts.49.555","url":null,"abstract":"Ferroptosis, a mode of cell death involving iron-dependent lipid peroxidation, has attracted widespread attention in the development of anticancer drugs and toxicological studies as a potential mechanism of chemical-induced cytotoxicity. This process is regulated by several antioxidant enzymes, of which the selenium-containing glutathione peroxidase 4 (GPx4) is the prime regulator. However, accurately and reproducibly evaluating ferroptosis in cultured cells is challenging since numerous experimental factors in in vitro setting can influence the results. In the present study, we found that the expression levels of selenoproteins, such as GPx4 and GPx1, fluctuate across several cell lines depending on the selenium content of different origin of fetal bovine serum (FBS). Cells cultured in FBS containing higher selenium concentrations exhibited elevated GPx4 expression, and were resistant to ferroptosis induced by erastin and RSL3. These findings suggest that the variability of selenium content in different FBS batches can significantly influence the susceptibility of cells to ferroptosis, highlighting the importance of standardizing these factors to enhance the reproducibility of ferroptosis-related experiments.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 12","pages":"555-563"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylmercury-induced brain neuronal death in CHOP-knockout mice. 甲基汞诱导的 CHOP 基因敲除小鼠脑神经元死亡。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.55

Yuta Iijima, Ryohei Miki, Masatake Fujimura, Seiichi Oyadomari, Takashi Uehara

引用次数: 0

Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs. 利用氟烷麻醉犬分析吗啡的心血流动力学和电生理学效应及其毒代动力学特征。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.269

Ai Goto, Ryuichi Kambayashi, Masaya Fujishiro, Chika Hasegawa, Hiroko Izumi-Nakaseko, Yoshinori Takei, Kunihiko Kurosaki, Atsushi Sugiyama

{"title":"Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.","authors":"Ai Goto, Ryuichi Kambayashi, Masaya Fujishiro, Chika Hasegawa, Hiroko Izumi-Nakaseko, Yoshinori Takei, Kunihiko Kurosaki, Atsushi Sugiyama","doi":"10.2131/jts.49.269","DOIUrl":"https://doi.org/10.2131/jts.49.269","url":null,"abstract":"Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 6","pages":"269-279"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protection of cultured vascular endothelial cells against cadmium cytotoxicity by simultaneous treatment or pretreatment with manganese. 锰同时处理或预处理可保护培养的血管内皮细胞免受镉的细胞毒性。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.349

Tomoya Fujie, Reika Ando, Momoka Abe, Natsumi Ichida, Keisuke Ito, Takato Hara, Chika Yamamoto, Toshiyuki Kaji

{"title":"Protection of cultured vascular endothelial cells against cadmium cytotoxicity by simultaneous treatment or pretreatment with manganese.","authors":"Tomoya Fujie, Reika Ando, Momoka Abe, Natsumi Ichida, Keisuke Ito, Takato Hara, Chika Yamamoto, Toshiyuki Kaji","doi":"10.2131/jts.49.349","DOIUrl":"https://doi.org/10.2131/jts.49.349","url":null,"abstract":"Cadmium is a heavy metal that pollutes the environment and foods and is a risk factor for vascular disorders. We have previously demonstrated that pretreatment of vascular endothelial cells with zinc and copper protects the cells against cadmium cytotoxicity. In contrast, cadmium cytotoxicity was potentiated in cells following exposure to lead, thereby indicating that in vascular endothelial cells, cadmium cytotoxicity can be differentially modified by the co-occurrence of other heavy metals. In this study, we revealed that simultaneous treatment or pretreatment with manganese protects vascular endothelial cells against cadmium cytotoxicity. Intracellular accumulation of cadmium was observed to be reduced by simultaneous treatment with manganese, although not by pretreatment. The mRNA expression of metal transporters that regulate the uptake of both cadmium and manganese (ZIP8, ZIP14, and DMT1) remained unaffected by either simultaneous treatment or pretreatment with manganese, and simultaneous treatment with manganese suppressed the cadmium-induced expression of metallothionein but pretreatment with manganese did not exhibit such suppressive effect. Thus, the protection of vascular endothelial cells against cadmium cytotoxicity conferred by simultaneous treatment with manganese is assumed to be partially attributed to a reduction in the intracellular accumulation of cadmium, whereas the effects of pretreatment with manganese are independent of both the reduced intracellular accumulation of cadmium and the induction of metallothionein. These observations accordingly indicate that the protective effects of manganese are mediated via alternative (as yet unidentified) mechanisms.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 8","pages":"349-358"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidative stress-induced TET1 upregulation mediates active DNA demethylation in human gastric epithelial cells. 氧化应激诱导的TET1上调介导人胃上皮细胞活性DNA去甲基化。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.273

Mengna Zuo, Jianing He, Qianxi Yin, Xiaoying He, Ying Liu, Yang Liu, Jiwei Liu, Shujun Liu, Libing Ma

{"title":"Oxidative stress-induced TET1 upregulation mediates active DNA demethylation in human gastric epithelial cells.","authors":"Mengna Zuo, Jianing He, Qianxi Yin, Xiaoying He, Ying Liu, Yang Liu, Jiwei Liu, Shujun Liu, Libing Ma","doi":"10.2131/jts.48.273","DOIUrl":"https://doi.org/10.2131/jts.48.273","url":null,"abstract":"The gastrointestinal (GI) tract is more vulnerable to effects by the outside environment, and experiences oxidative stress. A wide diversity of GI disorders can be partially attributed to oxidative stress. However, the mechanism of oxidative stress-caused GI pathological changes is not clear. In the present study, human gastric epithelial cells (hGECs) were treated with hydrogen peroxide (H2O2), and oxidative stress was determined. The effect of oxidative stress on the levels of some antioxidative enzymes, proliferation, nuclear DNA damage, apoptosis, expression of ten-eleven translocation (TET), and level of DNA methylation was determined in these cells. The results showed that H2O2 treatment caused oxidative stress, increased the levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), decreased the level of glutathione (GSH), inhibited proliferation, caused nuclear DNA damage and apoptosis, upregulated the expression of TET1 gene, and ultimately led to active DNA demethylation in hGECs. The present study presents a mechanism by which oxidative stress induces active DNA demethylation in hGECs. We propose that TET inhibitors can be used to restore the oxidative stress-induced DNA demethylation, and thus inhibit possible malignant transformation of GI cells.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 5","pages":"273-283"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9396786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human gut microbiota influences drug-metabolizing enzyme hepatic Cyp3a: A human flora-associated mice study. 人类肠道菌群影响药物代谢酶肝脏Cyp3a:人类菌群相关小鼠研究。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.333

Masao Togao, Takashi Kurakawa, Shinnosuke Tajima, Gaku Wagai, Yuki Ohta-Takada, Jun Otsuka, Akinobu Kurita, Koji Kawakami

{"title":"Human gut microbiota influences drug-metabolizing enzyme hepatic Cyp3a: A human flora-associated mice study.","authors":"Masao Togao, Takashi Kurakawa, Shinnosuke Tajima, Gaku Wagai, Yuki Ohta-Takada, Jun Otsuka, Akinobu Kurita, Koji Kawakami","doi":"10.2131/jts.48.333","DOIUrl":"https://doi.org/10.2131/jts.48.333","url":null,"abstract":"Several studies revealed that gut microbiota affects the hepatic drug-metabolizing enzyme cytochrome P450 (Cyp). We hypothesized that individual gut microbiota variations could contribute to CYP activity. Human flora-associated (HFA) mice are established from germ-free mice using human feces and are often used to determine the effect of the human gut microbiota on the host. This study generated two groups of HFA mice using feces from two healthy individuals. Then, the composition of gut microbiota and hepatic Cyp activity was compared to analyze the effects of gut microbiota in healthy individuals on hepatic Cyp activity. A principal coordinate analysis based on the UniFrac distance for the composition of the cecal and fecal microbiota revealed apparent differences between the recipient groups. Hepatic Cyp, which is a marked difference in Cyp3a activity and Cyp3a11 gene expression, was observed between the recipient groups. Cyp2c and Cyp1a activities did not differ between recipient groups, with significantly lower enzymatic activities in recipients than in germ-free mice. These results indicate that the human gut microbiota affects hepatic Cyp activity. Especially, human gut microbiota composition differences have a pronounced effect on Cyp3a activity via Cyp3a11 gene expression regulation. Therefore, human gut microbiota variations among individuals may affect numerous drug metabolism, leading to drug efficacy and toxicity.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 6","pages":"333-343"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a risk assessment method for the detailed consideration of the effects of liquid toxic substance leakage incidents on the human body: ethanol as a model substance. 制定详细考虑液体有毒物质泄漏事故对人体影响的风险评估方法：以乙醇为模型物质。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.49.37

Akio Horiguchi, Satoshi Numazawa

{"title":"Development of a risk assessment method for the detailed consideration of the effects of liquid toxic substance leakage incidents on the human body: ethanol as a model substance.","authors":"Akio Horiguchi, Satoshi Numazawa","doi":"10.2131/jts.49.37","DOIUrl":"https://doi.org/10.2131/jts.49.37","url":null,"abstract":"To ensure safety in chemical plants handling a wide variety of liquid and gaseous hazardous substances, it is necessary to carry out highly accurate risk assessments and take appropriate measures. In this study, a risk assessment method was developed for the problem of the leakage of liquid hazardous substances. The risk assessment of toxic liquid leaks must consider the exposure of workers to the liquid and toxic gases produced by vaporization. The absorption and subsequent metabolism of hazardous substances in the body via multiple pathways after exposure to liquids and gases was calculated using a pharmacokinetic model. Estimation of exposure concentrations of toxic gases volatilized from leaked liquids was reproduced by computational fluid dynamics simulation. In this study, ethanol was selected as the hazardous substance and the risk of hazardous liquid leakage was assessed. The results of the analysis, which considered liquid and gas exposure under the conditions of the assumed scenario, showed that the maximum blood concentration of ethanol was 1640 µmol/L, which is sufficiently low compared to the concentration of 10,900 µmol/L at which acute toxic effects become apparent. These results suggest that work can be carried out safely under the conditions of the assumed scenario. The risk assessment methodology for liquid spills in this study confirms that risk assessment is possible under multiple scenarios, including individual differences, activity conditions, and the use of protective equipment.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 1","pages":"37-47"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0