Toxicological Research最新文献

{"title":"N-methylformamide induces multiple organ toxicity in Fischer 344 rats.","authors":"Mi Ju Lee, Hyo-Geun Cha, Ka Young Park, Yong-Soon Kim, Byeongwoo Ahn","doi":"10.1007/s43188-022-00165-x","DOIUrl":"10.1007/s43188-022-00165-x","url":null,"abstract":"<p><p>N-Methylformamide (NMF) is a widely used chemical (CAS No.: 123-39-7) in several industries and its usage is continuously increasing. However, studies for NMF have been focused on hepatotoxicity from now. Its toxicity profile has not yet been established owing to limited toxicity data. Therefore, we evaluated systemic toxicity via NMF inhalation. We exposed 0, 30, 100, and 300 ppm NMF to Fischer 344 rats for 6 h/day, 5 days a week for 2 weeks. Clinical signs, body weights, food consumption, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathology were performed. Two females exposed to 300 ppm NMF died during exposure period. Decrease of food consumption and body weight in both sexes exposed to 300 ppm in females exposed to 100 ppm were noted during exposure period. Increased RBC and HGB were noted in females exposed to 300 ppm. A decrease in the levels of ALP and K and increase in the levels of TCHO and Na were observed in both sexes exposed to 300 and 100 ppm. Increased levels of ALT, AST, BUN and decreased levels of TP, ALB, Ca were observed in females exposed to 300 and 100 ppm. The relative liver weight was elevated in both sexes exposed to 300 and 100 ppm NMF. Hypertrophy in the liver and submandibular glands and nasal cavity injuries were noted in both sexes exposed to 300 and 100 ppm NMF. Tubular basophilia of the kidneys were noted in females exposed to 300 ppm NMF. We revealed that NMF affect several organs including the kidneys not only the liver and NMF-related toxicity is predominant in female rats. These results could contribute to the development of NMF toxicity profile and may help in developing strategies for the control of occupational environmental hazards related to NMF.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"263-274"},"PeriodicalIF":2.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of co-exposure to methyl paraben and dibutyl phthalate on cell line derived from human skin.","authors":"Katarzyna Miranowicz-Dzierżawska,&nbsp;Lidia Zapór,&nbsp;Jolanta Skowroń,&nbsp;Luiza Chojnacka-Puchta,&nbsp;Dorota Sawicka","doi":"10.1007/s43188-022-00151-3","DOIUrl":"https://doi.org/10.1007/s43188-022-00151-3","url":null,"abstract":"<p><p>Data on the cumulative effects of chemical substances are necessary for the proper risk assessment, but their availability is still insufficient. The aim of the study was to evaluate the cytotoxic effect of methyl paraben (MePB) and dibutyl phthalate (DBP) on the cells of the skin line (A431) and to compare the cytotoxic effects of the tested substances after single application to A431 cells with the effects of an equimolar/equitoxic (1:1) binary mixture of these compounds as well as their mixtures in ratio 1:3: and 3:1. On the basis of the obtained results, it was found that there were interactions between the tested compounds in terms of cytotoxic effect on A431, assessed on the basis of metabolic activity of cells (MTT test) and integrity of their cell membranes (NRU test). The obtained values of synergy coefficients (SI) and isobolographic analysis indicate that between the tested chemicals in a two-component equimolar mixture (1:1) there is a synergism of action, which, at a high DBP content in the mixture (> 50%) turned into antagonism. Observations using a holotomographic microscope show morphological changes in A431 cells after exposure to both DBP and MePB separately and binary mixtures of these compounds, compared to untreated cells. The observed changes in cell morphology seem to be more pronounced when the cells are exposed to the binary mixtures of DBP and MePB than when exposed to these substances individually, which may confirm the synergy of cytotoxic activity between them (this phenomenon was observed for the higher of the tested concentrations in all tested proportions). It is important to consider such effects when considering the effects of cumulative exposure in the risk assessment in order not to underestimate the risk of adverse effects associated with exposure to chemical mixtures.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"71-89"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9153189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro toxicological assessment of PhSeZnCl in human liver cells.","authors":"Raffaella di Vito,&nbsp;Sara Levorato,&nbsp;Cristina Fatigoni,&nbsp;Mattia Acito,&nbsp;Luca Sancineto,&nbsp;Giovanna Traina,&nbsp;Milena Villarini,&nbsp;Claudio Santi,&nbsp;Massimo Moretti","doi":"10.1007/s43188-022-00148-y","DOIUrl":"https://doi.org/10.1007/s43188-022-00148-y","url":null,"abstract":"<p><p>Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 µg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G₂/M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 µg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00148-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"105-114"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9153183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of complement C3 as a marker of alpha-amanitin toxicity by comparative secretome profiling.","authors":"Doeun Kim, Min Seo Lee, Hyunchae Sim, Sangkyu Lee, Hye Suk Lee","doi":"10.1007/s43188-022-00163-z","DOIUrl":"10.1007/s43188-022-00163-z","url":null,"abstract":"<p><p>In the human body, proteins secreted into peripheral blood vessels are known as the secretome, and they represent the physiological or pathological status of cells. The unique response of cells to toxin exposure can be confirmed <i>via</i> secretome analysis, which can be used to discover toxic mechanisms or exposure markers. Alpha-amanitin (α-AMA) is the most widely studied amatoxin and inhibits transcription and protein synthesis by directly interacting with RNA polymerase II. However, secretory proteins released during hepatic failure caused by α-AMA have not been fully characterized. In this study, we analyzed the secretome of α-AMA-treated Huh-7 cells and mice using a comparative proteomics technique. Overall, 1440 and 208 proteins were quantified in cell media and mouse serum, respectively. Based on the bioinformatics results for the commonly downregulated proteins in cell media and mouse serum, we identified complement component 3 (C3) as a marker for α-AMA-induced hepatotoxicity. Through western blot in cell secretome and C3 ELISA assays in mouse serum, we validated α-AMA-induced downregulation of C3. In conclusion, using comparative proteomics and molecular biology techniques, we found that α-AMA-induced hepatotoxicity reduced C3 levels in the secretome. We expect that this study will aid in identifying new toxic mechanisms, therapeutic targets, and exposure markers of α-AMA-induced hepatotoxicity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00163-z.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"251-262"},"PeriodicalIF":2.3,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood vessel remodeling in the cerebral cortex induced by binge alcohol intake in mice.","authors":"Hiroshi Hasegawa, Toshiya Tanaka, Mari Kondo, Koji Teramoto, Kei Nakayama, Gi-Wook Hwang","doi":"10.1007/s43188-022-00164-y","DOIUrl":"10.1007/s43188-022-00164-y","url":null,"abstract":"<p><p>Ethanol is toxic to the brain and causes various neurological disorders. Although ethanol can directly exert toxicity on neurons, it also acts on other cell types in the central nervous system. Blood vessel endothelial cells interact with, and are affected by blood ethanol. However, the effects of ethanol on the vascular structures of the brain have not been well documented. In this study, we examined the effects of binge levels of ethanol on brain vasculature. Immunostaining analysis indicated structural alterations of blood vessels in the cerebral cortex, which became more tortuous than those in the control mice after ethanol administration. The interaction between the blood vessels and astrocytes decreased, especially in the upper layers of the cerebral cortex. Messenger RNA expression analysis revealed a unique downregulation of <i>Vegfa</i> mRNA encoding vascular endothelial growth factor (VEGF)-A among VEGF, angiopoietin, endothelin family angiogenic and blood vessel remodeling factors. The expression of three proteoglycan core proteins, glypican-5, neurocan, and serglycin, was also altered after ethanol administration. Thus, binge levels of ethanol affect the expression of VEGF-A and blood vessel-supporting proteoglycans, resulting in changes in the vascular structure of the cerebral cortex.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00164-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"169-177"},"PeriodicalIF":2.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dynamics when mitochondrial toxic chemicals exposed in 3D cultured mouse embryonic stem cell.","authors":"Changhwan Ahn, SunHwa Jeong, Eui-Bae Jeung","doi":"10.1007/s43188-022-00161-1","DOIUrl":"10.1007/s43188-022-00161-1","url":null,"abstract":"<p><p>Mitochondria need to use considerable energy for the intracellular organelles that produce ATP. They are abundant in the cells of organs, such as muscles, liver, and kidneys. The heart, which requires a lot of energy, is also rich in mitochondria. Mitochondrial damage can induce cell death. Doxorubicin, acetaminophen, valproic acid, amiodarone, and hydroxytamoxifen are representative substances that induce mitochondrial damage. On the other hand, the effects of this substance on the progress of cardiomyocyte-differentiating stem cells have not been investigated. Therefore, a 3D cultured embryonic body toxicity test was performed. The results confirmed that the cytotoxic effects on cardiomyocytes were due to mitochondrial damage in the stage of cardiomyocyte differentiation. After drug treatment, the cells were raised in the embryoid body state for four days to obtain the ID₅₀ values, and the levels of mRNA expression associated with the mitochondrial complex were examined. The mitochondrial DNA copy numbers were also compared to prove that the substance affects the number of mitochondria in EB-state cardiomyocytes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00161-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"239-249"},"PeriodicalIF":2.3,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical method development and dermal absorption of 2-amino-5-nitrophenol (2A5NP), a hair dye ingredient under oxidative condition.","authors":"Yu Jin Kim, Hyang Yeon Kim, Jung Dae Lee, Hong Yoon Kim, Jueng Eun Im, Kyu-Bong Kim","doi":"10.1007/s43188-022-00159-9","DOIUrl":"10.1007/s43188-022-00159-9","url":null,"abstract":"<p><p>Although 2-amino-5-nitrophenol (2A5NP) is one of the ingredients of hair dye, there has been no information on the dermal absorption rate of 2A5NP. 2A5NP is managed at less than 1.5% in Korea and Japan. In this study, analytical methods were developed and validated using high-performance liquid chromatography (HPLC) in various matrices of wash, swab, stratum corneum (SC), skin (dermis + epidermis), and receptor fluid (RF). Validation results were acceptable based on Korea Ministry of Food and Drug Safety (MFDS) guideline. The HPLC analysis showed a good linearity (r² = 0.9992-0.9999), a high accuracy (93.1-110.2%), and a good precision (1.1-8.1%) in accordance with the validation guideline. Franz diffusion cell was used to determine dermal absorption of 2A5NP using mini pig skin. 2A5NP (1.5%) was applied to skin at 10 μl/cm². For certain cosmetic ingredients such as hair dye with short exposure time, an interim wash step (after 30 min) was added during the study. After application for 30 min and 24 h, skin was wiped off with swab and SC was collected using tape stripping. RF was sampled at 0, 1, 2, 4, 8, 12, and 24 h. Total dermal absorption rate of 2A5NP (1.5%) was determined to be 13.6 ± 2.9%.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"231-238"},"PeriodicalIF":2.3,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice.","authors":"Ishita Seal, Sidhanta Sil, Abhijit Das, Souvik Roy","doi":"10.1007/s43188-022-00158-w","DOIUrl":"10.1007/s43188-022-00158-w","url":null,"abstract":"<p><p>Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD₅₀ of the complex at 500 mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400 mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200 mg/kg group. In the histopathological analysis, the 50, 100, and 200 mg/kg groups were not associated with any toxicological alterations, whereas the 400 mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200 mg/kg without any toxicological and genotoxic potential.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"213-229"},"PeriodicalIF":2.3,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomic analysis of liver and kidney after 28 days of thioacetamide treatment in rats.","authors":"Hyoung-Yun Han, Se-Myo Park, Je-Won Ko, Jung-Hwa Oh, Sang Kyum Kim, Tae-Won Kim","doi":"10.1007/s43188-022-00156-y","DOIUrl":"10.1007/s43188-022-00156-y","url":null,"abstract":"<p><p>Thioacetamide (TAA) was developed as a pesticide; however, it was soon found to cause hepatic and renal toxicity. To evaluate target organ interactions during hepatotoxicity, we compared gene expression profiles in the liver and kidney after TAA treatment. Sprague-Dawley rats were treated daily with oral TAA and then sacrificed, and their tissues were evaluated for acute toxicity (30 and 100 mg/kg bw/day), 7-day (15 and 50 mg/kg bw/day), and 4-week repeated-dose toxicity (10 and 30 mg/kg). After the 4-week repeated toxicity study, total RNA was extracted from the liver and kidneys, and microarray analysis was performed. Differentially expressed genes were selected based on fold change and significance, and gene functions were analyzed using ingenuity pathway analysis. Microarray analysis showed that significantly regulated genes were involved in liver hyperplasia, renal tubule injury, and kidney failure in the TAA-treated group. Commonly regulated genes in the liver or kidney were associated with xenobiotic metabolism, lipid metabolism, and oxidative stress. We revealed changes in the molecular pathways of the target organs in response to TAA and provided information on candidate genes that can indicate TAA-induced toxicity. These results may help elucidate the underlying mechanisms of target organ interactions during TAA-induced hepatotoxicity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00156-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"201-211"},"PeriodicalIF":2.3,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats.","authors":"Yong-Soon Kim, Eun-Sang Cho, Chan-Hyuck Park, Hyo-Geun Cha","doi":"10.1007/s43188-022-00162-0","DOIUrl":"10.1007/s43188-022-00162-0","url":null,"abstract":"<p><p>Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6 h a day, 5 days per week) at target concentrations of 45, 90, and 180 mg/m³. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18 mg/m³, 90.69 ± 7.30 mg/m³, and 183.87 ± 15.21 mg/m³, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ± 0.07 μm, 1.47 ± 0.18 μm, and 1.68 ± 0.16 μm, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45 mg/m³.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"157-167"},"PeriodicalIF":2.3,"publicationDate":"2022-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}