Inhalation Toxicology最新文献

{"title":"Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers.","authors":"Neil E Alexis,&nbsp;Laura Y Zhou,&nbsp;Allison J Burbank,&nbsp;Martha Almond,&nbsp;Michelle L Hernandez,&nbsp;Katherine H Mills,&nbsp;Terry L Noah,&nbsp;Heather Wells,&nbsp;Haibo Zhou,&nbsp;David B Peden","doi":"10.1080/08958378.2022.2110334","DOIUrl":"10.1080/08958378.2022.2110334","url":null,"abstract":"<p><strong>Background: </strong>We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (&lt;i&gt;N&lt;/i&gt; = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP.</p><p><strong>Results: </strong>Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (&lt;i&gt;p&lt;/i&gt; &amp;lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response.</p><p><strong>Conclusions: </strong>The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 11-12","pages":"329-339"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519374/pdf/nihms-1921822.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999647","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":"Profile of atmospheric particulate PAHs near busy roadway in tropical megacity, India.","authors":"Saurabh Sonwani,&nbsp;Pallavi Saxena,&nbsp;P S Khillare","doi":"10.1080/08958378.2022.2030442","DOIUrl":"https://doi.org/10.1080/08958378.2022.2030442","url":null,"abstract":"<p><p><b>Objective:</b> This study focuses on the profile of ambient particulate polycyclic aromatic hydrocarbons (PAHs), their seasonal distribution, source identification and human health risk assessment due to inhalation exposure of ambient PAHs in Delhi, India.<b>Materials and Methods:</b> Two sampling sites were chosen, one at roadway (MH) and other at urban background (JNU) site in Delhi. Determination of PAHs was carried with the help of HPLC with UV detector. Principal component analysis and Molecular diagnostic ratios were used for the source apportionment of PAHs. Health risks associated with inhalation of particulate PAHs were assessed using benzo(a)pyrene equivalent concentration and incremental lifetime cancer risk (ILCR) approach.<b>Results:</b> The results showed that the average mass concentration of Σ₁₆ PAHs near roadway (67.8 ± 40.2 ng m^-3) is significantly higher than urban background site (56 ± 30 ng m^-3). Moreover, source apportionment study indicated that major PAH-emission sources in Delhi NCR are traffic and coal combustion. ILCR values at both the sites fall in the range of 10^-2-10^-4 that corresponds to the priority risk level (10^-3) and higher than the acceptable risk level (10^-6).<b>conclusions:</b> The high PAHs concentration at MH site was due to it's nearness to busy traffic area. Thus, the spatial variations in PAHs were influenced by local emission sources. The high PAHs level during the winter season can be due to their higher emissions from local heating sources, shift of gas/particle partitioning toward the particulate phase at low temperature and reduced photochemical degradation of some PAHs in winter. The low level of PAHs in monsoon season can be attributed to their wet scavenging and higher percentage in vapor phase. PCA showed that the emissions from vehicles predominate at MH site; whereas, coal combustion and traffic both are the significant PAHs sources at JNU site. Health risk assessment revealed that the highest exposure risks occur at busy traffic site, thereby indicating a significantly higher health risk to the population of Delhi.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1-2","pages":"39-50"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39883941","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}

{"title":"Arid2-IR downregulates miR-132-3p through methylation to promote LPS-induced ALI in pneumonia.","authors":"Yuanshui Liu,&nbsp;Chuanyu Bao,&nbsp;Gongping Deng,&nbsp;Yanhong Ouyang","doi":"10.1080/08958378.2022.2102699","DOIUrl":"https://doi.org/10.1080/08958378.2022.2102699","url":null,"abstract":"<p><strong>Objective: </strong>Arid2-IR is a long non-coding RNA (lncRNA) that promotes renal injury, while its role in lipopolysaccharides (LPS)-induced acute lung injury (ALI) is unknown. Our preliminary sequencing analysis revealed an inverse correlation of Arid2-IR and miR-132-3p, which is known to suppress LPS-induced ALI. Therefore, Arid2-IR and miR-132-3p may interact with each other to participate in LPS-induced ALI in pneumonia. This study aimed to investigate the interaction between Arid2-IR and miR-132-3p in ALI induced by pneumonia.</p><p><strong>Materials and methods: </strong>Plasma samples were obtained from patients with pneumonia (<i>n</i> = 98) and healthy controls (<i>n</i> = 98) to detect the expression of circulating Arid2-IR and miR-132-3p. The correlation between them was analyzed using Pearson's correlation coefficient. The crosstalk between them in human bronchial epithelial cells (HBEpC) was analyzed through overexpression assay. MSP was applied to determine the methylation of the miR-132-3p gene. Cell viability was evaluated by 2,5-diphenyl-2H-tetrazolium bromide assay.</p><p><strong>Results: </strong>Arid2-IR was highly upregulated in pneumonia group, while the expression levels of miR-132-3p decreased in pneumonia group compared to that in the controls. Arid2-IR and miR-132-3p were inversely correlated across patient samples. Overexpression of Arid2-IR decreased the expression levels of miR-132-3p in HBEpCs and increased the methylation of miR-132-3p gene. Arid2-IR suppressed the role of miR-132-3p in increasing the viability of HBEpCs induced by LPS.</p><p><strong>Discussion and conclusion: </strong>Arid2-IR is upregulated in pneumonia and may downregulate miR-132-3p by increasing its methylation to decrease cell viability, thereby promoting LPS-induced ALI in pneumonia.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 11-12","pages":"297-303"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10776551","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}

{"title":"Establishing an air-liquid interface exposure system for exposure of lung cells to gases.","authors":"Josée Guénette,&nbsp;Dalibor Breznan,&nbsp;Errol M Thomson","doi":"10.1080/08958378.2022.2039332","DOIUrl":"https://doi.org/10.1080/08958378.2022.2039332","url":null,"abstract":"<p><strong>Objective: </strong>Growing interest in non-animal-based models has led to the development of devices to expose cells to airborne substances. Cells/tissues grown at the air-liquid interface (ALI) are more representative of lung cells/tissues <i>in vivo</i> compared to submerged cell cultures. Additionally, airborne exposures should allow for closer modeling of human lung toxicity. However, such exposures present technical challenges, including maintaining optimal cell health, and establishing consistent exposure monitoring and control. We aimed to establish a reliable system and procedures for cell exposures to gases at the ALI.</p><p><strong>Methods: </strong>We tested and adapted a horizontal-flow ALI-exposure system to verify and optimize temperature, humidity/condensation, and control of atmosphere delivery. We measured temperature and relative humidity (RH) throughout the system, including at the outlet (surrogate measures) and at the well, and evaluated viability of lung epithelial A549 cells under control conditions. Exposure stability, dosimetry, and toxicity were tested using ozone.</p><p><strong>Results: </strong>Temperatures measured directly above wells vs. outflow differed; using above-well temperature enabled determination of near-well RH. Under optimized conditions, the viability of A549 cells exposed to clean air (2 h) in the ALI system was unchanged from incubator-grown cells. In-well ozone levels, determined through reaction with potassium indigotrisulfonate, confirmed dosing. Cells exposed to 200 ppb ozone at the ALI presented reduced viability, while submerged cells did not.</p><p><strong>Conclusion: </strong>Our results emphasize the importance of monitoring near-well conditions rather than relying on surrogate measures. Rigorous assessment of ALI exposure conditions led to procedures for reproducible exposure of cells to gases.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 3-4","pages":"80-89"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39656752","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}

{"title":"Analyses on the influence of normal nasal morphological variations on odorant transport to the olfactory cleft.","authors":"Ryan M Sicard, Reanna Shah, Dennis O Frank-Ito","doi":"10.1080/08958378.2022.2115175","DOIUrl":"10.1080/08958378.2022.2115175","url":null,"abstract":"<p><strong>Objective: </strong>Olfaction requires a combination of sensorineural components and conductive components, but conductive mechanisms have not typically received much attention. This study investigates the role of normal nasal vestibule morphological variations in ten healthy subjects on odorant flux in the olfactory cleft.</p><p><strong>Materials and methods: </strong>Computed tomography images were used to create subject-specific nasal models. Each subject's unilateral nasal cavity was classified according to its nasal vestibule shape as Standard or Notched. Inspiratory airflow simulations were performed at 15 L/min, simulating resting inspiration using computational fluid dynamics modeling. Odorant transport simulations for three odorants (limonene, 2,4-dinitrotoluene, and acetaldehyde) were then performed at concentrations of 200 ppm for limonene and acetaldehyde, and 0.2 ppm for dinitrotoluene. Olfactory cleft odorant flux was computed for each simulation.</p><p><strong>Results and discussion and conclusion: </strong>Simulated results showed airflow in the olfactory cleft was greater in the Standard phenotype compared to the Notched phenotype. For Standard, median airflow was greatest in the anterior region (0.5006 L/min) and lowest in the posterior region (0.1009 L/min). Median airflow in Notched was greatest in the medial region (0.3267 L/min) and lowest in the posterior region (0.0756 L/min). Median olfactory odorant flux for acetaldehyde and limonene was greater in Standard (Acetaldehyde: Standard = 140.45 pg/cm²-s; Notched = 122.20 pg/cm²-s. Limonene: Standard = 0.67 pg/cm²-s; Notched = 0.65 pg/cm²-s). Median dinitrotoluene flux was greater in Notched (Standard = 2.86 × 10^-4pg/cm²-s; Notched = 4.29 × 10^-4 pg/cm²-s). The impact of nasal vestibule morphological variations on odorant flux at the olfactory cleft may have implications on individual differences in olfaction, which should be investigated further.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 11-12","pages":"350-358"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799026/pdf/nihms-1850059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10120927","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":"Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products.","authors":"Philip J Kuehl,&nbsp;Jacob D McDonald,&nbsp;Derek T Weber,&nbsp;Andrey Khlystov,&nbsp;Matthew A Nystoriak,&nbsp;Daniel J Conklin","doi":"10.1080/08958378.2022.2103602","DOIUrl":"https://doi.org/10.1080/08958378.2022.2103602","url":null,"abstract":"<p><p><b>Aim:</b> The cardiovascular toxicity of unheated and heated flavorants and their products as commonly present in electronic cigarette liquids (e-liquids) was evaluated previously <i>in vitro</i>. Based on the results of <i>in vitro</i> assays, cinnamaldehyde, eugenol, menthol, and vanillin were selected to conduct a detailed chemical analysis of the aerosol generated following heating of each compound both at 250 and 750 °C. <b>Materials and Methods:</b> Each flavoring was heated in a drop-tube furnace within a quartz tube. The combustion atmosphere was captured using different methods to enable analysis of 308 formed compounds. Volatile organic compounds (VOCs) were captured with an evacuated Summa canister and assayed via gas chromatography interfaced with mass spectrometry (GC-MS). Carbonyls (aldehydes and ketones) were captured using a 2,4-dinitrophenylhydrazine (DNPH) cartridge and assayed via a high-performance liquid chromatography-ultra-violet (HPLC-UV) assay. Polyaromatic hydrocarbons (PAHs) were captured using an XAD cartridge and filter, and extracts were assayed using GC-MS/MS. Polar compounds were assayed after derivatization of the XAD/filter extracts and analyzed <i>via</i> GC-MS. <b>Conclusion:</b> At higher temperature, both cinnamaldehyde and menthol combustion significantly increased formaldehyde and acetaldehyde levels. At higher temperature, cinnamaldehyde, eugenol, and menthol resulted in increased benzene concentrations. At low temperature, all four compounds led to higher levels of benzoic acid. These data show that products of thermal degradation of common flavorant compounds vary by flavorant and by temperature and include a wide variety of harmful and potentially harmful constituents (HPHCs).</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 11-12","pages":"319-328"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830633/pdf/nihms-1850058.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9911943","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":"Evaluation of asbestos exposure resulting from simulated application of spiked talcum powders.","authors":"Eric W Miller,&nbsp;Benjamin Roberts,&nbsp;Kara Keeton,&nbsp;Andrew Monnot,&nbsp;Taylor Tarpey,&nbsp;Nicole Zoghby,&nbsp;Alan Segrave,&nbsp;Jennifer S Pierce","doi":"10.1080/08958378.2022.2132324","DOIUrl":"https://doi.org/10.1080/08958378.2022.2132324","url":null,"abstract":"<p><p>This study characterizes airborne asbestos exposures resulting from the adult application of cosmetic talc body powders spiked with known concentrations of tremolite. Raw talc ores were spiked with 0.005% and 0.1% asbestiform or non-asbestiform tremolite. Personal samples were collected during 16 simulated events, including puff and shaker application and associated clean-up activities. Airborne fiber levels (PCM) were not significantly different for simulations involving talc spiked with asbestiform and non-asbestiform tremolite (<i>p</i> = 0.6104). For application and clean-up of talc spiked with 0.005% asbestiform tremolite, 2 of 24 (8.3%) samples were above the LOD for TEM (0.003 f/cc). For application of talc spiked with 0.1% asbestiform tremolite, 21 of 24 (87.5%) were above the LOD for TEM. The corresponding mean PCME asbestos concentrations were 0.016 f/cc for puff and shaker for samples collected in the first 15 min, 0.002 f/cc for puff and 0.004 f/cc for shaker in the second 15 min, and 0.005 f/cc for puff and 0.013 f/cc for shaker for the full 30 min. Mean PCME concentrations for samples collected during clean-up following application of talc spiked with 0.1% asbestiform tremolite were 0.003 f/cc for samples collected in the first 15 min following puff application, 0.005 f/cc for samples collected in the second 15 min following shaker application, and 0 f/cc for the remaining clean-up samples. Using the EPA's exposure factors, we determined the range of cumulative asbestiform fiber exposures that would result from product use, assuming asbestiform tremolite was present at 0.1%.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 13-14","pages":"380-398"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10836991","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}

{"title":"Pulmonary toxicity and gene expression changes in response to whole-body inhalation exposure to multi-walled carbon nanotubes in rats.","authors":"Tina M Sager,&nbsp;Christina M Umbright,&nbsp;Gul Mehnaz Mustafa,&nbsp;Jenny R Roberts,&nbsp;Marlene S Orandle,&nbsp;Jared L Cumpston,&nbsp;Walter G McKinney,&nbsp;Theresa Boots,&nbsp;Michael L Kashon,&nbsp;Pius Joseph","doi":"10.1080/08958378.2022.2081386","DOIUrl":"https://doi.org/10.1080/08958378.2022.2081386","url":null,"abstract":"<p><p><b>Purpose:</b> To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7).<b>Materials and methods:</b> Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT-7 particles at target cumulative doses (concentration x time) ranging from 22.5 to 180 (mg/m³)h over a three-day (6 hours/day) period and toxicity and global gene expression profiles were determined in the lungs.<b>Results:</b> MWCNT-7 particles, associated with alveolar macrophages (AMs), were detected in rat lungs following the exposure. Mild to moderate lung pathological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and polymorphonuclear leukocytes (PMNs), intracellular oxidant generation by phagocytes, and levels of cytokines were significantly (<i>p</i> < 0.05) increased in response to exposure to MWCNT-7. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR <i>p</i> value <0.05) in all the MWCNT-7 exposed rats. Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure.<b>Conclusions:</b> Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 7-8","pages":"200-218"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885491/pdf/nihms-1862637.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10636887","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":"Lung toxicity profile of inhaled copper-nickel welding fume in A/J mice.","authors":"Patti C Zeidler-Erdely,&nbsp;Aaron Erdely,&nbsp;Vamsi Kodali,&nbsp;Ronnee Andrews,&nbsp;James Antonini,&nbsp;Taylor Trainor-DeArmitt,&nbsp;Rebecca Salmen,&nbsp;Lori Battelli,&nbsp;Lindsay Grose,&nbsp;Michael Kashon,&nbsp;Samantha Service,&nbsp;Walter McKinney,&nbsp;Samuel Stone,&nbsp;Lauryn Falcone","doi":"10.1080/08958378.2022.2089783","DOIUrl":"https://doi.org/10.1080/08958378.2022.2089783","url":null,"abstract":"<p><p><b>Objective:</b> Stainless steel welding creates fumes rich in carcinogenic metals such as chromium (Cr). Welding consumables devoid of Cr are being produced in an attempt to limit worker exposures to toxic and carcinogenic metals. The study objective was to characterize a copper-nickel (Cu-Ni) fume generated using gas metal arc welding (GMAW) and determine the pulmonary deposition and toxicity of the fume in mice exposed by inhalation. <b>Materials and Methods:</b> Male A/J mice (6-8 weeks of age) were exposed to air or Cu-Ni welding fumes for 2 (low deposition) or 4 (high deposition) hours/day for 10 days. Mice were sacrificed, and bronchoalveolar lavage (BAL), macrophage function, and histopathological analyses were performed at different timepoints post-exposure to evaluate resolution. <b>Results and Discussion:</b> Characterization of the fume indicated that most of the particles were between 0.1 and 1 µm in diameter, with a mass median aerodynamic diameter of 0.43 µm. Metal content of the fume was Cu (∼76%) and Ni (∼12%). Post-exposure, BAL macrophages had a reduced ability to phagocytose <i>E. coli</i>, and lung cytotoxicity was evident and significant (>12%-19% fold change). Loss of body weight was also significant at the early timepoints. Lung inflammation, the predominant finding identified by histopathology, was observed as a subacute response early that progressively resolved by 28 days with only macrophage aggregates remaining late (84 days). <b>Conclusions:</b> Overall, there was high acute lung toxicity with a resolution of the response in mice which suggests that the Cu-Ni fume may not be ideal for reducing toxic and inflammatory lung effects.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 9-10","pages":"275-286"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872095/pdf/nihms-1863224.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10663102","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":"World Trade Center dust induces nasal and neurological tissue injury while propagating reduced olfaction capabilities and increased anxiety behaviors.","authors":"Michelle Hernandez, Joshua Vaughan, Terry Gordon, Morton Lippmann, Sam Gandy, Lung-Chi Chen","doi":"10.1080/08958378.2022.2072027","DOIUrl":"10.1080/08958378.2022.2072027","url":null,"abstract":"<p><p><b>Objective:</b> Previous <i>in vitro</i> and in vivo World Trade Center particulate matter (WTC_PM) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTC_PM exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes.<b>Material and Methods:</b> WTC_PM was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints.<b>Results:</b> WTC_PM exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTC_PM dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTC_PM exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (<i>p</i><0.05).<b>Discussion:</b> The potential molecular drivers of WTC_PM-driven tissue injury and olfaction latency may be linked to oxidative/nitrative stress and inflammatory cascades in both upper respiratory nasal and brain tissues.<b>Conclusion:</b> Cumulatively, these data provide evidence of WTC_PM exposure in relation to tissue damage related to oxidative stress-driven inflammation identified in the nasal cavity, propagated to olfactory bulb tissues and, potentially, over extended periods, to other CNS tissues.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 7-8","pages":"175-188"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728549/pdf/nihms-1850055.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800397","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}