Inhalation Toxicology最新文献

{"title":"A study of pneumoproteins in crystalline silica exposed rock drillers","authors":"D. Ellingsen, B. Ulvestad, M. Lund, N. Skaugset, L. Sikkeland","doi":"10.1080/08958378.2022.2048745","DOIUrl":"https://doi.org/10.1080/08958378.2022.2048745","url":null,"abstract":"Abstract Objective: The objective was to assess serum concentrations of club cell protein 16 (CC-16) and the surfactant proteins A (SPs-A) and D (SP-D) in male rock drillers (N = 123) exposed to crystalline silica and in 48 occupationally non-exposed. Methods: The arithmetic mean (AM) duration of exposure was 10.7 years. The geometric mean (GM) crystalline silica exposure was 36 µg/m3 at the time of the study. The GM cumulative exposure was 239 µg/m3. Results: The concentrations of SP-D (GM 12.7 vs. 8.8 µg/L, p < 0.001) and SP-A (AM 1847 vs. 1378 ng/L, p = 0.051) were higher among rock drillers than among occupationally non-exposed. A positive significant association was observed between cumulative crystalline silica exposure and the SP-D concentrations (β = 0.07; p < 0.05). Rock drillers with small airway obstruction with maximal mid-expiratory flow % (MMEF%) <70% (N = 29) had higher SP-D concentrations than rock drillers with MMEF% ≥ 70% (N = 91) (GM 17.3 vs. 11.4 µg/L, p = 0.001). Rock drillers with MMEF% ≥70% (N = 91) had higher concentrations of SP-A (1957 vs. 1287 ng/L, p = 0.01) and SP-D (11.4 vs. 9.0 µg/L, p = 0.007) than non-exposed with MMEF% ≥70% (N = 39). Rock drillers with airway obstruction (FEV1/FVC < 0.70, N = 11) had significantly lower CC-16 concentrations than rock drillers with FEV1/FVC ≥0.70 (N = 109) after adjusting for relevant potential confounders (p = 0.02). Conclusion: The results indicate that pulmonary surfactant is a target for crystalline silica toxicity. The alterations appear to be driven by pulmonary alterations in the small airways and by exposure itself. Further studies on pneumoproteins and pulmonary function in other groups of workers exposed to crystalline silica are needed.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"99 - 105"},"PeriodicalIF":2.1,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45910732","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":"Assessing variability of aerosols generated from e-Cigarettes","authors":"Darpan Das, Sarah-Marie Alam El Din, Jairus C. Pulczinski, Jana N. Mihalic, Rui Chen, J. Bressler, A. Rule, G. Ramachandran","doi":"10.1080/08958378.2022.2044414","DOIUrl":"https://doi.org/10.1080/08958378.2022.2044414","url":null,"abstract":"Abstract While some in vitro and in vivo experiments have studied the toxic effects of e-cigarette (e-cig) components, the typical aerosol properties released from e-cigarettes have not been well characterized. In the present study, we characterized the variability in mass concentration and particle size distribution associated with the aerosol generation of different devices and e-liquid compositions in an experimental setup. The findings of this study indicate a large inter-day variability in the experiments, likely due to poor quality control in some e-cig devices, pointing to the need for a better understanding of all the factors affecting exposures in in vitro and in vivo experiments, and the development of standardized protocols for generation and measurement of e-cig aerosols.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"90 - 98"},"PeriodicalIF":2.1,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49354003","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":"Automated crude oil vapor inhalation exposure system.","authors":"Walter McKinney,&nbsp;Mark C Jackson,&nbsp;Brandon Law,&nbsp;Jeffrey S Fedan","doi":"10.1080/08958378.2022.2114562","DOIUrl":"https://doi.org/10.1080/08958378.2022.2114562","url":null,"abstract":"<p><p><b>Objective:</b> Inhalation exposure systems are tools for delivering compounds (particles, vapors, and gases) under well-controlled conditions for toxicological testing. The objective of this project was to develop an automated computer-controlled system to expose small laboratory animals to precise concentrations of crude oil vapor (COV).<b>Materials and Methods:</b> Vapor from heated Deepwater Horizon surrogate oil was atomized into a fine mist then diluted with filtered air, then the air/droplet mixture was routed into an evaporation column with an high efficiency particulate air (HEPA) filter on its exit port. The HEPA filter was used to remove oil particles, thus ensuring only vapor would pass. The vapor was then introduced into a custom-built exposure chamber housing rats. A calibrated flame ionization detector was used to read the total volatile organic compounds (TVOC) in real time, and custom software was developed to automatically adjust the amount of oil entering the atomizer with a syringe pump. The software also controlled relative humidity and pressure inside the exposure chamber. Other exposure chamber environmental parameters, e.g. temperature and CO₂ levels, were monitored. Four specific components within the COV were monitored during each exposure: benzene, toluene, ethylbenzene, and xylenes.<b>Results:</b> The TVOC vapor concentration control algorithm maintained median concentrations to within ±2 ppm of the target concentration (300 ppm) of TVOC during exposures lasting 6 h. The system could reach 90% of the desired target in less than 15 min, and repeat exposures were consistent and reproducible.<b>Conclusion:</b> This exposure system provided a highly automated tool for conducting COV inhalation toxicology studies.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 11-12","pages":"340-349"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876599/pdf/nihms-1861699.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9185115","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":"Heterogeneity of T cells and macrophages in chlorine-induced acute lung injury in mice using single-cell RNA sequencing.","authors":"Chen-Qian Zhao,&nbsp;Jiang-Zheng Liu,&nbsp;Meng-Meng Liu,&nbsp;Xiao-Ting Ren,&nbsp;De-Qin Kong,&nbsp;Jie Peng,&nbsp;Meng Cao,&nbsp;Rui Liu,&nbsp;Chun-Xu Hai,&nbsp;Xiao-di Zhang","doi":"10.1080/08958378.2022.2134526","DOIUrl":"https://doi.org/10.1080/08958378.2022.2134526","url":null,"abstract":"<p><strong>Objective: </strong>Chlorine (Cl₂), as an asphyxiant toxicant, induced poisoning incidents and acute lung injury (ALI) occur frequently. The specific pathogenesis of Cl₂-induced ALI remains unclear. Immune cells play an important role in the process of lung damage. We used single-cell RNA sequencing (scRNA-seq) technology to explore T cells and macrophages molecular mechanism.</p><p><strong>Methods: </strong>Female BALB/c mice were exposed to 400 ppm Cl₂ for 15 min. scRNA-seq technology was used to observe the heterogeneity of T cells and macrophages. Hematoxylin-eosin (H&E) staining was used to evaluate the degree of lung injury. Immunofluorescence was used to verify the highly expressed genes of our interest.</p><p><strong>Results: </strong>A total of 5316 to 7742 cells were classified into eight different cell types. Several new highly expressed anti-inflammatory and pro-inflammatory genes were found in T cells and macrophages, which were further verified in vitro. Through the pseudotime analysis of macrophages, it was found that the expression of pro-inflammatory and anti-inflammatory genes showed opposite trends in the development of Cl₂-induced ALI. This study also mapped T cells-macrophage communication and identified the development of several important receptor-ligand complexes in Cl₂-induced ALI.</p><p><strong>Conclusions: </strong>These findings are worthy of further exploration and provide new resources and directions for the study of Cl₂-induced ALI in mice, especially in immune and inflammation mechanisms.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 13-14","pages":"399-411"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10478653","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 exposure of mice to ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX) suppresses the innate immune response to carbon black nanoparticles and stimulates lung cell proliferation.","authors":"Ho Young Lee,&nbsp;Dorothy J You,&nbsp;Alexia J Taylor-Just,&nbsp;Keith E Linder,&nbsp;Hannah M Atkins,&nbsp;Lauren M Ralph,&nbsp;Gabriela De la Cruz,&nbsp;James C Bonner","doi":"10.1080/08958378.2022.2086651","DOIUrl":"https://doi.org/10.1080/08958378.2022.2086651","url":null,"abstract":"<p><strong>Background: </strong>Per- and polyfluoroalkyl substances (PFAS) have been associated with respiratory diseases in humans, yet the mechanisms through which PFAS cause susceptibility to inhaled agents is unknown. Herein, we investigated the effects of ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), an emerging PFAS, on the pulmonary immune response of mice to carbon black nanoparticles (CBNP). We hypothesized that pulmonary exposure to GenX would increase susceptibility to CBNP through suppression of innate immunity.</p><p><strong>Methods: </strong>Male C57BL/6 mice were exposed to vehicle, 4 mg/kg CBNP, 10 mg/kg GenX, or CBNP and GenX by oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) was collected at 1 and 14 days postexposure for cytokines and total protein. Lung tissue was harvested for histopathology, immunohistochemistry (Ki67 and phosphorylated (p)-STAT3), western blotting (p-STAT3 and p-NF-κB), and qRT-PCR for cytokine mRNAs.</p><p><strong>Results: </strong>CBNP increased CXCL-1 and neutrophils in BALF at both time points evaluated. However, GenX/CBNP co-exposure reduced CBNP-induced CXCL-1 and neutrophils in BALF. Moreover, CXCL-1, CXCL-2 and IL-1β mRNAs were increased by CBNP in lung tissue but reduced by GenX. Western blotting showed that CBNP induced p-NF-κB in lung tissue, while the GenX/CBNP co-exposed group displayed decreased p-NF-κB. Furthermore, mice exposed to GenX or GenX/CBNP displayed increased numbers of BALF macrophages undergoing mitosis and increased Ki67 immunostaining. This was correlated with increased p-STAT3 by western blotting and immunohistochemistry in lung tissue from mice co-exposed to GenX/CBNP.</p><p><strong>Conclusions: </strong>Pulmonary exposure to GenX suppressed CBNP-induced innate immune response in the lungs of mice yet promoted the proliferation of macrophages and lung epithelial cells.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 9-10","pages":"244-259"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731146/pdf/nihms-1850057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9638270","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":"Acute inhalation toxicity of aerosolized electrochemically generated solution of sodium hypochlorite.","authors":"Bohdan Murashevych,&nbsp;Dmitry Girenko,&nbsp;Hanna Maslak,&nbsp;Dmytro Stepanskyi,&nbsp;Olha Abraimova,&nbsp;Olha Netronina,&nbsp;Petro Zhminko","doi":"10.1080/08958378.2021.2013348","DOIUrl":"https://doi.org/10.1080/08958378.2021.2013348","url":null,"abstract":"<p><strong>Objective: </strong>The objective was to determine the inhalation toxicity of the electrochemically generated sodium hypochlorite solution after its single administration to laboratory animals in the form of a highly dispersed aerosol.</p><p><strong>Materials and methods: </strong>The study has been conducted according to the OECD Test Guideline №403 'Acute Inhalation Toxicity.' Laboratory animals were exposed to inhalation of an aerosol containing 1.7 ± 0.13 mg/m³ of active chlorine. The hematological and biochemical parameters of the blood of experimental animals have been determined, as well as specific parameters: the activity of cathepsins B and L, catalase, and α1-antitrypsin. Histological study of the lungs of animals has been carried out.</p><p><strong>Results: </strong>During inhalation and 14 days after it, no death of the animals was observed; the behavior, appearance, and weight gain did not differ from the control group. There were no significant deviations in hematological parameters, except the decrease in the level of platelets. The biochemical study showed slight changes in the activity of alkaline phosphatase and aspartate aminotransferase on the 1st day after inhalation; these parameters returned to normal within 14 days of observation. Specific biochemical parameters did not show the development of oxidative stress. No specific histological pathologies of lung tissue have been found.</p><p><strong>Conclusions: </strong>Thus, the studied electrochemically generated sodium hypochlorite solution under single inhalation exposure in aerosol form practically does not cause a toxic effect. The data obtained allow classifying such solution to the 4th (or even 5th - after additional studies) class of toxicity in accordance with Globally Harmonized System of Classification and Labeling of Chemicals.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1-2","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39731535","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 translocation of ultrafine carbon particles in COPD and IPF patients.","authors":"Mikaela Qvarfordt,&nbsp;Martin Anderson,&nbsp;Alejandro Sanchez-Crespo,&nbsp;Maria Diakopoulou,&nbsp;Magnus Svartengren","doi":"10.1080/08958378.2021.2019859","DOIUrl":"https://doi.org/10.1080/08958378.2021.2019859","url":null,"abstract":"<p><strong>Objective: </strong>Epidemiological studies indicate association between elevated air pollution and adverse health effects. Several mechanisms have been suggested, including translocation of inhaled ultrafine carbon (UFC) particles into the bloodstream. Previous studies in healthy subjects have shown no significant pulmonary translocation of UFC-particles. This study aimed to assess if UFC-particles translocate from damaged alveolar compartment in subjects suffering from chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).</p><p><strong>Methods: </strong>Eleven COPD and nine IPF subjects were exposed to a 100 nm UFC-particle-aerosol labeled with Indium-111. Activity in the body was followed up for 10 days using gamma camera planar-imaging as well as in blood and urine samples.</p><p><strong>Results: </strong>The pulmonary central to periphery activity ratio was significantly higher for COPD as compared to IPF subjects at exposure, 1.8 and 1.4, respectively and remained constant throughout the test period. Ten days after exposure, the estimated median pulmonary translocation of UFC particles was 22.8 and 25.8% for COPD and IPF, respectively. Bound activity was present in blood throughout the test period, peaking at 24-h postinhalation with a median concentration of 5.6 and 8.9 Bq/ml for the COPD and IPF, respectively. Median bound activity excreted in urine (% of inhaled) after 10 days was 1.4% in COPD and 0.7% in IPF. Activity accumulation in liver and spleen could not be demonstrated.</p><p><strong>Conclusions: </strong>Our results suggest that UFC particles leak through the damaged alveolar barrier to the bloodstream in COPD and IPF patients probably distributing in a wide spectrum of whole-body tissues.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1-2","pages":"14-23"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39775654","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":"Analyzing pesticides and metal(loid)s in imported tobacco to Saudi Arabia and risk assessment of inhalation exposure to certain metals.","authors":"Mohammed A Al Mutairi, Hatim A Al Herbish, Rakan S Al-Ajmi, Hatim Z Alhazmi, Reham A Al-Dhelaan, Abdullah M Alowaifeer","doi":"10.1080/08958378.2022.2037791","DOIUrl":"10.1080/08958378.2022.2037791","url":null,"abstract":"<p><p>Exposure to toxic chemicals through smoked tobacco is a significant global public health issue due to their genotoxic and carcinogenic properties. The study aims to (1) measure Arsenic (As), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Mercury (Hg), Nickle (Ni), lead (Pb), and 407 pesticides in tobacco commercialized in Saudi Arabia; and (2) evaluate human health risks associated with smoking tobacco. Thus, we analyzed 60 tobacco samples per brand from eight of the most popular tobacco brands in the Saudi market. The analyzed tobacco contained significant concentrations of toxic metal (loid)s and banned pesticides. Twenty-three out of 407 pesticide residues were found, with an average concentration of 0.004-1.155 µg/g. Average concentrations of As, Cd, Co, Cr, Hg, Ni, and Pb for all brands were 0.16, 0.57, 0.75, 1.36, 1.94, 0.01, and 0.37 µg/g, respectively. The risk assessment indicated that high cancer risks are associated with exposure to As, Cd, Cr, and Ni, while lower risks are associated with Pb. Additionally, the potential cancer risk estimated for Cr was higher than other toxic elements. The cumulative cancer risks (95%) under three different cases for all brands were greater than the permissible limits (=10^-4). The chances of getting cancer through inhalation of particulate As, Cd, Cr, Ni, and Pb was 4 in 10 000 cases in the best case scenario (1 cigarette per day). Therefore, metal content in cigarette tobacco should be reduced to improve public health.HIGHLIGHTSAll tested brands contained banned pesticide residues except for brand C.Tobacco samples contained significant concentrations of toxic metal(loid)s.A high risk of developing cancer is associated with exposure to As, Cd, Cr, and Ni, while a lower risk is associated with exposure to Pb.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"68-79"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45379093","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":"Dimensional characteristics of the major types of amphibole mineral particles and the implications for carcinogenic risk assessment.","authors":"Andrey A Korchevskiy,&nbsp;Ann G Wylie","doi":"10.1080/08958378.2021.2024304","DOIUrl":"https://doi.org/10.1080/08958378.2021.2024304","url":null,"abstract":"<p><p><b>Context:</b> Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.<b>Objective:</b> To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.<b>Methods:</b> A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.<b>Results:</b> The highest absolute Pearson correlation (<i>r</i> = 0.97, <i>r</i>² = 0.94, <i>p</i> < 0.05) was achieved between mesothelioma potency (R_M) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (<i>r</i> = 0.80, <i>r</i>² = 0.64, <i>p</i> < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and R_M. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.<b>Conclusions:</b> Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1-2","pages":"24-38"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799336","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":"Modeling of clearance, retention, and translocation of inhaled gold nanoparticles in rats.","authors":"A Krikas,&nbsp;P Neofytou,&nbsp;G P Gakis,&nbsp;I Xiarchos,&nbsp;C Charitidis,&nbsp;L Tran","doi":"10.1080/08958378.2022.2115592","DOIUrl":"https://doi.org/10.1080/08958378.2022.2115592","url":null,"abstract":"<p><p><b>Objective:</b> The increasing exposure to gold nanoparticles (AuNPs), due to their wide range of applications, has led to the need for thorough understanding of their biodistribution, following exposure. The objective of this paper is to develop a PBK model in order to study the clearance, retention and translocation of inhaled gold nanoparticles in rats, providing a basis for the understanding of the absorption, distribution, metabolism and elimination (ADME) mechanisms of AuNPs in various organs.<b>Materials and methods:</b> A rat PBK computational model was developed, connected to a detailed respiratory model, including the olfactory, tracheobronchial, and alveolar regions. This model was coupled with a Multiple Path Particle Dosimetry (MPPD) model to appropriately simulate the exposure to AuNPs. Three existing in vivo experimental datasets from scientific literature for the biodistribution of inhaled AuNPs for different AuNP sizes and exposure scenarios were utilized for model calibration and validation.<b>Results and Discussion:</b> The model was calibrated using two individual datasets for nose only inhaled and intratracheally instilled AuNPs, while an independent dataset for nose only inhaled AuNPs was used as external validation. The overall fitting over the three datasets was proved acceptable as shown by the relevant statistical metrics. The influence of several physiological parameters is also studied via a sensitivity analysis, providing useful insights into the mechanisms of NP pharmacokinetics. The key aspects of the inhaled AuNPs biodistribution are discussed, revealing the key mechanisms for the AuNPs absorption routes, the AuNP uptake by secondary organs and the influence of the AuNP size on the translocation from the lungs to blood circulation.<b>Conclusions:</b> The model results together with the model sensitivity analysis clarified the key mechanisms for the inhaled AuNPs biodistribution to secondary organs. It was observed that nose-only inhaled AuNPs of smaller size can enter the blood circulation through secondary routes, such as absorption through the gastrointestinal (GI) lumen, showing that such translocations should not be underestimated in biodistribution modelling. Finally, the computational framework presented in this study can be used as a basis for a more wide investigation of inhaled nanoparticles biodistribution, including interspecies extrapolation of the resulting PBK model for the inhalation and subsequent biodistribution of AuNPs in humans.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 13-14","pages":"361-379"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10836447","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}