Inhalation Toxicology最新文献

{"title":"Persistent changes in expression of genes involved in inflammation and fibrosis in the lungs of rats exposed to airborne lunar dust.","authors":"Ye Zhang,&nbsp;Michael Story,&nbsp;Samrawit Yeshitla,&nbsp;Xiaoyu Wang,&nbsp;Robert R Scully,&nbsp;Corey Theriot,&nbsp;Honglu Wu,&nbsp;Valerie E Ryder,&nbsp;Chiu-Wing Lam","doi":"10.1080/08958378.2023.2172485","DOIUrl":"https://doi.org/10.1080/08958378.2023.2172485","url":null,"abstract":"<p><p>NASA is currently planning return missions to the Moon for further exploration and research. The Moon is covered by a layer of potentially reactive fine dust, which could pose a toxicological risk of exposure to explorers. To assess this risk, we exposed rats to lunar dust (LD) that was collected during the Apollo14 mission. Rats were exposed to respirable sizes of LD at concentrations of 0, 2.1, 6.8, 20.8, or 60.6 mg/m³ for 4 weeks. At thirteen  weeks after exposure, we assessed 44,000 gene transcripts and found the expression of 614 genes with known functions were significantly altered in the rats exposed to the 2 higher concentrations of LD, whereas few changes in gene expression were detected in the group exposed to the lowest concentration of LD. Many of the significant changes in gene expression involved genes known to be associated with inflammation or fibrosis. Four genes encoding pro-inflammatory chemokines were analyzed further for all the sampling points at 1 day, and 1, 4, and 13 weeks after the 4-week dust exposure, using real-time polymerase chain reaction. The expression of these genes was altered in a dose- and time-dependent manner and persistently changed in the lungs of the rats exposed to the two higher concentrations of LD. Their expressions are consistent with changes we detected in pulmonary toxicity biomarkers and pathology in these animals during a previous study. Because Apollo-14 LD contains common mineral oxides similar to an Arizona volcanic ash, besides revealing the toxicity of LD, our findings could help elucidate the genomic and molecular mechanisms involved in pulmonary toxicity induced by terrestrial mineral dusts.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 5-6","pages":"139-156"},"PeriodicalIF":2.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494306","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":"Correction.","authors":"","doi":"10.1080/08958378.2022.2126145","DOIUrl":"10.1080/08958378.2022.2126145","url":null,"abstract":"","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"127"},"PeriodicalIF":2.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9140258","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":"Ambient PM_2.5 exposure and salivary cortisol output during pregnancy in a multi-ethnic urban sample.","authors":"Whitney Cowell, Itai Kloog, Allan C Just, Brent A Coull, Kecia Carroll, Rosalind J Wright","doi":"10.1080/08958378.2022.2051647","DOIUrl":"10.1080/08958378.2022.2051647","url":null,"abstract":"<p><strong>Objectives: </strong>Evidence from murine research supports that fine particulate matter (PM_2.5) may stimulate the hypothalamic-pituitary-adrenal axis, leading to elevated circulating glucocorticoid levels. Epidemiologic research examining parallel associations document similar associations. We examined these associations among a diverse sample of pregnant individuals exposed to lower levels of ambient PM_2.5.</p><p><strong>Materials and methods: </strong>Participants included pregnant individuals enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pre-birth cohort. Daily residential PM_2.5 exposure was estimated using a satellite-based spatial-temporal hybrid model. Maternal 3rd trimester salivary cortisol levels were used to calculate several features of the diurnal cortisol rhythm. We used multivariable linear regression to examine PM_2.5 during the pre-conception period and during each trimester in relation to cortisol awakening rise (CAR), slope, and area under the curve relative to ground (AUC_G).</p><p><strong>Results and discussion: </strong>The average PM_2.5 exposure level across pregnancy was 8.13 µg/m³. PM_2.5 in each exposure period was positively associated with AUC_G, a measure of total cortisol output across the day. We also observed an inverse association between PM_2.5 in the 3rd trimester and diurnal slope, indicating a steeper decline in cortisol throughout the day with increasing exposure. We did not detect strong associations between PM_2.5 and slope for the other exposure periods or between PM_2.5 and CAR for any exposure period.</p><p><strong>Conclusions: </strong>In this sample, PM_2.5 exposure across the preconception and pregnancy periods was associated with increased cortisol output, even at levels below the U.S. National Ambient Air Quality Annual Standard for PM_2.5 of 12.0 µg/m³.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"101-108"},"PeriodicalIF":2.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978019","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":"Air Pollutant impacts on the brain and neuroendocrine system with implications for peripheral organs: a perspective.","authors":"Urmila P Kodavanti, Thomas W Jackson, Andres R Henriquez, Samantha J Snow, Devin I Alewel, Daniel L Costa","doi":"10.1080/08958378.2023.2172486","DOIUrl":"10.1080/08958378.2023.2172486","url":null,"abstract":"<p><p>Air pollutants are being increasingly linked to extrapulmonary multi-organ effects. Specifically, recent studies associate air pollutants with brain disorders including psychiatric conditions, neuroinflammation and chronic diseases. Current evidence of the linkages between neuropsychiatric conditions and chronic peripheral immune and metabolic diseases provides insights on the potential role of the neuroendocrine system in mediating neural and systemic effects of inhaled pollutants (reactive particulates and gases). Autonomically-driven stress responses, involving sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal axes regulate cellular physiological processes through adrenal-derived hormones and diverse receptor systems. Recent experimental evidence demonstrates the contribution of the very stress system responding to non-chemical stressors, in mediating systemic and neural effects of reactive air pollutants. The assessment of how respiratory encounter of air pollutants induce lung and peripheral responses through brain and neuroendocrine system, and how the impairment of these stress pathways could be linked to chronic diseases will improve understanding of the causes of individual variations in susceptibility and the contribution of habituation/learning and resiliency. This review highlights effects of air pollution in the respiratory tract that impact the brain and neuroendocrine system, including the role of autonomic sensory nervous system in triggering neural stress response, the likely contribution of translocated nano particles or metal components, and biological mediators released systemically in causing effects remote to the respiratory tract. The perspective on the use of systems approaches that incorporate multiple chemical and non-chemical stressors, including environmental, physiological and psychosocial, with the assessment of interactive neural mechanisms and peripheral networks are emphasized.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"109-126"},"PeriodicalIF":2.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9203105","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":"Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation.","authors":"Devin I Alewel, Andres R Henriquez, Mette C Schladweiler, Rachel Grindstaff, Anna A Fisher, Samantha J Snow, Thomas W Jackson, Urmila P Kodavanti","doi":"10.1080/08958378.2022.2100019","DOIUrl":"10.1080/08958378.2022.2100019","url":null,"abstract":"<p><strong>Objective: </strong>Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation.</p><p><strong>Materials and methods: </strong>Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects.</p><p><strong>Results: </strong>IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T₃, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic <i>Fkbp5</i>, a glucocorticoid-sensitive gene.</p><p><strong>Conclusion: </strong>Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"59-75"},"PeriodicalIF":2.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199365","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":"Neuromodulatory and neurotoxic effects of e-cigarette vapor using a realistic exposure method.","authors":"Yvonne C M Staal,&nbsp;Yixuan Li,&nbsp;Lora-Sophie Gerber,&nbsp;Paul Fokkens,&nbsp;Hans Cremers,&nbsp;Flemming R Cassee,&nbsp;Reinskje Talhout,&nbsp;Remco H S Westerink,&nbsp;Harm J Heusinkveld","doi":"10.1080/08958378.2022.2118911","DOIUrl":"https://doi.org/10.1080/08958378.2022.2118911","url":null,"abstract":"<p><p>The most direct effects of inhaled harmful constituents are the effects on the airways. However, inhaled compounds can be rapidly absorbed and subsequently result in systemic effects. For example, e-cigarette vapor has been shown to evoke local effects in the lung, although little is known about subsequent effects in secondary target organs such as the brain. Traditionally, such effects are tested using <i>in vivo</i> models. As an alternative, we have combined two <i>in vitro</i> systems, which are Air-Liquid-Interface (ALI) cultured alveolar cells (A549) and rat primary cortical cultures grown on multi-well microelectrode arrays. This allows us to assess the neurological effects of inhaled compounds. We have used exposure to e-cigarette vapor, containing nicotine, menthol, or vanillin to test the model. Our results show that ALI cultured A549 cells respond to the exposure with the production of cytokines (IL8 and GROalpha). Furthermore, nicotine, menthol, and vanillin were found on the basolateral side of the cell culture, which indicates their translocation. Upon transfer of the basolateral medium to the primary cortical culture, exposure-related changes in spontaneous electrical activity were observed correlating with the presence of e-liquid components in the medium. These clear neuromodulatory effects demonstrate the feasibility of combining continuous exposure of ALI cultured cells with subsequent exposure of neuronal cells to assess neurotoxicity. Although further optimization steps are needed, such a combination of methods is important to assess the neurotoxic effects of inhaled compounds realistically. As such, an approach like this could play a role in future mechanism-based risk assessment strategies.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"76-85"},"PeriodicalIF":2.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193951","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":"Aging influence on pulmonary and systemic inflammation and neural metabolomics arising from pulmonary multi-walled carbon nanotube exposure in apolipoprotein E-deficient and C57BL/6 female mice.","authors":"Tamara L Young, David Scieszka, Jessica G Begay, Selita N Lucas, Guy Herbert, Katherine Zychowski, Russell Hunter, Raul Salazar, Andrew K Ottens, Aaron Erdely, Haiwei Gu, Matthew J Campen","doi":"10.1080/08958378.2022.2026538","DOIUrl":"10.1080/08958378.2022.2026538","url":null,"abstract":"<p><strong>Objective: </strong>Environmental exposures exacerbate age-related pathologies, such as cardiovascular and neurodegenerative diseases. Nanoparticulates, and specifically carbon nanomaterials, are a fast-growing contributor to the category of inhalable pollutants, whose risks to health are only now being unraveled. The current study assessed the exacerbating effect of age on multiwalled-carbon nanotube (MWCNT) exposure in young and old C57BL/6 and ApoE^-/- mice.</p><p><strong>Materials and methods: </strong>Female C57BL/6 and apolipoprotein E-deficient (ApoE^-/-) mice, aged 8 weeks and 15 months, were exposed to 0 or 40 µg MWCNT via oropharyngeal aspiration. Pulmonary inflammation, inflammatory bioactivity of serum, and neurometabolic changes were assessed at 24 h post-exposure.</p><p><strong>Results: </strong>Pulmonary neutrophil infiltration was induced by MWCNT in bronchoalveolar lavage fluid in both C57BL/6 and ApoE^-/-. Macrophage counts decreased with MWCNT exposure in ApoE^-/- mice but were unaffected by exposure in C57BL/6 mice. Older mice appeared to have greater MWCNT-induced total protein in lavage fluid. BALF cytokines and chemokines were elevated with MWCNT exposure, but CCL2, CXCL1, and CXCL10 showed reduced responses to MWCNT in older mice. However, no significant serum inflammatory bioactivity was detected. Cerebellar metabolic changes in response to MWCNT were modest, but age and strain significantly influenced metabolite profiles assessed. ApoE^-/- mice and older mice exhibited less robust metabolite changes in response to exposure, suggesting a reduced health reserve.</p><p><strong>Conclusions: </strong>Age influences the pulmonary and neurological responses to short-term MWCNT exposure. However, with only the model of moderate aging (15 months) in this study, the responses appeared modest compared to inhaled toxicant impacts in more advanced aging models.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 3-4","pages":"86-100"},"PeriodicalIF":2.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199235","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":"Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development.","authors":"Anbo Wang, Amit Gupta, Michael D Grimm, David T Pressburger, Barney R Sparrow, Jamie S Richey, John R Shaw, Karen E Elsass, Georgia K Roberts, Pei-Li Yao, Matthew D Stout, Benjamin J Ellis, Robyn L Ray","doi":"10.1080/08958378.2023.2220737","DOIUrl":"10.1080/08958378.2023.2220737","url":null,"abstract":"<p><strong>Background: </strong>Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project.</p><p><strong>Results: </strong>A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for <i>in vivo</i> inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically.</p><p><strong>Conclusions: </strong>Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for <i>in vivo</i> inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 7-8","pages":"201-213"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672722","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":"Toxicological evaluation of polycrystalline wools in human lung cells.","authors":"Aureliano Ciervo,&nbsp;Cinzia Lucia Ursini,&nbsp;Anna Maria Fresegna,&nbsp;Raffaele Maiello,&nbsp;Antonella Campopiano,&nbsp;Sergio Iavicoli,&nbsp;Delia Cavallo","doi":"10.1080/08958378.2023.2167023","DOIUrl":"https://doi.org/10.1080/08958378.2023.2167023","url":null,"abstract":"<p><p><b>Aim:</b> Polycrystalline wools (PCW) are included with Refractory ceramic fibers (RCF) in the alumino-silicates family of High Temperature Insulation Wools (HTIW). IARC includes PCW in the ceramic fibers group and considers them as possible human carcinogens (GROUP 2B). Since PCW toxicity is not yet clear, our aim was to evaluate their toxic and inflammatory effects and to compare them with the known RCF effects.<b>Method:</b> We exposed human bronchial (BEAS-2B) and alveolar (A549) cells to 2-100 µg/mL (2.4 × 10³-1.2 × 10⁵ fibers/mL; 2.51 × 10³-1.26 × 10⁵ fibers/cm² of PCW and 7.4 × 10³-3.7 × 10⁵ fibers/mL; 7.75 × 10³-3.87 × 10⁵ fibers/cm² of RCF) of the tested fibers to evaluate potential viability reduction, apoptosis, membrane damage, direct/oxidative DNA-damage, cytokine release.<b>Results:</b> In A549, PCW did not induce cytotoxicity and apoptosis but they induced significant dose-dependent DNA-damage, although lower than RCF; only RCF induced oxidative effects. PCW also induced an increase in IL-6 release at 100 µg/mL (1.2 × 10⁵ fibers/mL; 1.26 × 10⁵ fibers/cm²). In BEAS-2B, PCW did not induce cell-viability reduction RCF induced a dose-dependent cell-viability decrease. Both fibers show a dose-dependent increase of apoptosis. In BEAS-2B, PCW also induced dose-dependent DNA-damage, although lower than RCF, and slight oxidative effects similar to RCF. PCW also induced an increase of IL-6 release; RCF induced a decrease of IL-8. Summarizing, PCW induce direct-oxidative DNA-damage although to a lower extent than RCF observed by both mass-based and fiber number-based analysis.<b>Conclusion:</b> For the first time, the study shows the potential toxicity of PCW, usually considered safe, and suggests to perform further <i>in vitro</i> studies, also on other cell types, to confirm these findings.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 1-2","pages":"48-58"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10730834","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":"Predicting the <i>in vitro</i> dissolution rate constant of mineral wool fibers from fiber composition.","authors":"Russell M Potter,&nbsp;John W Hoffman,&nbsp;John G Hadley","doi":"10.1080/08958378.2023.2166167","DOIUrl":"https://doi.org/10.1080/08958378.2023.2166167","url":null,"abstract":"<p><strong>Objective: </strong>We developed predictive formulae for the <i>in vitro</i> dissolution rate constant k_dis of acid-soluble synthetic vitreous fibers (SVF), paralleling our earlier work with glass wools, which are typically more soluble at neutral pH. Developing simple models for predicting the k_dis of a fiber can allow prediction of <i>in vivo</i> behavior, aid fiber developers, and potentially reduce <i>in vivo</i> testing.</p><p><strong>Methods: </strong>The k_dis of several acid-soluble SVF were determined using high simulant fluid flow/fiber surface area (F/A) conditions <i>via</i> a single-fiber measurement system. Four fluids were employed, varying in base composition and citrate levels. Equations predicting the k_dis were derived from fiber chemistry and dissolution measurements for two of the fluids.</p><p><strong>Results: </strong>Testing of several fibers showed a ∼10× increase in the k_dis when citrate was included in the simulant solution. Data from tests with Stefaniak's citrate-free Phagoloysosmal Simulant Fluid (PSF) yielded k_dis values aligned with expectations from <i>in vivo</i> results, unlike results from citrate-containing modified Gamble's solution. Predictive equations relating fiber chemistry to k_dis showed reasonable agreement between the measured and predicted values.</p><p><strong>Conclusions: </strong>Citrate inclusion in the solution under high F/A conditions significantly increased the measured k_dis. This resulted in more biorelevant data being obtained using the PSF fluid with the high F/A method used. The developed predictive equations, sufficient for fiber development work, require refinement before a recommending their use in place of <i>in vivo</i> biopersistence testing. Significant fit improvements are possible through additional measurements under these experimental conditions.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"35 1-2","pages":"40-47"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10730835","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}