Inhalation Toxicology最新文献

Objectives: This study employed computational fluid dynamics (CFD), physiologically based toxicokinetics (PBTK), and statistical modeling to reconstruct exposure to methylene diphenyl-4,4'-diisocyanate (MDI) aerosol. By utilizing a validated CFD model, human respiratory deposition of MDI aerosol in different workload conditions was investigated, while a PBTK model was calibrated using experimental rat data. Biomonitoring data and Markov Chain Monte Carlo (MCMC) simulation were utilized for exposure assessment.

Results: Deposition fraction of MDI in the respiratory tract at the light, moderate, and heavy activity were 0.038, 0.079, and 0.153, respectively. Converged MCMC results as the posterior means and prior values were obtained for several PBTK model parameters. In our study, we calibrated a rat model to investigate the transport, absorption, and elimination of 4,4'-MDI via inhalation exposure. The calibration process successfully captured experimental data in the lungs, liver, blood, and kidneys, allowing for a reasonable representation of MDI distribution within the rat model. Our calibrated model also represents MDI dynamics in the bloodstream, facilitating the assessment of bioavailability. For human exposure, we validated the model for recent and long-term MDI exposure using data from relevant studies.

Conclusion: Our computational models provide reasonable insights into MDI exposure, contributing to informed risk assessment and the development of effective exposure reduction strategies.

Objectives: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations.

Methods: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length ≥1 µm and with length ≥5 µm. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values.

Results: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length ≥5 µm, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers.

Conclusions: On average we estimated that 1 amphibole fiber with length ≥5 µm corresponds to ∼8 amphibole fibers with length ≥1 µm in the lung. The values of the Helsinki criteria should be updated taking this into account.

Objective: Availability and consumer use of hemp products is rapidly increasing, but little work has been done to assess aerosol emissions of hemp pre-rolls. The objective of this research was to characterize the aerosol of pre-rolled joints from hemp material enriched for production of cannabigerol (CBG) that were smoked on a test system mimicking human use patterns.

Materials and methods: Aerosol emissions were collected and analyzed using glass microfiber filters and charcoal cartridges. The aerosol was screened for nine phytocannabinoids and 19 terpenes.

Results: Three phytocannabinoids (CBG, cannabichromene (CBC), and delta-9-tetrahydrocannabinol (THC)) were detected and quantified at a mean (SD) concentration of 19.4 (4.7), 0.48 (0.01), and 0.40 (0.04) mg per pre-roll, respectively. Five terpenes ((-)-α-bisabolol, (-)-guaiol, β-caryophyllene, nerolidol, and α-humulene) were detected and quantified at an average concentration of 352.7 (112.0), 194.3 (66.4), 106.0 (50.4), 28.3 (9.3), and 27.7 (11.2) µg per pre-roll, respectively. Particle size distribution testing via aerodynamic particle sizer and inertial impactor showed that average size of emitted aerosols was 0.77 (0.0) and 0.54 (0.1) µm, respectively.

Conclusions: This study describes methodology for characterization of cannabinoid and terpene dose in emitted aerosols and aerosolization efficiency from hemp pre-rolls. It also presents these data for one of the marketed products.

Objective: Inhalation of smoke from the burning of waste materials on military bases is associated with increased incidences of cardiopulmonary diseases. This study examined the respiratory and inflammatory effects of acute inhalation exposures in mice to smoke generated by military burn pit-related materials including plywood (PW), cardboard (CB), mixed plastics (PL), and a mixture of these three materials (MX) under smoldering (0.84 MCE) and flaming (0.97 MCE) burn conditions.

Methods: Mice were exposed nose-only for one hour on two consecutive days to whole or filtered smoke or clean air alone. Smoldering combustion emissions had greater concentrations of PM (∼40 mg/m³) and VOCs (∼5-12 ppmv) than flaming emissions (∼4 mg/m³ and ∼1-2 ppmv, respectively); filtered emissions had equivalent levels of VOCs with negligible PM. Breathing parameters were assessed during exposure by head-out plethysmography.

Results: All four smoldering burn pit emission types reduced breathing frequency (F) and minute volumes (MV) compared with baseline exposures to clean air, and HEPA filtration significantly reduced the effects of all smoldering materials except CB. Flaming emissions had significantly less suppression of F and MV compared with smoldering conditions. No acute effects on lung inflammatory cells, cytokines, lung injury markers, or hematology parameters were noted in smoke-exposed mice compared with air controls, likely due to reduced respiration and upper respiratory scrubbing to reduce the total deposited PM dose in this short-term exposure.

Conclusion: Our data suggest that material and combustion type influences respiratory responses to burn pit combustion emissions. Furthermore, PM filtration provides significant protective effects only for certain material types.

Background: Exposure to diesel exhaust particles (DEP) has been linked to a variety of adverse health effects, including increased morbidity and mortality from cardiovascular diseases, chronic obstructive pulmonary disease (COPD), metabolic syndrome, and lung cancer. The epigenetic changes caused by air pollution have been associated with increased health risks. However, the exact molecular mechanisms underlying the lncRNA-mediated pathogenesis induced by DEP exposure have not been revealed.

Methods: Through RNA-sequencing and integrative analysis of both mRNA and lncRNA profiles, this study investigated the role of lncRNAs in altered gene expression in healthy and diseased human primary epithelial cells (NHBE and DHBE-COPD) exposed to DEP at a dose of 30 μg/cm².

Results: We identified 503 and 563 differentially expressed (DE) mRNAs and a total of 10 and 14 DE lncRNAs in NHBE and DHBE-COPD cells exposed to DEP, respectively. In both NHBE and DHBE-COPD cells, enriched cancer-related pathways were identified at mRNA level, and 3 common lncRNAs OLMALINC, AC069234.2, and LINC00665 were found to be associated with cancer initiation and progression. In addition, we identified two cis-acting (TMEM51-AS1 and TTN-AS1) and several trans-acting lncRNAs (e.g. LINC01278, SNHG29, AC006064.4, TMEM51-AS1) only differentially expressed in COPD cells, which could potentially play a role in carcinogenesis and determine their susceptibility to DEP exposure.

Conclusions: Overall, our work highlights the potential importance of lncRNAs in regulating DEP-induced gene expression changes associated with carcinogenesis, and individuals suffering from COPD are likely to be more vulnerable to these environmental triggers.

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.

Objectives: 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.

Materials and methods: 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).

Results and discussion: 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.

Conclusions: 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.

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.

Objective: 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.

Materials and methods: 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.

Results: 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 Fkbp5, a glucocorticoid-sensitive gene.

Conclusion: 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.