Inhalation Toxicology最新文献

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 (p = 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%.

Objective: 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.

Materials and methods: 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.

Results and discussion and conclusion: 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.

Silicosis, induced by inhaling silica particles in workplaces, is one of the most common occupational diseases. The prognosis of silicosis and its consequent fibrosis is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. In this study, a Wistar rat model for silicosis fibrosis was established by intratracheal instillation of silica (0, 50, 100 and 200 mg/mL, 1 mL) with the evidence of Hematoxylin and Eosin (HE) and Masson staining and the expressions of inflammatory and fibrotic proteins of rats' lung tissues. RNA of lung tissues of rats exposed to 200 mg/mL silica particles and normal saline for 14 d and 28 d was extracted and sequenced to detect differentially expressed genes (DEGs) and to identify silicosis fibrosis-associated modules and hub genes by Weighted gene co-expression network analysis (WGCNA). Predictions of gene functions and signaling pathways were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In this study, it has been demonstrated the promising role of the Hippo signaling pathway in silicosis fibrosis, which will be conducive to elucidating the specific mechanism of pulmonary fibrosis induced by silica and to determining molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis fibrosis.

Purpose: To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7).Materials and methods: 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.Results: 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 (p < 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 p 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.Conclusions: Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7.

Objective: 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. Materials and Methods: 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. Results and Discussion: 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 E. coli, 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). Conclusions: 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.

Over 40% of veterans from the Persian Gulf War (GW) (1990-1991) suffer from Gulf War Illness (GWI). Thirty years since the GW, the exposure and mechanism contributing to GWI remain unclear. One possible exposure that has been attributed to GWI are chemical warfare agents (CWAs). While there are treatments for isolated symptoms of GWI, the number of respiratory and cognitive/neurological issues continues to rise with minimum treatment options. This issue does not only affect veterans of the GW, importantly these chronic multisymptom illnesses (CMIs) are also growing amongst veterans who have served in the Afghanistan-Iraq war. What both wars have in common are their regions and inhaled exposures. In this review, we will describe the CWA exposures, such as sarin, cyclosarin, and mustard gas in both wars and discuss the various respiratory and neurocognitive issues experienced by veterans. We will bridge the respiratory and neurological symptoms experienced to the various potential mechanisms described for each CWA provided with the most up-to-date models and hypotheses.

Background: Long-term exposure to air pollution triggers metabolic alterations along with oxidative stress and inflammation, while exercise interventions are widely used to improve those parameters.

Objective: Our study aimed to determine the effects of subchronic exposure to particulate matter 2.5 (PM_2.5) and endurance exercise training on glucose metabolism, oxidative stress, and inflammation of the heart and gastrocnemius muscle of rats.

Material and methods: Thirty-two male Wistar rats were assigned to 4 experimental groups: Untrained; Endurance training (ET); Untrained + PM_2.5; Endurance training + PM_2.5. Rats exposed to air pollution received 50 µg of PM_2.5 via intranasal instillation daily for 12 weeks. Exercised groups underwent endurance training, consisting in running on an electronic treadmill (70% of maximal capacity, 5 days/week, 5 times/week) for 12 weeks. Glucose metabolism markers, redox state, and inflammatory variables were evaluated in the heart and gastrocnemius muscle.

Results: ET and ET + PM_2.5 group had lower body mass gain and higher exercise capacity, and higher glycogen concentration in the heart and gastrocnemius muscle. In the heart, ET and ET + PM_2.5 groups had higher levels of GSH, and lower TBARS and TNF-α concentrations. In the gastrocnemius muscle, the ET group showed higher leptin and lower TBARS and IL-1β concentrations, ET and ET + PM_2.5 showed higher superoxide dismutase activity and ROS content.

Conclusion: PM_2.5 exposure partially blunts metabolic and inflammatory adaptations in heart and gastrocnemius muscle tissues induced by exercise training.

Objective: Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe^-/- mice exposed to tank/box-mod e-cig (e-cig_tank), pod e-cig (e-cig_pod), or cig smoke.

Materials and methods: Reproducible puff profiles were generated for each aerosol and delivered to Apoe^-/- mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry.

Results and discussion: Cig and e-cig_tank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cig_tank: 200 ± 34nm), while e-cig_pod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cig_tank (45.2 ± 9.2 mL/min) and e-cig_pod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cig_pod group ($t_{\max }$ = 14.5; $t_{1/2}^{\text{'}}$ = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cig_tank: 40.1 min) and eliminated (cig: 104.6, e-cig_tank: 94.1 min) similarly in the cig and e-cig_tank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cig_tank) and 4.6× (e-cig_pod) more nicotine deposited in e-cig compared to cig exposed mice.

Conclusions: This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.

Objective: Previous in vitro 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.Material and Methods: WTC_PM was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints.Results: 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 (p<0.05).Discussion: 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.Conclusion: 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.