Exposure to tungsten particles via inhalation triggers early toxicity marker expression in the rat brain.

OBJECTIVE: Our work is focused on tungsten, considered as an emerging contaminant. Its environmental dispersion is partly due to mining and military activities. Exposure scenario can also be occupational, in areas such as the hard metal industry and specific nuclear facilities. Our study investigated the cerebral effects induced by the inhalation of tungsten particles. METHODS: Inhalation exposure campaigns were carried out at two different concentrations (5 and 80 mg/m3) in single and repeated modes (4 consecutive days) in adult rats within a nose-only inhalation chamber. Processes involved in brain toxicity were investigated 24 h after exposure. RESULTS AND DISCUSSION: Site-specific effects in terms of neuroanatomy and concentration-dependent changes in specific cellular actors were observed. Results obtained in the olfactory bulb suggest a potential early effect on the survival of microglial cells. Depending on the mode of exposure, these cells showed a decrease in density accompanied by an increase in an apoptotic marker. An abnormal phenotype of the nuclei of mature neurons, suggesting neuronal suffering, was also observed in the frontal cortex, and can be linked to the involvement of oxidative stress. The differential effects observed according to exposure patterns could involve two components: local (brain-specific) and/or systemic. Indeed, tungsten, in addition to being found in the lungs and kidneys, was present in the brain of animals exposed to the high concentration. CONCLUSION: Our data question the perceived innocuity of tungsten relative to other metals and raise hypotheses regarding possible adaptive or neurotoxic mechanisms that could ultimately alter neuronal integrity.

Low-Level Respirable Crystalline Silica and Silicosis: Long-Term Follow-Up of Vermont Granite Workers.

The lifetime risk of silicosis associated with low-level occupational exposure to respirable crystalline silica remains unclear because most previous radiographic studies included workers with varying exposure concentrations and durations. This study assessed the prevalence of silicosis after lengthy exposure to respirable crystalline silica at levels ≤ 0.10 mg/m3. Vermont granite workers employed any time during 1979-1987 were traced and chest radiographs were obtained for 356 who were alive in 2017 and residing in Vermont. Work history, smoking habits and respiratory symptoms were obtained by interview, and exposure was estimated using a previously developed job-exposure matrix. Associations between radiographic findings, exposure, and respiratory symptoms were assessed by ANOVA, chi-square tests and binary regression. Fourteen workers (3.9%) had radiographic evidence of silicosis, and all had been employed ≥30 years. They were more likely to have been stone cutters or carvers and their average exposure concentrations and cumulative exposures to respirable crystalline silica were significantly higher than workers with similar durations of employment and no classifiable parenchymal abnormalities. This provides direct evidence that workers with long-term exposure to low-level respirable crystalline silica (≤0.10 mg/m3) are at risk of developing silicosis.

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure.

BACKGROUND: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. METHODS: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. RESULTS: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63Cu, 182W, 208Pb, and 238U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1ß, TNF-α, CXCL-1, CCL-5, TGF-ß, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1ß, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1ß, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. CONCLUSIONS: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

Cross-shift changes in pulmonary function and occupational exposure to particulate matter among e-waste workers in Ghana.

Introduction: Little is known on the association between cross-shift changes in pulmonary function and personal inhalation exposure to particulate matter (PM) among informal electronic-waste (e-waste) recovery workers who have substantial occupational exposure to airborne pollutants from burning e-waste. Methods: Using a cross-shift design, pre- and post-shift pulmonary function assessments and accompanying personal inhalation exposure to PM (sizes <1, <2.5 µm, and the coarse fraction, 2.5-10 µm in aerodynamic diameter) were measured among e-waste workers (n = 142) at the Agbogbloshie e-waste site and a comparison population (n = 65) in Accra, Ghana during 2017 and 2018. Linear mixed models estimated associations between percent changes in pulmonary function and personal PM. Results: Declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) per hour were not significantly associated with increases in PM (all sizes) among either study population, despite breathing zone concentrations of PM (all sizes) that exceeded health-based guidelines in both populations. E-waste workers who worked "yesterday" did, however, have larger cross-shift declines in FVC [-2.4% (95%CI: -4.04%, -0.81%)] in comparison to those who did not work "yesterday," suggesting a possible role of cumulative exposure. Discussion: Overall, short-term respiratory-related health effects related to PM exposure among e-waste workers were not seen in this sample. Selection bias due to the "healthy worker" effect, short shift duration, and inability to capture a true "pre-shift" pulmonary function test among workers who live at the worksite may explain results and suggest the need to adapt cross-shift studies for informal settings.

Inhalation exposure-induced toxicity and disease mediated via mTOR dysregulation.

Environmental air pollution is a global health concern, associated with multiple respiratory and systemic diseases. Epidemiological supports continued urbanization and industrialization increasing the prevalence of inhalation exposures. Exposure to these inhaled pollutants induces toxicity via activation of numerous cellular mechanisms including oxidative stress, autophagy, disrupted cellular metabolism, inflammation, tumorigenesis, and others contributing to disease development. The mechanistic target of rapamycin (mTOR) is a key regulator involved in various cellular processes related to the modulation of metabolism and maintenance of homeostasis. Dysregulation of mTOR occurs following inhalation exposures and has also been implicated in many diseases such as cancer, obesity, cardiovascular disease, diabetes, asthma, and neurodegeneration. Moreover, mTOR plays a fundamental role in protein transcription and translation involved in many inflammatory and autoimmune diseases. It is necessary to understand inhalation exposure-induced dysregulation of mTOR since it is key regulator which may contribute to numerous disease processes. This mini review evaluates the available literature regarding several types of inhalation exposure and their impacts on mTOR signaling. Particularly we focus on the mTOR signaling pathway related outcomes of autophagy, lipid metabolism, and inflammation. Furthermore, we will examine the implications of dysregulated mTOR pathway in exposure-induced diseases. Throughout this mini review, current gaps will be identified related to exposure-induced mTOR dysregulation which may enable the targeting of mTOR signaling for the development of therapeutics.

Investigating the temporal link between PM2.5 exposure and acceleration of myocardial ischemia reperfusion injury: Emphasizing the hazardous presence of metals in inhaled air.

Exposure to PM2.5 is widely acknowledged to induce cardiotoxic effects, leading to decreased myocardial tolerance to revascularization procedures and subsequent ischemia reperfusion injury (IR). However, the temporal relationship between PM2.5 exposure and vulnerability to IR, along with the underlying mechanisms, remains unclear and is the focus of this study. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m³ for 3 h daily over varying durations (7, 14, and 21 days), followed by IR induction. Our results demonstrated a significant increase in cardiac injury, as evidenced by increased infarct size and elevated cardiac injury markers, starting from day 14 of PM2.5 exposure, accompanied by declined cardiac function. These adverse effects were associated with apoptosis and impaired mitochondrial function, including reduced bioenergetics, mitochondrial DNA copy number and quality control mechanisms, along with inactivation of the PI3K/AKT/AMPK signalling pathways. Furthermore, analysis of myocardial tissue revealed elevated metal accumulation, particularly within mitochondria. Chelation of PM2.5 -associated metals using EDTA significantly mitigated the toxic effects on cardiac IR pathology, as confirmed in both rat myocardium and H9c2 cells. These findings suggest that metals in PM2.5 play a crucial role in inducing cardiotoxicity, impairing myocardial resilience to stress through mitochondrial accumulation and dysfunction.

Aristolochic Acid Exposure via Dermal Contact or Inhalation of Herbal Powders: Evidence of Occupational Exposure in Herbalists with Urothelial Cancer.

Emerging evidence showing urothelial cancer in herbalists is linked to aristolochic acid (AA) exposure; however, the exposure pathway remains unclear. Here, we show that dermal contact and inhalation of fine powders of AA-containing herbs are significant occupational AA exposure pathways for herbalists. We initiated the study by quantifying the amount of AA in the AA-containing powder deposited on gloves and face masks worn by the operators of an AA-containing herb grinding machine. Then, we measured the kinetics of dermal absorption and dissolution of AA from fine powders of AA-containing herbs into artificial sweat and surrogate lung fluid. Lastly, we quantified the mutagenic AA-DNA adduct levels formed in the kidneys of mice exposed to AA-containing fine powders through dermal contact. Our findings highlight an urgent occupational risk that should demand implementation of safety standards for herbalists exposed to AA-containing fine powders.

Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments.

Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (e.g., nose-only versus oronasal breathing), airway structure (e.g., complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

[Silica exposure among miners at high altitude. Inhaled dose and evaluation methods in hypobaric environments]. / Exposición a sílice de mineros en altitud. Dosis inhalada, método de evaluación en condición de hipobaria.

OBJECTIVE: To evaluate silica exposure among Chilean miners at high altitude, using different methodological approaches, for the purpose of determining the safest method to control exposures.  Methods: The 46 miners in the sample worked at 3000 meters above sea level in nonstandard work shifts, consisting of four consecutive 12-hour days, followed by four consecutive days off. Silica samples were obtained in each of the jobs positions of these 46 high-altitude miners. The results of the concentrations are presented in mg/m3. Exposures were evaluated in compatison to the Threshold Limit Value (Method 1) and using two other methodologies that incorporate respiratory parameters (Methods 2 and 3). The proportion of miners at risk was determined with each of these methods and compared. RESULTS: Based on the Threshold Limit Value (Method 1), 43.48% of miners were classified as being at risk. With the other two methods that incorporate respiratory parameters, the proportion of overexposed miners was 82.61% with Method 2, and 73.91% with Method 3. CONCLUSIONS: Of the three methods analyzed, the one that considers the respiratory parameter minute volume, through the estimation of the inhaled dose, is the safest to define the group of miners at risk due to exposure to silica at high altitude.

OBJETIVO: Evaluar la exposición a sílice de mineros chilenos en altitud usando diferentes metodologías, con el propósito de determinar el método más seguro para controlar la exposición.  Métodos: Los 46 mineros que conforman la muestra trabajan a 3000 metros sobre el nivel del mar con sistema de turnos no convencionales, en jornadas de 12 horas diarias por 4 días consecutivos, después de los cuales se descansa por otros 4 días. Se tomaron muestras de sílice en cada uno de los puestos de trabajo de estos 46 mineros en altitud. Los resultados de las concentraciones se presentan en (mg/m3). La exposición se evaluó usando el Threshold Limit Value y otras dos metodologías que incorporan parámetros respiratorios. Se determinó el grupo de mineros en riesgo con cada uno de estos métodos y se comparó la proporción de mineros expuestos en cada caso. RESULTADOS: evaluando con el Threshold Limit Value (método 1) se obtuvo un 43,48% de mineros en riesgo. Con los métodos que incluyen parámetros respiratorios se obtuvo una proporción de mineros sobre-expuestos del 82,61% con el método 2, y 73,91% con el método 3. CONCLUSIONES: de los tres métodos analizados, el que considera el parámetro respiratorio volumen minuto, a través de la estimación de la dosis inhalada, es el más seguro para definir el grupo de mineros en riesgo por exposición a sílice a gran altura.

Chronic inhalation of H2S in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats.

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Airborne indoor allergen serine proteases and their contribution to sensitisation and activation of innate immunity in allergic airway disease.

Common airborne allergens (pollen, animal dander and those from fungi and insects) are the main triggers of type I allergic disorder in the respiratory system and are associated with allergic rhinitis, allergic asthma, as well as immunoglobulin E (IgE)-mediated allergic bronchopulmonary aspergillosis. These allergens promote IgE crosslinking, vasodilation, infiltration of inflammatory cells, mucosal barrier dysfunction, extracellular matrix deposition and smooth muscle spasm, which collectively cause remodelling of the airways. Fungus and insect (house dust mite and cockroaches) indoor allergens are particularly rich in proteases. Indeed, more than 40 different types of aeroallergen proteases, which have both IgE-neutralising and tissue-destructive activities, have been documented in the Allergen Nomenclature database. Of all the inhaled protease allergens, 85% are classed as serine protease activities and include trypsin-like, chymotrypsin-like and collagenolytic serine proteases. In this article, we review and compare the allergenicity and proteolytic effect of allergen serine proteases as listed in the Allergen Nomenclature and MEROPS databases and highlight their contribution to allergic sensitisation, disruption of the epithelial barrier and activation of innate immunity in allergic airways disease. The utility of small-molecule inhibitors of allergen serine proteases as a potential treatment strategy for allergic airways disease will also be discussed.

[A case of acute inhalation dinitrogen tetroxide poisoning].

Dinitrogen tetroxide is often used as an oxidant in rocket propellant and has strong irritant and corrosive properties. This paper analyzes the clinical data of a patient with dinitrogen tetroxide poisoning admitted in the 63710 Army Hospital of Chinese People's Liberation Army, so as to further explore the poisoning mechanism, clinical characteristics and key points of acute inhaled dinitrogen tetroxide poisoning.

The Role of Inhalant Allergens on the Clinical Manifestations of Atopic Dermatitis.

BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.

Inhaled Pollutants of the Gero-Exposome and Later-Life Health.

Inhaled air pollutants (AirP) comprise extraordinarily diverse particles, volatiles, and gases from traffic, wildfire, cigarette smoke, dust, and various other sources. These pollutants contain numerous toxic components, which collectively differ in relative levels of components, but broadly share chemical classes. Exposure and health outcomes from AirP are complex, depending on pollutant source, duration of exposure, and socioeconomic status. We discuss examples in the current literature on organ responses to AirP, with a focus on lung, arteries, and brain. Some transcriptional responses are shared. It is well accepted that AirP contributes to Alzheimer's disease and other neurodegenerative conditions in the Gero-Exposome. However, we do not know which chemical compounds initiate these changes and how activation of these transcriptional pathways is further modified by genetics and prenatal development.

Human health impacts attributable to inhalation exposure of particulate matter (PM10 and PM2.5) during the Holi festival.

OBJECTIVE: The present study focuses on residential areas of Delhi to identify the elevated levels of ambient PM10 and PM2.5 due to biomass burning followed by the coloring activity in the Holi festival celebrated at the end of the winter season. This study also focuses on the health risk assessment and mortality among different age groups due to the change in particulate matter levels during the Holi festival in Delhi, India. MATERIALS AND METHODS: Secondary data of particulate matters have been procured from the Central Pollution Control Board (CPCB), Delhi Pollution Control Committee (DPCC), and Indian Institute of Tropical Meteorology (IITM), Pune for the period of the pre-, during, and post-Holi period for the year 2018-2020 at four selected residential locations in Delhi, India. The health impacts of particle inhalation were quantified using the AirQ + models. RESULTS: The results indicated the levels of PM10 and PM2.5 rise about 3-4 times higher during the Holi festival than on normal days, resulting in health risks and causing an excess number of mortality and Asthma cases in Delhi. Such cases were also found to be higher in 2018, followed by 2019 and 2020 at all the selected locations in Delhi. CONCLUSIONS: The study linked the increasing particulate levels in the Holi festival with the increased health risk through short-term exposure of the population. The excess number of cases (ENCs) of mortality, all causes of mortality among adults (age > 30 years) associated with short-term exposure to particulate were also identified.

Ambient air concentrations of plant protection products: Data collection for the combined air concentration database and associated risk assessment.

CropLife Europe collected literature values from monitoring studies measuring air concentrations of Plant Protection Products (PPPs) that may be inhaled by humans located in rural areas but not immediately adjacent to PPP applications. The resulting "Combined Air Concentration Database" (CACD) was used to determine whether air concentrations of PPPs reported by the French "Agency for Food, Environmental and Occupational Health & Safety" (ANSES) are consistent with those measured by others to increase confidence in values of exposure to humans. The results were put into risk assessment context. Results show that 25-90% of samples do not contain measurable PPP concentrations. Measured respirable fractions were below EU default air concentrations used for risk assessment for resident exposure by the European Food Safety Authority. All measured exposures in the CACD were also below established toxicological endpoints, even when considering the highest maximum average reported concentrations and very conservative inhalation rates. The highest recorded air concentration was for prosulfocarb (0.696 µg/m³ measured over 48 h) which is below the EFSA default limit of 1 µg/m³ for low volatility substances. In conclusion, based on the CACD, measured air concentrations of PPPs are significantly lower than EFSA default limits and relevant toxicological reference values.

The role of nanoparticles in bleed air in the etiology of Aerotoxic Syndrome: A review of cabin air-quality studies of 2003-2023.

Aerotoxic Syndrome may develop as a result of chronic, low-level exposure to organophosphates (OPs) and volatile organic compounds in the airplane cabin air, caused by engine oil leaking past wet seals. Additionally, acute high-level exposures, so-called "fume events," may occur. However, air quality monitoring studies concluded that levels of inhaled chemicals might be too low to cause adverse effects. The presence of aerosols of nanoparticles (NPs) in bleed air has often been described. The specific hypothesis is a relation between NPs acting as a vector for toxic compounds in the etiology of the Aerotoxic Syndrome. These NPs function as carriers for toxic engine oil compounds leaking into the cabin air. Inhaled by aircrew NPs carrying soluble and insoluble components deposit in the alveolar region, where they are absorbed into the bloodstream. Subsequently, they may cross the blood-brain barrier and release their toxic compounds in the central nervous system. Olfactory absorption is another route for NPs with access to the brain. To study the hypothesis, all published in-flight measurement studies (2003-2023) of airborne volatile (and low-volatile) organic pollutants in cabin air were reviewed, including NPs (10-100 nm). Twelve studies providing data for a total of 387 flights in 16 different large-passenger jet aircraft types were selected. Maximum particle number concentrations (PNC) varied from 104 to 2.8 × 106 #/cm3 and maximum mass concentrations from 9 to 29 µg/m3. NP-peaks occurred after full-power take-off, in tailwind condition, after auxiliary power unit (APU) bleed air introduction, and after air conditioning pack failure. Chemical characterization of the NPs showed aliphatic hydrocarbons, black carbon, and metallic core particles. An aerosol mass-spectrometry pattern was consistent with aircraft engine oil. It is concluded that chronic exposure of aircrew to NP-aerosols, carrying oil derivatives, maybe a significant feature in the etiology of Aerotoxic Syndrome. Mobile NP measuring equipment should be made available in the cockpit for long-term monitoring of bleed air. Consequently, risk assessment of bleed air should include monitoring and analysis of NPs, studied in a prospective cohort design.

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats.

Moon dust presents a significant hazard to manned moon exploration missions, yet our understanding of its toxicity remains limited. The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6 hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced oxidative stress response can lead to pulmonary inflammation, which potentially may progress to lung fibrosis. Transcriptome sequencing revealed that MDS suppresses the PI3K-AKT signaling pathway, triggers the Tnfr2 non-classical NF-kB pathway and IL-17 signaling pathway, ultimately causing lung inflammation and activating predominantly antioxidant immune responses. Moreover, the study identified the involvement of upregulated genes IL1b, csf2, and Sod2 in regulating immune responses in rat lungs, making them potential key targets for preventing pulmonary toxicity related to moon dust exposure. These findings are expected to aid in safeguarding astronauts against the hazardous effects of moon dust and offer fresh insights into the implications and mechanisms of moon dust toxicity.

Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats.

Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.