Inhalation Toxicology最新文献

Electronic nicotine delivery systems (ENDS) have become a growing health concern among both youth and adults. Rise in vaping-associated lung injury underscores the consequences of the ENDS usage under certain conditions. In response, stakeholders including researchers and public health regulators have launched awareness initiatives to highlight the hazards of vaping and promote harm reduction strategies. Within harm reduction frameworks, several strategies exist including vaping behavior assessments and monitoring, engineering controls, and limiting the variety of ENDS and e-liquid formats and formulations. From an engineering perspective, controls could be implemented to limit puff size, monitor e-liquid consumption, and explore attachable filters to reduce inhalation risks. Additionally, reducing the availability of flavored e-liquids and restricting modifications could minimize their appeal to youth. Marketing strategies should clearly communicate the harms of vaping devices through informative text, images, and digital campaigns. Additionally, warning labels should be placed directly on the devices, not just on packaging, to constantly remind users of the associated risks. This review which is a part of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement examines the challenges of vaping cessation methods and explores how stakeholders, users, manufacturers, and policymakers can contribute to vaping harm reduction.

Objective: To investigate the associations between long-term exposure to ambient air pollutants and incident cardiovascular disease (CVD) in a high-exposure setting and to evaluate whether multimorbidity affects this relationship in middle-aged and older Chinese individuals.

Methods: Data from 7,692 adults in the China Health and Retirement Longitudinal Study (CHARLS), with up to 8 years of follow-up, were used. Long-term exposure to particulate matter ≤1 μm (PM₁), ≤2.5 μm (PM₂.₅), ≤10 μm (PM₁₀), nitrogen dioxide (NO₂), and ozone (O₃) was analyzed using high-resolution satellite-based estimates. Next, a least absolute shrinkage and selection operator regression multipollutant index was constructed. Hazard ratios for incident CVD were estimated using Cox proportional hazards models, and effect modification by multimorbidity was examined.

Results: During follow-up, a total of 1,759 participants developed CVD. Compared with those in the lowest quartile, participants in the highest quartile of PM₁, PM₂.₅, PM₁₀, and NO₂ exposure had hazard ratios of 1.35 (95% CI: 1.18-1.54), 1.58 (95% CI: 1.38-1.81), 1.63 (95% CI: 1.42-1.87), and 1.25 (95% CI: 1.09-1.44), respectively. Combined multipollutant exposure had the strongest effect, with an HR of 2.05 (95% CI: 1.78-2.37). The corresponding HRs were 2.27 (95% CI: 1.89-2.72) among participants without multimorbidity and 3.02 (95% CI: 2.44-3.73) among those with multimorbidity (P for interaction = 0.029).

Conclusion: Long-term exposure to ambient air pollutants is associated with a substantially increased risk of CVD, particularly among individuals with multimorbidity. These findings highlight the need for multipollutant control strategies and targeted prevention efforts among clinically vulnerable populations.

Background: The use of alternative and renewable fuels in the transport sector is growing rapidly due to increasing demand for sustainable energy solutions, however implying an increased risk for human exposure to emissions from these new fuels.

Methods: In this study, we examined the effects on BEAS-2B cells of particulate matter (PM) emissions, derived from the use of petroleum diesel (SD10) and rapeseed methyl ester (RME100) in a truck engine. We assessed several endpoints, including the induction of apoptotic and necrotic cell death, reactive oxygen species generation inside cells, inflammatory response, and cell cycle alterations.

Results: The characteristics of the exhaust PM varied between the two fuels, where the RME100-derived PM contained lower levels of polycyclic aromatic hydrocarbons and elemental carbon compared to SD10. Toxicological analyses revealed that PM from RME100 induced weaker oxidative stress and cell death responses than SD10. However, unlike SD10, RME100 PM caused a notable arrest in the S-G2/M phase of the cell cycle.

Conclusions: In summary, fuel type clearly influenced the characteristics of PM emissions from a heavy-duty diesel engine, which in turn affected the particles' biological activity. Overall, RME100 exhaust PM exhibited lower toxicity compared to petroleum diesel PM in the BEAS-2B cell model.

Objective: Ammonia (NH₃) inhalation is a common occupational exposure, causing injuries similar to acute lung injury (ALI). Medical management is limited to supportive care, as no specific antidotes are currently available. This study aimed to evaluate the efficacy of potential therapeutic interventions to mitigate NH₃-induced damage using both in vivo (mouse) and in vitro (A549 alveolar epithelial cells) models.

Methods: BALB/c mice received 91.0 mg/kg NH₃ via intratracheal instillation, followed by intraperitoneal dexamethasone (100 mg/kg) at 1, 5, and 23 h post-exposure to assess therapeutic effects. Analyses were performed on days 1 and 7. The complementary studies in A549 cells examined whether therapeutic interventions could counteract NH₃-induced toxicity affecting cell viability and function.

Results: Dexamethasone-treatment did not counteract the lethal damage in mice or significantly reduce the severity of ALI that intensified over time, including increased lung inflammatory cell infiltration, lung hemorrhages, and coagulation abnormalities. However, treatment reduced methacholine-induced AHR, and MMP-9 and SP-D levels at 20h post-exposure. Most treatments in A549 cells failed to prevent apoptotic and necrotic cell death, oxidative stress, mitochondrial dysfunction, and membrane damage caused by NH₃ exposure however, the membrane stabilizer Poloxamer 188 (P188) highlighted the importance of stabilizing the cellular membrane damage to prevent further damages.

Conclusions: While standard treatment with corticosteroids offered limited protection in NH₃-exposed mice, the study's complementary in vitro investigations on new medical counter measures highlighted the complexity and severity of NH₃-induced lung injury. Together, the in vivo and in vitro findings emphasize the urgent need for effective medical countermeasures.

Background: Ozone (O₃) and nitrogen dioxide (NO₂) are highly reactive gases associated with all cause-mortality. Epidemiology studies suggest that the risk from O₃ and NO₂ exposure is modified by sex. O₃ is more strongly associated with declines in pulmonary function in males, but females show stronger associations with cardiovascular disease (CVD). For NO₂ exposure, females show stronger associations for increased risk of CVD, loss of lung function, and mortality. It remains unclear if these differences stem from social constructs or underlying biologic responses.

Methods: To investigate sex differences after pollutant exposure, we used a single blind, randomized crossover, controlled exposure study to examine the pulmonary, inflammatory, and clotting/fibrinolysis response after exposure to O₃ and NO₂ relative to clean air. Healthy adult participants (n = 22 male = 10, female = 12) underwent separate two-hour exposures to clean air, 300 ppb O₃, and 500 ppb NO₂ exposures while exercising intermittently.

Results: Compared to air, exposure to O₃ resulted in a mean percent change in FEV₁ (-5.74%, 95%CI: -7.83, -3.65, p < 0.001), FVC (-3.94%, 95%CI: -5.59, -2.30, p < 0.001), and FEV₁/FVC (-1.90%, 95%CI: -3.54, -0.25, p < 0.01), and elevated IL-6 (16.3%, 95%CI: 0.51, 32.14, p < 0.01), C-Reactive Protein (CRP) (44.54%; 95%CI: 15.44, 73.65, p < 0.001), and Serum amyloid A (SAA) (33.6%; 95%CI: 7.30, 60.0, p < 0.01). NO₂ exposure resulted in a mean percent change of D-dimer (10.9%, 95%CI: -0.23, 21.93, p < 0.05). When stratified by sex, after O₃ exposure, males displayed greater decrements in FEV₁ (males; -7.81% (95%CI: -11.45, -4.19) females: -4.00% (95%CI: -6.20, -1.80; p < 0.05)) and CRP increased in males by 78.50% (95%CI: 27.50, 129.50) compared to 16.20% (95%CI: -10.43, 42.84) in females (p < 0.01) and SAA increased in males by 60.25% (95%CI: 12.02, 108.48) compared to 15.18% (95%CI: -14.53, 44.90) in females (p = 0.051). TNFα was elevated in females by an average of 10.9% (95%CI: 0.75, 21.23) compared to males (-2.29%, 95%CI: -12.32, 7.75) (p < 0.05). After NO₂, D-dimer was elevated in females by 18.98% (95%CI: 4.69, 33.26) compared to males (1.52%, 95%CI: -16.12,19.16) (p = 0.062).

Conclusions: Sex modified the pulmonary and inflammatory response to O₃ and NO₂, a finding consistent with epidemiological observations of sex differences after O3 and NO2 exposure.

The widespread use of electronic nicotine delivery systems (ENDS) among youth and adults has become a significant public health concern. Approximately 19.6% of middle and high school students in the United States have reported using ENDS containing nicotine. Factors contributing to their popularity include social and recreational appeal, sensory satisfaction, ease of accessibility, and aggressive marketing strategies including influencer-driven promotions and youth-targeted campaigns through social media platforms. The variety of available flavors and modifiable features of ENDS devices further enhances their acceptance, often overshadowing their potential health risks. Despite their perceived advantages, misconceptions about ENDS persist, including beliefs that emissions are harmless, vaping is safer than smoking, and secondhand exposure is inconsequential. These misunderstandings contribute to the normalization of ENDS use, hindering public awareness of the associated health and environmental hazards. This manuscript addresses seven prevalent misconceptions about ENDS ranging from their safety during pregnancy to their environmental impact, highlighting the need for comprehensive education and community engagement to mitigate the risks of ENDS usage and promote informed decision-making. In the following section of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement (SERVICE), we will explore how these misconceptions not only encourage the societal acceptance and use of ENDS but also contribute to potential health risks.

Objective: Gaseous hypochlorous acid HOCl(g) is a promising agent for continuous complex disinfection of premises, but the toxic effect of its inhalation has been practically not studied. In this study, the effect of inhalation of 0.75 and 1.79 ppm HOCl(g) on ​​the activity of cysteine ​​cathepsins B, H and L, and alpha-1 antitrypsin in the blood plasma of rats was studied to assess the extent of lysosome damage as an element of oxidative stress.

Materials and methods: the inhalation exposure was carried out in the 'whole-body' mode during a single 4-hour treatment of animals of two age groups in inhalation chamber equipped with a specially designed evaporative unit. Biochemical parameters were analyzed 2 h and 24 h after the procedure.

Results and discussion: it was found that the activity of cathepsin L did not change in any of the animal groups, while the activities of cathepsins B and H significantly increased. Inhalation had the greatest effect on cathepsin H, which increased by 1.6-6.4 times in different groups, and the reaction of young animals was more intense. Alpha-1 antitrypsin levels were also elevated both 2 and 24 h after exposure, but age-dependent differences were not significant. In all cases, an increase in the deviation of biochemical parameters from the norm was noted with an increase in the HOCl(g) concentration.

Conclusions: HOCl(g) inhalation at the concentrations used causes pronounced oxidative stress in animals. More detailed biochemical, histological and immunohistochemical studies are needed to assess the toxic consequences of such exposure.

Introduction: Exposure to air pollution containing particulates (PM) and gas-phase volatile organic compounds (VOCs), is a leading cause of human morbidity and mortality globally. Devising effective protective public health strategies requires an assessment of the relative contribution of PM and VOCs to the health effects of air pollution exposure.

Methods: To enable studies of VOCs isolated from mixed atmospheres, we developed a positive air pressure exposure system that permits the subject to breathe unimpeded by the pressure drop imposed by filtering respirators. This system uses pumps to draw air through respirator filters and delivers it to a modified positive pressure respirator at a flow rate that exceeds the ventilatory requirements of the wearer, while preventing infiltration of the surrounding atmosphere.

Results: Tests showed negligible leaks (<5% flow reduction) and minimal VOC losses (95% recovery) to the system. When tested using an atmosphere containing woodsmoke, PM filters showed effective exclusion of particulates but minimal losses of VOCs, while activated carbon based cartridges effectively removed gaseous compounds and PM. A team member exercising moderately in a woodsmoke atmosphere for 2-hours reported no perveivable odors and experienced no discomfort during an exposure using charcoal filter cartridges.

Discussion: We report the development and validation of a novel human exposure system that allows selective exposure to the gaseous fraction of a mixed atmosphere. This system allows for moderate to vigorous exercise of the study subject and can be used in place of an exposure chamber, making it compatible with clinical and field studies.

Objective: To date, exposure thresholds for fragrance chemicals are most often extrapolated from oral administration data. Due to limited inhalation toxicity data, the potentially high exposure levels toward fragrances - especially in air care applications - are sometimes perceived as potentially critical. Herein, we assessed the potential inhalation toxicity of various commonly used fragrances with main focus on respiratory tract effects.

Methods: 19 high volume fragrances were screened for their cytotoxic potential by using rat precision cut lung slices (PCLuS). Based on the screening data, chemicals were categorized into low, mid, and high cytotoxicity groups. From these groups, five fragrances were selected for further in vivo investigation. In a 14-day inhalation study, male 7-week old Wistar rats were exposed to geraniol, geranyl acetate, citral, L-menthol, and p-tert-butyl-alpha-methylhydro-cinnamic aldehyde (BMHCA) to investigate the respiratory and sensory irritation potential.

Results: Ex vivo screening allowed for a preliminary classification of the cytotoxic potential, facilitating the selection of candidates for in vivo inhalation assessments. Local respiratory irritation was observed for liquid aerosol fractions of citral and geraniol, but not for other substances or vapor only exposure. Overall, no systemic effects related to treatment were observed. Sensory irritation was only observed for citral and BMHCA but not for other fragrance chemicals.

Discussion: While PCLuS and further model development could not fully replace animal testing at this stage, this study's findings contribute to the reduction and refinement according to 3 R principles and might serve as a foundation for future testing strategies aiming toward a complete replacement.

Objective: Elevated exposure to ozone (O₃) may occur episodically over short windows of time. However, laboratory investigations have consistently shown that repeated ozone exposures produce an adaptation response, reducing the effects of O₃ on ventilatory function. To better understand these responses, we developed a rodent model of episodic O₃ exposure to characterize differing exposure patterns on pulmonary toxicity.

Methods: Male, Long-Evans rats were exposed for either two days or two weeks of episodic exposure to 0.4 or 0.8 ppm O₃ (4 h/day). Rats in the two-week group were exposed for a total of five nonconsecutive days, with one- to four-day periods of recovery between each exposure. Whole body plethysmography was performed following each exposure. Markers of lung injury and inflammation in the bronchoalveolar lavage fluid were measured, and lung expression of select genes were assessed using qPCR ∼24 h after the final exposure.

Results: Concentration-dependent effects of O₃ on breathing parameters and lung injury were observed following two days of exposure. However, these responses were less evident in rats exposed episodically over two weeks. Comparable increases in bronchoalveolar lavage fluid inflammatory cells and cytokine concentrations were observed irrespective of exposure duration. Furthermore, reduced expression of genes involved in neuroendocrine signaling was detected only following two weeks of episodic exposure (Adrb2, Nr3c1, Dusp1, Glccl1).

Conclusions: Aspects of the adaptation response were still present in rats episodically exposed to O₃ over two weeks. On the other hand, O₃-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.