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.

Electronic nicotine delivery systems (ENDS), commonly known as e-cigarettes, are battery-operated devices that produce aerosols by vaporizing e-liquids, which typically contain propylene glycol and/or vegetable glycerin, nicotine, and flavorings. Since their launch in the U.S. in 2007, ENDS have evolved significantly to meet consumer demands, prompting federal regulation in 2016 under the Family Smoking Prevention and Tobacco Control Act. The first ENDS resembled conventional tobacco cigarettes and were initially marketed as smoking cessation tools. While their smoking cessation efficacy under advantageous conditions has been supported by randomized clinical trials, observational cohort studies have raised doubt about their utility for smoking cessation under more typical real-world use conditions. In 2018, the U.S. Surgeon General declared youth vaping a national epidemic as prevalence of current ENDS use rose to 27.5% among high school. The youth vaping trend alongside injury reports and deaths related to e-cigarette or vaping product use-associated lung injury (EVALI) raised public health alarms in 2019. Although youth vaping has since declined, over 1.6 million high school students and 410, 000 middle school students reported ENDS usage in 2024. Thus, the ongoing challenges surrounding vaping including adolescent usage and smoking cessation efficacy continue to attract public health concern and debate. Within this section of the Special Issue "Science Education and Research on Vaping and Interventions for Community Engagement", an overview of the history of the vaping epidemic, current formats and ENDS generations, usage statistics across various demographics along with market trends and regulatory guidelines will be discussed.

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.

Objective(s): Pulmonary fibrosis (PF) is a seriousand advancing respiratory condition that arises from various contributing factors. Bleomycin (BLM) is a chemotherapeutic drug known to cause different side effects, including PF. The current study aimed to assess the protective effects of the Tannic Acid/Iron complex (TAIC) against PF induced by BLM in a rat model.

Materials and methods: PF was induced in Wistar rats by a single dose of BLM (7.5 U/kg) on the 7th day. The rats were then randomly assigned to six groups: control, BLM, and four treatment groups receiving BLM + different doses of TAIC or TA alone (28 days, gavage). Animals were sacrificed on the 29th day and lung samples were collected to assess histopathological alterations and biochemical parameters such as lung index, nitric oxide (NO), malondialdehyde (MDA), hydroxyproline (HP), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and tumor necrosis factor- α (TNF-α).

Results: The results demonstrated that the TAIC complex significantly attenuated BLM-induced elevation in lung index as well as the levels of MDA, NO, HP, and TNF-α. Additionally, TAIC enhanced the activities of key antioxidant enzymes, including CAT, SOD, GPx, and increased GSH content. This complex also inhibited the infiltration of fibroblasts and inflammatory cells, thereby preventing alveolar thickening. Notably, the effect of TA at 400 mg/kg, while beneficial, was slightly less pronounced compared to the TAIC complex at the same dosage.

Conclusion: The results revealed that TAIC hasa protective effect on BLM -induced pulmonary fibrosis.

Objective: Rising childhood obesity is a global concern, with environmental tobacco exposure as a potential risk factor. However, the mechanisms linking secondhand smoke and e-cigarette aerosol to adolescent obesity remain unclear.

Methods: We analyzed data from 968 participants aged 3- 19 years in the NHANES 2017- 2020 cycles. Passive exposure was assessed using self-reported household exposure and objectively measured serum cotinine levels. Multivariate logistic regression was used to evaluate the associations between exposure categories and overweight/obesity status. Cotinine-related molecular targets were identified through network pharmacology and toxicology analyses, with protein-protein interaction networks, enrichment analyses, and molecular docking used to explore relevant pathways.

Results: Compared with unexposed individuals, participants exposed to both secondhand smoke and e-cigarette aerosols had significantly greater odds of overweight or obesity (adjusted odds ratio [aOR] = 3.9; 95% CI: 1.4-11.0; p = 0.009). Serum cotinine levels were also positively associated with obesity risk in a dose-dependent manner, with those in the highest quartile (Q4) showing aOR = 3.8 (95% CI: 2.1-6.8; p < 0.001) compared with those in Q1. Network analyses identified CHRNA2 and CHRNB2 as key targets involved in cholinergic signaling and metabolic regulation. Cotinine demonstrated strong binding affinity to these targets in molecular docking, supporting its potential biological activity beyond being a nicotine biomarker.

Conclusion: Passive nicotine exposure is significantly associated with overweight or obesity among adolescents, and cotinine may be involved in relevant biological pathways related to energy regulation. These findings may inform future research and preventive strategies.

Objective: Carbon monoxide (CO) poisoning impairs oxygen transport by forming carboxyhemoglobin (COHb). Normobaric oxygen (NBO) is standard therapy, but its COHb elimination rate is slow. This study compared the effectiveness of NBO, NIMV, and EzPAP in reducing COHb levels in acute CO poisoning.

Materials and methods: This prospective cohort study included patients with acute CO poisoning in an emergency department. Participants received one of three treatment modalities: standard NBO therapy, NIMV with positive pressure support, or the EzPAP system. COHb levels were recorded at baseline, 30 min, and 60 min after initiation of therapy. The primary outcome was the change in COHb concentration over time.

Results and discussion: A total of 66 patients were included in the study (NIMV: n = 29, EzPAP: n = 18, and NBO: n = 19). Significant differences were observed in symptom distribution, with headache more frequent in the EzPAP and NBO groups and dyspnea more common in NIMV and EzPAP groups (p < 0.001). Baseline COHb levels did not differ between groups (p = 0.849). At 30 and 60 min, NIMV achieved significantly greater COHb reduction compared to NBO (p < 0.001), while EzPAP showed superiority over NBO at 60 min (p = 0.031). Pairwise analyses indicated NIMV was also superior to EzPAP at 60 min (p = 0.003).

Conclusions: While NBO remains the standard therapy, this study suggests NIMV - and to a lesser extent, EzPAP - may serve as effective adjuncts in the management of CO poisoning. These findings provide a rationale for further randomized controlled trials.