Inhalation Toxicology最新文献

Objective: The objective was to determine the inhalation toxicity of the electrochemically generated sodium hypochlorite solution after its single administration to laboratory animals in the form of a highly dispersed aerosol.

Materials and methods: The study has been conducted according to the OECD Test Guideline №403 'Acute Inhalation Toxicity.' Laboratory animals were exposed to inhalation of an aerosol containing 1.7 ± 0.13 mg/m³ of active chlorine. The hematological and biochemical parameters of the blood of experimental animals have been determined, as well as specific parameters: the activity of cathepsins B and L, catalase, and α1-antitrypsin. Histological study of the lungs of animals has been carried out.

Results: During inhalation and 14 days after it, no death of the animals was observed; the behavior, appearance, and weight gain did not differ from the control group. There were no significant deviations in hematological parameters, except the decrease in the level of platelets. The biochemical study showed slight changes in the activity of alkaline phosphatase and aspartate aminotransferase on the 1st day after inhalation; these parameters returned to normal within 14 days of observation. Specific biochemical parameters did not show the development of oxidative stress. No specific histological pathologies of lung tissue have been found.

Conclusions: Thus, the studied electrochemically generated sodium hypochlorite solution under single inhalation exposure in aerosol form practically does not cause a toxic effect. The data obtained allow classifying such solution to the 4th (or even 5th - after additional studies) class of toxicity in accordance with Globally Harmonized System of Classification and Labeling of Chemicals.

Objective: Epidemiological studies indicate association between elevated air pollution and adverse health effects. Several mechanisms have been suggested, including translocation of inhaled ultrafine carbon (UFC) particles into the bloodstream. Previous studies in healthy subjects have shown no significant pulmonary translocation of UFC-particles. This study aimed to assess if UFC-particles translocate from damaged alveolar compartment in subjects suffering from chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Methods: Eleven COPD and nine IPF subjects were exposed to a 100 nm UFC-particle-aerosol labeled with Indium-111. Activity in the body was followed up for 10 days using gamma camera planar-imaging as well as in blood and urine samples.

Results: The pulmonary central to periphery activity ratio was significantly higher for COPD as compared to IPF subjects at exposure, 1.8 and 1.4, respectively and remained constant throughout the test period. Ten days after exposure, the estimated median pulmonary translocation of UFC particles was 22.8 and 25.8% for COPD and IPF, respectively. Bound activity was present in blood throughout the test period, peaking at 24-h postinhalation with a median concentration of 5.6 and 8.9 Bq/ml for the COPD and IPF, respectively. Median bound activity excreted in urine (% of inhaled) after 10 days was 1.4% in COPD and 0.7% in IPF. Activity accumulation in liver and spleen could not be demonstrated.

Conclusions: Our results suggest that UFC particles leak through the damaged alveolar barrier to the bloodstream in COPD and IPF patients probably distributing in a wide spectrum of whole-body tissues.

Exposure to toxic chemicals through smoked tobacco is a significant global public health issue due to their genotoxic and carcinogenic properties. The study aims to (1) measure Arsenic (As), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Mercury (Hg), Nickle (Ni), lead (Pb), and 407 pesticides in tobacco commercialized in Saudi Arabia; and (2) evaluate human health risks associated with smoking tobacco. Thus, we analyzed 60 tobacco samples per brand from eight of the most popular tobacco brands in the Saudi market. The analyzed tobacco contained significant concentrations of toxic metal (loid)s and banned pesticides. Twenty-three out of 407 pesticide residues were found, with an average concentration of 0.004-1.155 µg/g. Average concentrations of As, Cd, Co, Cr, Hg, Ni, and Pb for all brands were 0.16, 0.57, 0.75, 1.36, 1.94, 0.01, and 0.37 µg/g, respectively. The risk assessment indicated that high cancer risks are associated with exposure to As, Cd, Cr, and Ni, while lower risks are associated with Pb. Additionally, the potential cancer risk estimated for Cr was higher than other toxic elements. The cumulative cancer risks (95%) under three different cases for all brands were greater than the permissible limits (=10^-4). The chances of getting cancer through inhalation of particulate As, Cd, Cr, Ni, and Pb was 4 in 10 000 cases in the best case scenario (1 cigarette per day). Therefore, metal content in cigarette tobacco should be reduced to improve public health.HIGHLIGHTSAll tested brands contained banned pesticide residues except for brand C.Tobacco samples contained significant concentrations of toxic metal(loid)s.A high risk of developing cancer is associated with exposure to As, Cd, Cr, and Ni, while a lower risk is associated with exposure to Pb.

Objective: The increasing exposure to gold nanoparticles (AuNPs), due to their wide range of applications, has led to the need for thorough understanding of their biodistribution, following exposure. The objective of this paper is to develop a PBK model in order to study the clearance, retention and translocation of inhaled gold nanoparticles in rats, providing a basis for the understanding of the absorption, distribution, metabolism and elimination (ADME) mechanisms of AuNPs in various organs.Materials and methods: A rat PBK computational model was developed, connected to a detailed respiratory model, including the olfactory, tracheobronchial, and alveolar regions. This model was coupled with a Multiple Path Particle Dosimetry (MPPD) model to appropriately simulate the exposure to AuNPs. Three existing in vivo experimental datasets from scientific literature for the biodistribution of inhaled AuNPs for different AuNP sizes and exposure scenarios were utilized for model calibration and validation.Results and Discussion: The model was calibrated using two individual datasets for nose only inhaled and intratracheally instilled AuNPs, while an independent dataset for nose only inhaled AuNPs was used as external validation. The overall fitting over the three datasets was proved acceptable as shown by the relevant statistical metrics. The influence of several physiological parameters is also studied via a sensitivity analysis, providing useful insights into the mechanisms of NP pharmacokinetics. The key aspects of the inhaled AuNPs biodistribution are discussed, revealing the key mechanisms for the AuNPs absorption routes, the AuNP uptake by secondary organs and the influence of the AuNP size on the translocation from the lungs to blood circulation.Conclusions: The model results together with the model sensitivity analysis clarified the key mechanisms for the inhaled AuNPs biodistribution to secondary organs. It was observed that nose-only inhaled AuNPs of smaller size can enter the blood circulation through secondary routes, such as absorption through the gastrointestinal (GI) lumen, showing that such translocations should not be underestimated in biodistribution modelling. Finally, the computational framework presented in this study can be used as a basis for a more wide investigation of inhaled nanoparticles biodistribution, including interspecies extrapolation of the resulting PBK model for the inhalation and subsequent biodistribution of AuNPs in humans.

Context: Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.Objective: To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.Methods: A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.Results: The highest absolute Pearson correlation (r = 0.97, r² = 0.94, p < 0.05) was achieved between mesothelioma potency (R_M) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (r = 0.80, r² = 0.64, p < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and R_M. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.Conclusions: Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.

Background: We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (<i>N</i> = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP.

Results: Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (<i>p</i> &lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response.

Conclusions: The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.

Objective: This study focuses on the profile of ambient particulate polycyclic aromatic hydrocarbons (PAHs), their seasonal distribution, source identification and human health risk assessment due to inhalation exposure of ambient PAHs in Delhi, India.Materials and Methods: Two sampling sites were chosen, one at roadway (MH) and other at urban background (JNU) site in Delhi. Determination of PAHs was carried with the help of HPLC with UV detector. Principal component analysis and Molecular diagnostic ratios were used for the source apportionment of PAHs. Health risks associated with inhalation of particulate PAHs were assessed using benzo(a)pyrene equivalent concentration and incremental lifetime cancer risk (ILCR) approach.Results: The results showed that the average mass concentration of Σ₁₆ PAHs near roadway (67.8 ± 40.2 ng m^-3) is significantly higher than urban background site (56 ± 30 ng m^-3). Moreover, source apportionment study indicated that major PAH-emission sources in Delhi NCR are traffic and coal combustion. ILCR values at both the sites fall in the range of 10^-2-10^-4 that corresponds to the priority risk level (10^-3) and higher than the acceptable risk level (10^-6).conclusions: The high PAHs concentration at MH site was due to it's nearness to busy traffic area. Thus, the spatial variations in PAHs were influenced by local emission sources. The high PAHs level during the winter season can be due to their higher emissions from local heating sources, shift of gas/particle partitioning toward the particulate phase at low temperature and reduced photochemical degradation of some PAHs in winter. The low level of PAHs in monsoon season can be attributed to their wet scavenging and higher percentage in vapor phase. PCA showed that the emissions from vehicles predominate at MH site; whereas, coal combustion and traffic both are the significant PAHs sources at JNU site. Health risk assessment revealed that the highest exposure risks occur at busy traffic site, thereby indicating a significantly higher health risk to the population of Delhi.

Objective: Arid2-IR is a long non-coding RNA (lncRNA) that promotes renal injury, while its role in lipopolysaccharides (LPS)-induced acute lung injury (ALI) is unknown. Our preliminary sequencing analysis revealed an inverse correlation of Arid2-IR and miR-132-3p, which is known to suppress LPS-induced ALI. Therefore, Arid2-IR and miR-132-3p may interact with each other to participate in LPS-induced ALI in pneumonia. This study aimed to investigate the interaction between Arid2-IR and miR-132-3p in ALI induced by pneumonia.

Materials and methods: Plasma samples were obtained from patients with pneumonia (n = 98) and healthy controls (n = 98) to detect the expression of circulating Arid2-IR and miR-132-3p. The correlation between them was analyzed using Pearson's correlation coefficient. The crosstalk between them in human bronchial epithelial cells (HBEpC) was analyzed through overexpression assay. MSP was applied to determine the methylation of the miR-132-3p gene. Cell viability was evaluated by 2,5-diphenyl-2H-tetrazolium bromide assay.

Results: Arid2-IR was highly upregulated in pneumonia group, while the expression levels of miR-132-3p decreased in pneumonia group compared to that in the controls. Arid2-IR and miR-132-3p were inversely correlated across patient samples. Overexpression of Arid2-IR decreased the expression levels of miR-132-3p in HBEpCs and increased the methylation of miR-132-3p gene. Arid2-IR suppressed the role of miR-132-3p in increasing the viability of HBEpCs induced by LPS.

Discussion and conclusion: Arid2-IR is upregulated in pneumonia and may downregulate miR-132-3p by increasing its methylation to decrease cell viability, thereby promoting LPS-induced ALI in pneumonia.

Objective: Growing interest in non-animal-based models has led to the development of devices to expose cells to airborne substances. Cells/tissues grown at the air-liquid interface (ALI) are more representative of lung cells/tissues in vivo compared to submerged cell cultures. Additionally, airborne exposures should allow for closer modeling of human lung toxicity. However, such exposures present technical challenges, including maintaining optimal cell health, and establishing consistent exposure monitoring and control. We aimed to establish a reliable system and procedures for cell exposures to gases at the ALI.

Methods: We tested and adapted a horizontal-flow ALI-exposure system to verify and optimize temperature, humidity/condensation, and control of atmosphere delivery. We measured temperature and relative humidity (RH) throughout the system, including at the outlet (surrogate measures) and at the well, and evaluated viability of lung epithelial A549 cells under control conditions. Exposure stability, dosimetry, and toxicity were tested using ozone.

Results: Temperatures measured directly above wells vs. outflow differed; using above-well temperature enabled determination of near-well RH. Under optimized conditions, the viability of A549 cells exposed to clean air (2 h) in the ALI system was unchanged from incubator-grown cells. In-well ozone levels, determined through reaction with potassium indigotrisulfonate, confirmed dosing. Cells exposed to 200 ppb ozone at the ALI presented reduced viability, while submerged cells did not.

Conclusion: Our results emphasize the importance of monitoring near-well conditions rather than relying on surrogate measures. Rigorous assessment of ALI exposure conditions led to procedures for reproducible exposure of cells to gases.

Aim: The cardiovascular toxicity of unheated and heated flavorants and their products as commonly present in electronic cigarette liquids (e-liquids) was evaluated previously in vitro. Based on the results of in vitro assays, cinnamaldehyde, eugenol, menthol, and vanillin were selected to conduct a detailed chemical analysis of the aerosol generated following heating of each compound both at 250 and 750 °C. Materials and Methods: Each flavoring was heated in a drop-tube furnace within a quartz tube. The combustion atmosphere was captured using different methods to enable analysis of 308 formed compounds. Volatile organic compounds (VOCs) were captured with an evacuated Summa canister and assayed via gas chromatography interfaced with mass spectrometry (GC-MS). Carbonyls (aldehydes and ketones) were captured using a 2,4-dinitrophenylhydrazine (DNPH) cartridge and assayed via a high-performance liquid chromatography-ultra-violet (HPLC-UV) assay. Polyaromatic hydrocarbons (PAHs) were captured using an XAD cartridge and filter, and extracts were assayed using GC-MS/MS. Polar compounds were assayed after derivatization of the XAD/filter extracts and analyzed via GC-MS. Conclusion: At higher temperature, both cinnamaldehyde and menthol combustion significantly increased formaldehyde and acetaldehyde levels. At higher temperature, cinnamaldehyde, eugenol, and menthol resulted in increased benzene concentrations. At low temperature, all four compounds led to higher levels of benzoic acid. These data show that products of thermal degradation of common flavorant compounds vary by flavorant and by temperature and include a wide variety of harmful and potentially harmful constituents (HPHCs).