The legal cannabis industry is expanding rapidly across the United States, yet indoor air quality (IAQ) characterizations of cultivation facilities remain scarce. Oklahoma's medical marijuana program grew to over 7,300 commercial licenses and 380,000 registered patients by 2023, but no published study has characterized occupational exposures within the state's cultivation facilities. Cannabis workers face poorly understood respiratory hazards, including elevated carbon dioxide (CO2) from plant respiration, particulate matter (PM) from cultivation activities, volatile organic compounds (VOCs), and extreme thermal and humidity conditions. This pilot study addresses this critical knowledge gap. We conducted continuous monitoring (10 July to 1 August 2023) in a 2,000 ft2 (approximately 186 m2) heating, ventilation, and air conditioning (HVAC)-equipped indoor medical cannabis cultivation facility in Central Oklahoma housing approximately 900 plants. The monitored room used an approximately 12-h light:12-h dark photoperiod, intermittent supplemental CO2, and a continuously operating single-zone HVAC system. Seven instruments were deployed across 3 spatial zones at breathing zone height (1.5 m): 3 Aranet4 nondispersive infrared (NDIR) CO2 sensors, 2 TSI AirAssure (8144) multi-parameter monitors (CO2, CO, NO2, O3, SO2, total volatile organic compound [tVOC], size-resolved PM), and 2 PurpleAir PA-II-FLEX dual-channel particle counters. Approximately 113,000 quality-controlled records were analyzed. CO2 concentrations exhibited a photoperiod-linked diurnal pattern driven by the plant light/dark cycle, with Aranet4 means ranging from 979 to 1,086 ppm and maxima exceeding 2,200 ppm. Elevated nighttime CO2 was consistent with the combined influence of plant metabolism, intermittent CO2 enrichment, and ventilation dynamics; worker respiration at night was unlikely to be the dominant explanation because workers generally left the room after lights were turned off. Median PM2.5 concentrations were low (1.4 to 3.1 µg/m3), but episodic spikes reached 5,000 to 35,000 µg/m3. The largest daytime PM excursion coincided with an in-flower canopy-maintenance event, which was trimming, defoliation, or canopy maintenance. Mean tVOC concentrations reached 3.61 mg/m3, and ethanol proxies exceeded 8,000 ppb at the 95th percentile. Temperature and relative humidity frequently reached levels that may increase heat stress and may also influence sensor performance under high-humidity conditions. This pilot study demonstrates that indoor medical cannabis cultivation facilities can present a complex, multi-hazard exposure environment involving CO2 enrichment and photoperiod-linked CO2 variability, episodic PM excursions, VOCs, and elevated heat and humidity. These findings highlight an urgent need for cannabis-specific occupational exposure research, facility ventilation guidance, activity-resolved monitoring, and worker health surveillance programs, particularly in states like Oklahoma where rapid industry growth has outpaced occupational health infrastructure.
The use of respiratory protective devices (RPDs) is essential in various work environments, including those with dust generation. When the work environment is cold, the low ambient temperature can accentuate discomfort from cooling and may influence workers' selection of RPDs, potentially affecting protective efficiency. This study aimed to quantify facial cooling while wearing particle-filtering facepiece respirators in cold conditions. Six different RPDs were selected: two filtering facepiece respirators (FFRs), two powered air-purifying respirators with constant airflow (PAPRC) and two breath-responsive air-supplied respirators (PAPRBR). Ten volunteers (six males and four females) participated, using the RPDs during rest and exercise for 40 min at an ambient temperature of -20 °C. Skin temperatures on four areas of the face and the air temperature inside the mask were recorded throughout the test. In addition, accumulated moisture in the facepiece was measured. The mean face skin temperature (MFST) was calculated as the average of the four skin temperatures. The results showed that MFST declined, on average, to 12.9 °C, 17.7 °C and 21.8 °C when PAPRC, PAPRBR and FFR were used, respectively. In conclusion, the use of RPDs in cold conditions presents particular occupational health and safety risks. Moisture retention is high when RPDs are used in cold conditions, and accumulated moisture inside the facepiece may cause discomfort and impair visibility. PAPRC decreases facial skin temperatures to an uncomfortable level, while PAPRBR and FFRs reduce cooling in cold environments. However, the required level of protection should be prioritised, even in cold conditions.
INTRODUCTION:It has been estimated that 2% to 8% of cancers in high-income countries are linked to carcinogenic exposures in workplaces. In Finland, employers are obliged by law to provide data annually on selected carcinogens and carcinogenic working processes to the Finnish Register of Employees Exposed to Carcinogens (ASA). In this study, we expand the follow-up period of a previous study on cancer incidence in exposed employees by 16 years and add estimates of cancer mortality. METHODS:The study population included all 142,204 workers registered in ASA from 1979 to 2018. For the cancer follow-up, the data were linked to the Finnish Cancer Registry. To compare the incidence and mortality with those of the Finnish general population, we estimated standardized incidence ratios (SIRs) and standardized mortality ratios. RESULTS:A total of 12,687 cancer cases and 3,640 cancer deaths were reported among ASA workers over time by the end of 2019. In the entire ASA cohort, the all-site cancer incidence was similar to the general population (SIR 0.98, 95% confidence interval [CI] 0.96 to 0.99). Persons exposed to asbestos showed an excess incidence of mesothelioma (SIR 1.80, CI 1.17 to 2.66) and small cell carcinoma of the lungs (SIR 1.32, CI 1.02 to 1.67). Exposure to hardwood dust (oak and beech) was associated with an increased incidence of nasal cancer (8.69, 1.05 to 31.4), specifically nasal adenocarcinoma (SIR 58.3, CI 7.06 to 211). Increased mortality was observed for exposure-cancer combinations that also showed increased cancer incidence. CONCLUSIONS:This study demonstrated the strongest confirmed associations between occupational exposures and cancer. The absence of many known exposure-cancer associations may point to low levels of exposure among workers registered in ASA or to small effect sizes of the agents investigated.
Abstract Background With the increasing integration of nanomaterials (NMs) into daily life, their technological advantages have become evident. However, their intricate interactions with biological systems introduce complexities that can lead to unpredictable toxicological outcomes. This study investigated the in vivo toxicokinetics and toxicodynamics of single- and multi-component NMs composed of silicon carbide (SiC), titanium dioxide (TiO2), and a SiC@TiO2 composite, along with a physical mixture of SiC and TiO2 in the same ratio as the composite. Rats were exposed to these materials via single intratracheal instillation, and biological responses were assessed over time (1 h to 28 d) to identify the no-observed-adverse-effect level (NOAEL). Results All NMs induced minimal structural alterations in lung tissue and prompted varying degrees of inflammatory cell infiltration. Over time, translocation from the lungs to secondary organs (heart, spleen, liver, kidney) was observed, with distinct distribution patterns between Si- and Ti-containing NMs. Bronchoalveolar lavage fluid analysis revealed a minimal to mild inflammatory response that evolved in a time-dependent manner, even at NOAEL exposure levels, suggesting delayed-onset biological effects. Conclusions SiC@TiO2 demonstrated a reduced pulmonary toxicological profile relative to its single-component counterparts, likely due to antagonistic effects between its constituents. These findings highlight the need to assess multicomponent nanomaterials as distinct entities and suggest that rational material design may help mitigate adverse biological effects, supporting safer nanotechnology development.
Abstract Combustion of composite solid propellants in rockets and missiles releases high concentrations of alumina nanoparticles (Al₂O₃ NPs) and gaseous hydrogen chloride (HCl), raising concerns about pulmonary toxicity from repeated inhalation, especially in military contexts. Advanced air–liquid interface (ALI) exposure systems offer promising non-animal alternatives for aerosol toxicity assessment. However, their predictive value for repeated inhalation toxicity of mixtures still requires evaluation against animal models, the current gold standard. This study compared in vivo and in vitro inhalation approaches to assess respiratory toxicity of Al₂O₃ NPs and HCl mixtures. Wistar rats were exposed nose-only to low, medium, or high concentrations once daily for 4 d. In parallel, an alveolar barrier co-culture (hAELVI/HPMEC-ST1.6R) was exposed at the ALI using a Vitrocell® Cloud system, following either a single exposure or a repeated 4-d exposure. Biological responses were analyzed 24 h after the last exposure, focusing on cytotoxicity, inflammation, and genotoxicity. Dose normalization (µg/cm²) enabled quantitative extrapolation between models. In vitro, only the highest dose (2.64 µg/cm²) induced toxicity, with inflammation after single exposure and cytotoxicity after repeated exposure. In vivo, the highest concentration (20 mg/m³) also induced inflammation. Notably, the dose causing toxicity in vivo (0.12 µg/cm²) was ∼20-fold lower than in vitro. Genotoxicity evaluation is ongoing, both in vitro and in vivo. Overall, ALI models predicted key pulmonary effects after single and repeated exposures, supporting their value as complementary or alternative methods. Yet, sensitivity differences highlight the need for further refinement before regulatory or risk-assessment use.
Abstract Introduction Understanding the dynamic processes of nanoparticle (NP) deposition and subsequent biokinetics in the lung plays a pivotal role in inhalation nanotoxicology and nanomedicine. Here we introduce LungVis1.0, an artificial intelligence (AI) powered imaging ecosystem that enables precise, single-cell resolution mapping of NP distribution and NP-cell interaction in non-dissected lungs. Method NPs (600 nm, melamine) were delivered to murine lungs using four different bulk-liquid and aerosol-based delivery modalities. Whole lung samples were collected at 0 h, 2 h, 1 d, and 14 d post-administration. Tissue clearing and light sheet fluorescence microscopy processed with active/deep learning AI algorithms allowed localization of NPs in precisely segmented, non-dissected airway trees. Complementary data from intravital microscopy, perfused lung models, and flow cytometry is available. Results LungVis1.0 revealed substantial differences in bronchial and acinar NP distribution patterns depending on NP delivery route at macroscopical and microscopical levels. Briefly, bulk-liquid delivery results in patchy NP distribution with elevated bronchial-to-acinar dose ratio (B/A > 0.2), whereas aerosol inhalation achieves globally uniform, more alveolar NP deposition with local dose hot-spots in the proximal acinar region. Moreover, lung tissue-resident macrophages (TRMs) exhibited dynamic behaviour, actively patrolling and redistributing NPs within alveoli, challenging the traditional view of TRMs as static cells. Discussion/Conclusions LungVis1.0 provides a comprehensive framework for studying the delivery, biokinetics and cell interaction of NPs in the lung fostering progress in inhalation nanotoxicology/-medicine. The findings underscore the advantages of aerosol delivery for achieving uniform pulmonary NP distribution and the presence of high NP doses in the acinar region, potentially bridging the “sensitivity gap” between in vitro and in vivo models in nanotoxicology.
Abstract Evidence that inhaled particulate matter reaches the central nervous system has increased over the past two decades, alongside the growing use of nanoparticles (NPs). We examined the effects of silica NPs (SiO₂) on a lung triculture model to assess lung-blood barrier integrity, and on the neurobehavior of C. elegans wild-type (N2) and neurodegenerative disease models—GMC101 (Alzheimer’s) and NL5901 (Parkinson’s). Characterization of SiO₂ (DLS, XRD, XPS) showed a hydrodynamic diameter of 135.6 ± 2.1 nm, PDI = 0.136 ± 0.036, amorphous structure, and an O/Si ratio of 1.94. Preliminary results using the lung model (10 to 100 µg/cm²/72 h) under submerged and quasi-ALI conditions did not alter TEER values. In contrast, continuous exposure of C. elegans (0.005 to 50 µg/mL SiO₂) caused developmental delays and reduced reproductive capacity, with significant toxicity from 5 µg/mL. Growth rate declined from 3.01 ± 0.71 µm²/h (control) to 2.22 ± 0.82 µm²/h, and progeny accumulation decreased from 4.41 ± 1.44 to 3.25 ± 1.45 progeny/h. Neurobehavioral assays revealed impaired locomotion—reduced body bending frequency and velocity—in all strains (N2, GMC101, NL5901) after 11 days of exposure to 5 µg/mL SiO₂. Survival rates were unaffected, indicating that neurotoxicity occurred independent of lethality. The mechanism of translocation from the lung under our experimental conditions seems to be independent of the tight junction integrity. Regarding our in vivo model, these results show that SiO₂ NPs cause developmental and neurobehavioral toxicity in C. elegans, suggesting a general mechanism of neurotoxicity not limited to neurodegenerative disease models.
Abstract Air pollution is a significant environmental risk to human health, causing around 4.2 million premature deaths annually due to cardiovascular, respiratory, and cancer-related conditions. Despite this, few studies have explored the neurotoxic effects of atmospheric pollutants, even though fine particles (PM₂.₅ and PM₁₀) can reach the brain through the bloodstream or olfactory bulb, leading to neuronal damage, oxidative stress, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This study investigates the neurotoxic effects induced by atmospheric pollutants extracted from PM₁₀ filters collected at various air quality stations in Catalonia, including the rural background location Bellver and suburban locations Manlleu and Mollet del Vallès. Neurotoxicity was assessed using SH-SY5Y neuroblastoma cells to evaluate cell viability, reactive oxygen species (ROS) production, xenobiotic response (XRE), antioxidant response (ARE), and p53 pathway activation, as well as acetylcholinesterase (AChE) inhibition. Neurocortical brain organoids were used for lipidomic profiling to investigate the involvement of lipids in neurotoxic mechanisms. The chemical composition of filters, analysed via gas chromatography–mass spectrometry (GC–MS), quantified around 30 organic compounds, including biomarkers of biomass burning (levoglucosan, mannosan) and polycyclic aromatic hydrocarbons (PAHs). Multivariate analysis using Principal Component Analysis (PCA) and Multivariate Curve Resolution–Alternating Least Squares (MCR–ALS) integrated chemical and biological data, revealing seasonal patterns: winter samples showed greater oxidative stress, gene activation, and cytotoxicity, while warm-season samples exhibited milder oxidative and cholinergic responses. These findings provide insights into the biochemical mechanisms linking air pollution and neurotoxicity, highlighting the importance of integrated chemical–biological and multivariate approaches to assess the neurological risks of air pollution.
Abstract Automobile-derived fine particulate matter (PM2.5, <2.5 µm), especially originating from brake wear, is emitted in greater quantities than exhaust particles and has recently emerged as a growing regulatory concern. However, its toxicological mechanisms remain elusive. In this study, we investigated the cellular effects of PM2.5 generated from diesel exhaust and brake wear materials, including non-asbestos organic and low-metallic brake pads, on THP-1 human monocytic cells. Transmission electron microscopy was employed to examine ultrastructural alterations, while transcriptomic and proteomic analyses—using next-generation sequencing and LC-MS/MS—were integrated to delineate molecular pathways and potential pharmacological targets. A 24-hour exposure to either exhaust- or brake-derived PM2.5 (≥50 µg/mL) resulted in approximately a 10% decrease in cell viability and a substantial elevation of intracellular reactive oxygen species. The particles accumulated within lysosomes, causing their swelling, diminished proteolytic activity, and impairment of autophagic flux. Transcriptomic profiling indicated enrichment of pathways associated with lysosomal dysfunction, autophagy suppression, G1 phase arrest, and cellular senescence, findings that were further supported by proteomic evidence. In line with these results, PM2.5-treated cells exhibited increased senescence-associated β-galactosidase activity. Integrated network analysis identified key upstream regulators mediating these senescence-like responses. Collectively, our results demonstrate that both exhaust- and brake wear-derived PM2.5 disrupt lysosomal homeostasis and promote senescence-associated phenotypes in macrophages. The integration of transcriptomic and proteomic datasets provided mechanistic insights into PM2.5-induced cellular toxicity and highlighted molecular drivers that may serve as potential therapeutic or regulatory targets. These findings advance the current understanding of traffic-related PM2.5 toxicity and offer a foundation for developing strategies to mitigate its health impacts.
Abstract Micro- and nanoplastics (MNPs) have emerged as global environmental pollutants, raising growing concerns about their potential respiratory toxicity. MNPs are classified into primary forms, which are manufactured directly, and secondary forms, which originate from the fragmentation and environmental aging of larger plastic debris. Although most previous studies have focused only on primary MNPs, information regarding the toxicity of environmentally relevant secondary MNPs remains limited. Hence, this study aimed to comparatively evaluate in vitro and in vivo toxicities of primary and secondary polystyrene (PS) MNPs. In vitro, secondary PS induced greater cytotoxicity than primary PS at 24 h post-treatment, which was associated with cellular reactive oxygen species (ROS) accumulation, NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and subsequent interleukin (IL)-1β release. These processes are known to be triggered by ROS production, lysosomal damage, and frustrated phagocytosis. Moreover, conditioned medium from PS-exposed macrophages did not directly cause cytotoxicity in epithelial cells but markedly enhanced cytokine expression, indicating indirect inflammatory signalling. In a single pharyngeal aspiration exposure study using BALB/c mice, secondary PS showed higher levels of pulmonary inflammatory parameters in bronchoalveolar lavage fluid, including lactate dehydrogenase, total protein, cytokines, and the numbers of total cells and neutrophils, compared with primary PS at 24 h post-exposure. Furthermore, UV irradiation of the particle surface enhanced intrinsic ROS generation, thereby amplifying the subsequent toxic and inflammatory responses. Collectively, these findings provide mechanistic insights into how primary and secondary microplastics differentially induce respiratory inflammation and contribute to the safety assessment of airborne microplastics.
Abstract Inhalation represents a significant route of human exposure to micro- and nanoplastics (MNP). However, there is limited knowledge regarding their specific effects on the respiratory tract, particularly concerning the roles of polymer type, weathering, and synthesis method in determining toxicity. To address these gaps, we assessed the effects of nine MNP types, pristine and weathered particles of various sizes, in two in vitro models: one alveolar macrophage model and one 3D-alveolar model. Rat alveolar macrophages (NR8383) were exposed under serum-free conditions at four concentrations (22.5, 45, 90, and 180 µg/mL) to six polyamide-6 (PA-6) particles (pristine or UV-weathered, micro- or nano-sized, synthesized by spray drying or solvent precipitation), polyethylene terephthalate (PET), and multicomponent acrylic paint particles. H2O2 generation was assessed using Ampliflu™ Red after 90 min, while cytotoxicity and macrophage activation were evaluated by lactate dehydrogenase and β-glucuronidase release after 16 h. Cytotoxicity of PET and pristine PA-6 (precipitated) was assessed in EpiAlveolar™. In NR8383, PET and micro-sized precipitated PA-6 induced H2O2 generation. Cytotoxicity was observed for PET, PA-6 (precipitated, micro and nano-sized), and UV-weathered PA-6 (spray drying). These particles, except UV-weathered and nano-sized precipitated PA-6, also induced macrophage activation. In EpiAlveolar™, PET and pristine PA-6 (precipitated) induced a slight cytotoxicity at 300 µg/cm², but not at 60 µg/cm². Our findings show that MNP toxicity is strongly influenced by synthesis method, weathering, and polymer type. Future transcriptomic analyses of these samples will provide mechanistic insights, increasing our understanding of how these factors shape the inhalation toxicity of MNP.
Abstract Ambient particulate matter (PM) air pollution and elevated copper (Cu) exposure are associated with increased Alzheimer’s disease (AD) risk. We hypothesize that inhaled copper-containing ultrafine particles (Cu-UFPs) that model the reactive metal fraction of ambient ultrafine PM (<100 nm) translocate from the lungs to distal organs, triggering inflammation and oxidative stress that exacerbate AD-related pathology. This study examined acute pulmonary inflammation and distribution of Cu following short-term inhalation exposures. Male and female APP/PS1 and wild-type (WT) mice were exposed to filtered air or Cu-UFP aerosols (mass concentration: 196 µg/m3; number concentration: 8.05 × 106 particles/cm3; count median diameter: 38.8 nm; geometric standard deviation: 1.7) via whole-body inhalation for three consecutive days. Bronchoalveolar lavage (BAL) fluid and tissues were collected 24 h post-exposure. BAL samples were analysed for cell counts, viability, lactate dehydrogenase activity, and total protein. Cu tissue burdens were quantified via inductively-coupled plasma mass spectrometry. Cu-UFP exposure caused small but statistically significant elevations in BAL neutrophils and protein content. Cu-exposed mice had elevated Cu in BAL fluid and cell pellets, though Cu concentrations did not differ across most extrapulmonary tissues. APP/PS1 mice showed lower frontal cortex Cu than WT mice, regardless of exposure. Acute Cu-UFP inhalation induced modest lung inflammation and barrier disruption without Cu accumulation in distal tissues, likely reflecting high particle solubility and effective clearance. These findings suggest that reactive metal components of ultrafine PM pollution may contribute to AD risk through inflammatory mechanisms. Supported by R01 AG083020, P30 ES001247, and T32 ES007026.
Abstract In recent decades, increasing attention has been directed toward the smallest fraction of airborne particulate matter—ultrafine particles (UFPs, <100 nm, also referred to as nanoparticles)—due to their potential health risks. The extent to which nanoparticles from different sources vary in toxicity remains insufficiently understood. Within the EU-funded project nPETS (Nanoparticle Emissions from the Transport Sector: Health and Policy Impacts), we investigated the toxicity of nanoparticles generated across various transport-related environments. These included laboratory-generated particles from rail systems and brake/clutch wear, as well as ambient nanoparticles collected from diverse European sites: a road tunnel, subway, harbour, and airport. For selected sources, we compared the toxicity of nanoparticles with that of larger particles (PM2.5 or micron-sized), performed air–liquid interface (ALI) exposures, and in certain scenarios, modelled long-term pulmonary deposition using the Multiple-Path Particle Dosimetry Model. Toxicity assessments using A549 cells and differentiated THP-1 cells focused on cytotoxicity, DNA damage, and inflammatory responses (IL-8, IL-6, TNFα, IL-1β secretion). Our findings showed that both nano- and micron-sized particles from the road tunnel and subway in Stockholm induced DNA strand breaks and inflammatory cytokine release. Overall, the collected particles exhibited low cytotoxicity but high variability in inflammatory potential. Nanoparticles from the harbour and airport (Barcelona), for example, displayed pronounced inflammatory activity. Variations in endotoxin content complicate interpretation of the role of chemical composition in the observed effects. We are currently developing a “toxicity score” framework to support future regulatory and mitigation strategies.
Abstract Interpreting in vitro toxicology data with nanomaterials requires accurate determination of the dose effectively delivered to cells. For carbon nanotubes (CNTs), this remains particularly challenging due to the difficulty of quantifying inorganic carbon within complex biological matrices. Moreover, existing deposition models typically assume spherical particles, which may not adequately reflect the behaviour of fibrous CNTs. We developed an analytical method to quantify CNTs remaining in suspension, loosely associated with cells, or strongly bound/internalized. The approach combines UV-Vis-NIR spectrophotometry with chemical digestion or lyophilization, depending on the fraction analysed. The method was validated for selectivity, linearity, limits of detection and quantification, lyophilization yield, bias, and precision (within- and between-run). It was applied to ten multi-walled CNTs of various morphologies (long or short, thin or thick) and surface chemistries (hydroxyl- or carboxyl-functionalized), dispersed at four to six exposure concentrations in cell culture medium. Human bronchial epithelial cells (BEAS-2B) were exposed for 96 h prior to quantification. The method successfully estimated both delivered and cellular CNT doses, which did not always match nominal concentrations. CNT distribution among fractions varied with morphology: for short CNTs, the delivered dose closely matched the applied dose, whereas for long CNTs (functionalized or not), up to 20% remained suspended in the medium at the highest concentrations, likely due to a “pool noodle” effect that limits sedimentation. The approach also revealed that cell death contributed to the release of nanotube-containing cells into the culture medium.
Abstract We previously investigated the carcinogenic potential of different types of carbon nanotubes (CNTs) in rats. Rigid and straight CNTs (MWCNT-7 and MWCNT-N) caused lung cancer and pleural mesothelioma. Thin and tangled CNTs (MWCNT-B, DWCNT and SWCNT) induced lung cancer. Exposure to carbon nano horns (CNHs) and carbon nano brushes (CNBs) did not cause lung or pleural tumours. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis of lung tissues of male F344 rats exposed to four doses of carcinogenic CNTs (MWCNT-7, MWCNT-N, MWCNT-B, DWCNT, SWCNT) or non-carcinogenic CNH injected by TIPS at total dose of 0.5 mg/rat and compared it with those induced by DHPN (a known chemical carcinogen) injected intraperitoneally at total dose of 1,000 mg/rat. Pulmonary toxicity and the entire gene expression profiles were analysed six weeks after the final dose. The RNA- sequencing analysis identified a large number of significantly differentially expressed genes between groups. The GO enrichment analysis revealed that the genes of phagocytes regulating migration and chemotaxis up-regulated in carcinogenic CNTs versus non-carcinogenic CNH. The KEGG analysis revealed that exposure to carcinogenic CNTs up-regulated inflammation-elicited signalling pathways: cytokine signalling pathways, cytokine-cytokine receptor interaction, IL-17 signalling pathway and TNF signalling pathway. Interestingly, the gene expression profile of carcinogenic CNT was totally different compared to that of DPHN-treated rats. qRT-PCR indicated that expression of inflammatory cytokines, Ccl2, Ccl3, Ccl9, Il-1b and TGF-b up-regulated by carcinogenic CNTs but not by DHPN. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of CNT carcinogenicity.
Abstract Reliable New Approach Methodologies (NAMs) are crucial for advancing inhalation toxicology towards mechanism-based and animal-free assessment strategies. This study evaluated the predictive value of an established 3D bronchial co-culture model combining human epithelial (Calu-3) cells and monocyte-derived macrophages for assessing particle-induced inflammatory and oxidative stress responses following exposure to materials with different physicochemical properties. Using crystalline quartz (DQ12) as a reference material, exposure duration was extended to 7 d post-exposure. This revealed time-dependent increases in interleukin (IL)-1β and IL-8 on days 3 and 7, consistent with early inflammatory key events. Subsequent testing of cerium oxide (CeO₂) and barium sulfate (BaSO₄) particles demonstrated the model’s ability to distinguish active from passive particle responses: CeO₂-induced dose-dependent activation of oxidative stress and DNA repair pathways on day 3, followed by downregulation on day 7, while BaSO₄ caused only transient effects on day 3. The in vitro outcomes correlated well with known in vivo data, supporting the model’s mechanistic relevance and identifying the most relevant time points. These findings demonstrate that this in vitro co-culture model effectively captures early biological key events relevant to particle-induced inflammation and oxidative stress, reinforcing its value as a predictive NAM for inhalation toxicology.
Abstract Purpose Excessive paper dust during paper manufacturing can harm workers’ respiratory health. We aimed to assess inhalable paper dust levels and their determinants among paper mill industry workers. Methods A study was conducted in Ethiopia to measure personal exposure to inhalable paper dust in four paper industries. A total of 150 samples were collected using the IOM sampler attached to Side Kick Casella pumps at a flow rate of 2 L/min. Samples were analysed at Nemko Norlab, Norway. Linear mixed-effect models were used to identify determinants of inhalable paper dust. Results The arithmetic mean of personal inhalable paper dust was 4.5 mg/m3, with 80% of measurements exceeding the Swedish occupational exposure limit (OEL) of 2 mg/m3. The linear mixed-effects model revealed that dust levels were 28% higher when using high-speed compared to low-speed rewinding machines. Additionally, factories with more than four machines per job group had 22% higher exposure than those with fewer machines. Additionally, working in packing and preparation areas was associated with higher dust exposure than other areas. Conclusions Dust exposure levels exceeded the OEL in 80% of samples. The exposure model identified high-speed rewinding machines, a higher number of machines, and work in preparation and packing as factors linked to increased paper dust exposure. These findings suggest that preventive measures, including engineering control, should be implemented in the industry.
In a cross-sectional study of UK brick and stone workers exposed to respirable crystalline silica, Club cell protein (CC16), neutrophil gelatinase-associated lipocalin, platelet-derived growth factor (PDGFββ), C-reactive protein, rheumatoid factor, antinuclear antibodies, lung surfactant proteins A & D, and monocyte chemoattractant protein 1 were measured in serum samples from 261 workers. Questionnaire data on health outcomes were also recorded, along with spirometry and a chest X-ray. Individual cumulative respirable crystalline silica exposures were calculated. Four subjects (1.5%) had silicosis, and these were characterised by evidence of small airways obstruction, reduced predicted forced expiratory volume in 1 s and noticeable increases in monocyte chemoattractant protein 1 and surfactant protein A. CC16 and surfactant protein D significantly increased with cumulative respirable crystalline silica exposure, but CC16 also independently decreased with evidence of airflow obstruction or small airways obstruction. Therefore, the interpretation of serum CC16 levels in silica-exposed populations may be complex. There was some evidence of down-regulation of the PDGFββ pathway with increasing exposure. Surfactant protein D levels were also associated with several chronic respiratory symptoms reported by workers. Serum surfactant protein A, monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin showed little or no relationship to cumulative respirable crystalline silica levels. These data raise the possibility that surfactant protein D, CC16, surfactant protein A, and monocyte chemoattractant protein 1 may have a role in defining the natural history of silicosis, with the latter 2 biomarkers possibly reflecting where pathology is evidenced on imaging techniques.
INTRODUCTION:Nitrous oxide, sevoflurane, and desflurane are hazardous chemicals used in surgery and dentistry to anaesthetise or sedate patients. During the use, they can be dispersed into the environment, causing exposure of healthcare workers. This study summarises 10 yrs of surveys in a large hospital in Milan, Italy. MATERIALS AND METHODS:Annual surveys were conducted from 2015 to 2024. Real-time monitoring and personal monitoring of exposure were performed. Biological monitoring was assessed by urinary nitrous oxide, desflurane, and hexafluoroisopropanol (metabolite of sevoflurane). RESULTS:101 surveys were performed in 25 operating theatres and 5 dentistry rooms, observing 219 interventions; 383 workers were investigated with 600 paired personal and biological measurements. Sevoflurane was the most used gas (49% alone, 5% with nitrous oxide), followed by nitrous oxide (7%) and desflurane (3% alone, 2% with nitrous oxide); no gas was used in 32% of cases. Median personal exposure for sevoflurane, nitrous oxide, and desflurane was <0.1, 1.4, and <0.1 ppm, with a 95th percentile of 1.2 ppm for sevoflurane in the anaesthesiologist and 428 ppm for nitrous oxide in the dentist. Median urinary hexafluoroisopropanol, nitrous oxide, and desflurane were <0.02 mg/L, <2 µg/L, and <0.3 µg/L, respectively. Real-time monitoring showed peaks of sevoflurane and desflurane during the refill of the vaporiser, the use of a facial mask for the induction, and the tracheal extubation; nitrous oxide peaks were observed during sedation in dentistry. Exposures were higher in paediatric than in adult surgery. CONCLUSION:Exposure to sevoflurane and desflurane in general anaesthesia is low; exposure to nitrous oxide in dentistry during sedation may overcome occupational limit values.
