Generation of Eroded Nanoplastics from Domestic Wastes and Their Impact on Macrophage Cell Viability and Gene Expression.

This study reports an innovative approach for producing nanoplastics (NP) from various types of domestic waste plastics without the use of chemicals. The plastic materials used included water bottles, styrofoam plates, milk bottles, centrifuge tubes, to-go food boxes, and plastic bags, comprising polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE), and Poly (Ethylene-co-Methacrylic Acid) (PEMA). The chemical composition of these plastics was confirmed using Raman and FTIR spectroscopy, and they were found to have irregular shapes. The resulting NP particles ranged from 50 to 400 nm in size and demonstrated relative stability when suspended in water. To assess their impact, the study investigated the effects of these NP particulates on cell viability and the expression of genes involved in inflammation and oxidative stress using a macrophage cell line. The findings revealed that all types of NP reduced cell viability in a concentration-dependent manner. Notably, PS, HDPE, and PP induced significant reductions in cell viability at lower concentrations, compared to PEMA and PET. Moreover, exposure to NP led to differential alterations in the expression of inflammatory genes in the macrophage cell line. Overall, this study presents a viable method for producing NP from waste materials that closely resemble real-world NP. Furthermore, the toxicity studies demonstrated distinct cellular responses based on the composition of the NP, shedding light on the potential environmental and health impacts of these particles.

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.

Implementation of multiomic mass spectrometry approaches for the evaluation of human health following environmental exposure.

Omics analyses collectively refer to the possibility of profiling genetic variants, RNA, epigenetic markers, proteins, lipids, and metabolites. The most common analytical approaches used for detecting molecules present within biofluids related to metabolism are vibrational spectroscopy techniques, represented by infrared, Raman, and nuclear magnetic resonance (NMR) spectroscopies and mass spectrometry (MS). Omics-based assessments utilizing MS are rapidly expanding and being applied to various scientific disciplines and clinical settings. Most of the omics instruments are operated by specialists in dedicated laboratories; however, the development of miniature portable omics has made the technology more available to users for field applications. Variations in molecular information gained from omics approaches are useful for evaluating human health following environmental exposure and the development and progression of numerous diseases. As MS technology develops so do statistical and machine learning methods for the detection of molecular deviations from personalized metabolism, which are correlated to altered health conditions, and they are intended to provide a multi-disciplinary overview for researchers interested in adding multiomic analysis to their current efforts. This includes an introduction to mass spectrometry-based omics technologies, current state-of-the-art capabilities and their respective strengths and limitations for surveying molecular information. Furthermore, we describe how knowledge gained from these assessments can be applied to personalized medicine and diagnostic strategies.

Lipid mediators of inhalation exposure-induced pulmonary toxicity and inflammation.

Many inhalation exposures induce pulmonary inflammation contributing to disease progression. Inflammatory processes are actively regulated via mediators including bioactive lipids. Bioactive lipids are potent signaling molecules involved in both pro-inflammatory and resolution processes through receptor interactions. The formation and clearance of lipid signaling mediators are controlled by multiple metabolic enzymes. An imbalance of these lipids can result in exacerbated and sustained inflammatory processes which may result in pulmonary damage and disease. Dysregulation of pulmonary bioactive lipids contribute to inflammation and pulmonary toxicity following exposures. For example, inhalation of cigarette smoke induces activation of pro-inflammatory bioactive lipids such as sphingolipids, and ceramides contributing to chronic obstructive pulmonary disease. Additionally, exposure to silver nanoparticles causes dysregulation of inflammatory resolution lipids. As inflammation is a common consequence resulting from inhaled exposures and a component of numerous diseases it represents a broadly applicable target for therapeutic intervention. With new appreciation for bioactive lipids, technological advances to reliably identify and quantify lipids have occurred. In this review, we will summarize, integrate, and discuss findings from recent studies investigating the impact of inhaled exposures on pro-inflammatory and resolution lipids within the lung and their contribution to disease. Throughout the review current knowledge gaps in our understanding of bioactive lipids and their contribution to pulmonary effects of inhaled exposures will be presented. New methods being employed to detect and quantify disruption of pulmonary lipid levels following inhalation exposures will be highlighted. Lastly, we will describe how lipid dysregulation could potentially be addressed by therapeutic strategies to address inflammation.

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells.

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air-liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1ß, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Imipramine Treatment Alters Sphingomyelin, Cholesterol, and Glycerophospholipid Metabolism in Isolated Macrophage Lysosomes.

Lysosomes are degradative organelles that facilitate the removal and recycling of potentially cytotoxic materials and mediate a variety of other cellular processes, such as nutrient sensing, intracellular signaling, and lipid metabolism. Due to these central roles, lysosome dysfunction can lead to deleterious outcomes, including the accumulation of cytotoxic material, inflammation, and cell death. We previously reported that cationic amphiphilic drugs, such as imipramine, alter pH and lipid metabolism within macrophage lysosomes. Therefore, the ability for imipramine to induce changes to the lipid content of isolated macrophage lysosomes was investigated, focusing on sphingomyelin, cholesterol, and glycerophospholipid metabolism as these lipid classes have important roles in inflammation and disease. The lysosomes were isolated from control and imipramine-treated macrophages using density gradient ultracentrifugation, and mass spectrometry was used to measure the changes in their lipid composition. An unsupervised hierarchical cluster analysis revealed a clear differentiation between the imipramine-treated and control lysosomes. There was a significant overall increase in the abundance of specific lipids mostly composed of cholesterol esters, sphingomyelins, and phosphatidylcholines, while lysophosphatidylcholines and ceramides were overall decreased. These results support the conclusion that imipramine's ability to change the lysosomal pH inhibits multiple pH-sensitive enzymes in macrophage lysosomes.

Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle tissue in mice.

Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. EVs were isolated from primarily oxidative or glycolytic muscle tissue from mice. MicroRNA (miR) contents were determined and endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways, compared to GLY-EV. OXI-EV improved in vitro angiogenesis, which may have been mediated through nitric oxide synthase (NOS) related pathways, as treatment of endothelial cells with a non-selective NOS inhibitor abolished the angiogenic benefits of OXI-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.

Compositional variations in metal nanoparticle components of welding fumes impact lung epithelial cell toxicity.

Welding fumes contain harmful metals and gas by-products associated with development of lung dysfunction, asthma, bronchitis, and lung cancer. Two prominent welding fume particulate metal components are nanosized iron (Fe) and manganese (Mn) which might induce oxidative stress and inflammation resulting in pulmonary injury. Welding fume toxicity may be dependent upon metal nanoparticle (NP) components. To examine toxicity of welding fume NP components, a system was constructed for controlled and continuous NP generation from commercial welding and customized electrodes with varying proportions of Fe and Mn. Aerosols generated consisted of nanosized particles and were compositionally consistent with each electrode. Human alveolar lung A459 epithelial cells were exposed to freshly generated metal NP mixtures at a target concentration of 100 µg/m3 for 6 hr and then harvested for assessment of cytotoxicity, generation of reactive oxygen species (ROS), and alterations in the expression of genes and proteins involved in metal regulation, inflammatory responses, and oxidative stress. Aerosol exposures decreased cell viability and induced increased ROS production. Assessment of gene expression demonstrated variable up-regulation in cellular mechanisms related to metal transport and storage, inflammation, and oxidative stress based upon aerosol composition. Specifically, interleukin-8 (IL-8) demonstrated the most robust changes in both transcriptional and protein levels after exposure. Interleukin-8 has been determined to serve as a primary cytokine mediating inflammatory responses induced by welding fume exposures in alveolar epithelial cells. Overall, this study demonstrated variations in cellular responses to metal NP mixtures suggesting compositional variations in NP content within welding fumes may influence inhalation toxicity.

Lung-gut axis of microbiome alterations following co-exposure to ultrafine carbon black and ozone.

BACKGROUND: Microbial dysbiosis is a potential mediator of air pollution-induced adverse outcomes. However, a systemic comparison of the lung and gut microbiome alterations and lung-gut axis following air pollution exposure is scant. In this study, we exposed male C57BL/6J mice to inhaled air, CB (10 mg/m3), O3 (2 ppm) or CB + O3 mixture for 3 h/day for either one day or four consecutive days and were euthanized 24 h post last exposure. The lung and gut microbiome were quantified by 16 s sequencing. RESULTS: Multiple CB + O3 exposures induced an increase in the lung inflammatory cells (neutrophils, eosinophils and B lymphocytes), reduced absolute bacterial load in the lungs and increased load in the gut. CB + O3 exposure was more potent as it decreased lung microbiome alpha diversity just after a single exposure. CB + O3 co-exposure uniquely increased Clostridiaceae and Prevotellaceae in the lungs. Serum short chain fatty acids (SCFA) (acetate and propionate) were increased significantly only after CB + O3 co-exposure. A significant increase in SCFA producing bacterial families (Ruminococcaceae, Lachnospiraceae, and Eubacterium) were also observed in the gut after multiple exposures. Co-exposure induced significant alterations in the gut derived metabolite receptors/mediator (Gcg, Glp-1r, Cck) mRNA expression. Oxidative stress related mRNA expression in lungs, and oxidant levels in the BALF, serum and gut significantly increased after CB + O3 exposures. CONCLUSION: Our study confirms distinct gut and lung microbiome alterations after CB + O3 inhalation co-exposure and indicate a potential homeostatic shift in the gut microbiome to counter deleterious impacts of environmental exposures on metabolic system.

Pulmonary and neurological health effects associated with exposure to representative composite manufacturing emissions and corresponding alterations in circulating metabolite profiles.

Cured-in-place pipe (CIPP) technology is increasingly being utilized to repair aging and damaged pipes, however, there are concerns associated with the public health hazards of emissions. CIPP installation involves the manufacture of a new plastic composite pipe at the worksite and includes multiple variable components including resin material, curing methods, and operational conditions. We hypothesize styrene-based composite manufacturing emissions (CMEs) will induce greater pulmonary inflammatory responses and oxidative stress, as well as neurological toxicity compared with nonstyrene CMEs. Further, these CME-toxicological responses will be sex- and time-dependent. To test the hypothesis, representative CMEs were generated using a laboratory curing chamber and characterized using thermal desorption-gas chromatography-mass spectrometry and photoionization detector. Styrene was released during staying, isothermal curing, and cooling phases of the process and peaked during the cooling phase. Male and female C57BL6/J mice were utilized to examine alterations in pulmonary responses and neurotoxicity 1 day and 7 days following exposure to air (controls), nonstyrene-CMEs, or styrene-CMEs. Serum styrene metabolites were increased in mice exposed to styrene-CMEs. Metabolic and lipid profiling revealed alterations related to CIPP emissions that were resin-, time-, and sex-dependent. Exposure to styrene-CMEs resulted in an influx of lymphocytes in both sexes. Expression of inflammatory and oxidative stress markers, including Tnfα, Vcam1, Ccl2, Cxcl2, Il6, Cxcl1, Tgfß1, Tgmt2, and Hmox1, displayed alterations following exposure to emissions. These changes in pulmonary and neurological markers of toxicity were dependent on resin type, sex, and time. Overall, this study demonstrates resin-specific differences in representative CMEs and alterations in toxicity endpoints, which can potentially inform safer utilization of composite manufacturing processes.

Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles.

The choroid plexus (CP) in brain ventricles secrete cerebrospinal fluid (CSF) that bathes the adjacent subventricular zone (SVZ); the latter is the largest neurogenic region in adult brain harboring neural stem/progenitor cells (NSPCs) and supplies newborn neurons to the olfactory bulb (OB) for normal olfaction. We discovered the presence of a CP-SVZ regulatory (CSR) axis in which the CP, by secreting small extracellular vesicles (sEVs), regulated adult neurogenesis in the SVZ and maintained olfaction. The proposed CSR axis was supported by 1) differential neurogenesis outcomes in the OB when animals treated with intracerebroventricular (ICV) infusion of sEVs collected from the CP of normal or manganese (Mn)-poisoned mice, 2) progressively diminished SVZ adult neurogenesis in mice following CP-targeted knockdown of SMPD3 to suppress CP sEV secretion, and 3) compromised olfactory performance in these CP-SMPD3-knockdown mice. Collectively, our findings demonstrate the biological and physiological presence of this sEV-dependent CSR axis in adult brains. Highlights: CP-secreted sEVs regulate adult neurogenesis in the SVZ.CP-secreted sEVs modulate newborn neurons in the OB.Suppression of sEV secretion from the CP deteriorates olfactory performance.

Regulatory Significance of Plastic Manufacturing Air Pollution Discharged into Terrestrial Environments and Real-Time Sensing Challenges.

Cured-in-place-pipe (CIPP) is an onsite plastic manufacturing technology used in the U.S. and has not been evaluated for regulatory compliance with federal air pollution laws. The practice involves the discharge of manufacturing waste into the environment. The study goal was to estimate the magnitude of volatile organic compounds (VOCs) discharged into the atmosphere for styrene and nonstyrene composite manufacture and examine low-cost air monitoring sensor reliability. Time-resolved emission analysis revealed that VOC emission was not only isolated to the thermal curing period but also occurred before and after curing. In addition to the styrene monomer, other gas-phase hazardous air pollutants regulated under the Clean Air Act were also emitted. Based on typical CIPP installations, 0.9 to 16.6 U.S. tons of emitted VOCs were estimated for styrene CIPPs, and 0.09 to 1.6 U.S. tons of emitted VOCs were estimated for nonstyrene CIPPs. Because the number and size of CIPPs manufactured in a single community can vary, the total air pollution burden will significantly differ across communities. Low-cost VOC sensors commonly utilized near CIPP manufacturing activities did not accurately quantify styrene and should not be relied upon for that purpose. Up to several thousand-fold detection differences were observed. Regulatory evaluation of CIPP air pollution and PID sensor reliability assessments are recommended.

Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation.

Damage associated molecular patterns (DAMPs) are molecules released from dead/dying cells following toxicant and/or environmental exposures that activate the immune response through binding of pattern recognition receptors (PRRs). Excessive production of DAMPs or failed clearance leads to chronic inflammation and delayed inflammation resolution. One category of DAMPs are oxidized phospholipids (oxPLs) produced upon exposure to high levels of oxidative stress, such as following ozone (O3) induced inflammation. OxPLs are bound by multiple classes of PRRs that include scavenger receptors (SRs) such as SR class B-1 (SR-BI) and toll-like receptors (TLRs). Interactions between oxPLs and PRRs appear to regulate inflammation; however, the role of SR-BI in oxPL-induced lung inflammation has not been defined. Therefore, we hypothesize that SR-BI is critical in protecting the lung from oxPL-induced pulmonary inflammation/injury. To test this hypothesis, C57BL/6J (WT) female mice were dosed with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (oxPAPC) by oropharyngeal aspiration which increased pulmonary SR-BI expression. Following oxPAPC exposure, SR-BI deficient (SR-BI-/-) mice exhibited increased lung pathology and inflammatory cytokine/chemokine production. Lipidomic analysis revealed that SR-BI-/- mice had an altered pulmonary lipidome prior to and following oxPAPC exposure, which correlated with increased oxidized phosphatidylcholines (PCs). Finally, we characterized TLR4-mediated activation of NF-κB following oxPAPC exposure and discovered that SR-BI-/- mice had increased TLR4 mRNA expression in lung tissue and macrophages, increased nuclear p65, and decreased cytoplasmic IκBα. Overall, we conclude that SR-BI is required for limiting oxPAPC-induced lung pathology by maintaining lipid homeostasis, reducing oxidized PCs, and attenuating TLR4-NF-κB activation, thereby preventing excessive and persistent inflammation.

Enhanced silver nanoparticle-induced pulmonary inflammation in a metabolic syndrome mouse model and resolvin D1 treatment.

BACKGROUND: Metabolic syndrome (MetS) exacerbates susceptibility to inhalation exposures such as particulate air pollution, however, the mechanisms responsible remain unelucidated. Previously, we determined a MetS mouse model exhibited exacerbated pulmonary inflammation 24 h following AgNP exposure compared to a healthy mouse model. This enhanced response corresponded with reduction of distinct resolution mediators. We hypothesized silver nanoparticle (AgNP) exposure in MetS results in sustained pulmonary inflammation. Further, we hypothesized treatment with resolvin D1 (RvD1) will reduce exacerbations in AgNP-induced inflammation due to MetS. RESULTS: To evaluate these hypotheses, healthy and MetS mouse models were exposed to vehicle (control) or AgNPs and a day later, treated with resolvin D1 (RvD1) or vehicle (control) via oropharyngeal aspiration. Pulmonary lung toxicity was evaluated at 3-, 7-, 14-, and 21-days following AgNP exposure. MetS mice exposed to AgNPs and receiving vehicle treatment, demonstrated exacerbated pulmonary inflammatory responses compared to healthy mice. In the AgNP exposed mice receiving RvD1, pulmonary inflammatory response in MetS was reduced to levels comparable to healthy mice exposed to AgNPs. This included decreases in neutrophil influx and inflammatory cytokines, as well as elevated anti-inflammatory cytokines. CONCLUSIONS: Inefficient resolution may contribute to enhancements in MetS susceptibility to AgNP exposure causing an increased pulmonary inflammatory response. Treatments utilizing specific resolution mediators may be beneficial to individuals suffering MetS following inhalation exposures.

Modulation of Pulmonary Toxicity in Metabolic Syndrome Due to Variations in Iron Oxide Nanoparticle-Biocorona Composition.

Nanoparticles (NPs) interact with biomolecules by forming a biocorona (BC) on their surface after introduction into the body and alter cell interactions and toxicity. Metabolic syndrome (MetS) is a prevalent condition and enhances susceptibility to inhaled exposures. We hypothesize that distinct NP-biomolecule interactions occur in the lungs due to MetS resulting in the formation of unique NP-BCs contributing to enhanced toxicity. Bronchoalveolar lavage fluid (BALF) was collected from healthy and MetS mouse models and used to evaluate variations in the BC formation on 20 nm iron oxide (Fe3O4) NPs. Fe3O4 NPs without or with BCs were characterized for hydrodynamic size and zeta potential. Unique and differentially associated proteins and lipids with the Fe3O4 NPs were identified through proteomic and lipidomic analyses to evaluate BC alterations based on disease state. A mouse macrophage cell line was utilized to examine alterations in cell interactions and toxicity due to BCs. Exposures to 6.25, 12.5, 25, and 50 µg/mL of Fe3O4 NPs with BCs for 1 h or 24 h did not demonstrate overt cytotoxicity. Macrophages increasingly associated Fe3O4 NPs following addition of the MetS BC compared to the healthy BC. Macrophages exposed to Fe3O4 NPs with a MetS-BC for 1 h or 24 h at a concentration of 25 µg/mL demonstrated enhanced gene expression of inflammatory markers: CCL2, IL-6, and TNF-α compared to Fe3O4 NPs with a healthy BC. Western blot analysis revealed activation of STAT3, NF-κB, and ERK pathways due to the MetS-BC. Specifically, the Jak/Stat pathway was the most upregulated inflammatory pathway following exposure to NPs with a MetS BC. Overall, our study suggests the formation of distinct BCs due to NP exposure in MetS, which may contribute to exacerbated inflammatory effects and susceptibility.

Emergency responder and public health considerations for plastic sewer lining chemical waste exposures in indoor environments.

The cured-in-place pipe (CIPP) manufacturing process is used to repair buried pipes, and its waste commonly discharged into the air can enter nearby buildings. Exposure can prompt illness and the need for medical care. A mass balance model was applied to estimate indoor styrene concentrations due to intrusion of CIPP emissions through plumbing under different bathroom ventilation conditions. To better understand building contamination and recommend emergency response actions, calculations to estimate chemical intrusion through plumbing were developed. Field reports and study calculations showed that contractor-applied external pressures during plastic manufacture have and can displace plumbing trap water seals. Modeled styrene vapor concentrations that entered the building (1, 300, 1000 ppm) were similar to those measured at CIPP worksites. Modeling revealed that in some cases, bathroom exhaust fan operation during a CIPP project may increase indoor styrene concentrations due to enhanced entrainment of styrene-laden air from the sink and toilet. However, styrene concentrations decreased with increasing air leakage across the bathroom door due to reduced suction from the plumbing system. CIPP waste discharge should be treated as a hazardous material release and can pose a threat to human health. Immediate building evacuation, respiratory protection, provision of medical assistance, source elimination, and building decontamination are recommended.

Bystander chemical exposures and injuries associated with nearby plastic sewer pipe manufacture: public health practice and lessons.

Cured-in-place pipes (CIPPs) are plastic liners manufactured inside existing damaged sanitary sewer, storm sewer, and water pipes that extend the service life of host pipes. This process often is conducted in neighborhoods and near roadways. Before, during, and after plastic manufacture, waste materials that include volatile materials are released into the air. Emissions from this manufacturing process can affect outdoor air quality and indoor air quality for buildings connected to the sewer system. We identified key issues and solicited stakeholder feedback to estimate and manage public health risks of CIPP-generated chemical air pollution. A work group representing 13 U.S. agencies and public health associations provided feedback and prioritized public health issues for action. To mitigate potential public and occupational health risks, additional testing and public health educational efforts were recommended. An improved understanding of CIPP chemical exposure pathways, as well as stakeholder needs and interests, is essential.

Disruption of pulmonary resolution mediators contribute to exacerbated silver nanoparticle-induced acute inflammation in a metabolic syndrome mouse model.

Pre-existing conditions modulate sensitivity to numerous xenobiotic exposures such as air pollution. Specifically, individuals suffering from metabolic syndrome (MetS) demonstrate enhanced acute inflammatory responses following particulate matter inhalation. The mechanisms associated with these exacerbated inflammatory responses are unknown, impairing interventional strategies and our understanding of susceptible populations. We hypothesize MetS-associated lipid dysregulation influences mediators of inflammatory resolution signaling contributing to increased acute pulmonary toxicity. To evaluate this hypothesis, healthy and MetS mouse models were treated with either 18-hydroxy eicosapentaenoic acid (18-HEPE), 14-hydroxy docosahexaenoic acid (14-HDHA), 17-hydroxy docosahexaenoic acid (17-HDHA), or saline (control) via intraperitoneal injection prior to oropharyngeal aspiration of silver nanoparticles (AgNP). In mice receiving saline treatment, AgNP exposure resulted in an acute pulmonary inflammatory response that was exacerbated in MetS mice. A targeted lipid assessment demonstrated 18-HEPE, 14-HDHA, and 17-HDHA treatments altered lung levels of specialized pro-resolving lipid mediators (SPMs). 14-HDHA and 17-HDHA treatments more efficiently reduced the exacerbated acute inflammatory response in AgNP exposed MetS mice as compared to 18-HEPE. This included decreased neutrophilic influx, diminished induction of inflammatory cytokines/chemokines, and reduced alterations in SPMs. Examination of SPM receptors determined baseline reductions in MetS mice compared to healthy as well as decreases due to AgNP exposure. Overall, these results demonstrate AgNP exposure disrupts inflammatory resolution, specifically 14-HDHA and 17-HDHA derived SPMs, in MetS contributing to exacerbated acute inflammatory responses. Our findings identify a potential mechanism responsible for enhanced susceptibility in MetS that can be targeted for interventional therapeutic approaches.

Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance.

Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding adult rats with Cu-restricted diets plus ip. injection of a Cu chelator (ammonium tetrathiomolybdate) and excess Cu, respectively. CuD reduced Cu levels in the olfactory bulb (OB), subventricular zone (SVZ), rostral migratory stream (RMS), and striatum, while CuO increased Cu levels in these areas. The buried pellet test revealed both CuD and CuO prolonged the latency to uncover food. CuD increased neural proliferation and stem cells in the SVZ and newly differentiated neurons in the OB, whereas CuO caused opposite alterations, suggesting a "switch"-type function of Cu in regulating adult neurogenesis. CuO increased GABA in the OB, while both CuD and CuO reduced DOPAC, HVA, 5-HT and the DA turnover rate in olfactory-associated brain regions. Altered mRNA expression of Cu transport and storage proteins in tested brain areas were observed under both conditions. Together, results support an association between systemic Cu dyshomeostasis and olfactory dysfunction. Specifically, altered adult neurogenesis along the SVZ-RMS-OB pathway and neurochemical imbalance could be the factors that may contribute to olfactory dysfunction.