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1.
Front Toxicol ; 5: 1280230, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090360

RESUMO

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

2.
Toxicol Lett ; 382: 22-32, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37201588

RESUMO

Acrolein and trichloroethylene (TCE) are priority hazardous air pollutants due to environmental prevalence and adverse health effects; however, neuroendocrine stress-related systemic effects are not characterized. Comparing acrolein, an airway irritant, and TCE with low irritancy, we hypothesized that airway injury would be linked to neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30 min, followed by 3.5-hr exposure to the highest concentration (acrolein - 0.0, 0.1, 0.316, 1, 3.16 ppm; TCE - 0.0, 3.16, 10, 31.6, 100 ppm). Real-time head-out plethysmography revealed acrolein decreased minute volume and increased inspiratory-time (males>females), while TCE reduced tidal-volume. Acrolein, but not TCE, inhalation increased nasal-lavage-fluid protein, lactate-dehydrogenase activity, and inflammatory cell influx (males>females). Neither acrolein nor TCE increased bronchoalveolar-lavage-fluid injury markers, although macrophages and neutrophils increased in acrolein-exposed males and females. Systemic neuroendocrine stress response assessment indicated acrolein, but not TCE, increased circulating adrenocorticotrophic hormone, and consequently corticosterone, and caused lymphopenia, but only in males. Acrolein also reduced circulating thyroid-stimulating hormone, prolactin, and testosterone in males. In conclusion, acute acrolein inhalation resulted in sex-specific upper respiratory irritation/inflammation and systemic neuroendocrine alterations linked to hypothalamic-pituitary-adrenal axes activation, which is critical in mediating extra-respiratory effects.


Assuntos
Tricloroetileno , Ratos , Animais , Masculino , Feminino , Tricloroetileno/toxicidade , Acroleína/toxicidade , Ratos Endogâmicos WKY , Sistema Respiratório , Administração por Inalação , Inflamação
3.
Inhal Toxicol ; 35(5-6): 129-138, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36692431

RESUMO

OBJECTIVE: Inhalation of smoke from the burning of waste materials on military bases is associated with increased incidences of cardiopulmonary diseases. This study examined the respiratory and inflammatory effects of acute inhalation exposures in mice to smoke generated by military burn pit-related materials including plywood (PW), cardboard (CB), mixed plastics (PL), and a mixture of these three materials (MX) under smoldering (0.84 MCE) and flaming (0.97 MCE) burn conditions. METHODS: Mice were exposed nose-only for one hour on two consecutive days to whole or filtered smoke or clean air alone. Smoldering combustion emissions had greater concentrations of PM (∼40 mg/m3) and VOCs (∼5-12 ppmv) than flaming emissions (∼4 mg/m3 and ∼1-2 ppmv, respectively); filtered emissions had equivalent levels of VOCs with negligible PM. Breathing parameters were assessed during exposure by head-out plethysmography. RESULTS: All four smoldering burn pit emission types reduced breathing frequency (F) and minute volumes (MV) compared with baseline exposures to clean air, and HEPA filtration significantly reduced the effects of all smoldering materials except CB. Flaming emissions had significantly less suppression of F and MV compared with smoldering conditions. No acute effects on lung inflammatory cells, cytokines, lung injury markers, or hematology parameters were noted in smoke-exposed mice compared with air controls, likely due to reduced respiration and upper respiratory scrubbing to reduce the total deposited PM dose in this short-term exposure. CONCLUSION: Our data suggest that material and combustion type influences respiratory responses to burn pit combustion emissions. Furthermore, PM filtration provides significant protective effects only for certain material types.


Assuntos
Poluentes Atmosféricos , Camundongos , Animais , Poluentes Atmosféricos/análise , Incineração , Poeira , Pulmão/química , Respiração , Material Particulado/toxicidade , Material Particulado/análise
4.
Toxicol Sci ; 191(1): 106-122, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36269214

RESUMO

Recent epidemiological findings link asthma to adverse cardiovascular responses. Yet, the precise cardiovascular impacts of asthma have been challenging to disentangle from the potential cardiovascular effects caused by asthma medication. The purpose of this study was to determine the impacts of allergic airways disease alone on cardiovascular function in an experimental model. Female Wistar rats were intranasally sensitized and then challenged once per week for 5 weeks with saline vehicle or a mixture of environmental allergens (ragweed, house dust mite, and Aspergillus fumigatus). Ventilatory and cardiovascular function, measured using double-chamber plethysmography and implantable blood pressure (BP) telemetry and cardiovascular ultrasound, respectively, were assessed before sensitization and after single and final allergen challenge. Responses to a single 0.5 ppm ozone exposure and to the cardiac arrhythmogenic agent aconitine were also assessed after final challenge. A single allergen challenge in sensitized rats increased tidal volume and specific airways resistance in response to provocation with methacholine and increased bronchoalveolar lavage fluid (BALF) eosinophils, neutrophils, lymphocytes, cytokines interleukin (IL)-4, IL-5, IL-10, IL-1ß, tumor necrosis factor-α, and keratinocyte chemoattract-growth-related oncogene characteristic of allergic airways responses. Lung responses after final allergen challenge in sensitized rats were diminished, although ozone exposure increased BALF IL-6, IL-13, IL-1 ß, and interferon-γ and modified ventilatory responses only in the allergen group. Final allergen challenge also increased systolic and mean arterial BP, stroke volume, cardiac output, end-diastolic volume, sensitivity to aconitine-induced cardiac arrhythmia, and cardiac gene expression with lesser effects after a single challenge. These findings demonstrate that allergic airways responses may increase cardiovascular risk in part by altering BP and myocardial function and by causing cardiac electrical instability.


Assuntos
Asma , Doenças Cardiovasculares , Hipersensibilidade , Ozônio , Ratos , Feminino , Animais , Eosinófilos/patologia , Aconitina , Doenças Cardiovasculares/patologia , Ratos Wistar , Fatores de Risco , Pulmão , Citocinas , Alérgenos/toxicidade , Líquido da Lavagem Broncoalveolar , Fatores de Risco de Doenças Cardíacas
5.
Sci Rep ; 12(1): 20722, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456643

RESUMO

Smoke emissions produced by firearms contain hazardous chemicals, but little is known if their properties change depending on firearm and ammunition type and whether such changes affect toxicity outcomes. Pulmonary toxicity was assessed in mice exposed by oropharyngeal aspiration to six different types of smoke-related particulate matter (PM) samples; (1) handgun PM, (2) rifle PM, (3) copper (Cu) particles (a surrogate for Cu in the rifle PM) with and without the Cu chelator penicillamine, (4) water-soluble components of the rifle PM, (5) soluble components with removal of metal ions, and (6) insoluble components of the rifle PM. Gun firing smoke PM was in the respirable size range but the chemical composition varied with high levels of Pb in the handgun and Cu in the rifle smoke. The handgun PM did not induce appreciable lung toxicity at 4 and 24 h post-exposure while the rifle PM significantly increased lung inflammation and reduced lung function. The same levels of pure Cu particles alone and the soluble components from the rifle fire PM increased neutrophil numbers but did not cause appreciable cellular damage or lung function changes when compared to the negative (saline) control. Penicillamine treated rifle PM or Cu, slightly reduced lung inflammation and injury but did not improve the lung function decrements. Chelation of the soluble metal ions from the rifle fire PM neutralized the lung toxicity while the insoluble components induced the lung toxicity to the same degree as the rifle PM. The results show that different firearm types can generate contrasting chemical spectra in their emissions and that the rifle PM effects were mostly driven by water-insoluble components containing high levels of Cu. These findings provide better knowledge of hazardous substances in gun firing smoke and their potential toxicological profile.


Assuntos
Armas de Fogo , Material Particulado , Animais , Camundongos , Material Particulado/toxicidade , Penicilamina , Substâncias Perigosas , Quelantes , Água , Pulmão
6.
Part Fibre Toxicol ; 18(1): 45, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915899

RESUMO

BACKGROUND: Open burning of anthropogenic sources can release hazardous emissions and has been associated with increased prevalence of cardiopulmonary health outcomes. Exposure to smoke emitted from burn pits in military bases has been linked with respiratory illness among military and civilian personnel returning from war zones. Although the composition of the materials being burned is well studied, the resulting chemistry and potential toxicity of the emissions are not. METHODS: Smoke emission condensates from either flaming or smoldering combustion of five different types of burn pit-related waste: cardboard; plywood; plastic; mixture; and mixture/diesel, were obtained from a laboratory-scale furnace coupled to a multistage cryotrap system. The primary emissions and smoke condensates were analyzed for a standardized suite of chemical species, and the condensates were studied for pulmonary toxicity in female CD-1 mice and mutagenic activity in Salmonella (Ames) mutagenicity assay using the frameshift strain TA98 and the base-substitution strain TA100 with and without metabolic activation (S9 from rat liver). RESULTS: Most of the particles in the smoke emitted from flaming and smoldering combustion were less than 2.5 µm in diameter. Burning of plastic containing wastes (plastic, mixture, or mixture/diesel) emitted larger amounts of particulate matter (PM) compared to other types of waste. On an equal mass basis, the smoke PM from flaming combustion of plastic containing wastes caused more inflammation and lung injury and was more mutagenic than other samples, and the biological responses were associated with elevated polycyclic aromatic hydrocarbon levels. CONCLUSIONS: This study suggests that adverse health effects of burn pit smoke exposure vary depending on waste type and combustion temperature; however, burning plastic at high temperature was the most significant contributor to the toxicity outcomes. These findings will provide a better understanding of the complex chemical and combustion temperature factors that determine toxicity of burn pit smoke and its potential health risks at military bases.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Animais , Feminino , Incineração , Pulmão , Camundongos , Testes de Mutagenicidade , Mutagênicos , Material Particulado/toxicidade , Ratos
7.
Toxicology ; 458: 152823, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34051339

RESUMO

Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. It was hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes- and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4 h exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 h. After each time point, circulating stress hormones, cytokines, and lung gene expression were assessed along with live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, Th, and Tc) in blood, thymus, and spleen using flow cytometry. Circulating stress hormones began to increase at 1 h of ozone exposure. Lung expression of inflammatory cytokines (Cxcl2, Il6, and Hmox1) and glucocorticoid-responsive genes (Nr3c1, Fkbp5 and Tsc22d3) increased in both a time- and ozone concentration-dependent manner. Circulating granulocytes increased at 0.5 h of ozone exposure but tended to decrease at 2 and 4 h, suggesting a rapid egress and then margination to the lung. Classical monocytes decreased over 4 h of exposure periods (∼80 % at 0.8 ppm). B and Tc lymphocytes significantly decreased after ozone exposure at 2 and 4 h. Despite dynamic shifts in circulating immune cell populations, few differences were measured in serum cytokines. Ozone neither increased apoptotic cells nor altered thymus and spleen lymphocytes. The data show that ozone-induced increases in adrenal-derived stress hormones precede the dynamic migration of circulating immune cells, likely to the lung to mediate inflammation.


Assuntos
Corticosteroides/metabolismo , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Leucócitos/efeitos dos fármacos , Ozônio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Regulação da Expressão Gênica , Granulócitos/efeitos dos fármacos , Pulmão/metabolismo , Linfócitos/efeitos dos fármacos , Masculino , Monócitos/efeitos dos fármacos , Ratos , Ratos Endogâmicos WKY , Baço/citologia , Baço/efeitos dos fármacos , Linfócitos T
8.
Inhal Toxicol ; 31(6): 236-247, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31431109

RESUMO

Background: Acute and chronic exposures to biomass wildfire smoke pose significant health risks to firefighters and impacted communities. Susceptible populations such as asthmatics may be particularly sensitive to wildfire effects. We examined pulmonary responses to biomass smoke generated from combustion of peat, oak, or eucalyptus in control and house dust mite (HDM)-allergic mice. Methods: Mice were exposed 1 h/d for 2 consecutive days to emissions from each fuel type under smoldering or flaming conditions (∼40 or ∼3.3 mg PM/m3, respectively) while maintaining comparable CO levels (∼60-120 ppm). Results: Control and allergic mice reduced breathing frequency during exposure to all biomass emissions compared with pre-exposure to clean air. Smoldering eucalyptus and oak, but not peat, further reduced frequency compared to flaming conditions in control and allergic groups, while also reducing minute volume and peak inspiratory flow in control mice. Several biochemical and cellular markers of lung injury and inflammation were suppressed by all biomass emission types in both HDM-allergic and control mice. Control mice exposed to flaming eucalyptus at different PM concentrations (C) and times (T) with the same C × T product had a greater decrease in breathing frequency with high concentration acute exposure compared with lower concentration episodic exposure. This decrease was ameliorated by PM HEPA filtration, indicating that the respiratory changes were partially mediated by biomass smoke particles. Conclusion: These data show that exposure to smoldering eucalyptus or oak smoke inhibits respiratory responses to a greater degree than peat smoke. Anti-inflammatory effects of CO may possibly contribute to smoke-induced suppression of allergic inflammatory responses.


Assuntos
Biomassa , Hipersensibilidade/fisiopatologia , Fumaça , Madeira , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Eucalyptus , Feminino , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Quercus , Testes de Função Respiratória , Solo
9.
Arch Toxicol ; 93(6): 1501-1513, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006059

RESUMO

The characteristics of wildland fire smoke exposures which initiate or exacerbate cardiopulmonary conditions are unclear. We previously reported that, on a mass basis, lung toxicity associated with particulate matter (PM) from flaming smoke aspirated into mouse lungs is greater than smoldering PM. In this study, we developed a computer-controlled inhalation system which can precisely control complex biomass smoke emissions from different combustion conditions. This system was used to examine the toxicity of inhaled biomass smoke from peat, eucalyptus, and oak fuels generated under smoldering and flaming phases with emissions set to the same approximate concentration of carbon monoxide (CO) for each exposure (60-110 ppm), resulting in PM levels of ~ 4 mg/m3 for flaming and ~ 40 mg/m3 for smoldering conditions. Mice were exposed by inhalation 1 h/day for 2 days, and assessed for lung toxicity at 4 and 24 h after the final exposure. Peat (flaming and smoldering) and eucalyptus (smoldering) smoke elicited significant inflammation (neutrophil influx) in mouse lungs at 4 h with the peat (flaming) smoke causing even greater lung inflammation at 24-h post-exposure. A significant alteration in ventilatory timing was also observed in mice exposed to the peat (flaming) and eucalyptus (flaming and smoldering) smoke immediately after each day of exposure. No responses were seen for exposures to similar concentrations of flaming or smoldering oak smoke. The lung toxicity potencies (neutrophil influx per PM mass) agreed well between the inhalation and previously reported aspiration studies, demonstrating that although flaming smoke contains much less PM mass than smoldering smoke, it is more toxic on a mass basis than smoldering smoke exposure, and that fuel type is also a controlling factor.


Assuntos
Biomassa , Exposição por Inalação/efeitos adversos , Fumaça/efeitos adversos , Poluentes Atmosféricos/toxicidade , Animais , Monóxido de Carbono/análise , Eucalyptus , Feminino , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Camundongos , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Material Particulado/toxicidade , Quercus , Testes de Função Respiratória , Solo , Madeira
10.
Inhal Toxicol ; 30(11-12): 405-415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30516399

RESUMO

Exposure to coarse particulate matter (PM) is associated with lung inflammation and exacerbation of respiratory symptoms in sensitive populations, but the degree to which specific emission sources contribute to these effects is unclear. We examined whether coarse PM samples enriched with diverse sources differentially exacerbate allergic airway responses. Coarse PM was collected weekly (7/2009-6/2010) from urban (G.T. Craig [GTC]) and rural (Chippewa Lake Monitor [CLM]) sites in the Cleveland, Ohio area. Source apportionment results were used to pool GTC filter PM extracts into five samples dominated by traffic, coal, steel (two samples), or road salt sources. Five CLM samples were prepared from corresponding weeks. Control non-allergic and house dust mite (HDM)-allergic Balb/cJ mice were exposed by oropharyngeal aspiration to 100 µg coarse GTC or CLM, control filter extract, or saline only, and responses were examined 2 d after PM exposures. In allergic mice, CLM traffic, CLM road salt and all GTC samples except steel-1 significantly increased airway responsiveness to methacholine (MCh) compared with control treatments. In non-allergic mice, CLM traffic, CLM steel-2 and all GTC samples except coal significantly increased bronchoalveolar lavage fluid (BALF) neutrophils, while only CLM traffic PM increased eosinophils in allergic mice. In non-allergic mice, CLM coal PM increased BALF interleukin (IL)-13 and GTC steel-1 PM increased TNF-α levels. These results demonstrate that equal masses of GTC and CLM coarse PM enriched with a variety of sources exacerbate allergic airway disease. Greater PM concentrations at the urban GTC site signify a greater potential for human health effects.


Assuntos
Poluentes Atmosféricos/toxicidade , Material Particulado/toxicidade , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Emissões de Veículos/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Citocinas/imunologia , Feminino , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Pyroglyphidae/imunologia
11.
Cardiovasc Toxicol ; 18(6): 569-578, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29943085

RESUMO

The health effects of individual criteria air pollutants have been well investigated. However, little is known about the health effects of air pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the cardiac effects of inhaled simulated smog atmospheres (SA) generated from the photochemistry of either gasoline and isoprene (SA-G) or isoprene (SA-Is) in mice. Four-month-old female mice were exposed for 4 h to filtered air (FA), SA-G, or SA-Is. Immediately and 20 h after exposure, cardiac responses were assessed with a Langendorff preparation using a protocol consisting of 20 min of global ischemia followed by 2 h of reperfusion. Cardiac function was measured by index of left-ventricular developed pressure (LVDP) and cardiac contractility (dP/dt) before ischemia. Pre-ischemic LVDP was lower in mice immediately after SA-Is exposure (52.2 ± 5.7 cm H2O compared to 83.9 ± 7.4 cm H2O after FA exposure; p = 0.008) and 20 h after SA-G exposure (54.0 ± 12.7 cm H2O compared to 79.3 ± 7.4 cm H2O after FA exposure; p = 0.047). Pre-ischemic left ventricular contraction dP/dtmax was lower in mice immediately after SA-Is exposure (2025 ± 169 cm H2O/sec compared to 3044 ± 219 cm H2O/sec after FA exposure; p < 0.05) and 20 h after SA-G exposure (1864 ± 328 cm H2O/sec compared to 2650 ± 258 cm H2O/sec after FA exposure; p = 0.05). In addition, SA-G reduced the coronary artery flow rate 20 h after exposure compared to the FA control. This study demonstrates that acute SA-G and SA-Is exposures decrease LVDP and cardiac contractility in mice, indicating that photochemically-altered atmospheres affect the cardiovascular system.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Butadienos/toxicidade , Gasolina/toxicidade , Hemiterpenos/toxicidade , Exposição por Inalação/efeitos adversos , Contração Miocárdica/efeitos dos fármacos , Smog/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos , Animais , Cardiotoxicidade , Circulação Coronária/efeitos dos fármacos , Feminino , Preparação de Coração Isolado , Camundongos Endogâmicos C57BL , Disfunção Ventricular Esquerda/fisiopatologia
13.
Environ Sci Technol ; 52(5): 3045-3053, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29406743

RESUMO

No study has evaluated the mutagenicity of atmospheres with a calculated air quality health index (AQHI). Thus, we generated in a UV-light-containing reaction chamber two simulated atmospheres (SAs) with similar AQHIs but different proportions of criteria pollutants and evaluated them for mutagenicity in three Salmonella strains at the air-agar interface. We continuously injected into the chamber gasoline, nitric oxide, and ammonium sulfate, as well as either α-pinene to produce SA-PM, which had a high concentration of particulate matter (PM): 119 ppb ozone (O3), 321 ppb NO2, and 1007 µg/m3 PM2.5; or isoprene to produce SA-O3, which had a high ozone (O3) concentration: 415 ppb O3, 633 ppb NO2, and 55 µg/m3 PM2.5. Neither PM2.5 extracts, NO2, or O3 alone, nor nonphoto-oxidized mixtures were mutagenic or cytotoxic. Both photo-oxidized atmospheres were largely direct-acting base-substitution mutagens with similar mutagenic potencies in TA100 and TA104. The mutagenic potencies [(revertants/h)/(mgC/m3)] of SA-PM (4.3 ± 0.4) and SA-O3 (9.5 ± 1.3) in TA100 were significantly different ( P < 0.0001), but the mutation spectra were not ( P = 0.16), being ∼54% C → T and ∼46% C → A. Thus, the AQHI may have some predictive value for the mutagenicity of the gas phase of air.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Atmosfera , Testes de Mutagenicidade , Mutagênicos , Material Particulado
14.
Environ Sci Technol ; 52(5): 3062-3070, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29384667

RESUMO

Air pollution is a diverse and dynamic mixture of gaseous and particulate matter, limiting our understanding of associated adverse health outcomes. The biological effects of two simulated smog atmospheres (SA) with different compositions but similar air quality health indexes were compared in a nonobese diabetic rat model (Goto-Kakizaki, GK) and three mouse immune models (house dust mite (HDM) allergy, antibody response to heat-killed pneumococcus, and resistance to influenza A infection). In GK rats, both SA-PM (high particulate matter) and SA-O3 (high ozone) decreased cholesterol levels immediately after a 4-h exposure, whereas only SA-O3 increased airflow limitation. Airway responsiveness to methacholine was increased in HDM-allergic mice compared with nonallergic mice, but exposure to SA-PM or SA-O3 did not significantly alter responsiveness. Exposure to SA-PM did not affect the IgM response to pneumococcus, and SA-O3 did not affect virus titers, although inflammatory cytokine levels were decreased in mice infected at the end of a 7-day exposure. Collectively, acute SA exposures produced limited health effects in animal models of metabolic and immune diseases. Effects of SA-O3 tended to be greater than those of SA-PM, suggesting that gas-phase components in photochemically derived multipollutant mixtures may be of greater concern than secondary organic aerosol PM.


Assuntos
Poluentes Atmosféricos , Ozônio , Animais , Atmosfera , Camundongos , Material Particulado , Ratos , Roedores , Smog
15.
Environ Sci Technol ; 52(5): 3037-3044, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29381868

RESUMO

The production of photochemical atmospheres under controlled conditions in an irradiation chamber permits the manipulation of parameters that influence the resulting air-pollutant chemistry and potential biological effects. To date, no studies have examined how contrasting atmospheres with a similar Air Quality Health Index (AQHI), but with differing ratios of criteria air pollutants, might differentially affect health end points. Here, we produced two atmospheres with similar AQHIs based on the final concentrations of ozone, nitrogen dioxide, and particulate matter (PM2.5). One simulated atmosphere (SA-PM) generated from irradiation of ∼23 ppmC gasoline, 5 ppmC α-pinene, 529 ppb NO, and 3 µg m-3 (NH4)2SO4 as a seed resulted in an average of 976 µg m-3 PM2.5, 326 ppb NO2, and 141 ppb O3 (AQHI 97.7). The other atmosphere (SA-O3) generated from 8 ppmC gasoline, 5 ppmC isoprene, 874 ppb NO, and 2 µg m-3 (NH4)2SO4 resulted in an average of 55 µg m-3 PM2.5, 643 ppb NO2, and 430 ppb O3 (AQHI of 99.8). Chemical speciation by gas chromatography showed that photo-oxidation degraded the organic precursors and promoted the de novo formation of secondary reaction products such as formaldehyde and acrolein. Further work in accompanying papers describe toxicological outcomes from the two distinct photochemical atmospheres.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Dióxido de Nitrogênio , Material Particulado
16.
Part Fibre Toxicol ; 13: 17, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27083413

RESUMO

BACKGROUND: Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure. METHODS: Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m(3) targets), or AM (3.5 mg/m(3) target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m(3)), or AM (3.3 mg/m(3)) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m(3) LA, mean length of all structures was 3.7 µm and 1% were longer than 20 µm. RESULTS: Ten days exposure to 25.0 mg/m(3) LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m(3) LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m(3)) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups. CONCLUSIONS: Inhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.


Assuntos
Adenocarcinoma Bronquioloalveolar/induzido quimicamente , Adenoma/induzido quimicamente , Amianto Amosita/toxicidade , Amiantos Anfibólicos/toxicidade , Exposição por Inalação , Neoplasias Pulmonares/induzido quimicamente , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Adenoma/metabolismo , Adenoma/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Hiperplasia , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pneumonia/genética , Pneumonia/metabolismo , Pneumonia/patologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos Endogâmicos F344 , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
17.
J Toxicol Environ Health A ; 79(2): 49-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26818398

RESUMO

Naturally occurring asbestos (NOA) fibers are found in geologic deposits that may be disturbed by mining, earthworks, or natural processes, resulting in adverse health risks to exposed individuals. The toxicities of Libby amphibole and NOA samples including Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) were compared in male Fischer 344 (F344) rats 15 mo after exposure. Rat-respirable fractions of LA and SM displayed greater mean lengths and aspect ratios than ED and ON. After a single intratracheal (IT) instillation (0.5 or 1.5 mg/rat), persistent changes in ventilatory parameters and a significant increase in lung resistance at baseline and after methacholine aerosol dosing were found only in rats exposed to 1.5 mg SM. High-dose ED significantly elevated bronchoalveolar lavage lactate dehydrogenase (LDH) activity and protein levels, while high-dose SM increased γ-glutamyl transferase and LDH activities. A moderate degree of lung interstitial fibrosis after exposure to 1.5 mg SM persisted 15 mo after exposure, unchanged from previous findings at 3 mo. LA induced mild fibrosis, while ED and ON produced minimal and no apparent fibrosis, respectively. Bronchioloalveolar carcinoma was observed 15 mo after exposure to LA or ED. Data demonstrated that SM, given by bolus IT dosing on an equivalent mass basis, induced greater pulmonary function deficits, airway hyperresponsiveness, and interstitial fibrosis than other NOA, although unlike LA and ED, no apparent evidence for carcinogenicity was found. All NOA samples except ON cleavage fragments produced some degree of long-term toxicity.


Assuntos
Amianto/toxicidade , Carcinógenos/toxicidade , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Amiantos Anfibólicos , Asbestos Serpentinas , Asbestose/patologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/patologia , Líquido da Lavagem Broncoalveolar/química , Broncoconstritores/farmacologia , Exposição por Inalação , Intubação Intratraqueal , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Masculino , Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/farmacologia , Ratos , Ratos Endogâmicos F344 , Testes de Função Respiratória , Análise de Sobrevida , gama-Glutamiltransferase/metabolismo
18.
Inhal Toxicol ; 27(11): 533-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26514781

RESUMO

Toxicity of exhaust from combustion of petroleum diesel (B0), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM(2.5)) concentrations of 50, 150, or 500 µg/m(3). Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoalveolar lavage (BAL) fluid 2 h after a single 4-h exposure to B0 compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5 d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergic mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM-allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among B0-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to B0, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of T(H)2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500 µg/m(3)) can induce inflammation acutely in healthy mice and exacerbate some components of allergic responses, while comparable concentrations of B20 or B100 soy biodiesel fuels did not elicit responses different from those caused by air exposure alone.


Assuntos
Biocombustíveis/toxicidade , Glycine max/toxicidade , Hipersensibilidade/metabolismo , Mediadores da Inflamação/metabolismo , Exposição por Inalação/efeitos adversos , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/toxicidade , Animais , Feminino , Hipersensibilidade/etiologia , Hipersensibilidade/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Material Particulado/toxicidade
19.
Environ Health Perspect ; 123(8): A194-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26230287

RESUMO

Asbestos-related diseases continue to result in approximately 120,000 deaths every year in the United States and worldwide. Although extensive research has been conducted on health effects of occupational exposures to asbestos, many issues related to environmental asbestos exposures remain unresolved. For example, environmental asbestos exposures associated with a former mine in Libby, Montana, have resulted in high rates of nonoccupational asbestos-related disease. Additionally, other areas with naturally occurring asbestos deposits near communities in the United States and overseas are undergoing investigations to assess exposures and potential health risks. Some of the latest public health, epidemiological, and basic research findings were presented at a workshop on asbestos at the 2014 annual meeting of the Society of Toxicology in Phoenix, Arizona. The following focus areas were discussed: a) mechanisms resulting in fibrosis and/or tumor development; b) relative toxicity of different forms of asbestos and other hazardous elongated mineral particles (EMPs); c) proper dose metrics (e.g., mass, fiber number, or surface area of fibers) when interpreting asbestos toxicity; d) asbestos exposure to susceptible populations; and e) using toxicological findings for risk assessment and remediation efforts. The workshop also featured asbestos research supported by the National Institute of Environmental Health Sciences, the Agency for Toxic Substances and Disease Registry, and the U.S. Environmental Protection Agency. Better protection of individuals from asbestos-related health effects will require stimulation of new multidisciplinary research to further our understanding of what constitutes hazardous exposures and risk factors associated with toxicity of asbestos and other hazardous EMPs (e.g., nanomaterials).


Assuntos
Amianto/toxicidade , Asbestose/etiologia , Exposição Ambiental , Poluentes Ambientais/toxicidade , Recuperação e Remediação Ambiental , Humanos , Medição de Risco
20.
Respir Physiol Neurobiol ; 212-214: 20-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25842220

RESUMO

We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate matter in order to boost the allergic response. In control mice, methacholine (i.v.) caused a dose-dependent increase in respiratory tract resistance (RT) that only modestly decreased if the vagi were severed bilaterally just prior to the methacholine challenge. Sensitized and challenged mice, however, manifested an airway reactivity increase that was abolished by severing the vagi prior to methacholine challenge. In an innervated ex vivo mouse lung model, methacholine selectively evoked action potential discharge in a subset of distension-sensitive A-fibers. These data support the hypothesis that the major component of the increased airway reactivity in inflamed mice is due to a vagal reflex initiated by activation of afferent fibers, even in response to a direct (i.e., smooth muscle)-acting muscarinic agonist.


Assuntos
Alérgenos/toxicidade , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/cirurgia , Vagotomia/métodos , Potenciais de Ação/efeitos dos fármacos , Análise de Variância , Animais , Lavagem Broncoalveolar/métodos , Broncoconstritores/uso terapêutico , Feminino , Inflamação/induzido quimicamente , Cloreto de Metacolina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/tratamento farmacológico , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiologia
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