Showing papers in "Inhalation Toxicology in 2011"

Health effects of particulate air pollution: A review of epidemiological evidence.

Abstract: ACS,American Cancer Society;AD,Alzheimer’s disease;AMI,acute myocardial infarction;APHEA,air pollution and health effects—a European approach;APHENA,air pollution and health: a European and North A...

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice.

Abstract: Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of Sao Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 μL of saline (CTRL) or PM2.5 at 5 or 15 μg in 30 μL of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical imped...

Exposure assessment of workplaces manufacturing nanosized TiO2 and silver

Abstract: With the increased production and widespread use of nanomaterials, human and environmental exposure to nanomaterials is inevitably increasing. Therefore, this study monitored the possible exposure to nanoparticles at workplaces that manufacture nano-TiO2 and nano-silver. To estimate the potential exposure of workers, personal sampling, area monitoring, and real-time monitoring using a scanning mobility particle sizer (SMPS) and dust monitor were conducted at workplaces where the workers handle nanomaterials. The gravimetric concentrations of TiO2 ranged from 0.10 to 4.99 mg/m3, which were lower than the occupational exposure limit 10 mg/m3 set by the Korean Ministry of Labor or American Conference of Governmental Industrial Hygienists (ACGIH). Meanwhile, the silver metal concentrations ranged from 0.00002 to 0.00118 mg/m3, which were also lower than the silver dust 0.1 mg/m3 and silver soluble compound 0.01 mg/m3 occupational exposure limits set by the ACGIH. The particle number concentrations at the nano...

Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: a review

Abstract: Sulfur mustard (SM), a potent chemical weapon agent, was used by Iraqi forces against Iranian in the Iraq-Iran war (1981-1989). Chronic obstructive pulmonary disease (COPD) is a late toxic pulmonary consequence after SM exposure. The COPD observed in these patients is unique (described as Mustard Lung) and to some extent different from COPD resulted from other well-known causes. Several mechanisms have been hypothesized to contribute to the pathogenesis of COPD including oxidative stress, disruption of the balance between apoptosis and replenishment, proteinase-antiproteinase imbalance and inflammation. However, it is not obvious which of these pathways are relevant to the pathogenesis of mustard lung. In this paper, we reviewed studies addressing the pathogenicity of mustard lung, and reduced some recent ambiguities in this field. There is ample evidence in favor of crucial role of both oxidative stress and apoptosis as two known mechanisms that are more involved in pathogenesis of mustard lung comparing to COPD. However, according to available evidences there are no such considerable data supporting neither proteolytic activity nor inflammation mechanism as the main underlying pathogenesis in Mustard Lung.

Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: Mass and surface area as an exposure metric

Abstract: The total surface area is known to be an effective exposure metric for predicting the lung toxicity of low solubility nanoparticles (NPs). However, if NPs are dissolved quickly enough in the lungs, the mass may be correlated with the toxicity. Recent studies have found that the toxicity of zinc oxide (ZnO) NPs was caused by the release of zinc ions. Thus, we hypothesized that mass could be used as an exposure metric for the toxicity of ZnO NPs. Healthy Sprague-Dawley rats were exposed to a low, moderate, or high dose of 35 and 250 nm ZnO particles or filtered air. Bronchoalveolar lavage fluid was collected to determine lung inflammation, injury and oxidative stress. The lung inflammation induced by ZnO particles according to different concentration metrics, including number, mass and surface area, was compared. The mass concentration was significantly correlated with the percentage of neutrophils (R2 = 0.84), number of neutrophils (R2 = 0.84) and total cells (R2 = 0.73). Similarly, surface area concentrat...

Inhaled whole exhaust and its effect on exercise performance and vascular function.

Abstract: Context: Internal combustion engines are a major source of particulate matter (PM) which has been shown to result in vasoconstriction, yet no present study to our knowledge has investigated the effect of exhaust emissions on both exercise performance and the vasculature. Objective: To examine the effect of freshly generated whole exhaust on exercise performance, pulmonary arterial pressure (PP), and flow-mediated vasodilation (FMD) of the brachial artery. Materials and Methods: Sixteen male, collegiate athletes (age: 20.8 ± 1.28 years) were randomly assigned to submaximal exercise for 20 min followed by a 6 min maximal work accumulation exercise test in either high PM (HPM) or low PM (LPM) conditions on two consecutive days. After a 7-day washout period, subjects completed identical exercise trials in the alternate condition. HPM conditions were generated from a 4-cycle gasoline engine. The participants’ PP and FMD were assessed before and after each exercise trial by tricuspid regurgitant velocity and br...

Flow cytometry of sputum: assessing inflammation and immune response elements in the bronchial airways

Abstract: Background: The evaluation of sputum leukocytes by flow cytometry (FCM) is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris.Objective: To develop a gating strategy based on specific antibody panels in combination with light scatter properties for flow cytometric evaluation of sputum cells.Methods: Healthy and mild asthmatic volunteers underwent sputum induction. Manually selected mucus “plug” material was treated with dithiothreitol, filtered and total leukocytes acquired. Multicolor FCM was performed using specific gating strategies based on light scatter properties, differential expression of CD45 and cell lineage markers to discriminate leukocytes from squamous epithelial cells and debris.Results: The combination of forward scatter and CD45 expression reliably segregated sputum leukocytes from contaminating squamous epithelial cells and debris...

Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice.

Abstract: Context: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet.Objectives: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice.Materials and methods: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group.Results: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P > 0.05). The total cell count and the number of neutrophil cells in BALF were ...

The Air Pollution Exposure Laboratory (APEL) for controlled human exposure to diesel exhaust and other inhalants: characterization and comparison to existing facilities.

Abstract: Objective: The Air Pollution Exposure Laboratory (APEL) was designed for the controlled inhalation of human subjects to aged and diluted diesel exhaust (DE) to mimic “real-world” occupational and environmental conditions.Methods: An EPA Tier 3-compliant, 6.0 kW diesel generator is operated under discrete cyclic loads to simulate diesel on-road emissions. The engine accepts standard ultra-low sulfur diesel or a variety of alternative fuels (such as biodiesel) via a partitioned tank. A portion of raw exhaust is drawn into the primary dilution system and is diluted 9:1 with compressed air at standard temperature (20°C) and humidity (40%) levels. The exhaust is further diluted approximately 25:1 by high efficiency particulate air (HEPA)-filtered air (FA) and then aged for 4 min before entering the 4 × 6 × 7-foot exposure booth. An optional HEPA filter path immediately proximal to the booth can generate a particle-reduced (gas-enriched) exposure. In-booth particulate is read by a nephelometer to provide an ins...

Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation.

Abstract: Context: Epidemiological studies indicate that diabetes is a sub-population at risk for particulate matter (PM)-associated cardiovascular disease (CVD). Recent animal studies suggested PM might impair glucose tolerance, which may lead to CVD. However, the mechanism remains unclear.Objective: To investigate further the PM effect on insulin resistance (IR) in obese and healthy rats.Materials and methods: Male Sprague–Dawley rats were fed with either a high fat diet (HFD) or normal chow diet (NCD) for 6 weeks. Both groups were then further assigned to receive PM10, PM2.5 or normal saline (n = 6 per group) by intratracheal instillation (IT) once per week for 3 weeks. Fasting glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess IR. Biochemistry tests and lipids profile were examined at sacrifice. The markers of fibrinogen and [nitrate+nitrite], an indicator of nitric oxide (NO) production, C-reactive protein (CRP) and white blood counts (WBCs) in pe...

Pulmonary and systemic responses of highly pure and well-dispersed single-wall carbon nanotubes after intratracheal instillation in rats.

Abstract: The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2 mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the fore...

Pre- and postnatal exposure to ambient levels of urban particulate matter (PM2.5) affects mice spermatogenesis

Abstract: This work characterizes the effects of ambient levels of urban particulate matter (PM2.5) from the city of Sao Paulo on spermatogenesis using mice exposed during the embryo–fetal and/or postnatal phases of development. Parental generations (BALB/c mice) were exposed to air pollution in chambers with or without filtering PM2.5 for 4 months. Animals were mated, and half of the 1-day-old offspring were moved between chambers, which yielded prenatal and postnatal groups. Remaining offspring comprised the non-exposed and pre+postnatal exposed groups. After 90 days, the animals were sacrificed for testis collection and weighing. Optical microscopy was used for the morphometric analyses of the cell counts, spermatogenic cycle, proliferation, and apoptosis. Prenatally exposed animals presented reduced body and testicular weight with an increased gonadosomatic index (GSI). Testicular volume also decreased, as well as the tubular diameter in testes of the same animals. Proliferation, apoptosis, and spermatogenic cy...

A review of controlled human SO₂ exposure studies contributing to the US EPA integrated science assessment for sulfur oxides.

Abstract: Laboratory studies involving intentional and highly controlled exposures to air pollutants among groups of human volunteers provide valuable information related to the potential health effects of pollutants regulated under the US Clean Air Act. These controlled human exposure studies often provide biological plausibility for the associations between air-pollutant concentration and a given health endpoint observed in epidemiologic investigations. In some cases, results from human laboratory studies provide evidence of a relevant health effect at ambient or near-ambient concentrations and thus directly support the selection of air quality standard levels. In the recently completed review of the US National Ambient Air Quality Standards (NAAQS) for sulfur dioxide (SO₂), the US Environmental Protection Agency (EPA) concluded that short-term exposures to SO₂ are causally associated with an increase in respiratory morbidity. This determination was based in large part on findings from laboratory studies of controlled exposures to SO₂ among small groups of asthmatic individuals. The purpose of this review is to concisely present an overview of the evidence from controlled human exposure studies of SO₂-induced respiratory health effects following short-term exposures. While the majority of these studies were conducted over 20 years ago, the findings and insights gained from this work continues to play an integral role in evaluating the respiratory effects of ambient exposures to SO₂.

Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways

Abstract: Context and objective: Lead (Pb) is a heavy metal harmful for human health and environment. From leaded gasoline (still used in certain countries), and in Pb processing and reprocessing industries, airborne particles are emitted which can be inhaled. In such exposure, the size of particles entering the airways is crucial. The nervous system is a primary target for Pb, and consequences like occupational neuropathy and delayed mental development of children are well-known. The aim of this work was to investigate the neurotoxicity of Pb nanoparticles (NPs) applied into the airways of rats.Methods: Nano-sized lead oxide particles (mean diameter ca. 20 nm) were suspended in distilled water and instilled into the trachea of adult male Wistar rats (in doses equivalent to 2 and 4 mg/kg Pb), 5 times a week for 3 and 6 weeks. At the end, open field motility was tested, then central and peripheral nervous activity was recorded in urethane anesthesia.Results and conclusion: The treated rats’ body weight gain was sign...

Urinary biomarkers of oxidative/nitrosative stress in healthy smokers

Abstract: Objective: To evaluate the effect of cigarette smoking on oxidative and nitrosative stress, we assessed urinary levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), isoprostane 15-F2t-IsoP, thiobarbituric acid-reacting substances (TBARS), advanced glycation end-products (AGEs), dityrosine (diTyr), hydrogen peroxide, total nitrite and nitrate and trolox equivalent antioxidant capacity (TEAC) in healthy smokers.Methods: Fluorimetric and spectrophotometric assays were performed in urine samples of 33 healthy smokers and 58 age-matched controls.Results: Levels of 8-OHdG, 15-F2t-IsoP and AGES were found significantly higher in smokers than in controls (10.7 ng/mg Cr vs. 8.3 ng/mg Cr, 1.41 ng/mg Cr vs. 1.01 ng/mg Cr and 189 AFU/mg Cr vs. 143 AFU/mg Cr, respectively; P < 0.05 for all). Positive correlations were found between age and levels of AGEs and diTyr in smokers (r = 0.380, P < 0.035 and r = 0.418, P < 0.019, respectively) and also between age and AGEs, diTyr and TEAC in controls (r = 0.474, P < 0.001, r = 0.4...

Toxicological evaluation of realistic emission source aerosols (TERESA): summary and conclusions

Abstract: The toxicological evaluation of realistic emissions of source aerosols (TERESA) study seeks to delineate health effects of aerosols formed from emissions of particulate matter sources. This series of papers reports the findings of experiments using coal-fired power plants as the source of emissions and this paper summarizes the findings and knowledge acquired from these studies. Emissions were drawn directly from the stacks of three coal-fired power plants in the US, and photochemically aged in a mobile laboratory to simulate downwind power plant plume processing. The power plants used different sources of coal and had different emission controls. Exposure scenarios included primary particles, secondary particles and mixtures of these with common atmospheric constituents (α-pinene and ammonia). Extensive exposure characterization was carried out, and toxicological outcomes were evaluated in Sprague-Dawley rats exposed to different emission scenarios. Breathing pattern, pulmonary inflammatory responses, in vivo pulmonary and cardiac chemiluminescence and cardiac response in a model of acute myocardial infarction were assessed. The results showed no response or relatively mild responses to the inhaled aerosols studied; complex scenarios which included oxidized emissions and α-pinene to simulate biogenic secondary organic aerosol tended to induce more statistically significant responses than scenarios of oxidized and non-oxidized emissions alone. Relating adverse effects to specific components did not consistently identify a toxic constituent. These findings are consistent with most of the previously published studies using pure compounds to model secondary power plant emissions, but importantly add substantial complexity and thus have considerable merit in defining toxicological responses.

Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure

Abstract: The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods. The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the inte...

Amorphous silica coatings on magnetic nanoparticles enhance stability and reduce toxicity to in vitro BEAS-2B cells.

Abstract: Background: Nanoparticles are being rapidly assimilated into numerous research fields and consumer products A concurrent increase in human exposure to such materials is expected Magnetic nanoparticles (MNPs) possess unique and beneficial features, increasing their functionality and integrative potential However, MNP toxicity characterization is limited, especially in regards to the human respiratory system This study aimed to assess the in vitro effects of airborne MNPs on BEAS-2B cells Uncoated iron oxide was compared with two amorphous silica-coated MNPs, hypothesizing the coatings reduced toxicity and increased particle stabilityMethod: BEAS-2B cells were cultured at an air–liquid interface and exposed to airborne MNPs using a fabricated exposure device Indices of cytotoxicity, inflammatory response, oxidative stress, and iron homeostasis were monitored postexposure via cell viability assays and qRT-PCR Concentrations of soluble iron-associated with different MNPs were also examined before and

An evaluation of the toxicity of 95 ingredients added individually to experimental cigarettes: approach and methods

Abstract: Context: Ingredients have been used in modern cigarette manufacturing to facilitate tobacco processing, provide flavor, and preserve tobacco. Concern has been raised regarding the use of ingredients in cigarette manufacturing due to the possible generation of toxic chemicals resulting from their combustion when added to tobacco.Objective: Investigate the impact of individual ingredients on cigarette smoke toxicity.Materials and methods: A total of 95 ingredients were tested individually through addition at different concentrations to the tobacco of experimental cigarettes. Mainstream cigarette smoke chemistry analysis, bacterial mutagenicity testing, and cytotoxicity testing were conducted. Additionally, 31 of the ingredients were tested in 90-day nose-only rat inhalation studies using mainstream cigarette smoke. Studies were designed following conventional toxicity testing methods employed for food additives and other consumer products.Results: The studies reported here demonstrate that high levels of so...

Wood smoke in a controlled exposure experiment with human volunteers

Abstract: Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure.Twenty nonsmoking atopic human participants with normal lung function and normal bronchial reactivity were randomly exposed for 3 h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions. The range for PM2.5 load observed for single experiments was 165–303 µg/m3 for the low exposure and 205–662 µg/m3 for the high exposure, whereas particle loads during clean air exposure most often were below the detection limit (<20 µg/m3).Health effects were evaluated in relation to rated changes in symptoms and environmental perception using a computerized questionnaire and a potentiometer. Subjective symptoms w...

Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice

Abstract: Context: Inhalation of ambient fine particulate matter (PM2.5) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM2.5 in urban settings is diesel exhaust particulate (DEP), and DEP-induced lung inflammation is likely a critical event mediating many of its adverse health effects. Oxidative stress has been proposed to be an important factor in PM2.5-induced lung inflammation, and the balance between pro- and antioxidants is an important regulator of this inflammation. An important intracellular antioxidant is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL) carries out the first step in GSH synthesis. In humans, relatively common genetic polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL have been associated with increased risk for lung and cardiovascular diseases.Objective: This study was aimed to determine the effects of Gclm expression on lung inflammation following DEP exposure in mice.Materials and methods: We expo...

Role of size and composition of traffic and agricultural aerosols in the molecular responses triggered in airway epithelial cells.

Abstract: The increased levels of fine particles in the atmosphere are suspected of aggravating cardiopulmonary diseases, but the determinants of particle toxicity are poorly understood. This work aims at studying the role of composition and size in the toxicity of size-segregated particulate matter (PM) collected at different sites on human bronchial epithelial cells. PM were sampled at a traffic urban site (Urb S) and a rural site (Rur S) during the pesticide-spreading period. Ultrafine (UF), fine (F), and coarse (C) PM were characterized by their shape and chemical composition. Whatever the site, the finest PM (UF and F) induced the mRNA expression of CYP1A1, a biomarker of polyaromatic hydrocarbons (PAH) exposure, NQO-1 and heme HO-1, two antioxidant responsive element-driven genes; and two effect biomarkers, GM-CSF, a proinflammatory cytokine and amphiregulin (AR), a growth factor. C PM have a low or no effect. Interestingly, AR is more strongly induced by rural PM at the same mass exposure. These discrepancies suggest involvement of PM chemical composition: rural PM bearing the characteristics of aged aerosols with a high content of water-soluble components, and PM at urban kerbside sites containing mainly water-insoluble components. To conclude, we provide evidence that the finest PM fractions, whatever their origin, are more prone to induce exposure and effect biomarkers. The AR differential expression suggests a source-dependent effect requiring further investigation because of the role of this growth factor in airway remodeling, a characteristic feature of chronic lung respiratory diseases exacerbated by particulate pollution.

Binding of polystyrene and carbon black nanoparticles to blood serum proteins.

Abstract: Context: Once inhaled, nanoparticles (NP) deposit on the lung surface and have first contact with the epithelial lung lining fluid (ELF) rich in proteins, which may bind to NP.Objective: In this study, we investigate the parameters that influence the binding between NP and proteins.Materials and methods: We used the proteins albumin, transferrin (TF), and apolipoprotein A-1 (all known as proteins from ELF) and different NP (polystyrene NP with negative, positive, and neutral surface coatings, Printex G and Printex 90) as models.Results: In all cases, a linear correlation of the added NP amount and the amount of bound proteins was found and was described quantitatively by binding indices. Bovine serum albumin (BSA), TF, and apo A-1 were bound to the largest extent to hydrophobic NP, which shows the extraordinary importance of the NP’s surface properties.Discussion: The binding index indicates the relevance of primary particle size and surface properties, including hydrophobicity.Conclusion: Size and surfac...

The relationship between traffic-related air pollutants and cardiac autonomic function in a panel of healthy adults: a further analysis with existing data

Abstract: Context: Epidemiological studies have linked particulate matter (PM) and carbon monoxide (CO) exposures with alterations in cardiac autonomic function as measured by heart rate variability (HRV) in populations. Recently, we reported association of several HRV indices with marked changes in particulate air pollution around the Beijing 2008 Olympic Games in a panel of healthy adults.Objective: We further investigated the cardiac effects of traffic-related air pollutants over wide exposure ranges with expanded data set in this panel of healthy adults.Methods: We obtained real-time data on nine taxi drivers’ in-car exposures to PM ≤2.5 µm in aerodynamic diameter (PM2.5) and CO and on multiple HRV indices during a separate daily work shift in four study periods with dramatically changing air pollution levels around the Beijing 2008 Olympic Games. Mixed effect models and a loess smoother method were used to investigate the associations of exposures with HRV indices.Results: Results showed overall negative assoc...

EGFR upregulates inflammatory and proliferative responses in human lung adenocarcinoma cell line (A549), induced by lower dose of cadmium chloride.

Abstract: Exposure to cadmium is associated with the development of pulmonary damage such as emphysema and lung cancer. This metal is also a powerful inducer of different proinflammatory and cell cycle regulatory proteins in many biologic models. Previously, we showed that prolonged exposure of low concentration of cadmium resulted in upregulation of proinflammatory cytokines and cell cycle regulatory molecules in mice lung cell. The present study was undertaken to determine molecular mechanism of inflammation and its relation to cell proliferation in a transformed human lung adenocarcinoma epithelial cell line (A549) in response to cadmium chloride. In comparative studies, we examine that short-duration exposure to lower doses of cadmium significantly increase the growth of A549 cells, whereas higher doses are toxic and cause cell death. We also observed that cadmium induced elevated expression of epidermal growth factor receptor (EGFR) along with different proinflammatory cytokines like interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). The possible occurrence of cell proliferation events was evaluated via analysis of the physical state of the DNA and the expression of Ki-67 and proliferating cell nuclear antigen (PCNA). We also checked the pattern of expression of different cell cycle regulatory molecules involved in the onset of cell proliferation. Our results indicate that cadmium treatment appears to induce inflammatory and growth responses in transformed A549 cell line by activating EGFR and its downstream modulators. These results may contribute to better understand the toxic mechanism of cadmium; moreover, the expression profile of cadmium-induced regulatory molecules could provide potential biomarkers for cadmium exposure.

Lung function changes in wildland firefighters working at prescribed burns

Abstract: Context: Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function.Objectives: We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.Materials and Methods: We measured forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow from 25% to 75% of FVC (FEF25–75), and peak expiratory flow (PEF) of wildland firefighters before and after their workshifts. In all, 501 pre-shift and 488 post-shift measurements were collected over 22 prescribed burn days and 43 non-burn days from 24 non-smoking wildland firefighters during the dormant winter burn seasons of 2003 and 2004. We compared changes in the spirometry measures across the workshift on burn days to...

Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility.

Abstract: In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4 h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and n...

Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay

Abstract: The current carcinogenicity study with female rats focused on the toxicity and carcinogenicity of intratracheally instilled fine and ultrafine granular dusts. The positive control, crystalline silica, elicited the greatest magnitude and progression of pulmonary inflammatory reactions, fibrosis and the highest incidence of primary lung tumors (39.6%). Addition of poly-2-vinylpyridine-N-oxide decreased inflammatory responses, fibrosis, and the incidence of pulmonary tumors induced by crystalline quartz to 21.4%. After repeated instillation of soluble, ultrafine amorphous silica (15 mg) a statistically significant tumor response (9.4%) was observed, although, the inflammatory response in the lung was not as persistently severe as in rats treated with carbon black. Instillation of ultrafine carbon black (5 mg) caused a lung tumor incidence of 15%. In contrast to a preceding study using a dose of 66 mg coal dust, lung tumors were not detected after exposure to the same coal dust at a dose of 10 mg in this study. Pulmonary inflammatory responses to coal dust were very low indicating a mechanistic threshold for the development of lung tumors connected with particle related chronic inflammation. The animals treated with ultrafine carbon black and ultrafine amorphous silica showed significantly more severe lesions in non-cancerous endpoints when compared to animals treated with fine coal dust. Furthermore, carbon black treated rats showed more severe non-cancerous lung lesions than amorphous silica treated rats. Our data show a relationship between tumor frequencies and increasing scores when using a qualitative scoring system for specific non-cancerous endpoints such as inflammation, fibrosis, epithelial hyperplasia, and squamous metaplasia.

The genotoxic effect of nicotine on chromosomes of human fetal cells: The first report described as an important study

Abstract: Context: Recent studies have suggested a direct contribution of nicotine − the addictive component of tobacco and tobacco smoke − to human carcinogenesis, and it remains the most common harmful substance to which pregnant women are exposed. Also, it has deleterious effects on the fetus. The sperm of smoking fathers and newborns of smoking mothers have elevated frequencies of chromosome translocations and DNA strand breaks.Objective: We tried to understand the genotoxic effect of nicotine in pregnancies of active or passive smoking mothers. For this reason, we provide the evidence that nicotine exposure in vitro has detrimental effects on fetal cells.Materials and methods: We examined the effect of nicotine sulphate on amniotic cells by designing an experimental setting consisting fetal cells grown in nicotine containing medium (25 ng/mL) in study group and fetal cells grown in control medium, which did not contain nicotine.Results: According to our findings, there is a significant difference of chromosoma...

Aged particles derived from emissions of coal-fired power plants: the TERESA field results.

Abstract: The Toxicological Evaluation of Realistic Emissions Source Aerosols (TERESA) study was carried out at three US coal-fired power plants to investigate the potential toxicological effects of primary and photochemically aged (secondary) particles using in situ stack emissions. The exposure system designed successfully simulated chemical reactions that power plant emissions undergo in a plume during transport from the stack to receptor areas (e.g., urban areas). Test atmospheres developed for toxicological experiments included scenarios to simulate a sequence of atmospheric reactions that can occur in a plume: (1) primary emissions only; (2) H2SO4 aerosol from oxidation of SO2; (3) H2SO4 aerosol neutralized by gas-phase NH3; (4) neutralized H2SO4 with secondary organic aerosol (SOA) formed by the reaction of α-pinene with O3; and (5) three control scenarios excluding primary particles. The aged particle mass concentrations varied significantly from 43.8 to 257.1 µg/m3 with respect to scenario and power plant....