Biomedical subjects

W G Kreyling

Publications and source records attributed to W G Kreyling.

At least 19 recordsLinked to original sources

PubMed2006

Dose-controlled exposure of A549 epithelial cells at the air-liquid interface to airborne ultrafine carbonaceous particles.

The geometry of commercially available perfusion chambers designed for harbouring three membrane-based cell cultures was modified for reliable and dose-controlled air-liquid interface (ALI) exposures. Confluent A549 epithelial cells grown on membranes were integrated in the chamber system and supplied with medium from the chamber bottom. Cell viability was not impaired by the conditions of ALI exposure without particles. Expression of the inflammatory cytokines interleukin 6 and interleukin 8 by A549 cells during ALI exposure to filtered air for 6h and subsequent stimulation with tumor necrosis factor was not altered compared to submersed controls, indicating that the cells maintained their functional integrity. Ultrafine carbonaceous model particles with a count median mobility diameter of about 95+/-5 nm were produced by spark discharge at a stable concentration of about 2 x 10(6) cm(-3) and continuously monitored for accurate determination of the exposure dose. Delivery to the ALI exposure system yielded a homogeneous particle deposition over the membranes with a deposition efficiency of 2%. Mid dose exposure of A549 cells to this aerosol for 6h yielded a total particle deposition of (2.6+/-0.4) x 10(8) cm(-2) corresponding to (87+/-23) ng cm(-2). The 2.7-fold (p < or = 0.05) increased transcription of heme oxygenase-1 indicated a sensitive antioxidant and stress response, while cell viability did not reveal a toxic mechanism.

Aerosols↗

PubMed2006

Negligible clearance of ultrafine particles retained in healthy and affected human lungs.

Ambient particles are believed to be a specific health hazard, although the underlying mechanisms are not fully understood. There are data in the literature indicating fast and substantial systemic uptake of particles from the lung. The present authors have developed an improved method to produce ultrafine particles with more stable radiolabelling and defined particle size range. Fifteen subjects inhaled technetium 99m (99mTc)-labelled carbonaceous particles of 100 nm in size. Radioactivity over the lung was followed for 70 h. The clearance of these ultrafine particles from the lungs and specifically translocation to the circulation was tested. Lung retention for all subjects at 46 h was mean+/-sd 99+/-4.6%. Cumulative leaching of 99mTc activity from the particles was 2.6+/-0.96% at 70 h. The 24-h activity leaching in urine was 1.0+/-0.55%. No evidence of a quantitatively important translocation of 100-nm particles to the systemic circulation from the lungs was found. More research is needed to establish if the approximately 1% cleared activity originates from leached activity or insoluble translocated particles, and whether a few per cent of translocated particles is sufficient to cause harmful effects.

Administration, Inhalation↗

PubMed2006

Distribution pattern of inhaled ultrafine gold particles in the rat lung.

The role of alveolar macrophages in the fate of ultrafine particles in the lung was investigated. Male Wistar-Kyoto rats were exposed to ultrafine gold particles, generated by a spark generator, for 6 h at a concentration of 88 microg/m3 (4 x 10(6)/cm3, 16 nm modal mobility diameter). Up to 7 days, the animals were serially sacrificed, and lavaged cells and lung tissues were examined by transmission electron microscopy. The gold concentration/content in the lung, lavage fluid, and blood was estimated by inductively coupled plasma-mass spectrometry. Gold particles used were spherical and electron dense with diameters of 5-8 nm. The particles were individual or slightly agglomerated. By inductively coupled plasma-mass spectrometry analysis of the lung, 1945 +/- 57 ng (mean +/- SD) and 1512 +/- 184 ng of gold were detected on day 0 and on day 7, respectively, indicating that a large portion of the deposited gold particles was retained in the lung tissue. In the lavage fluid, 573 +/- 67 ng and 96 +/- 29 ng were found on day 0 and day 7, respectively, which means that 29% and 6% of the retained gold particles were lavageable on these days. A low but significant increase of gold (0.03 to 0.06% of lung concentration) was found in the blood. Small vesicles containing gold particles were found in the cytoplasm of alveolar macrophages. In the alveolar septum, the gold particles were enclosed in vesicles observed in the cytoplasm of alveolar type I epithelial cells. These results indicate that inhaled ultrafine gold particles in alveolar macrophages and type I epithelial cells are processed by endocytotic pathways, though the uptake of the gold particles by alveolar macrophages is limited. To a low degree, systemic particle translocation took place.

Animals↗

PubMed2005

Sources and elemental composition of ambient PM(2.5) in three European cities.

Source apportionment of urban fine particle mass (PM(2.5)) was performed from data collected during 1998-1999 in Amsterdam (The Netherlands), Erfurt (Germany) and Helsinki (Finland), using principal component analysis (PCA) and multiple linear regression. Six source categories of PM(2.5) were identified in Amsterdam. They were traffic-related particles (30% of the average PM(2.5)), secondary particles (34%), crustal material (7%), oil combustion (11%), industrial and incineration processes (9%), and sea salt (2%). The unidentified PM(2.5) fraction was 7% on the average. In Erfurt, four source categories were extracted with some difficulties in interpretation of source profiles. They were combustion emissions related to traffic (32%), secondary PM (32%), crustal material (21%) and industrial processes (8%). In Erfurt, 3% of PM(2.5) remained unidentified. Air pollution data and source apportionment results from the two Central European cities were compared to previously published results from Helsinki, where about 80% of average PM(2.5) was attributed to transboundary air pollution and particles from traffic and other regional combustion sources. Our results indicate that secondary particles and local combustion processes (mainly traffic) were the most important source categories in all cities; their impact on the average PM(2.5) was almost equal in Amsterdam and Erfurt whereas, in Helsinki, secondary particles made up for as much as half of the total average PM(2.5).

Air Pollution↗

PubMed2004

Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs.

Recently it was speculated that ultrafine particles (UFP) may translocate from deposition sites in the lungs to systemic circulation and whether long-term clearance differs between ultrafine and micrometer-sized particles. We have studied lung retention and clearance kinetics in 12 healthy male adult WKY rats up to 6 mo after an inhalation of (192)Ir-radiolabeled, insoluble, ultrafine 15- to 20-nm iridium particles. Whole-body retention was followed by external gamma counting, and particle clearance kinetics were determined by excretion radioanalysis. Four rats each were sacrificed after 3 wk and 2 and 6 mo; all organs as well as tissues and the carcass were radioanalyzed to balance the entire deposited radioactivity of the particles. The most prominent fraction was retained in the lungs at each time point of sacrifice (26%, 15%, 6%, respectively), and clearance out of the body was solely via excretion. Extrapulmonary particle uptake did not continue to increase but decreased with time in liver, spleen, heart, and brain when compared to previous data obtained during the first 7 days after inhalation (Kreyling et al., 2002). UFP long-term lung retention derived from whole-body measurements was comparable to previously reported data using insoluble micrometer-sized particles (Bellmann et al., 1994; Lehnert et al., 1989). In addition, differential analysis including daily excretion data revealed a pattern of fractional particle clearance rate of the ultrafine iridium particles similar to that of micrometer-sized particles reported by Snipes et al. (1983) and Bailey et al. (1985).

Administration, Inhalation↗

PubMed2004

Fate and toxic effects of inhaled ultrafine cadmium oxide particles in the rat lung.

Female Fischer 344 rats were exposed to ultrafine cadmium oxide particles, generated by spark discharging, for 6 h at a concentration of 70 microg Cd/m(3) (1 x 10(6)/cm(3)) (40 nm modal diameter). Lung morphology and quantification of Cd content/concentration by inductively coupled plasma (ICP)-mass spectrometry were performed on days 0, 1, 4, and 7 after exposure. Cd content in the lung on day 0 was 0.53 +/- 0.12 microg/lung, corresponding to 19% of the estimated total inhaled cumulative dose, and the amount remained constant throughout the study. In the liver no significant increase of Cd content was found up to 4 days. A slight but statistically significant increase was observed in the liver on day 7. We found neither exposure-related morphological changes of lungs nor inflammatory responses in lavaged cells. Another group of rats were exposed to a higher concentration of ultrafine CdO particles (550 microg Cd/m(3) for 6 h, 51 nm modal diameter). The rats were sacrificed immediately and 1 day after exposure. The lavage study performed on day 0 showed an increase in the percentage of neutrophils. Multifocal alveolar inflammation was seen histologically on day 0 and day 1. Although the Cd content in the lung was comparable between day 0 and day 1 (3.9 microg/lung), significant elevation of Cd levels in the liver and kidneys was observed on both days. Two of 4 rats examined on day 0 showed elevation of blood cadmium, indicating systemic translocation of a fraction of deposited Cd from the lung in this group. These results and comparison with reported data using fine CdO particles indicate that inhalation of ultrafine CdO particles results in efficient deposition in the rat lung. With regard to the deposition dose, adverse health effects of ultrafine CdO and fine CdO appear to be comparable. Apparent systemic translocation of Cd took place only in animals exposed to a high concentration that induced lung injury.

Animals↗

PubMed2004

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

Body Burden↗

PubMed2004

Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16.

BACKGROUND: Daily variations in ambient particulate air pollution have been associated with respiratory mortality and morbidity. AIMS: To assess the associations between urinary concentration of lung Clara cell protein CC16, a marker for lung damage, and daily variation in fine and ultrafine particulate air pollution. METHODS: Spot urinary samples (n = 1249) were collected biweekly for six months in subjects with coronary heart disease in Amsterdam, Netherlands (n = 37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient particulate air pollution was monitored at a central site in each city. RESULTS: The mean 24 hour number concentration of ultrafine particles was 17.3x10(3) cm(-3) in Amsterdam, 21.1x10(3) cm(-3) in Erfurt, and 17.0x10(3) cm(-3) in Helsinki. The mean 24 hour PM2.5 concentrations were 20, 23, and 13 microg/m3, respectively. Daily variation in ultrafine particle levels was not associated with CC16. In contrast, CC16 concentration seemed to increase with increasing levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16 concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 microg/m3 increase in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1% (95% CI -1.3 to 5.6). CONCLUSION: The results suggest that exposure to particulate air pollution may lead to increased epithelial barrier permeability in lungs.

Aged↗

PubMed2003

Elemental composition and sources of fine and ultrafine ambient particles in Erfurt, Germany.

We present the first results of a source apportionment for the urban aerosol in Erfurt, Germany, for the period 1995-1998. The analysis is based on data of particle number concentrations (0.01-2.5 microm; mean 1.8 x 10(4) cm(-3), continuous), the concentration of the ambient gases SO(2), NO, NO(2) and CO (continuous), particle mass less than 2.5 microm (PM(2.5)) and less than 10 microm (PM(10)) (Harvard Impactor sampling, mean PM(2.5) 26.3 micro/m(3), mean PM(10) 38.2 microg/m(3)) and the size fractionated concentrations of 19 elements (impactor sampling 0.05-1.62 microm, PIXE analysis). We determined: (a) the correlations between (i) the 1- and 24-h average concentrations of the gaseous pollutants and the particle number as well as the particle mass concentration and (ii) between the 24-h elemental concentrations; (b) Crustal Enrichment Factors for the PIXE elements using Si as reference element; and (c) the diurnal pattern of the measured pollutants on weekdays and on weekends. The highly correlated PIXE elements Si, Al, Ti and Ca having low enrichment factors were identified as soil elements. The strong correlation of particle number concentrations with NO, which is considered to be typically emitted by traffic, and the striking similarity of their diurnal variation suggest that a sizable fraction of the particle number concentration is associated with emission from vehicles. Besides NO and particle number concentrations other pollutants such as NO(2), CO as well as the elements Zn and Cu were strongly correlated and appear to reflect motor vehicle traffic. Sulfur could be a tracer for coal combustion, however, it was not correlated with any of the quoted elements. Highly correlated elements V and Ni have similar enrichment factors and are considered as tracers for oil combustion.

Aerosols↗

PubMed2003

RBDATA-EULEP: providing information to improve internal dosimetry.

The overall aim of the concerted action RBDATA-EULEP is to provide information to improve the assessments of intakes of radionuclides and of the resulting doses. This involves a review of the behaviour of radionuclides following intake, and the transfer of expertise on methodology by organising small training workshops. The main activity is the development of an electronic database, effectively an annotated bibliography, but the electronic format used facilitates extension, updating and information retrieval. It consists of linked tables of references and experiments, with details and comments on the materials, procedures and results. By June 2002 it contained information on 524 inhalation, 282 ingestion and 164 injection experiments from 391 references. It will be extended, and Internet access provided. Prospective users include groups developing standards for internal dosimetry, scientists conducting research on radionuclide biokinetics and health physicists assessing the consequences of accidental intakes.

Body Burden↗

PubMed2003

Comparison of predicted with observed biokinetics of inhaled plutonium nitrate and gadolinium oxide in humans.

The absorption kinetics to blood of plutonium and gadolinium after inhalation as nitrate and oxide in humans and animals has been studied. For each material, values describing the time dependence of absorption were derived from the studies in animals and used with the ICRP human respiratory tract model to predict lung retention and cumulative amounts to blood for the volunteers inhaling the same materials. Comparison with the observed behaviour in the volunteers suggests that absorption of plutonium and gadolinium is reasonably species independent, and that data obtained from animal studies can be used to assess their biokinetic behaviour in humans.

Absorption↗

PubMed2002

Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low.

Recently it was speculated that ultrafine particles may translocate from deposition sites in the lungs to systemic circulation. This could lead to accumulation and potentially adverse reactions in critical organs such as liver, heart, and even brain, consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases, as growing evidence from epidemiological studies suggests. Ultrafine (192)Ir radio-labeled iridium particles (15 and 80 nm count median diameter) generated by spark discharging were inhaled by young adult, healthy, male WKY rats ventilated for 1 h via an endotracheal tube. After exposure, excreta were collected quantitatively. At time points ranging from 6 h to 7 d, rats were sacrificed, and a complete balance of (192)Ir activity retained in the body and cleared by excretion was determined gamma spectroscopically. Thoracic deposition fractions of inhaled 15- and 80-nm (192)Ir particles were 0.49 and 0.28, respectively. Both batches of ultrafine iridium particles proved to be insoluble (<1% in 7 d). During wk 1 after inhalation particles were predominantly cleared via airways into the gastrointestinal tract and feces. This cleared fraction includes particles deposited in the alveolar region. Additionally, minute particle translocation of <1% of the deposited particles into secondary organs such as liver, spleen, heart, and brain was measured after systemic uptake from the lungs. The translocated fraction of the 80-nm particles was about an order of magnitude less than that of 15-nm particles. In additional studies, the biokinetics of ultrafine particles and soluble (192)Ir was studied after administration by either gavage or intratracheal instillation or intravenous injection. They confirmed the low solubility of the particles and proved that (1) particles were neither dissolved nor absorbed from the gut, (2) systemically circulating particles were rapidly and quantitatively accumulated in the liver and spleen and retained there, and (3) soluble (192)Ir instilled in the lungs was rapidly excreted via urine with little retention in the lungs and other organs. This study indicates that only a rather small fraction of ultrafine#10; iridium particles has access from peripheral lungs to systemic circulation and extrapulmonary organs. Therefore, the hypothesis that systemic access of ultrafine insoluble particles may generally induce adverse reactions in the cardiovascular system and liver leading to the onset of cardiovascular diseases needs additional detailed and differentiated consideration.

Administration, Inhalation↗

PubMed2002

Increased asthma medication use in association with ambient fine and ultrafine particles.

The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01-0.1 microm in diameter (NC(0.01-0.1), mean 17,300 x cm(-3), and mass concentrations of fine particles 0.01-2.5 microm in diameter (MC(0.01-2.5)), mean 30.3 microg x m(-3), were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled beta2-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. Beta2-agonist use was associated with 5-day mean NC(0.01-0.1) and MC(0.01-2.5). The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.

Adrenergic beta-Agonists↗

PubMed2001

Air quality in postunification Erfurt, East Germany: associating changes in pollutant concentrations with changes in emissions.

The unification of East and West Germany in 1990 resulted in sharp decreases in emissions of major air pollutants. This change in air quality has provided an opportunity for a natural experiment to evaluate the health impacts of air pollution. We evaluated airborne particle size distribution and gaseous co-pollutant data collected in Erfurt, Germany, throughout the 1990s and assessed the extent to which the observed changes are associated with changes in the two major emission sources: coal burning for power production and residential heating, and motor vehicles. Continuous data for sulfur dioxide, total suspended particulates (TSP), nitric oxide, carbon monoxide, and meteorologic parameters were available for 1990-1999, and size-selective particle number and mass concentration measurements were made during winters of 1991 and 1998. We used hourly profiles of pollutants and linear regression analyses, stratified by year, weekday/weekend, and hour, using NO and SO(2) as markers of traffic- and heating-related combustion sources, respectively, to study the patterns of various particle size fractions. Supplementary data on traffic and heating-related sources were gathered to support hypotheses linking these sources with observed changes in ambient air pollution levels. Substantially decreased (19-91%) concentrations were observed for all pollutants, with the exception of particles in the 0.01-0.03 microm size range (representing the smallest ultrafine particles that were measured). The number concentration for these particles increased by 115% between 1991 and 1998. The ratio of these ultrafine particles to TSP also increased by more than 500%, indicating a dramatic change in the size distribution of airborne particles. Analysis of hourly concentration patterns indicated that in 1991, concentrations of SO(2) and larger particle sizes were related to residential heating with coal. These peaks were no longer evident in 1998 due to decreases in coal consumption and consequent decreased emissions of SO(2) and larger particles. These decreases in coal combustion and the decreased concentrations of SO(2) and particles of larger size classes may have led to decreased particle scavenging and may be partially responsible for the observed increases in ultrafine particles. Traffic-related changes, such as increased numbers of trucks and increased use of diesel vehicles in Erfurt, were also associated with increased number concentrations of ultrafine particles. Morning particle peaks of all sizes were associated with NO and CO (markers for traffic) in both the 1991 and 1998 periods. There were significant differences in the ultrafine particle levels for morning hours between 1991 and 1998, suggesting that traffic was the cause of this increase.

Air Pollutants↗

PubMed2000

Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass.

Increases in morbidity and mortality have been observed consistently and coherently in association with ambient air pollution. A number of studies on short-term effects have identified ambient particles as a major pollutant in urban air. This study, conducted in Erfurt, Germany, investigated the association of mortality not only with ambient particles but also with gaseous pollutants and indicators of sources. Part I of this study concentrates on particles. Data were collected prospectively over a 3.5-year period from September 1995 to December 1998. Death certificates were obtained from the local authorities and aggregated to daily time series of total counts and counts for subgroups. In addition to standard data for particle mass with diameters < or = 2.5 microm (PM2.5)* or < or = 10 microm (PM10) from impactors, a mobile aerosol spectrometer (MAS) was used to obtain size-specific number and mass concentration data in six size classes between 0.01 microm and 2.5 microm. Particles smaller than 0.1 microm were labeled ultrafine particles (three size classes), and particles between 0.1 and 2.5 microm were termed fine particles (three size classes). Concentrations of the gases sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) were also measured. The daily average total number concentration was 18,000 particles/cm3 with 88% of particles below 0.1 pm and 58% below 0.03 microm in diameter. The average mass concentration (PM2.5) was 26 microg/m3; of this, 75% of particles were between 0.1 and 0.5 microm in diameter. Other average concentrations were 38 microg/m3 for PM10, 17 microg/m3 for SO2, 36 microg/m3 for NO2, and 600 microg/m3 for CO. Ambient air pollution demonstrated a strong seasonality with maximum concentrations in winter. Across the study period, fine particle mass decreased, whereas ultrafine particle number was unchanged. The proportion of ultrafine particles below 0.03 microm diameter increased compared with the proportion of other particles. During the study, concentrations of SO2 and CO also decreased, whereas the concentration of NO2 remained unchanged. The data were analyzed using Poisson regression techniques with generalized additive modeling (GAM) to allow nonparametric adjustment for the confounders. Both the best single-day lag and the overall association of multiple days fitted by a polynomial distributed lag model were used to assess the lag structure between air pollution and death. Mortality increased in association with level of ambient air pollution after adjustment for season, influenza epidemics, day of week, and weather. In the sensitivity analyses, the results proved stable against changes of the confounder model. We saw comparable associations for ultrafine and fine particles in a distributed lag model where the contribution of the previous 4 to 5 days was considered. Furthermore, the data suggest a somewhat more delayed association of ultrafine particles than of fine particles if single-day lags are considered. The associations tended to be stronger in winter than in summer and at ages below 70 years compared to ages above 70 years. Analysis of the prevalent diseases mentioned on death certificates revealed that the overall association for respiratory diseases was slightly stronger than for cardiovascular diseases. In two-pollutant models, associations of ultrafine and fine particles seemed to be largely independent of each other, and the risk was enhanced if both were considered at the same time. Furthermore, when the associations were summed for the six size classes between 0.01 and 2.5 microm, the overall association was clearly stronger than the associations of the individual size classes alone. Associations were observed for SO2, NO2, and CO with mortality despite low concentrations of these gases. These associations disappeared in two-pollutant models for NO2 and CO, but they remained stable for SO2. The persistence of the SO2 effect was interpreted as artifact, however, because the SO2 concentration was much below levels at which effects are usually expected. Furthermore, the results for SO2 were inconsistent with those from earlier studies conducted in Erfurt. We conclude that both fine particles (represented by particle mass) and ultrafine particles (represented by particle number) showed independent effects on mortality at ambient concentrations. Comparable associations for gaseous pollutants were interpreted as artifacts of collinearity with particles from the same sources.

Adolescent↗

PubMed1999

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Air Pollutants, Occupational↗

PubMed1999

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗

PubMed1999

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

Aerosols↗