Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panel.

Unique physicochemical characteristics of engineered nanomaterials (ENMs) suggest the need for nanomaterial-specific occupational exposure limits (OELs). Setting these limits remains a challenge. Therefore, the aim of this study was to set out a framework to evaluate the feasibility of deriving advisory health-based occupational limit values for groups of ENMs, based on scientific knowledge. We have used an expert panel approach to address three questions: 1) What ENM-categories should be distinguished to derive advisory health-based occupational limit values (or health-based Nano Reference Values, HNRVs) for groups of ENMs? 2) What evidence would be needed to define values for these categories? And 3) How much effort would it take to achieve this? The panel experts distinguished six possible categories of HNRVs: A) WHO-fiber-like high aspect ratio ENMs (HARNs), B) Non-WHO-fiber-like HARNs and other non-spheroidal ENMs, C) readily soluble spheroidal ENMs, D) biopersistent spheroidal ENMs with unknown toxicity, E) biopersistent spheroidal ENMs with substance-specific toxicity and F) biopersistent spheroidal ENMs with relatively low substance-specific toxicity. For category A, the WHO-fiber-like HARNs, agreement was reached on criteria defining this category and the approach of using health-based risk estimates for asbestos to derive the HNRV. For category B, a quite heterogeneous category, more toxicity data are needed to set an HNRV. For category C, readily soluble spheroidal ENMs, using the OEL of their molecular or ionic counterpart would be a good starting point. For the biopersistent ENMs with unknown toxicity, HNRVs cannot be applied as case-by-case testing is required. For the other biopersistent ENMs in category E and F, we make several recommendations that can facilitate the derivation of these HNRVs. The proposed categories and recommendations as outlined by this expert panel can serve as a reference point for derivation of HNRVs when health-based OELs for ENMs are not yet available.

Chronic exposure to metal fume PM2.5 on inflammation and stress hormone cortisol in shipyard workers: A repeat measurement study.

Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) has been linked to adverse health outcomes in welding workers. The objective of this study was to investigate associations of chronic exposure to metal fume PM2.5 in shipyard workers with health outcomes. A longitudinal study was conducted to determine the effects of metal fume PM2.5 on FeNO, urinary metals, urinary oxidative stress, inflammation, and stress hormones in workers. There were 20 office workers and 49 welding workers enrolled in this study who were followed-up for a second year. We observed that Fe, Zn, and Mn were abundant in PM2.5 to which welding workers were personally exposed, whereas PM2.5 to which office workers were personally exposed was dominated by Pb, Cu, and Zn. We observed in the first and/or second visits that urinary 8-iso-prostaglandin F2-α (PGF2α) and 8-hydroxy-2'-deoxy guanosine (8-OHdG) were significantly increased by exposure. An increase in urinary interleukin (IL)-6 and decreases in urinary serotonin and cortisol were observed in the first and/or second visits after exposure. PM2.5 was associated with decreases in urinary 8-OHdG and cortisol among workers. Next, we observed that urinary Ni, Co, and Fe had significantly increased among workers after a year of exposure. Urinary metals were associated with decreases in urinary 8-iso-PGF2α and cortisol among workers. Urinary Ni, Cu, and Fe levels were associated with an increase in urinary IL-6 and a decrease in urinary cortisol among workers. In conclusion, chronic exposure to metal fume PM2.5 was associated with inflammation and a cortisol deficiency in shipyard workers, which could associate with adrenal glands dysfunction.

From nano to micrometer size particles - A characterization of airborne cement particles during construction activities.

Although, photocatalytic cement contains nanosized TiO2, a possibly carcinogen, no exposure assessments exist for construction workers. We characterized airborne nanoparticle exposures during construction activities simulated in an exposure chamber. We collected some construction site samples for regular cement in Switzerland and Thailand for comparison. Airborne nanoparticles were characterized using scanning mobility particle sizer (SMPS), portable aerosol spectrometer (PAS), diffusion size classifier (DiSCmini), transmission electron microscopy (TEM), scanning electron microscope energy dispersive X-ray spectroscopy (SEM-EDX), and X-ray diffraction. Bagged photocatalytic cement had 2.0 wt% (GSD ± 0.55) TiO2, while TiO2 in aerosols reached 16.5 wt% (GSD ± 1.72) during bag emptying and 9.7 wt% (GSD ± 1.36) after sweeping. The airborne photocatalytic cement particles were far smaller (approximately 50 nm) compared to regular cement. Cutting blocks made from photocatalytic cement or concrete, resulted in similar amounts of airborne nano TiO2 (2.0 wt% GSD ± 0.57) particles as in bagged material. Both photocatalytic and regular cement had a geometric mean diameter (GMD) < 3.5 µm. Main exposures for Thai workers were during sweeping and Swiss workers during drilling and polishing cement blocks. Targeted nanoparticle exposure assessments are needed as a significantly greater exposure to nano TiO2 were observed than what would have been predicted from the material's nano- TiO2 contents.

Effects of short- and long-term exposures to particulate matter on inflammatory marker levels in the general population.

The effect of particulate matter (PM) on health increases with exposure duration but the change from short to longer term is not well studied. We examined the exposure to PM smaller 10 µm (PM10) from short to longer duration and their associations with levels of inflammatory markers in the population-based CoLaus cohort in Lausanne, Switzerland. Baseline and follow-up CoLaus data were used to study the associations between PM10 exposure and inflammatory markers, including the high-sensitivity C-reactive protein (CRP), as well as interleukin 1-beta (IL-1ß), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) using mixed models. Exposure was determined for each participant's home address from hourly air quality simulations at a 5-m resolution. Short-term exposure intervals were 1 day, 1 week, and 1 month prior to the hospital visit (blood withdrawal); long-term exposure intervals were 3 and 6 months prior to the visit. In most time windows, IL-6, IL-1ß, and TNF-α were positively associated with PM10. No significant associations were identified for CRP. Adjusted associations with long-term exposures were stronger and more significant than those for short-term exposures. In stratified models, gender, age, smoking status, and hypertension only led to small modifications in effect estimates, though a few of the estimates for IL-6 and TNF-α became non-significant. In this general adult cohort exposed to relatively low average PM10 levels, clear associations with markers of systemic inflammation were observed. Longer duration of elevated exposure was associated with an exacerbated inflammatory response. This may partially explain the elevated disease risk observed with chronic PM10 exposure. It also suggests that reducing prolonged episodes of high PM exposure may be a strategy to reduce inflammatory risk.

Occupational exposure to inhaled nanoparticles: Are young workers being left in the dust?

OBJECTIVES: Occupational exposure to inhaled nanoparticles (NPs) represents a significant concern for worker health. Adolescent workers may face unique risks for exposure and resulting health effects when compared with adult workers. METHODS: This manuscript discusses key differences in risks for occupational exposures to inhaled NPs and resulting health effects between young workers and adult workers via an examination of both physiological and occupational setting factors. RESULTS: Previous studies document how adolescents often face distinct and unique exposure scenarios to occupational hazards when compared to adults. Moreover, they also face different and unpredictable health effects because biological functions such as detoxification pathways and neurological mechanisms are still developing well into late adolescence. Early exposure also increases the chances of developing long-latency disease earlier in life. Taken together, adolescents' rapid growth and development encompasses highly dynamic and complex processes. An aggravating factor is that these processes do not necessarily fall in line with legal classifications of adulthood, nor with occupational exposure limits created for adult workers. CONCLUSIONS: The differences in exposures and health consequences from NPs on young workers are insufficiently understood. Research is needed to better understand what adolescent-specific mitigation strategies may be most suitable to address these risk factors.

Air-Liquid Interface Cell Exposures to Nanoparticle Aerosols.

The field of nanomedicine is steadily growing and several nanomedicines are currently approved for clinical use with even more in the pipeline. Yet, while the use of nanotechnology to improve targeted drug delivery to the lungs has received some attention, the use of nanoparticles for inhalation drug delivery has not yet resulted in successful translation to market as compared to intravenous drug delivery. The reasons behind the lack of inhaled nanomedicines approved for clinical use or under preclinical development are unclear, but challenges related to safety are likely to contribute. Although inhalation toxicology studies often begin using animal models, there has been an increase in the development and use of in vitro air-liquid interface (ALI) exposure systems for toxicity testing of engineered nanoparticle aerosols, which will be useful for rapid testing of candidate substances and formulations. This chapter describes an ALI cell exposure assay for measuring toxicological effects, specifically cell viability and oxidative stress, resulting from exposure to aerosols containing nanoparticles.

Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

BACKGROUND: Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. METHODS: Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. RESULTS: Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). CONCLUSION: A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.

Characterization of Tungsten Inert Gas (TIG) Welding Fume Generated by Apprentice Welders.

Tungsten inert gas welding (TIG) represents one of the most widely used metal joining processes in industry. Its propensity to generate a greater portion of welding fume particles at the nanoscale poses a potential occupational health hazard for workers. However, current literature lacks comprehensive characterization of TIG welding fume particles. Even less is known about welding fumes generated by welding apprentices with little experience in welding. We characterized TIG welding fume generated by apprentice welders (N = 20) in a ventilated exposure cabin. Exposure assessment was conducted for each apprentice welder at the breathing zone (BZ) inside of the welding helmet and at a near-field (NF) location, 60cm away from the welding task. We characterized particulate matter (PM4), particle number concentration and particle size, particle morphology, chemical composition, reactive oxygen species (ROS) production potential, and gaseous components. The mean particle number concentration at the BZ was 1.69E+06 particles cm(-3), with a mean geometric mean diameter of 45nm. On average across all subjects, 92% of the particle counts at the BZ were below 100nm. We observed elevated concentrations of tungsten, which was most likely due to electrode consumption. Mean ROS production potential of TIG welding fumes at the BZ exceeded average concentrations previously found in traffic-polluted air. Furthermore, ROS production potential was significantly higher for apprentices that burned their metal during their welding task. We recommend that future exposure assessments take into consideration welding performance as a potential exposure modifier for apprentice welders or welders with minimal training.

The oxidative potential of differently charged silver and gold nanoparticles on three human lung epithelial cell types.

BACKGROUND: Nanoparticle (NPs) functionalization has been shown to affect their cellular toxicity. To study this, differently functionalized silver (Ag) and gold (Au) NPs were synthesised, characterised and tested using lung epithelial cell systems. METHODS: Monodispersed Ag and Au NPs with a size range of 7 to 10 nm were coated with either sodium citrate or chitosan resulting in surface charges from -50 mV to +70 mV. NP-induced cytotoxicity and oxidative stress were determined using A549 cells, BEAS-2B cells and primary lung epithelial cells (NHBE cells). TEER measurements and immunofluorescence staining of tight junctions were performed to test the growth characteristics of the cells. Cytotoxicity was measured by means of the CellTiter-Blue ® and the lactate dehydrogenase assay and cellular and cell-free reactive oxygen species (ROS) production was measured using the DCFH-DA assay. RESULTS: Different growth characteristics were shown in the three cell types used. A549 cells grew into a confluent mono-layer, BEAS-2B cells grew into a multilayer and NHBE cells did not form a confluent layer. A549 cells were least susceptible towards NPs, irrespective of the NP functionalization. Cytotoxicity in BEAS-2B cells increased when exposed to high positive charged (+65-75 mV) Au NPs. The greatest cytotoxicity was observed in NHBE cells, where both Ag and Au NPs with a charge above +40 mV induced cytotoxicity. ROS production was most prominent in A549 cells where Au NPs (+65-75 mV) induced the highest amount of ROS. In addition, cell-free ROS measurements showed a significant increase in ROS production with an increase in chitosan coating. CONCLUSIONS: Chitosan functionalization of NPs, with resultant high surface charges plays an important role in NP-toxicity. Au NPs, which have been shown to be inert and often non-cytotoxic, can become toxic upon coating with certain charged molecules. Notably, these effects are dependent on the core material of the particle, the cell type used for testing and the growth characteristics of these cell culture model systems.

Physicochemical characterization of nebulized superparamagnetic iron oxide nanoparticles (SPIONs).

BACKGROUND: Aerosol-mediated delivery of nano-based therapeutics to the lung has emerged as a promising alternative for treatment and prevention of lung diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted significant attention for such applications due to their biocompatibility and magnetic properties. However, information is lacking about the characteristics of nebulized SPIONs for use as a therapeutic aerosol. To address this need, we conducted a physicochemical characterization of nebulized Rienso, a SPION-based formulation for intravenous treatment of anemia. METHODS: Four different concentrations of SPION suspensions were nebulized with a one-jet nebulizer. Particle size was measured in suspension by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and nanoparticle tracking analysis (NTA), and in the aerosol by a scanning mobility particle sizer (SMPS). RESULTS: The average particle size in suspension as measured by TEM, PCS, and NTA was 9±2 nm, 27±7 nm, and 56±10 nm, respectively. The particle size in suspension remained the same before and after the nebulization process. However, after aerosol collection in an impinger, the suspended particle size increased to 159±46 nm as measured by NTA. The aerosol particle concentration increased linearly with increasing suspension concentration, and the aerodynamic diameter remained relatively stable at around 75 nm as measured by SMPS. CONCLUSIONS: We demonstrated that the total number and particle size in the aerosol were modulated as a function of the initial concentration in the nebulizer. The data obtained mark the first known independent characterization of nebulized Rienso and, as such, provide critical information on the behavior of Rienso nanoparticles in an aerosol. The data obtained in this study add new knowledge to the existing body of literature on potential applications of SPION suspensions as inhaled aerosol therapeutics.

Exhaled breath condensate as a matrix for combustion-based nanoparticle exposure and health effect evaluation.

BACKGROUND: Health assessment and medical surveillance of workers exposed to combustion nanoparticles are challenging. The aim was to evaluate the feasibility of using exhaled breath condensate (EBC) from healthy volunteers for (1) assessing the lung deposited dose of combustion nanoparticles and (2) determining the resulting oxidative stress by measuring hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA). METHODS: Fifteen healthy nonsmoker volunteers were exposed to three different levels of sidestream cigarette smoke under controlled conditions. EBC was repeatedly collected before, during, and 1 and 2 hr after exposure. Exposure variables were measured by direct reading instruments and by active sampling. The different EBC samples were analyzed for particle number concentration (light-scattering-based method) and for selected compounds considered oxidative stress markers. RESULTS: Subjects were exposed to an average airborne concentration up to 4.3×10(5) particles/cm(3) (average geometric size ∼60-80 nm). Up to 10×10(8) particles/mL could be measured in the collected EBC with a broad size distribution (50(th) percentile ∼160 nm), but these biological concentrations were not related to the exposure level of cigarette smoke particles. Although H(2)O(2) and MDA concentrations in EBC increased during exposure, only H2O2 showed a transient normalization 1 hr after exposure and increased afterward. In contrast, MDA levels stayed elevated during the 2 hr post exposure. CONCLUSIONS: The use of diffusion light scattering for particle counting proved to be sufficiently sensitive to detect objects in EBC, but lacked the specificity for carbonaceous tobacco smoke particles. Our results suggest two phases of oxidation markers in EBC: first, the initial deposition of particles and gases in the lung lining liquid, and later the start of oxidative stress with associated cell membrane damage. Future studies should extend the follow-up time and should remove gases or particles from the air to allow differentiation between the different sources of H(2)O(2) and MDA.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers.

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, both of which have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hr periods from a total of 50 observation days. We measured their exposure to fine particulate matter (diameter ≤ 2.5 µm; PM2.5), ultrafine particles, and noise, and the cardiopulmonary health end points: blood pressure, proinflammatory and prothrombotic markers in the blood, lung function, and fractional exhaled nitric oxide (FeNO) measured approximately 15 hr after work. Heart rate variability was assessed during a sleep period approximately 10 hr after work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and was negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased high-frequency and low-frequency power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and nonsignificantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

Effects of particulate matter on inflammatory markers in the general adult population.

BACKGROUND: Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway. METHODS: We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM(10) (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1ß), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) by robust linear regressions, controlling for potential confounding factors and assessing effect modification. RESULTS: In adjusted analyses, for every 10 µg/m(3) elevation in PM(10), IL-1ß increased by 0.034 (95 % confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-α by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels. CONCLUSIONS: Short-term exposure to PM(10) was positively associated with higher levels of circulating IL-1ß, IL-6 and TNF-α in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM(10) to cardiovascular risk.

In vitro assessment of the pulmonary toxicity and gastric availability of lead-rich particles from a lead recycling plant.

Epidemiological studies in urban areas have linked increasing respiratory and cardiovascular pathologies with atmospheric particulate matter (PM) from anthropic activities. However, the biological fate of metal-rich PM industrial emissions in urban areas of developed countries remains understudied. Lead toxicity and bioaccessibility assessments were therefore performed on emissions from a lead recycling plant, using complementary chemical acellular tests and toxicological assays, as a function of PM size (PM(10-2.5), PM(2.5-1) and PM(1)) and origin (furnace, refining and channeled emissions). Process PM displayed differences in metal content, granulometry, and percentage of inhalable fraction as a function of their origin. Lead gastric bioaccessibility was relatively low (maximum 25%) versus previous studies; although, because of high total lead concentrations, significant metal quantities were solubilized in simulated gastrointestinal fluids. Regardless of origin, the finest PM(1) particles induced the most significant pro-inflammatory response in human bronchial epithelial cells. Moreover, this biological response correlated with pro-oxidant potential assay results, suggesting some biological predictive value for acellular tests. Pulmonary effects from lead-rich PM could be driven by thiol complexation with either lead ions or directly on the particulate surface. Finally, health concern of PM was discussed on the basis of pro-inflammatory effects, accellular test results, and PM size distribution.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

BACKGROUND: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. METHODS: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. RESULTS: Workers were exposed to low levels of respirable PM4 (range 25-71 µg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). CONCLUSIONS: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Probing functional groups at the gas-aerosol interface using heterogeneous titration reactions: a tool for predicting aerosol health effects?

The complex chemical and physical nature of combustion and secondary organic aerosols (SOAs) in general precludes the complete characterization of both bulk and interfacial components. The bulk composition reveals the history of the growth process and therefore the source region, whereas the interface controls--to a large extent--the interaction with gases, biological membranes, and solid supports. We summarize the development of a soft interrogation technique, using heterogeneous chemistry, for the interfacial functional groups of selected probe gases [N(CH(3))(3), NH(2)OH, CF(3)COOH, HCl, O(3), NO(2)] of different reactivity. The technique reveals the identity and density of surface functional groups. Examples include acidic and basic sites, olefinic and polycyclic aromatic hydrocarbon (PAH) sites, and partially and completely oxidized surface sites. We report on the surface composition and oxidation states of laboratory-generated aerosols and of aerosols sampled in several bus depots. In the latter case, the biomarker 8-hydroxy-2'-deoxyguanosine, signaling oxidative stress caused by aerosol exposure, was isolated. The increase in biomarker levels over a working day is correlated with the surface density N(i)(O3) of olefinic and/or PAH sites obtained from O(3) uptakes as well as with the initial uptake coefficient, γ(0), of five probe gases used in the field. This correlation with γ(0) suggests the idea of competing pathways occurring at the interface of the aerosol particles between the generation of reactive oxygen species (ROS) responsible for oxidative stress and cellular antioxidants.

Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways.

Combustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the (pro-)inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-alpha concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure.

Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions.

BACKGROUND: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. RESULTS: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. CONCLUSION: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits pro-inflammatory and pro-thrombotic responses in healthy young men.