Development and validation of a quantitative wipe sampling method to determine platinum contamination from antineoplastic drugs on surfaces in workplaces at Swedish hospitals.

INTRODUCTION: Antineoplastic drugs (ADs) are frequently used pharmaceuticals in the healthcare, and healthcare workers can be occupationally exposed to ADs. Monitoring of surface contamination is a common way to assess occupational exposure to ADs. The objective was to develop and validate a sensitive and quantitative monitoring method to determine surface contaminations of Pt as a marker for Pt-containing ADs. The surface contaminations of Pt-containing ADs were monitored at four Swedish hospital workplaces. METHODS: An analytical method was developed based on inductively coupled plasma mass spectrometry. The wipe sampling procedure was validated regarding different surface materials. The stability of collected wipe samples was investigated. Workplace surfaces were monitored by wipe sampling to determine contaminations of Pt-containing ADs. RESULTS: A wipe sampling and analytical method with a limit of detection of 0.1 pg Pt/cm2 was developed. Pt was detected in 67% of the wipe samples collected from four workplaces, and the concentrations ranged from <0.10 to 21100 pg/cm2. In 4% of samples, the detected surface contaminations of Pt in three hospital wards were above proposed hygienic guidance value (HGV) of Pt. In the hospital pharmacy, 9% of the detected surface contaminations of Pt were above lowest proposed HGV. CONCLUSIONS: A user-friendly, specific, and sensitive method for determination of surface contaminations of Pt from ADs in work environments was developed and validated. A large variation of contaminations was observed between detected surface contaminations of Pt in samples collected in wards, and it likely reflects differences in amounts handled and work practices between the wards.

Serum biomarkers in patients with hand-arm vibration injury and in controls.

Hand-arm vibration injury is a well-known occupational disorder that affects many workers globally. The diagnosis is based mainly on quantitative psychophysical tests and medical history. Typical manifestations of hand-arm vibration injury entail episodes of finger blanching, Raynaud's phenomenon (RP) and sensorineural symptoms from affected nerve fibres and mechanoreceptors in the skin. Differences in serum levels of 17 different biomarkers between 92 patients with hand-arm vibration injury and 51 controls were analysed. Patients with hand-arm vibration injury entailing RP and sensorineural manifestations showed elevated levels of biomarkers associated with endothelial injury or dysfunction, inflammation, vaso- or neuroprotective compensatory, or apoptotic mechanisms: intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1); thrombomodulin (TM), heat shock protein 27 (HSP27); von Willebrand factor, calcitonin gene-related peptide (CGRP) and caspase-3. This study adds important knowledge on pathophysiological mechanisms that can contribute to the implementation of a more objective method for diagnosis of hand-arm vibration injury.

Characterization of airborne dust emissions from three types of crushed multi-walled carbon nanotube-enhanced concretes.

Dispersing Multi-Walled Carbon Nanotubes (MWCNTs) into concrete at low (<1 wt% in cement) concentrations may improve concrete performance and properties and provide enhanced functionalities. When MWCNT-enhanced concrete is fragmented during remodelling or demolition, the stiff, fibrous and carcinogenic MWCNTs will, however, also be part of the respirable particulate matter released in the process. Consequently, systematic aerosolizing of crushed MWCNT-enhanced concretes in a controlled environment and measuring the properties of this aerosol can give valuable insights into the characteristics of the emissions such as concentrations, size range and morphology. These properties impact to which extent the emissions can be inhaled as well as where they are expected to deposit in the lung, which is critical to assess whether these materials might constitute a future health risk for construction and demolition workers. In this work, the impact from MWCNTs on aerosol characteristics was assessed for samples of three concrete types with various amounts of MWCNT, using a novel methodology based on the continuous drop method. MWCNT-enhanced concretes were crushed, aerosolized and the emitted particles were characterized with online and offline techniques. For light-weight porous concrete, the addition of MWCNT significantly reduced the respirable mass fraction (RESP) and particle number concentrations (PNC) across all size ranges (7 nm - 20 µm), indicating that MWCNTs dampened the fragmentation process by possibly reinforcing the microstructure of brittle concrete. For normal concrete, the opposite could be seen, where MWCNTs resulted in drastic increases in RESP and PNC, suggesting that the MWCNTs may be acting as defects in the concrete matrix, thus enhancing the fragmentation process. For the high strength concrete, the fragmentation decreased at the lowest MWCNT concentration, but increased again for the highest MWCNT concentration. All tested concrete types emitted <100 nm particles, regardless of CNT content. SEM imaging displayed CNTs protruding from concrete fragments, but no free fibres were detected.

Pilot study: External surface contamination of gemcitabine and 5-fluorouracil on drug packaging.

INTRODUCTION: Antineoplastic drugs (ADs) are commonly used pharmaceuticals for anticancer treatments. It has previously been shown that the external surface of drug vials frequently is contaminated with ADs. More than a decade ago methods to prevent occupational exposure were introduced by using plastic coverage of the glass vials or packing vials in a secondary plastic container. The aim of the pilot study was to determine contamination levels of ADs on different parts of AD packaging of two different commercially available drug vials on the Swedish market and to investigate the occurrence of cross contamination of ADs. METHODS: Packagings of gemcitabine (GEM) and 5-fluorouracil (5-FU) were tested by wipe sampling. Five ADs; GEM, 5-FU, cyclophosphamide (CP), ifosfamide and etoposide were quantified using liquid chromatography mass spectrometry. RESULTS: AD contaminations were detected in 69% and 60% of the GEM and 5-FU packaging samples. Highest levels, up to approximately 5 µg/sample, were observed on the glass vials. The protective shrink-wrap of 5-FU vials and the plastic container of GEM were contaminated with low levels of 5-FU and GEM, respectively, and furthermore the 5-FU vials with shrink-wrap were cross-contaminated with GEM. Cross-contamination of CP and GEM was detected on 5-FU vials with plastic shrink-wrap removed. CONCLUSIONS: External contamination of ADs are still present at primary drug packagings on the Swedish market. Protection of AD vials by plastic shrink-wrap or a secondary plastic container does not remove the external contamination levels completely. The presence of cross contamination of ADs on drug packagings was also observed.

Compositional tuning of gas-phase synthesized Pd-Cu nanoparticles.

Bimetallic nanoparticles have gained significant attention in catalysis as potential alternatives to expensive catalysts based on noble metals. In this study, we investigate the compositional tuning of Pd-Cu bimetallic nanoparticles using a physical synthesis method called spark ablation. By utilizing pure and alloyed electrodes in different configurations, we demonstrate the ability to tailor the chemical composition of nanoparticles within the range of approximately 80 : 20 at% to 40 : 60 at% (Pd : Cu), measured using X-ray fluorescence (XRF) and transmission electron microscopy energy dispersive X-ray spectroscopy (TEM-EDXS). Time-resolved XRF measurements revealed a shift in composition throughout the ablation process, potentially influenced by material transfer between electrodes. Powder X-ray diffraction confirmed the predominantly fcc phase of the nanoparticles while high-resolution TEM and scanning TEM-EDXS confirmed the mixing of Pd and Cu within individual nanoparticles. X-ray photoelectron and absorption spectroscopy were used to analyze the outermost atomic layers of the nanoparticles, which is highly important for catalytic applications. Such comprehensive analyses offer insights into the formation and structure of bimetallic nanoparticles and pave the way for the development of efficient and affordable catalysts for various applications.

Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models.

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.

Sensitive methods for assessment of lung health in welders and controls.

BACKGROUND: Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. METHODS: This study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). RESULTS: According to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. CONCLUSIONS: This study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Size-resolved characterization of particles >10 nm emitted to air during metal recycling.

BACKGROUND: In the strive towards a circular economy, metal waste recycling is a growing industry. During the recycling process, particulate matter containing toxic and allergenic metals will be emitted to the air causing unintentional exposure to humans and environment. OBJECTIVE: In this study detailed characterization of particle emissions and workplace exposures were performed, covering the full size range from 10 nm to 10 µm, during recycling of three different material flows: Waste of electrical and electronic equipment (WEEE), metal scrap, and cables. METHODS: Both direct-reading instruments (minute resolution), and time-integrated filter measurements for gravimetric and chemical analysis were used. Additionally, optical sensors were applied and evaluated for long-term online monitoring of air quality in industrial settings. RESULTS: The highest concentrations, in all particle sizes, and with respect both to particle mass and number, were measured in the WEEE flow, followed by the metal scrap flow. The number fraction of nanoparticles was high for all material flows (0.66-0.86). The most abundant metals were Fe, Al, Zn, Pb and Cu. Other elements of toxicological interest were Mn, Ba and Co. SIGNIFICANCE: The large fraction of nanoparticles, and the fact that their chemical composition deviate from that of the coarse particles, raises questions that needs to be further addressed including toxicological implications, both for humans and for the environment.

Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders.

Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis. Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O2) or normoxia (21% O2) during 24 h, with or without transforming growth factor (TGF)-ß1. mRNA expression of genes and proteins related to disease pathology were analysed with qPCR, ELISA or immunocytochemistry. Alterations in cell viability and metabolic activity were determined. Results: In BEAS-2B and hAELVi, hypoxia significantly dowregulated genes related to fibrosis, mitochondrial stress, oxidative stress, apoptosis and inflammation whereas VEGF receptor 2 increased. Hypoxia increased the expression of Tenascin-C, whereas both hypoxia and TGF-ß1 stimuli increased the release of VEGF, IL-6, IL-8 and MCP-1 in BEAS-2B. In hAELVi, hypoxia reduced the release of fibroblast growth factor, epidermal growth factor, PGE2, IL-6 and IL-8, whereas TGF-ß1 stimulus significantly increased the release of PGE2 and IL-6. TGF-ß1 stimulated BEAS-2B cells showed a decreased release of VEGF-A and IL-8, while TGF-ß1 stimulated hAELVi cells showed a decreased release of PGE2 and IL-8 during hypoxia compared to normoxia. Metabolic activity was significantly increased by hypoxia in both epithelial cell types. Discussion: In conclusion, our data indicate that bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodelling processes compared to the alveoli, suggesting that hypoxia may be a driver of pathogenesis in chronic lung disorders.

Effects of cleaning spray use on eyes, airways, and ergonomic load.

BACKGROUND: Cleaning workers are exposed to chemicals and high physical workload, commonly resulting in airway problems and pain. In this study the response in the upper airways and the physical workload following airborne and ergonomic exposure of cleaning spray was investigated. METHODS: A survey was answered by professional cleaning workers to investigate their use of cleaning sprays and the perceived effects on eyes, airways and musculoskeletal pain. A human chamber exposure study was then conducted with 11 professional cleaning workers and 8 non-professional cleaning workers to investigate the airborne exposure, acute effects on eyes and airways, and physical load during cleaning with sprays, foam application and microfiber cloths premoistened with water. All cleaning products used were bleach, chlorine, and ammonia free. The medical assessment included eye and airway parameters, inflammatory markers in blood and nasal lavage, as well as technical recordings of the physical workload. RESULTS: A high frequency of spray use (77%) was found among the 225 professional cleaning workers that answered the survey. Based on the survey, there was an eight times higher risk (p < 0.001) of self-experienced symptoms (including symptoms in the nose, eyes and throat, coughing or difficulty breathing) when they used sprays compared to when they cleaned with other methods. During the chamber study, when switching from spray to foam, the airborne particle and volatile organic compound (VOC) concentrations showed a decrease by 7 and 2.5 times, respectively. For the whole group, the peak nasal inspiratory flow decreased (-10.9 L/min, p = 0.01) during spray use compared to using only water-premoistened microfiber cloths. These effects were lower during foam use (-4.7 L/min, p = 0.19). The technical recordings showed a high physical workload regardless of cleaning with spray or with water. CONCLUSION: Switching from a spraying to a foaming nozzle decreases the exposure of both airborne particles and VOCs, and thereby reduces eye and airway effects, and does not increase the ergonomic load. If the use of cleaning products tested in this study, i.e. bleach, chlorine, and ammonia free, cannot be avoided, foam application is preferable to spray application to improve the occupational environment.

Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles.

BACKGROUND: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 µg m-3, EC: 54 µg m-3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: ~ 1 µg m-3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. RESULTS: The average total respiratory tract deposition of PM1 during HVOPM+NOx was 27 µg h-1. The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOx exhaust. Compared to FA, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to HVOPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L min-1, p < 0.001), and for the HVOPM+NOx (- 7.4 (- 15.6 to 0.8) L min-1, p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). CONCLUSION: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.

A quantitative LC-MS method to determine surface contamination of antineoplastic drugs by wipe sampling.

The main objective was to develop a wipe sampling test to measure surface contamination of the most frequently used antineoplastic drugs (ADs) in Swedish healthcare and, furthermore, to develop an analysis method sensitive enough to assess low levels of contamination. Two wipe sampling tests with separate sample processing methods assessing (i) cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5-FU), etoposide (ETO), gemcitabine (GEM) and cytarabine (CYT) (Wipe Test 1); and (ii) GEM, CYT and methotrexate (MTX) (Wipe Test 2), respectively, were developed by optimization of absorption and extraction efficiencies using different wipe tissue materials, tissue wetting solution, and extraction solvents. A fast liquid chromatography tandem mass spectrometry method was developed for simultaneous detection of the studied ADs. The limit of quantification for the method was between 0.04 to 2.4 ng/wipe sample (0.10 to 6.1 pg/cm2 for an area of 400 cm2) and at 50 ng/sample the within-day precision was between 1.3 and 15%, and the accuracy between 102 and 127%. Wipe Test 1 was applied in an assessment of cleaning efficiency of five different cleaning solutions (formic acid, water, sodium hydroxide, ethanol, and sodium dodecyl sulfate (SDS) for removal of ADs from surfaces made of stainless steel or plastic. For CP, IF, 5-FU, GEM, and CYT 92% of the AD were removed regardless of surface and cleaning solution. In conclusion, a user-friendly assessment method to measure low levels of seven ADs in the work environment was developed and validated. Assessment of the decontamination efficiency of cleaning solutions concerning removal of ADs from stainless steel showed that efficiencies differed depending on the AD with water being the least effective cleaning agent. The results suggests that a combination of different cleaning agents including detergent and a solution with an organic component would be optimal to efficiently remove the measured ADs from surfaces in the workplace.

Toxicological effects of zinc oxide nanoparticle exposure: an in vitro comparison between dry aerosol air-liquid interface and submerged exposure systems.

Engineered nanomaterials (ENMs) are increasingly produced and used today, but health risks due to their occupational airborne exposure are incompletely understood. Traditionally, nanoparticle (NP) toxicity is tested by introducing NPs to cells through suspension in the growth media, but this does not mimic respiratory exposures. Different methods to introduce aerosolized NPs to cells cultured at the air-liquid-interface (ALI) have been developed, but require specialized equipment and are associated with higher cost and time. Therefore, it is important to determine whether aerosolized setups induce different cellular responses to NPs than traditional ones, which could provide new insights into toxicological responses of NP exposure. This study evaluates the response of human alveolar epithelial cells (A549) to zinc oxide (ZnO) NPs after dry aerosol exposure in the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) system as compared to conventional, suspension-based exposure: cells at ALI or submerged. Similar to other studies using nebulization of ZnO NPs, we found that dry aerosol exposure of ZnO NPs via the NACIVT system induced different cellular responses as compared to conventional methods. ZnO NPs delivered at 1.0 µg/cm2 in the NACIVT system, mimicking occupational exposure, induced significant increases in metabolic activity and release of the cytokines IL-8 and MCP-1, but no differences were observed using traditional exposures. While factors associated with the method of exposure, such as differing NP aggregation, may contribute toward the different cellular responses observed, our results further encourage the use of more physiologically realistic exposure systems for evaluating airborne ENM toxicity.

Release of carbon nanotubes during combustion of polymer nanocomposites in a pilot-scale facility for waste incineration.

Nanocomposites, formed by incorporating nanoparticles into a matrix of standard materials, are increasing on the market. Little focus has been directed towards safe disposal and recycling of these new materials even though the disposal has been identified as a phase of the products' life cycle with a high risk of uncontrolled emissions of nanomaterials. In this study, we investigate if the carbon nanotubes (CNTs), when used as a filler in two types of polymers, are fully destructed in a pilot-scale combustion unit designed to mimic the combustion under waste incineration. The two polymer nanocomposites studied, polycarbonate (PC) with CNT and high-density polyethylene (HDPE) with CNT, were incinerated at two temperatures where the lower temperature just about fulfilled the European waste incineration directive while the upper was chosen to be on the safe side of fulfilling the directive. Particles in the flue gas were sampled and analysed with online and offline instrumentation along with samples of the bottom ash. CNTs could be identified in the flue gas in all experiments, although present to a greater extent when the CNTs were introduced in PC as compared to in HDPE. In the case of using PC as polymer matrix, CNTs were identified in 3-10% of the analysed SEM images while for HDPE in only ~0.5% of the images. In the case of PC, the presence of CNTs decreased with increasing bed temperature (from 10% to 3% of the images). The CNTs identified were always in bundles, often coated with remnants of the polymer, forming particles of ~1-4 µm in diameter. No CNTs were identified in the bottom ash, likely explained by the difference in time when the bottom ash and fly ash are exposed to high temperatures (~hours compared to seconds) in the pilot facility. The results suggest that the residence time of the fly ash in the combustion zone is not long enough to allow full oxidation of the CNTs. Thus, the current regulation on waste incineration (requiring a residence time of the flue gas >850 °C during at least 2 s) may not be enough to obtain complete destruction of CNTs in polymer composites. Since several types of CNTs are known to be toxic, we stress the need for further investigation of the fate and toxicity of CNTs in waste treatment processes.

Silver Nanoparticles Alter Cell Viability Ex Vivo and in Vitro and Induce Proinflammatory Effects in Human Lung Fibroblasts.

Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 µg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 µg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.

Exposure, respiratory symptoms, lung function and inflammation response of road-paving asphalt workers.

BACKGROUND: Controversy exists as to the health effects of exposure to asphalt and crumb rubber modified (CRM) asphalt, which contains recycled rubber tyres. OBJECTIVE: To assess exposures and effects on airway symptoms, lung function and inflammation biomarkers in conventional and CRM asphalt road pavers. METHODS: 116 conventional asphalt workers, 51 CRM asphalt workers and 100 controls were investigated. A repeated-measures analysis included 31 workers paving with both types of asphalt. Exposure to dust, nitrosamines, benzothiazole and polycyclic aromatic hydrocarbon (PAH) was measured in worksites. Self-reported symptoms, spirometry test and blood sampling were conducted prework and postwork. Symptoms were further collected during off-season for asphalt paving. RESULTS: Dust, PAHs and nitrosamine exposure was highly varied, without difference between conventional and CRM asphalt workers. Benzothiazole was higher in CRM asphalt workers (p<0.001). Higher proportions of asphalt workers than controls reported eye symptoms with onset in the current job. Decreased lung function from preworking to postworking was found in CRM asphalt workers and controls. Preworking interleukin-8 was higher in CRM asphalt workers than in the controls, followed by a decrement after 4 days of working. No differences in any studied effects were found between conventional and CRM asphalt paving. CONCLUSION: CRM asphalt workers are exposed to higher benzothiazole. Further studies are needed to identify the source of nitrosamines in conventional asphalt. Mild decrease in lung function in CRM asphalt workers and work-related eye symptoms in both asphalt workers were observed. However, our study did not find strong evidence for severe respiratory symptoms and inflammation response among asphalt workers.

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix.

BACKGROUND: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. METHODS: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. RESULTS: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. CONCLUSION: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

Dust-free bleaching powder may not prevent symptoms in hairdressers with bleaching-associated rhinitis.

OBJECTIVE: Hairdressers have an increased risk for airway symptoms especially when using hair-bleaching powder containing persulfate. To minimize exposure, dust-free bleaching powder (DFP) has been made available. We studied the effects of regular powder (RP) or DFP on the airway symptoms of hairdressers with hair-bleaching associated rhinitis. METHODS: Twelve hairdressers each performed three hair-bleachings on a wig in an exposure chamber. Half of the subjects used RP and half used DFP. Exposure to persulfate and ammonia was measured. Before and after each bleaching, the participants stated their degree of airway symptoms on a visual analogue scale. Nasal lavage and blood were sampled before exposure, after the last bleaching, and in the morning after exposure to measure inflammatory markers. RESULTS: Exposure to persulfate was higher when using RP compared to DFP, 22 (11-55) vs. 12 (8-13) µg/m3; median (min-max). Exposure to ammonia did not differ between the groups. Both groups reported an increase in asthma-like symptoms and this increase was significant. Neutrophils, lymphocytes, and monocytes increased after exposure in both groups; monocytes decreased the day after. In nasal lavage, IL-8 was increased the morning after for both types of powder, and the increase was significant in the total group. IL-6 increased immediately after exposure and the day after only in the group using RP. CONCLUSIONS: Although DFP powder emits lower levels of persulfate, effects are still elicited in symptomatic hairdressers.

Characterization of Hairdresser Exposure to Airborne Particles during Hair Bleaching.

Respiratory symptoms among hairdressers are often ascribed to the use of bleaching powders that contain persulfate salts. Such salts can act as allergens and airway irritants but the mechanisms behind the negative health effects are not fully known. In order to understand why some hairdressers experience respiratory symptoms during, and after, sessions of hair bleaching, it is of importance to characterize how exposure occurs. In this work we used time and particle size resolved instrumentation with the aim to measure the concentration of particles that hairdressers are exposed to during sessions of hair bleaching. We also used filter samples to collect particles for quantitative determination of persulfate (S2O8(2-)) content and for analysis by light microscopy. Two different types of bleaching powders were used, one marked as dust-free and one without this marking (denoted regular). The time resolved instrumentation revealed that particles <10 µm were emitted, specifically when the regular powder was prepared and mixed with hydrogen peroxide. In contrast to other research our work also revealed that supercoarse particles (>10 µm) were emitted during application of the bleaching, when both the regular and the dust-free powders were used. The measured level of persulfate, sampled in the breathing zone of the hairdressers, was on average 26 µg m(-3) when the regular powder was used and 11 µg m(-3) when the dust-free powder was used. This indicates that use of dust-free powder does not eliminate exposure to persulfates, it only lowers the concentration. We show that the site of sampling, or position of the hairdresser with regards to the hair being bleached, is of high importance in the determination of persulfate levels and exposure. This work focuses on the physical and chemical characterization of the particles released to the air and the results are important for accurate exposure assessments. Accurate assessments may in turn lead to a better understanding of why some hairdressers experience respiratory symptoms from hair bleaching sessions.