Human nasal mucosal C-reactive protein responses after inhalation of ultrafine welding fume particles: positive correlation to systemic C-reactive protein responses.

Exposures to occupationally relevant ultrafine, zinc- and copper-containing welding fumes cause inflammatory responses involving systemic IL-6, C-reactive protein (CRP) and serum amyloid A (SAA), all associated with elevated risk of cardiovascular events. We investigated whether the systemic response is preceded by nasal inflammatory reactions. Fifteen nonsmoking male subjects were exposed for 6 h under controlled conditions to zinc-/copper-containing welding fumes (at 2.5 mg/m3) or ambient air control in a randomized order. Nasal secretions were collected before and at 1, 3, 6, 10, and 29 h after exposure. Nasal levels of selected biomarkers were determined by electrochemiluminescent assays and related to their systemic levels. Nasal interferon-γ (IFN-γ) peaked significantly 1 h after start of exposure compared to baseline. Nasal CRP as well as SAA increased significantly at 10 and 29 h compared to baseline. Receiver operating characteristic (ROC) curve analysis for differentiating welding fume from control exposure was performed: The highest area under ROC curve (AUC) values were found for the CRP increases (10, 29 h versus 0 h): AUC = 0.83, and for IFN-γ increases (1 h versus 0 h): AUC = 0.92. Nasal and systemic changes of CRP at 29 h revealed a strong correlation (Spearman rank test: increases compared to baseline: r = 0.815, p = 0.0022; absolute levels: r = 0.9, p = 0.0002). In conclusion, short-term exposure to a zinc- and copper-containing welding fume causes significant increases of inflammatory mediators in nasal mucosal lining fluid. Therefore, measurement of nasal inflammatory mediators may provide a useful means for occupational surveillance of workers exposed to ultrafine metal fume particles.

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes.

Zinc- and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P=0.0005, "zinc only": P=0.027, "copper and zinc": P=0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper- and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders.

IL-6, a central acute-phase mediator, as an early biomarker for exposure to zinc-based metal fumes.

AIMS: Systemic C-reactive protein (CRP) increases 1day after short-term inhalation of welding fumes containing zinc and/or copper. The aim of the current study was to find further, possibly earlier systemic biomarkers after inhalation of different welding fumes containing zinc and traces of aluminum, with or without copper, as these metal combinations become more common in modern joining technology. METHODS: The study group consisted of 15 non-smoking male volunteers with healthy lung function data and without any occupational metal fume exposure. On 4 different exposure days, the members of the study group were exposed under controlled conditions to ambient air or 3 different welding fumes for 6h. Spirometric and impulse oscillometric measurements and differential blood counts were performed and serum samples were collected before exposure and 6, 10 and 29h after start of exposure. The biomarker concentrations in serum were measured by electrochemiluminescent assays. RESULTS: Systemic increases of IL-6 peaked significantly at 10h compared to baseline ("ZincZinc": P=0.0005 (median increase (m. incr.)=1.36pg/mL); "ZincAlu": P=0.0012 (m. incr.=1.48pg/mL); "AluBronze": P=0.0005 (m. incr.=2.66pg/mL)). At 29h, CRP and serum amyloid A (SAA) increased distinctively ("ZincZinc": P=0.032 (m. incr.=0.65µg/mL) [CRP], 0.077 (m. incr.=0.61µg/mL) [SAA]; "ZincAlu": P=0.001 (m. incr.=1.15µg/mL) [CRP], 0.0024 (m. incr.=0.94µg/mL) [SAA]; "AluBronze": P=0.002 (m. incr.=2.5µg/mL) [CRP], 0.002 (m. incr.=0.97µg/mL) [SAA]). The median increases of CRP and IL-6 were most pronounced for the welding fume which contained besides zinc also copper (AluBronze). For differentiating AluBronze from control exposure, receiver operating characteristic (ROC) curve analysis was performed and the area under the ROC curve (AUC) for the IL-6 increases (10h versus 0h) was 0.931. The additional inflammatory mediators [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interferon-γ (IFN-γ), cell counts] and the lung function parameters did not show any significant changes after exposure. CONCLUSIONS: Consistent with its role of the mediation of the acute-phase response, systemic increases of IL-6 after welding fume exposure peak at 10h before the increases of the acute-phase reactants CRP and SAA at 29h. IL-6 may represent a highly sensitive and early biomarker for the exposure to metal fumes containing zinc and copper. As IL-6, CRP and SAA are independent, strong risk markers for future cardiovascular diseases, these data may particularly be important for long-term welders with respect to their cardiovascular health.

Biological effects of inhaled nitrogen dioxide in healthy human subjects.

PURPOSE: Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques. METHODS: Twenty-five subjects were exposed for 3 h to NO2 concentrations 0, 0.1, 0.5, and 1.5 ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate. RESULTS: From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5 ppm (p = 0.048) compared to 0.1 ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p = 0.05). CONCLUSION: These results do not suggest a considerable acute adverse response in human subjects after 3 h of exposure to NO2 in the NO2 concentration range investigated in this study.

Neuromuscular and athletic performance following core strength training in elite youth soccer: Role of instability.

Cross-sectional studies revealed that inclusion of unstable elements in core-strengthening exercises produced increases in trunk muscle activity and thus potential extra stimuli to induce more pronounced performance enhancements in youth athletes. Thus, the purpose of the study was to investigate changes in neuromuscular and athletic performance following core strength training performed on unstable (CSTU) compared with stable surfaces (CSTS) in youth soccer players. Thirty-nine male elite soccer players (age: 17 ± 1 years) were assigned to two groups performing a progressive core strength-training program for 9 weeks (2-3 times/week) in addition to regular in-season soccer training. CSTS group conducted core exercises on stable (i.e., floor, bench) and CSTU group on unstable (e.g., Thera-Band® Stability Trainer, Togu© Swiss ball) surfaces. Measurements included tests for assessing trunk muscle strength/activation, countermovement jump height, sprint time, agility time, and kicking performance. Statistical analysis revealed significant main effects of test (pre vs post) for trunk extensor strength (5%, P < 0.05, d = 0.86), 10-20-m sprint time (3%, P < 0.05, d = 2.56), and kicking performance (1%, P < 0.01, d = 1.28). No significant Group × test interactions were observed for any variable. In conclusion, trunk muscle strength, sprint, and kicking performance improved following CSTU and CSTS when conducted in combination with regular soccer training.

Effect of occupational polychlorinated biphenyls exposure on quality-adjusted life years over time at the HELPcB surveillance program.

HELPcB (Health Effects in High-Level Exposure to Polychlorinated Biphenyls [PCB]) is a surveillance program for former PCB-exposed workers of a capacitor recycling company and other concerned individuals. The aim of this study was to examine the influence of polychlorinated biphenyls (PCB) on the health-related quality of life (HRQL) and on quality-adjusted life years (QALY). The EQ-5D-3L questionnaire was used to determine the HRQL. After three cross-sectional examinations at intervals of 1 yr, the longitudinal development of QALY was compared by repeated-measurement analysis of covariance (ANCOVA). The cohort was split at the 95th percentile of the comparison group for each PCB congener; known confounders such as age were taken into account. A significant difference in height and development of QALY over time was shown for the higher chlorinated non-dioxin-like PCB (hcPCB) congeners. A significant between-groups effect was found on PCB 153, PCB 180, and the sum of hcPCB. It was found that QALY decreased in the high-burden group and QALY stabilized after yr 2 in the normal-burden group. Taking the dimensions of the EQ-5D into account, the between-groups effect seems to be based predominantly on the dimension anxiety. The development of the within-group effect, however, seems to be based on the dimension mobility. This study detected a significant influence of hcPCB on the development of HRQL and QALYs over time according to the level of internal PCB burden.

Assessment of the biological effects of welding fumes emitted from metal inert gas welding processes of aluminium and zinc-plated materials in humans.

The aim of this study was to investigate biological effects and potential health risks due to two different metal-inert-gas (MIG) welding fumes (MIG welding of aluminium and MIG soldering of zinc coated steel) in healthy humans. In a threefold cross-over design study 12 male subjects were exposed to three different exposure scenarios. Exposures were performed under controlled conditions in the Aachener Workplace Simulation Laboratory (AWSL). On three different days the subjects were either exposed to filtered ambient air, to welding fumes from MIG welding of aluminium, or to fumes from MIG soldering of zinc coated materials. Exposure was performed for 6 h and the average fume concentration was 2.5 mg m(-3). Before, directly after, 1 day after, and 7 days after exposure spirometric and impulse oscillometric measurements were performed, exhaled breath condensate (EBC) was collected and blood samples were taken and analyzed for inflammatory markers. During MIG welding of aluminium high ozone concentrations (up to 250 µg m(-3)) were observed, whereas ozone was negligible for MIG soldering. For MIG soldering, concentrations of high-sensitivity CRP (hsCRP) and factor VIII were significantly increased but remained mostly within the normal range. The concentration of neutrophils increased in tendency. For MIG welding of aluminium, the lung function showed significant decreases in Peak Expiratory Flow (PEF) and Mean Expiratory Flow at 75% vital capacity (MEF 75) 7 days after exposure. The concentration of ristocetin cofactor was increased. The observed increase of hsCRP during MIG-soldering can be understood as an indicator for asymptomatic systemic inflammation probably due to zinc (zinc concentration 1.5 mg m(-3)). The change in lung function observed after MIG welding of aluminium may be attributed to ozone inhalation, although the late response (7 days after exposure) is surprising.

Exposure of healthy subjects with emissions from a gas metal arc welding process: part 1--exposure technique and external exposure.

BACKGROUND: Studies concerning welding fume-related adverse health effects in welders are hampered by the heterogeneity of workplace situations, resulting in complex and non-standardized exposure conditions. METHODS: In order to carry out welding fume exposure studies under controlled and standardized conditions, the Aachen Workplace Simulation Laboratory was developed. This laboratory consists of an emission room, in which welding fume is produced, and an exposure room in which human subjects are exposed to these fumes. Both rooms are connected by a ventilation system which allows the welding fume concentration to be regulated. Particle mass concentration was measured with a TEOM microbalance and the particle number-size distribution using a Grimm SMPS device. RESULTS: In a study, which is the subject of this paper, it has been shown that welding fume concentration can easily be regulated between 1 and about 3 mg m(-3). The chosen concentration can be kept constant for more than 8 h. However, transport of the particles from the emission room into the exposure room leads to a change in particle size distribution, which is probably due to coagulation of the fraction of smallest particles. CONCLUSION: The Aachen Workplace Simulation Laboratory is suitable for controlled exposure studies with human subjects.

Exposure of healthy subjects with emissions from a gas metal arc welding process: part 3--biological effect markers and lung function.

BACKGROUND: Metal active gas welding (MAG) is a widely-used welding technique resulting in high emissions of welding fume particles. This study investigated whether short-term exposure to these fume particles results in changes in lung function and early stages of inflammatory reactions. METHODS: Twelve healthy, young male subjects were exposed to MAG fumes for 6 h with three different exposure concentrations in a three-fold cross-over study design. Exposure was performed in the "Aachen Workplace Simulation Laboratory" under controlled conditions with constant fume concentration. Fume concentrations were 0, 1, and 2.5 mg m(-3) in randomized order. Before and after each exposure, spirometry, and impulse oscillometry were performed and breath condensate samples were collected in order to quantify inflammatory markers like Nitrate, Nitrite, Nitrotyrosine, Hydroxyprolin and Malondialdehyde. RESULTS: A significant dependency on the exposure concentration could not be established for any of the endpoint parameters. CONCLUSION: In healthy, young subjects neither changes in spirometry nor changes in inflammatory markers measured in exhaled breath condensate could be detected after short-term exposure.

Pilot study on the exposure of the German general population to non-dioxin-like and dioxin-like PCBs.

In the past, polychlorinated biphenyls (PCBs) have been widely used and were distributed in the environment. Due to their high persistence and bioaccumulative potential, they can still be detected in the blood of the general population, despite their ban more than 20 years ago. Among the various congeners, the presence of dioxin-like PCBs in blood raises the highest environmental concerns due to their critical toxicological properties. We determined the plasma concentrations of 6 non-dioxin-like and 12 dioxin-like PCBs as well as the organochlorine pesticides HCB and p,p'-DDE (p,p'-dichlorodiphenyldichloroethylene) in a group of 105 non-smokers out of the German general population by GC/MS as an estimate of the background burden to these compounds. The organochlorine compounds were extracted from plasma with n-hexane, cleaned up on a silica gel column and finally quantified using GC/MS and (13)C(12)-labelled internal standards. The limit of detection for all congeners was determined to be 0.01 µg/Lplasma. Age had a strong influence on the plasma levels of HCB (hexachlorobenzene), p,p'-DDE and all higher chlorinated PCB congeners, while no gender difference was observed. Among the dioxin-like PCBs, PCB 118, PCB 156 and PCB 167 were detectable in 74-98% of all samples. Highly significant correlations between several PCB-congeners were observed. Our results provide for the first time volume-based data on the extent of the age-related background burden to dioxin-like PCBs in Germany.

Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos.

The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers.

Internal exposure of hairdressers to permanent hair dyes: a biomonitoring study using urinary aromatic diamines as biomarkers of exposure.

PURPOSE: To determine whether the occupational exposure of hairdressers to permanent hair dyes can be quantified by the use of biological monitoring of urinary aromatic diamines as one of the main constituents and to compare these levels to those recently determined in persons after personal application of hair dyes. METHODS: Fifty-two hairdressers (40 female and 12 male) from 16 hairdresser salons in and around the city of Aachen took part in this field study. Subjects were asked to document all operations associated with possible exposure to permanent hair dyes like mixing colour, application of colour, washing after dyeing, and cutting of freshly coloured hair. Excretion of aromatic diamines 2,5-toluylene diamine (2,5-TDA) and p-phenylene diamine (p-PDA) as main constituents of commercially available hair dyes was measured in urine samples using a highly specific and accurate GC/MS-method. Urine samples were taken at 5 points of time during the work week: pre-shift before the start of the work week, pre- and post-shift on the third day of the work week and finally pre- and post-shift on the last day of a work week in order to meet different workloads and possible accumulative effects over the week. Nineteen persons matched for age served as a control group and gave spot urine samples. RESULTS: Although the levels were generally low, we could determine a significantly higher internal exposure to 2,5-TDA in hairdressers (medians ranged from <0.2 µg/g creatinine up to 1.7 µg/g creatinine at various sampling times, with a maximum of 155.8 µg/g creatinine) compared to the control group (median <0.2 µg/g creatinine, maximum 3.33 µg/g creatinine). At the same time, p-PDA was detectable only in selected cases in the group of hairdressers but not in the control group. Overall, there was neither an intra-shift effect seen nor an effect across the work week. There was also no significant difference in urinary excretion of participants who reported wearing protective gloves compared to those who reported not wearing protective gloves. CONCLUSION: The internal exposure to aromatic diamines in hairdressers using permanent hair dyes can be determined using biological monitoring. The extent of exposure is low compared to subjects after personal application of hair dyes, who excreted more than 200 times higher amounts of aromatic diamines. This slight work-related exposure might be reduced by the strict adherence to the use of suitable gloves as well as long-sleeved clothing.

Neuron loss in the mouse hippocampus following prenatal injection of tritiated thymidine or saline.

To investigate possible effects of injections of tritiated thymidine ([3H]dThd) into pregnant mice or the injection procedure itself on the proliferation of neuronal precursor cells in the fetuses, pregnant mice received intraperitoneal injections of either [3H]dThd or saline on embryonic days 12, 14, and 19, while their offspring remained untreated. A second group of dams was not injected but their male offspring received a subcutaneous injection of again either [3H]dThd or saline on postnatal day 10. Then total numbers of hippocampal pyramidal cells (areas CA1 to CA3) and granular cells (dentate gyrus) were determined stereologically for 20-day-old as well as for 80-day-old male pups. No significant differences were found for the mean total number of pyramidal cells between the investigated groups of pups. However, the mean total number of granular cells was significantly reduced in those groups in which the dams had received an intraperitoneal injection, irrespective of whether [3H]dThd or saline was injected. This revives the repeated warning in the literature to consider the effect of the injection procedure on the developing brain when interpreting possible effects of agents administered during pregnancy.