Monika Gube

Plasma Polychlorinated Biphenyls (PCB) Levels of Workers in a Transformer Recycling Company, their Family Members, and Employees of Surrounding Companies

In spring 2010, high internal exposures (up to 236 μg/L plasma) for the sum of indicator polychlorinated biphenyls (PCB) were discovered in workers in a transformer recycling company in Germany, where PCB-contaminated material was not handled according to proper occupational hygiene. The release of PCB from this company raised growing concerns regarding possible adverse human health effects correlated with this exposure. This provided a basis for a large biological monitoring study in order to examine the internal exposure to PCB in individuals working in that recycling company, their family members, and relatives, as well as subjects working or living in the surroundings of this company. Blood samples from 116 individuals (formerly) employed in the transformer recycling company and 45 direct relatives of these persons were obtained. Further, blood samples of 190 subjects working in close vicinity of the recycling plant, 277 persons working in the larger area, and 41 residents of the area were investigated. Plasma samples were analyzed for the 6 indicator PCB (PCB 28, 52, 101, 138, 153, 180) and 12 dioxin-like PCB using gas chromatography/mass spectroscopy (GC/MS; limit of detection [LOD] at 0.01 μg/L). Median concentrations (maximum) for the sum of the 6 indicator PCB in blood of the employees, their relatives, individuals working in close vicinity, persons working in the larger area, and the residents were 3.68 (236.3), 1.86 (22.8), 1.34 (22.9), 1.19 (6.42), and 0.85 (7.22) μg/L plasma, respectively. The (former) employees of the transformer recycling plant partly showed the highest plasma PCB levels determined thus far in Germany. Even family members displayed highly elevated levels of PCB in blood due to contaminations of their homes by laundering of contaminated clothes. Vicinity to the recycling plant including reported contact with possibly contaminated scrap was the main contributor to the PCB levels of the workers of the surrounding companies. Residents of the area did not show significantly elevated blood PCB levels compared to the general population. Our biomonitoring results served as a basis for individual risk communication and successful risk management.

Internal exposure, effect monitoring, and lung function in welders after acute short-term exposure to welding fumes from different welding processes.

Objective: In this study, the effect of short-term exposure to welding fumes emitted by different welding techniques on workers was investigated. Methods: In a 3-fold crossover study, six welders used three different welding techniques for 3 hours. Before and after welding, blood and urine samples were collected to perform biomonitoring of metals. Breath condensate was collected to assess inflammatory reactions, and lung function measurements were performed. Results: Welding led to a significant increase of chromium and nickel in blood and urine and of nitrate and nitrite in exhaled breath condensate. These increases were higher for manual metal arc welding with alloyed material (MAW-a). Several lung function parameters decreased after welding. This decrease was significantly higher after MAW-a. Conclusions: In respect to biological effects, MAW-a seems to be more important than other welding techniques.

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.

Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.

The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.

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.

Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and CYFRA21-1 in Serum

The purpose of this analysis was to evaluate if serum levels of potential tumor markers for the diagnosis of malignant mesothelioma and lung cancer are affected by confounding factors in a surveillance cohort of workers formerly exposed to asbestos. SMRP, CA125, and CYFRA21-1 concentrations were determined in about 1,700 serum samples from 627 workers formerly exposed to asbestos. The impact of factors that could modify the concentrations of the tumor markers was examined with linear mixed models. SMRP values increased with age 1.02-fold (95% CI 1.01–1.03) and serum creatinine concentration 1.32-fold (95% CI 1.20–1.45). Levels differed by study centers and were higher after 40 years of asbestos exposure. CA125 levels increased with longer storage of the samples. CYFRA21-1 values correlated with age 1.02-fold (95% CI 1.01–1.02), serum creatinine 1.21-fold (95% CI 1.14–1.30) and varied by study centers due to differences in sample handling. Tumor marker concentrations are influenced by subject-related factors, sample handling, and storage. These factors need to be taken into account in screening routine.

Relationship between welding fume concentration and systemic inflammation after controlled exposure of human subjects with welding fumes from metal inert gas brazing of zinc-coated materials.

Objectives:It has been shown that exposure of subjects to emissions from a metal inert gas (MIG) brazing process of zinc-coated material led to an increase of high-sensitivity C-reactive protein (hsCRP) in the blood. In this study, the no-observed-effect level (NOEL) for such emissions was assessed. Methods:Twelve healthy subjects were exposed for 6 hours to different concentrations of MIG brazing fumes under controlled conditions. High-sensitivity C-reactive protein was measured in the blood. Results:For welding fumes containing 1.20 and 1.50 mg m−3 zinc, high-sensitivity C-reactive protein was increased the day after exposure. For 0.90 mg m−3 zinc, no increase was detected. Conclusions:These data indicate that the no-observed-effect level for emissions from a MIG brazing process of zinc-coated material in respect to systemic inflammation is found for welding fumes with zinc concentrations between 0.90 and 1.20 mg m−3.

Spirometry, Impulse Oscillometry and Capnovolumetry in welders and healthy male subjects

BACKGROUND Welding processes emit fine and ultrafine aerosol particles which are potentially harmful to the lungs of welders. In the past, changes in lung function were mostly determined by conventional spirometry. In this study spirometry was combined with new techniques such as Impulse Oscillometry (IOS) and Capnovolumetry (CVS) in order to assess welding associated changes in lung function. METHODS 45 Male welders and 24 non-welders were investigated at two time points: before work shift (baseline) and after work shift. RESULTS At baseline there were no differences between both study populations in spirometric, IOS, and CVS parameters. However, parameters of the flow-volume curve decreased with increasing long-term welding fume exposure (welding years). Airway resistances measured by IOS increased with welding years. IOS central airway resistance and several parameters of CVS increased during the work shift indicating airway narrowing and more inhomogeneous ventilation. CONCLUSIONS In this study it has been shown that welding associated long-term and short-term effects could be detected in a population of welders, although exposure conditions were quite heterogeneous. The parameters of IOS and Capnovolumetry showed effects even more pronounced than conventional lung function parameters. Thus, these techniques may be considered as an additional tool for occupational medicine research.

Single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes Lead to Asymptomatic Systemic Inflammation.

Objective: Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect. Methods: Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc. Results: For each exposure blood C-reactive protein increased. Conclusions: Copper- and zinc-containing welding fumes are able to induce systemic inflammation.

Immunotoxicity Monitoring in a Population Exposed to Polychlorinated Biphenyls

The relationship between polychlorinated biphenyl (PCB) burden and several indicators of immune function was investigated as part of the HELPcB (Health Effects in High-Level Exposure to PCB) program, offering bio-monitoring to workers, relatives, and neighbors exposed to PCBs by a German transformers and capacitors recycling company. The present retrospective observational study evaluates the correlation of plasma levels of total PCBs, five indicator congeners (28, 101, 138, 153, 180), and seven dioxin-like congeners (105, 114, 118, 156, 157, 167, 189) with several parameters of immune function. The cross-sectional study was performed immediately after the end of exposure (258 subjects), and one (218 subjects), and two (177 subjects) years later. At the first time point, measurements showed significant positive correlation between congeners with low to medium chlorination and the relative proportion of CD19 positive B-cells among lymphocytes, as well as a negative correlation of PCB114 with serum IgM, and of PCB 28 with suppressor T-cell and NK-cell numbers. Congeners with a high degree of chlorination, in particular PCB157 and 189, were positively associated with expression of the activation marker CD25 on T-cells in the cohort of the second time point. No associations between PCB levels and IFN-y production by T-cells and killing by NK-cells were found. In conclusion, there were several effects on the cellular composition of adaptive immunity, affecting both T- and B-cells. However, the values were not generally outside the reference ranges for healthy adult individuals and did not indicate overt functional immunodeficiency, even in subjects with the uppermost PCB burden.