Functional and structural liver abnormalities in former PCB exposed workers - analyses from the HELPcB cohort.

The effects of polychlorinated biphenyls (PCB) on liver function and structure are still under debate. Although higher transaminase activity and tumor promoting potential of PCB reported for animal and human studies was suggested, these studies were not able to provide definitive evidence on the ability of these chemicals to affect liver function and contribution to tumor development. The aim of this study was to determine the influence of PCB on liver function and morphology in a cohort of former PCB exposed workers. Over 5 years, a longitudinal analysis of the association between PCB concentration and hepatic transaminases such as alanine transaminase (ALT) aspartate amino transaminase (AST) and gamma glutamyltransferase (γGT), as well as liver size and structure was undertaken. Data demonstrated a significant inverse association between PCB concentration and γGT activity levels but there was no marked relationship with AST and ALT activities. Regarding sonographic examination, a significant association was found between liver size and PCB concentration. This association remained, even after adjusting for alcohol consumption, liver affecting drugs, timespan of internal exposure, or age. No marked correlation was noted between PCB concentration and liver structure changes. In summary, an association was observed between PCB concentration and γGT activity levels as well as liver size in humans. The long-term health consequences attributed to PCB on liver and in particular in tumorigenesis are not foreseeable in our cohort thus far, but remain a focus in further ongoing surveillance.

Hyperpigmentation and higher incidence of cutaneous malignancies in moderate-high PCB- and dioxin exposed individuals.

Polychlorinated biphenyls (PCB) are well known persistent and toxic environmental pollutants. Our aim was to identify effects of moderate-high exposure to dioxin-like (dl) and non-dioxin-like (ndl)-PCBs on the skin in order to provide more insight in the pathophysiological effects of these compounds. We performed a dermatological examination on 92 former workers from a transformer recycling company with known elevated serum PCB and/or dioxin (polychlorinated dibenzo-p-dioxin/polychlorinated dibenzo-p-furan (PCDD/F)) levels. In addition, we performed a skin cancer screening over a period of seven years (2010-2016) on resp. 268, 271, 210, 149, 92, 129 and 79 participants. We found a higher incidence of acne and malignancies of the skin (malignant melanoma, basal cell carcinoma and mycosis fungoides) in the workers compared to normal population. The probability of having hyperpigmentation on the skin was statistically significantly higher in workers with higher sumPCBs- (OR:1.09(1.12-2.17)), dioxin-like (dl)-PCBs- (OR:1.56(1.12-2.17)) and dioxin (PCDD/Fs) (OR:1.09(1.02-1.16)) levels. Age was a confounding factor in this model. Formation of hyperpigmentation could be an indicator for (moderate-high) exposure to toxic compounds like PCBs. The higher incidence of cutaneous malignancies found in the workers might be associated with PCB- and dioxin exposure, warranting further investigation on larger cohorts.

Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) is associated with depressive symptomatology. A cause of depressive symptoms is a disturbance in the neurotransmitter system of dopamine (DA). Animal as well as human studies report that PCBs can influence the DA system. This study examined whether PCB-related depressive symptoms are affected by DA metabolites in humans with high PCB body burden. METHODS: This study is part of the German HELPcB surveillance program (Health Effects in high Level exposure to PCB) for occupationally exposed workers and their relatives. Data was collected from 178 participants on two measurement time points (t1 and t2) with a one-year time lag in between the two time points. PCBs were analyzed in plasma via human biomonitoring and a validated questionnaire was used to identify existence and severity of depressive symptoms. As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test whether the association between PCB exposure and severity of depressive symptoms is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation was tested with the SPSS macro MEDIATE. RESULTS: We found a significant mediation over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The positive association between PCB exposure with severity of depressive symptoms was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was associated with lower concentration in urinary HVA. A reduced HVA concentration at t1 was correlated with increased depressive symptoms severity at t2. No meditations were found for VMA. CONCLUSIONS: This work indicates that the association of PCB exposure and an increase of depressive symptoms after one year is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps towards finding an explanation for an underlying neurochemical pathomechanism of PCB-related depressive symptomatology.

Exposure to polychlorinated biphenyls and the thyroid gland - examining and discussing possible longitudinal health effects in humans.

BACKGROUND: Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. OBJECTIVES: The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. METHODS: A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. RESULTS: There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. CONCLUSION: This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation.

Parental education and neighbourhood socioeconomic status in the prediction of childhood overweight: A multilevel analysis.

OBJECTIVE: This study examined cross-level interaction between parental education and neighbourhood SES in predicting overweight including obesity among school-aged children. METHODS: This analysis used data from 19 984 children aged 5-6 years participating in the school-entry examination of the years 2015 to 2019 in the Aachen city region in Germany. We employed multilevel logistic regression models to predict overweight based on parental education and neighbourhood SES, along with their cross-level interaction, while controlling for several characteristics of the child. RESULTS: Children from families with intermediate (OR: 1.99; 95% CI, 1.65-2.40) and low parental education (OR: 2.55; 95% CI, 1.92-3.39) and from neighbourhoods with intermediate (OR: 1.25; 95% CI, 1.02-1.53) and low SES (OR: 1.61; 95% CI, 1.29-2.02) were at significantly higher odds for overweight. There was an indication of a cross-level interaction effect (p-value <0.10) to the disadvantage of children with higher parental education, suggesting that inequalities in overweight decrease in more deprived neighbourhoods. The predicted probability of overweight for children with high parental education increased from 6.4% in high SES neighbourhoods to 7.8% in intermediate and 9.9% in low SES neighbourhoods. Sensitivity analyses for obesity and a higher context level of spatial SES confirmed the results. CONCLUSIONS: The results highlight the crucial role of both individual and contextual socioeconomic conditions in predicting childhood overweight. They also suggest that the impact of neighbourhood socioeconomic status on childhood overweight varies by parental education, particularly disadvantaging children with higher parental education, indicating a social contagion of overweight through spatial disadvantage.

Experimental exposure of healthy subjects with emissions from a gas metal arc welding process--part II: biomonitoring of chromium and nickel.

OBJECTIVES: The objective of this study was to investigate whether there is a relationship between the external exposure dose of chromium and nickel caused by a metal active gas welding process with a solid high-alloyed steel welding wire and inner exposure of subjects. In order to perform welding fume exposure under controlled and standardized conditions, the investigations were conducted in the "Aachen Workplace Simulation Laboratory". METHODS: To perform biological monitoring of chromium and nickel, blood and urine samples of 12 healthy male non-smokers who never worked as welders were collected before and after a 6-h exposure to ambient air (0 mg/m(3)) and to welding fumes of a metal active gas welding process once with a concentration of the welding fume of 1 mg/m(3) and once with a concentration of 2.5 mg/m(3). RESULTS: Although the internal exposure to chromium and nickel in this study was comparatively low, the subjects showed significantly increased concentrations of these metals in urine after exposure to welding fume compared to the values at baseline. Moreover, the observed increase was significantly dose dependent for both of the substances. CONCLUSION: For the biological monitoring of chromium and nickel in urine of subjects exposed to welding fumes, a dependency on exposure dose was seen under standardized conditions after a single exposure over a period of 6 h. Thus, this study contributes to a better understanding of the relationship between ambient and biological exposures from welding fumes and provides a good basis for evaluating future biological threshold values for these metals in welding occupation.

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.

Surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company, family members, employees of surrounding companies, and area residents--executive summary.

In a German company polychlorinated biphenyls (PCB)-containing transformers and capacitors were recycled on a large scale. Human biomonitoring revealed a high PCB body burden in workers of the recycling company, in surrounding locations of this plant, in companies in the neighborhood of this plant, and in family members of these employees. In order to clarify whether possible adverse health effects occurred or may occur in the future, a prospective surveillance program was initiated. After an extensive literature search, an interdisciplinary group of experts developed a surveillance program based on current knowledge with respect to possible adverse health effects that might occur in the recycling process of transformers and capacitors. Exposure to various hazardous substances (PCB, polychlorinated dibenzo-p-dioxins and dibenzo-furans [PCDD/F], metals, solvents) was considered. Criteria derived from human biomonitoring results of PCB were used for admission to the program. Participants in the surveillance program are first informed about risks and aims of the program. Subsequently, physicians started a detailed documentation of participants' general and occupational history, with their complaints, diseases, and nutritional habits, as well as information regarding their living areas, by means of a standardized questionnaire. In addition, separate examinations were performed to detect possible neurological, immunological, (neuro)psychological, hormonal, and skin effects. Moreover, DNA exposure as assessed by the comet assay and antioxidative status were determined. The program will be offered at yearly intervals for 3 years, and then at 5 and 10 years after program onset. Until now the program has proved to be feasible, and acceptance among workers and their families has been high. Based on the results, criteria will be developed to define adverse health effects that might be attributable to a hazardous substance exposure.

Determination of 2,5-toluylenediamine (2,5-TDA) and aromatic amines in urine after personal application of hair dyes: kinetics and doses.

The personal use of hair dye products is currently under discussion due to the potentially increased risk of bladder cancer among long-time users described in epidemiological literature. In order to investigate the dermal absorption of aromatic diamines as well as aromatic amines possibly present as contaminants in hair dye formulations, we conducted a biomonitoring study under real-life conditions and calculated kinetics and doses for the urinary excretion. Urine samples of two female subjects were collected for a time period of 48 h after personal application of a hair dye cream and analysed for aromatic diamines as well as o-toluidine and 4-aminobiphenyl using highly specific GC/MS-methods. 2,5-Toluylenediamine (2,5-TDA) as active ingredient of hair dyes is rapidly absorbed dermally. After a distribution phase of 12 h, 2,5-TDA is excreted with a half-time of 8 h. Excretion was 90% complete within 24 h after application. The doses of 2,5-TDA excreted within 48 h were 700 µg for application of a brown-reddish hair dye cream and 1.5 mg for the application of a brown-black hair dye cream. Urinary 4-aminobiphenyl as well as contaminations with other aromatic diamines were not detectable in our study. Due to the artifactual formation of o-toluidine in the presence of high concentrations of urinary 2,5-TDA, our results could not prove an increased internal exposure of humans to carcinogenic amines after personal application of hair dyes.

Biological effect markers in exhaled breath condensate and biomonitoring in welders: impact of smoking and protection equipment.

PURPOSE: The objective of this study was to investigate the effect of welding as well as the impact of smoking and protection measures on biological effect markers in exhaled breath condensate. Additionally, biomonitoring of chromium, aluminium and nickel in urine was performed to quantify internal exposure. METHODS: Exhaled breath condensate (EBC) and urine samples of 45 male welders and 24 male non-exposed control subjects were collected on Friday pre-shift and after 8 h of work post-shift. In EBC, biological effect markers such as malondialdehyde, nitrite, nitrate, 3-nitrotyrosine, tyrosine, hydroxyproline, proline, H(2)O(2) and pH-value were measured while aluminium, nickel, and chromium were measured in the urine samples. RESULTS: Although internal exposure to aluminium, nickel and chromium in this study was low, welders showed significantly increased concentrations of all these parameters at baseline compared to non-exposed controls. Moreover, welders had higher nitrate concentrations in EBC at baseline and after shift. Nitrate concentration was considerably lower after shift if personal protection equipment was used. H(2)O(2) was increased only when subjects smoked during shift. CONCLUSION: It has been shown that welding-associated long-term and short-term health effects could be detected in a population of welders. The results also showed that using personal protection equipment is of high importance and H(2)O(2) may be an effect marker associated with smoking rather than with welding fumes, while nitrate in EBC seems to be sensitive to welding fume exposure.

Cross-Sectional and Longitudinal Effects of PCB Exposure on Human Stress Hormones in the German HELPcB Surveillance Program.

Multiple pathological associations are attributed to PCBs (polychlorinated biphenyls). Research shows a positive association of PCBs with dehydroepiandrosterone sulfate (DHEAS) concentration but the results on the stress hormone cortisol have been inconsistent so far. This study is the first to examine not only the cross-sectional but also the longitudinal effects of PCB exposure on the stress hormones DHEAS and cortisol. Over a period of three years, 112 former employees occupationally exposed to PCBs were tested for their body burden with different types of PCBs (lower and higher chlorinated, dioxin-like and hydroxylated) and for their stress hormone concentration. Highly exposed employees showed a significantly higher risk for higher DHEAS values. Multiple linear regression analysis revealed a positive relationship between the exposure to lower chlorinated PCBs and DHEAS. Mixed models also revealed a significantly positive correlation between lower chlorinated PCBs with DHEAS when controlled for a cross-section. However, an effect for cortisol was not found. These results suggest a causal pathophysiological relationship between PCB exposure and DHEAS concentration, but not with cortisol. The health consequences of high DHEAS concentrations are discussed.

Depressive Symptoms After PCB Exposure: Hypotheses for Underlying Pathomechanisms via the Thyroid and Dopamine System.

Polychlorinated biphenyls' (PCB) exposure has been reported to be associated with depressive symptoms, which is correlated to lower dopamine- (DA) and thyroxine-concentrations (T4). T4 is necessary for DA-synthesis and it binds to transthyretin (TTR) being transported into the brain. PCBs can displace T4 by binding to TTR itself, being transported into the brain and disturbing DA-synthesis, where depressive symptoms might occur. Consequently, the free T4-concentration (fT4) increases when PCBs bind to TTR. The interaction of PCBs with fT4 and its associations with the main DA metabolite, homovanillic acid (HVA), and depressive symptoms were investigated. In total, 116 participants (91.6% men) were investigated, who took part in three annual examinations (t1⁻t3) of the HELPcB health surveillance program. Blood was collected for measuring PCBs, hydroxy PCBs (OH-PCBs), and fT4 and urine for HVA. Depressive Symptoms were assessed with a standardized questionnaire. Interactions were tested cross-sectionally with multiple hierarchical regressions and longitudinally with mixed effect models. Related to HVA, an interaction was cross-sectionally found for lower-chlorinated PCBs (LPCBs) and dioxin-like PCBs (dlPCBs); longitudinally only for LPCBs. Related to depressive symptoms, the interaction was found for LPCBs, dlPCBs, and OH-PCBs; longitudinally again only for LPCBs. The results give first hints that a physiological process involving the thyroid and DA system is responsible for depressive symptoms after PCB exposure.

Expression of CYP1A1, CYP1B1 and IL-1ß in PBMCs and skin samples of PCB exposed individuals.

Polychlorinated biphenyls (PCBs) are well- known man-made persistent environmental pollutants and endocrine disruptors. As a result of mass production in the past, background levels of these compounds can be measured in human blood worldwide. In 2010 high internal levels of PCBs were discovered in workers of a transformer-recycling company in Germany. Our aim was to measure, whether the expression of CYP1A1, CYP1B1, and IL-1ß is dysregulated in peripheral blood mononuclear cells (PBMCs) of the exposed individuals (n = max 308). Further, we measured the regulation of CYP1A1, CYP1B1, AHRR (aromatic hydrocarbon receptor repressor) and IL-1ß in skin samples of 25 workers with elevated plasma PCB levels using quantitative PCR (q-RT-PCR). We found a significant correlation between the regulation of IL-1ß in skin samples and lipid adjusted PCB levels. In the PBMCs, the expression levels of CYP1A1, CYP1B1 and IL-1ß decreased over time with decreasing PCB plasma levels. The upregulation of the cytokine IL-1ß in exposed individuals with higher PCB plasma levels warrants further investigation in order to examine its role in the pathophysiology of autoimmune disorders and tumor promotion.

Use of plasma exchange or double filtration plasmapheresis to reduce body burden of polychlorinated biphenyls: A pilot trial.

The aim of the study was to examine whether plasma exchange (PE) or selective double filtration plasmapheresis (DFPP) is able to reduce the internal Polychlorinated biphenyl (PCB) burden of highly exposed participants of the health effects in high-level exposure to PCB (HELPcB) cohort. HELPcB is a surveillance program for former PCB-exposed workers of a German capacitor recycling company. After comparative evaluation of PE and DFPP in a phase I, DFPP was chosen as method for further treatment. In phase II, five participants underwent DFPP at weekly intervals for the duration of 12 weeks. Six PCB species were selected as indicators and were analyzed in the plasma before and after each treatment and 4 weeks after the last treatment. The PCB levels before and after each DFPP treatment showed a significant reduction in PCB blood levels; however, there was no significant change in PCB levels within the samples collected before each treatment as compared with the samples collected in the following week before treatment. Even the difference between PCB levels at the onset of the study and 4 weeks after the last treatment was not significant. The results of this pilot trial do not encourage further investigations in using therapeutic apheresis to reduce the PCB body burden.

Association between polychlorinated biphenyls and diabetes mellitus in the German HELPcB cohort.

AIMS: The aim of the present study was to examine whether there is an association between the prevalence of diabetes mellitus, the levels of HbA1c and the internal PCB burden of the initial 263 participants of HELPcB (Health Effects in High-Level Exposure to PCB). Four waves of follow ups were examined with a cross sectional and a longitudinal approach between 2010 and 2013. HELPcB is a surveillance program for formerly PCB-exposed workers of a capacitor recycling company and other potentially affected people. METHODS: During 4 waves of follow up, medical history and blood samples were taken. Biomonitoring for PCB was conducted by gas chromatography coupled with mass spectrometry. Serum analysis of blood glucose, HbA1c, GAD, IAA, IA-2 and ICA were conducted at the centre of laboratory diagnostics of the local university hospital. RESULTS: The mean levels of PCB were comparable to other investigations of occupational cohorts like Persky et al. (2012). A logistic regression model showed higher prevalence rates in comparison to the German general population for diagnosed or undiagnosed diabetes mellitus for several PCB congeners in the second, third or fourth quartile of PCB burden. The adjusted odds ratio was significantly increased for PCB 52 at the third quartile (7.6; 95% CI: 1.4-41.0). A multiple linear regression model showed a significant influence of several PCB congeners on the HbA1c level at year 3 and 4. The development of HbA1c over time was examined with the same regression model applied to a longitudinal data set of 119 participants who met all 4 follow ups. An analysis of the autoantibodies GAD, IAA, IA-2 and ICA showed no association to PCB burden. CONCLUSIONS: In summary there is a detectable association between internal PCB burden and glucose metabolism in the cohort of HELPcB, however it is difficult to find a possible mechanism or a congener with outstanding influence. Further research and more follow ups for the HELPcB cohort are scheduled.

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.

Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective.

BACKGROUND: Polychlorinated biphenyls (PCBs) are chemicals which were used for industrial purposes and are known to induce various adverse health effects. They are also known to be neurotoxic and numerous targets within the central nervous system have been identified in previous studies. Specifically, the neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as indicated in studies involving animals. However, limited evidence has been published documenting PCB induced changes in the neurotransmitter system in humans. OBJECTIVE: In the present study, we examined the association between a higher PCB body burden following occupational exposure and possible changes in human neurotransmitter metabolites. METHODS: Within a medical surveillance programme called HELPcB (Health Effects in High-Level Exposure to PCB) that monitors adverse health effects of occupational PCB exposure, urine samples were obtained (n(T1) = 166; n(T2) = 177 and n(T3) = 141). The urinary concentrations of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in order to determine the internal exposure to PCBs with human biomonitoring. RESULTS: A cross-sectional analysis indicated a significant negative effect of PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to higher chlorinated PCBs was followed by constant reduced HVA level over three consecutive years. Exploratory analyses show different long-term effects for different PCBs according to their chlorination degree. A higher exposure with lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher exposure to all PCBs results in a reduction of HVA. CONCLUSION: This study, to our knowledge, is the first to document changes in neurotransmitter metabolites after occupational PCB exposure in humans. This finding advances evidence obtained from past research, and identifies one potential pathomechanism in the central dopaminergic system of humans.

Assessment of the Biological Effects of Welding Fumes Emitted From Metal Active Gas and Manual Metal Arc Welding in Humans.

OBJECTIVE: Emissions from a particular welding process, metal inert gas brazing of zinc-coated steel, induce an increase in C-reactive protein. In this study, it was investigated whether inflammatory effects could also be observed for other welding procedures. METHODS: Twelve male subjects were separately exposed to (1) manual metal arc welding fumes, (2) filtered air, and (3) metal active gas welding fumes for 6 hours. Inflammatory markers were measured in serum before, and directly, 1 and 7 days after exposure. RESULTS: Although C-reactive protein concentrations remained unchanged, neutrophil concentrations increased directly after exposure to manual metal arc welding fumes, and endothelin-1 concentrations increased directly and 24 hours after exposure. After exposure to metal active gas and filtered air, endothelin-1 concentrations decreased. CONCLUSIONS: The increase in the concentrations of neutrophils and endothelin-1 may characterize a subclinical inflammatory reaction, whereas the decrease of endothelin-1 may indicate stress reduction.

QALY as evaluation tool in a health surveillance program.

BACKGROUND: Quality adjusted life years (QALYs), based on health related quality of life (HRQL), are a commonly used concept in health economics. The aim of this study was to apply the concept of QALY to the evaluation of a surveillance program for health related effects of PCB exposure and measure the impact of occupational PCB-exposure on the remaining QALYs of participants. METHODS: The internal PCB exposure was determined by gas chromatography with mass spectrometry in plasma. The HRQOL was assessed via the EQ-5D-3L instrument and combined with the remaining lifetime (RLE) at the time point of cessation of exposure. For comparative reasons we used both the linear calculation and the complex-number-model from Prieto and Sacristan. The impact of several PCB congeners was regressed on the percentage of discounted QALYs on RLE via hierarchical multiple regression, controlling for gender, relational and educational status. RESULTS: Findings were able to detect a small but significant effect of elevated plasma levels of PCB on QALY for the linear calculation and partially for the complex number calculation. This means that an internal exposure to PCB reduced HRQOL in the RLE of participants in the surveillance program. CONCLUSION: QALYs can be applied successfully to monitor HRQL effects in surveillance programs. The exposure to a hazardous substance has an influence on QALYs. Findings have to be interpreted as a first hint. In the following assessment it has to be monitored whether there is an improvement or worsening of HRQL.