Occupational exposure to polychlorinated biphenyls: Development of neuropsychological functions over time.

Occupational exposure to polychlorinated biphenyls (PCBs) continues to affect the health of exposed individuals until today. This study aims to expand previous findings by examining the development of neuropsychological functions of occupationally exposed participants over time. Especially verbal fluency and sensorimotor processing, found to be impaired in a previous study, were thus of particular interest. A total of 116 participants, who were part of the HELPcB cohort, underwent a neuropsychological test battery covering a multitude of cognitive functions. Plasma PCB levels were determined for each participant and classified as elevated or normal based on comparative values drawn from the German general population. Two structural equation models were then used to examine the effects of elevated PCB levels on neuropsychological functions. Results suggest that participants who displayed increased PCB plasma levels continued to show impairments in verbal fluency but not in sensorimotor processing after a second examination one year after the first measurement. Specifically, low chlorinated PCBs are associated with impaired verbal fluency, as compared to high-chlorinated and dioxin-like congeners. Alteration of dopamine concentration in response to PCB exposure might be a potential explanation of this result.

Determinants of exposure to acrylamide in European children and adults based on urinary biomarkers: results from the "European Human Biomonitoring Initiative" HBM4EU participating studies.

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (ß coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:ß = - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: ß = - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:ß = - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:ß = - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:ß = - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:ß = - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.

Ten years after: findings from the medical surveillance program on Health Effects in High-Level Exposure to PCB (HELPcB).

After the detection of high environmental and occupational exposure to polychlorinated biphenyls (PCBs) in a German recycling company for transformers and capacitors in 2010, the multidisciplinary medical surveillance program "HELPcB" (Health Effects in High-Level Exposure to PCB) was established for former PCB-exposed workers of the company, their family members, employees of surrounding companies, and area residents to investigate potential adverse health effects by PCB exposure in a longitudinal study approach with up to seven examination time points between 2010 and 2019. More than 300 individuals were enrolled into the program. Assessments particularly included plasma and urine concentrations of PCB congeners and their metabolites, clinical laboratory parameters, Comet assay, analysis of telomere length, neuropsychological examinations, psychological screening, abdominal and thyroid ultrasound examination. This review summarizes the main results of the studies conducted in the HELPcB program yielding relevant new data on potential adverse effects of PCB exposure in humans and potential mechanisms that underlie these effects. Even larger studies in PCB-exposed individuals are warranted to confirm the results of this program and to further establish causality between PCB exposure and clinical effects in humans.

Quantification of 26 metals in human urine samples using ICP-MSMS in a random sample collective of an occupational and environmental health care center in Aachen, Germany.

Despite several studies on metal exposure in the general population, the knowledge on the background burden of distinct metals is still sparse (e.g. Cu, In, Mn, Pb, Sn, Sr, Ta, Te). While up to date reference values exist for 16 distinct metals as Biological Reference Value (BAR) or the 95th percentile for Al, As, Ba, Be, Cd, Co, Cr, Hg, Li, Mo, Ni, Pt, Sb, Se, Tl and U respectively, the background burden of the general population for the remaining elements is unknown or yet no matter of scientific counselling. We established and validated an inductively coupled plasma triple quadrupole mass spectrometry (ICP-MSMS) human biomonitoring method (HBM), that enabled us to determine 26 metals in urine. Al, As, Ba, Be, Cd, Co, Cu, Ga, Gd, Hg, In, Li, Mo, Ni, Pb, Sb, Se, Sn, Sr, Ta, Te, Tl, V and Zn were analyzed. The method was applied to 88 urine samples collected in the ambulance of the Institute for Occupational, Social and Environmental Medicine (IASU) Aachen, Germany. Patients from two major metal processing companies (steel and copper) and a more heterogenous group of occupational exposed and non-exposed persons were defined and distinguished. HBM data from about 88, in general occupationally unexposed persons against certain metals served as a collective representing the general population in first approximation. For these the 95th percentiles are reported. Significant differences of urinary metal concentrations of the employees of the two metal processing companies compared to the third group were observed among others for Cu, Cr, Ni, Mn and are discussed, thus demonstrating the usefulness of the method for both environmental and occupational purposes.

Blood lead monitoring in a former mining area in Euskirchen, Germany: results of a representative random sample in 3- to 17-year-old children and minors.

Heavy metal residues in former mining areas can pose a burden to the local environment and population even decades after closure of the mining sites. In the North Rhine-Westphalian (Germany) communities of Mechernich and Kall, both parts of the district of Euskirchen, lead residues are a source of health concerns for local residents. A statistically representative collective of both communities depending on sex, age, and area of residence was created, mirroring the local underage population. The blood lead levels (BLL) of 182 children and minors in the two adjacent communities were assessed via ICP-MSMS. The results were compared to German lead reference values, valid for the general underage population. In total, 32 (17.6%) of the subjects investigated exceeded the according reference values of 15 µg/L and 20 µg/L, respectively, depending on sex and age, thus pointing out an additional lead burden affecting children in the area. Potential lead sources contributing to the BLL were evaluated using a questionnaire. Factors that showed significant impact on the BLL were, other than age, sex, height, and weight, the factors occupancy, time spend in the garden, garden hand-to-mouth contact, consumption frequency of homegrown products, and lifestyle factors. The data presented enable both residents and the local authorities to further reduce lead exposure and to take appropriate personal and public action.

Environmental release of non-Aroclor polychlorinated biphenyls by a silicone rubber production site did not lead to elevated plasma levels in the nearby population.

In 2019, high concentrations of the non-Aroclor PCB congeners 47, 51, and 68 were released by a silicone rubber production site in North-Rhine Westphalia, Germany. Local authorities announced a consumption alert for home-grown fruits and vegetables for the affected area which led to a great level of insecurity among the population regarding potential health effects. The aim of study was to determine the plasma levels of the non-Aroclor congeners and the six ndl-indicator congeners (PCB 28, 52, 101, 138, 153, 180) in children and women with child-bearing potential living close to the production site. Altogether n = 111 participants, with n = 73 female adults and n = 38 children were included in this analysis. For the non-Aroclor-PCBs as well as the lower-clorinated ndl-indicator PCBs 28, 52, and 101, the median plasma concentrations were below the LOQ. Only one adult showed an elevated PCB 47 value. In conclusion, no elevated plasma levels could be detected for PCB 47, 51, or 68 in the nearby population of the silicone-rubber production site. However, our study was highly important for risk characterisation as well as risk communication.

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021).

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Decomposition Products of the Initiator Bis(2,4-dichlorobenzoyl)peroxide in the Silicone Industry: Human Biomonitoring in Plasma and Urine of Workers.

Bis(2,4-dichlorobenzoyl)peroxide (2,4-DCBP) is used as an initiator for silicone rubber production. During hot curing, 2,4-DCBP decomposes into 2,4-dichlorobenzoic acid, 1,3-dichlorobenzene, and the polychlorinated biphenyl (PCB) congeners PCB-47, PCB-51, and PCB-68. The extent of occupational exposure to these decomposition products has not been investigated yet. We determined for the first time the corresponding internal exposure of employees (n = 104) of a German silicone rubber facility by human biomonitoring in plasma and urine. Collected samples were investigated by gas chromatography/mass spectrometry for levels of PCBs in plasma and by liquid chromatography/tandem mass spectrometry for urinary post-shift levels of 2,4-dichlorobenzoic acid (2,4-DCBA) and the metabolites 3,5-dichlorocatechol (3,5-DCK), 2,4-dichlorophenol (2,4-DCP), and 3,5-dichlorophenol (3,5-DCP). PCB-47 and PCB-68 levels correlated significantly and were found in >97% of all samples with maximum values of 4.43 and 0.77 µg/L, respectively. 2,4-DCBA, 3,5-DCK, 2,4-DCP, and 3,5-DCP were quantified in >80% of all urine samples with maximum levels of 1.46; 26.92; 7.68; and 0.39 mg/L, respectively. There is a considerable uptake of decomposition products of 2,4-DCBP in workers of a silicone rubber facility, affecting employees in all work areas. Individual levels depended on the work task. Considering the carcinogenic potential of PCBs, the workers' additional exposure to PCB-47 and PCB-68 might be of concern.

Concept for the Evaluation of Carcinogenic Substances in Population-Based Human Biomonitoring.

The Human Biomonitoring (HBM) Commission at the German Environment Agency holds the opinion that for environmental carcinogens for which no exposure levels can be assumed and are harmless to health, health-based guidance values corresponding to the classical definition of the HBM-I or HBM-II value cannot be established. Therefore, only reference values have been derived so far for genotoxic carcinogens from exposure data of the general population or subpopulations. The concept presented here opens up the possibility of performing health risk assessments of carcinogenic substances in human biomonitoring, and thus goes decisively beyond the purely descriptive statistical reference value concept. Using the presented method, quantitative dose descriptors of internal exposure can be derived from those of external exposure, provided that sufficient toxicokinetic information is available. Dose descriptors of internal exposure then allow the simple estimate of additional lifetime cancer risks for measured biomarker concentrations or, conversely, of equivalent concentrations for selected risks, such as those considered as tolerable for the general population. HBM data of chronic exposures to genotoxic carcinogens can thus be used to assess the additional lifetime cancer risk referring to the general population and to justify and prioritize risk management measures.

Blood Lead Monitoring in a Former Mining Area in Euskirchen, Germany-Volunteers across the Entire Population.

After centuries of mining in the district of Euskirchen, that is, in the communities of Mechernich and Kall, the lead concentration in the soil remains high, often exceeding regulatory guidelines. To clarify the lead body burden among residents in the region, a human biomonitoring study on a voluntary basis was initiated in which the blood lead level (BLL) was assessed. A questionnaire was distributed to evaluate lead exposure routes and confounders. Overall, 506 volunteers participated in the study, of whom 7.5% were children and adolescents, 71.9% were adults from 18 to 69 years, and 19.4% were residents 70 years or older. While the BLLs in the adult population were inconspicuous, among the children and adolescents investigated, 16.7% of the children between 3 and 17 years had BLLs above the recently revised German reference values for BLL in children. These results point towards a higher lead exposure in children living in the region. The hierarchical regression analysis based on the BLL and the questionnaire revealed the significant influence of the factors age, sex, smoking, construction age of the real estate, occupancy, and intensive contact with soil on the BLL. Measures to reduce lead exposure include a focus on improved personal and domestic hygiene to minimize lead intake.

Plasma levels of unintentionally produced non-Aroclor polychlorinated biphenyl (PCB) congeners in workers from the silicone rubber industry.

The unintentional release of non-Aroclor-PCBs 47, PCB 68 and PCB 51 by a silicone manufacturing company in North Rhine-Westphalia, Germany, due to the use of bis-(2,4-dichlorobenzoyl)peroxide (2,4-DCBP) as an initiator has raised serious concerns about the possible uptake of these congeners by workers in silicone rubber production. We have conducted a pilot study in Germany to quantify these congeners in plasma samples of employees working in and handling silicone rubber during production and electrical cable manufacturing. A total of 117 plasma samples were collected from workers in 7 companies and 84 plasma samples from control subjects not working in silicone industry. PCB 47 and PCB 68 were detected in plasma above the limit of quantification (0.01 µg/L) in 84% and 66% of the silicone industry workers, respectively, whereas both congeners were undetectable in plasma of the control group. The maximum levels for PCB 47 were 2.56 µg/L and for PCB 68 were 0.42 µg/L. PCB 51 could not be determined in any plasma sample. Plasma samples of workers making electric cables had in general lower levels than those from workers making silicone rubber. Due to the high persistence of PCBs and the poorly defined toxicological properties of PCB 47 and PCB 68, a replacement of 2,4-DCBP as initiator in silicone rubber production should be considered. Given the large market for silicone products, our results might have a global impact on silicone industry.

Upregulation of CCL7, CCL20, CXCL2, IL-1ß, IL-6 and MMP-9 in Skin Samples of PCB Exposed Individuals-A Preliminary Study.

Polychlorinated biphenyls (PCBs) are well known immunotoxic and carcinogenic compounds. Although cutaneous symptoms are the hallmark of exposure to these compounds, exact pathophysiologic mechanisms are not well understood. We took skin biopsies from moderately high PCB exposed workers (n = 25) after an informed consent and investigated the expression of immunological markers such as CCL-7, CCL-20, CXCL2, IL-1ß and IL-6, as well as the matrix metalloproteinase MMP-9, EPGN and NRF2 by RT-qPCR, and compared expression levels with plasma PCB levels. Statistical analyses showed a significant correlation between CCL-20, CXCL2, IL-6, IL-1ß, CCL-7 and MMP-9 and PCB serum levels. EPGN and NRF2 were not correlated to PCB levels in the blood. We found a significant correlation of genes involved in autoimmune, auto-inflammatory and carcinogenesis in skin samples of PCB exposed individuals with elevated plasma PCB levels. Confirmation of these findings needs to be performed in bigger study groups and larger gen-sets, including multiple housekeeping genes. Further study needs to be performed to see whether a chronical exposure to these and similar compounds can cause higher incidence of malignancies and inflammatory disease.

Which factors influence the frequency of participation in longitudinal cohort studies? - An analysis of demographics, social factors, and medical preconditions in participants of the health effects in high level exposure to polychlorinated biphenyls (HELPcB) cohort.

The continuous drop out of participants in longitudinal studies is a trend that may be observed in nearly all fields of medical research. A reduced participation rate might compromise the power of statistical analysis as well as lead to an attrition bias of the study. The aim of this analysis was to identify influencing factors on participation frequency in the monitoring program Health Effects in High Level Exposure to polychlorinated biphenyls (HELPcB) study, a cohort investigation of occupationally polychlorinated biphenyls (PCB) exposed individuals. The HELPcB study was initiated in 2010 and consisted of 7 study visits. At the last cross-section in 2019, less than one third of the included patients still actively participated. As possible influencing factors on study participation frequency, demographic, social, and medical characteristics of the participants were examined. In addition, a logistic regression model to predict study participation behavior was calculated. An overall higher frequency of participation was observed, if participants joined the program together with relatives or friends and had a higher age. For PCB plasma levels, an exceedance of the biological reference value (BAR) and further factors, such as (1) professional qualification, (2) later inclusion, (3) type of participant and (4) occupational-related disease notification, significant differences in the participation frequency were observed in the univariate analysis. Only age and joined study participation remained significant in the multivariate logistic regression. In conclusion, it was possible to identify several social and occupational-related factors that influence the frequency of participation of study attendees.

Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study.

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (DIO1) and 2 (DIO2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the DIO1 (rs2235544) and DIO2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for DIO1-CC and DIO2-CT genotypes, although interaction p-values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by DIO enzyme genes was observed.

Modelling past human internal exposure to lower chlorinated indicator PCBs using proxies - A calculation based on multiple longitudinal PCB analyses.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with former applications in electric transformers, capacitors, hydraulic fluids or joint sealants. While current internal exposure to PCBs can be readily assessed by human biomonitoring, the evaluation of longgone past exposures, in particular the estimation of past exposure to lower chlorinated non-dioxin-like PCB 28, 52 or 101 is limited due to the relatively short biological half-life of these PCB-congeners. This study was aimed to find a proxy that would allow an estimation of the former plasma level for these congeners even several years after exposure cessation. We used biomonitoring data of the German HELPcB cohort with six consecutive follow-up investigations and identified the congeners PCB 66, 74 and 99 as suitable proxies for the congeners of interest. The biological half-lives of the proxies as well as their individual correlation with the plasma levels of PCB 28, 52 and 101 was considered in the calculation models. The correlation coefficients and the inter correlation coefficient 3 (ICC3) between measured and calculated initial values were applied for validation. For external validation purposes we used longitudinal biomonitoring data from two different cohorts with indoor exposure to lower chlorinated PCBs. The backward estimation from current PCB 74 levels to former PCB 28 levels led to an ICC3 of 0.682 and a correlation of rho = 0.724 within the HELPcB cohort. The external validation revealed an ICC3 of 0.723 and a correlation of rho = 0.654. The external validation for PCB 101 was feasible, but measures were not comparably good (ICC3 = 0.460; Rho = 0.516). External validation for PCB 52 was not successful, maybe due to the lower level of burden. Our model shows that a rough estimation of former plasma levels of lower chlorinated PCBs is possible even years after exposure cessation using current measurements of PCB74.

PCB plasma level in different occupational groups in Iran.

Despite the ban of polychlorinated biphenyls (PCBs) some decades ago, concerns regarding their adverse health effects are continuing, because the workers employed for installation and repair of electrical equipment may be still exposed to PCBs. This study aimed to assess serum PCBs levels in workers in different industries. To do this, we determined the serum concentrations of 9 non-dioxin-like PCBs and 12 dioxin-like PCBs in 147 workers from seven occupational groups and 35 housewives. An electrical distribution company, paint manufacturer, and pesticide manufacturer were categorized as high probability exposure jobs, whereas turning and casting operations, polymer plastic manufacturing, professional driving, and office work were categorized as low probability exposure jobs. In addition, the average of PCB 138, 153, and 180 and PCB sums were observed to be significantly higher in paint manufacture workers compared to the another groups. In addition, the average PCB 118 level was higher in electrical distribution workers and housewives. Following the adjustment for age, blood lipid, residency place, and seafood in the regression model, the association of PCB 118 in electrical distribution workers and PCB 153 in paint manufacture workers remained significant. The results of this study served as further support for the hypothesis for an occupational basis for bioaccumulation of some PCB types. However, the plasma levels of almost all PCB congeners in Iran were found to be lower than many other countries.