Christa Schröter-Kermani

Bisphenol A in 24 h urine and plasma samples of the German Environmental Specimen Bank from 1995 to 2009: A retrospective exposure evaluation

Human exposure to Bisphenol A (BPA) is omnipresent. Both the extent of the exposure and its toxicological relevance are controversially discussed. We aim to reliably determine and evaluate the extent of BPA body burden in the German population from 1995 to 2009 based on 600 24 h urine samples and corresponding plasma samples from the Environmental Specimen Bank. We determined total and unconjugated BPA in urine and plasma using on-line solid-phase extraction high-performance liquid chromatography coupled to isotope dilution tandem mass spectrometry with a limit of quantification (LOQ) of 0.1 μg/l. In the stored urines, total BPA was quantifiable in >96% (median: 1.49 μg/l; 95th percentile: 7.37 μg/l), whereas unconjugated BPA was quantifiable only in <15% of the samples. Total BPA concentrations decreased over time, but 24 h urine volumes increased. Therefore, daily intakes calculated from the 24 h urines remained rather constant at a median of 0.037 and a 95th percentile of 0.171 μg BPA/kg body weight/day. In 60 corresponding plasma samples, total BPA levels were generally below the LOQ of 0.1 μg/l and, if quantifiable, most BPA was unconjugated, thus hinting to external contamination. We see total BPA in urine as the most appropriate and robust marker for BPA exposure assessment (if controlled for BPA contamination). Unconjugated BPA in urine and unconjugated or total BPA in plasma where contamination or breakdown of the glucuronide cannot be ruled out are of no value for human exposure assessment.

Retrospective monitoring of synthetic musk compounds in aquatic biota from German rivers and coastal areas

The polycyclic musk compounds HHCB (Galaxolide) and AHTN (Tonalide) are commonly used as synthetic fragrances in personal care products and household cleaners. These and other synthetic musk fragrances were quantified in different aquatic samples from the German Environmental Specimen Bank (ESB). While HHCB and AHTN were found in almost all samples, most of the other musk fragrances were detected only in a few samples and mostly at lower concentration levels. Blue mussels from the North Sea showed varying levels of 0.5-1.7 ng g(-1) ww for HHCB and 0.4-2.5 ng g(-1) ww for AHTN (ww, wet weight) in the period from 1986 to 2000, while blue mussels from the Baltic Sea were only slightly contaminated with synthetic musk fragrances. Lipid weight-related concentrations of synthetic musk compounds in blue mussels were higher than in eelpout muscles, bladder wrack and herring gull eggs. In comparison to the marine specimens, muscles of bream from German rivers had higher concentrations of HHCB and AHTN. The ranges of HHCB and AHTN concentrations in bream from the Elbe River were 545-6400 ng g(-1) lw and 48-2130 ng g(-1) lw, respectively (lw, lipid weight; five sampling sites, period 1993-2003). In the Rhine River, HHCB and AHTN levels of bream muscles were highest at the Iffezheim site (up to 9750 ng g(-1) lw HHCB, 1998). Even higher synthetic musk levels were detected in bream from the rivers Saale and Saar. In recent years, levels of both compounds determined in bream from most sampling sites have decreased from maximum values in the 1990s. As the concentrations of AHTN have decreased faster, the ratio of HHCB to AHTN increased from 2-4 in the 1990s to 10-20 in recent years.

Retrospective monitoring of perfluorocarboxylates and perfluorosulfonates in human plasma archived by the German Environmental Specimen Bank.

Due to the increased awareness of the ubiquitous contamination of all environmental compartments and of human beings with perfluoroalkyl substances (PFAS), voluntary withdrawals and shifts in products and manufacturing technologies, as well as in regulatory measures, have been made. To investigate whether these activities are reflected in the human exposure to PFASS, we examined human blood archived by the German Environmental Specimen Bank. Plasma samples (n=258, age range 20-29 years) covering the observation period 1982-2010 were analyzed for eleven perfluoroalkylcarboxylates (C4-C14) and five perfluoroalkylsulfonates (C4-C10) by HPLC-MS-MS. We detected perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) most often of all PFASs. Following a sharp increase from 1982 to 1986, median PFOS concentrations remained in the range of 20-24ng/mL until the end of the 1990s. Between 2001 and 2010, PFOS concentrations decreased steadily to 4ng/mL in plasma. Except for a similar strong increase from 1982 to 1986, we observed PFOA concentrations fluctuating between 4.8 and 6.3ng/mL in the following years. Since 2008, ESB data suggest a decreasing trend of PFOA. PFHxS concentrations increased continuously between 1982 and 2001 from about 1-2ng/mL. After nearly unchanged concentrations until 2005, a downward trend of PFHxS in plasma became apparent and in 2010 resulted in levels which were about 20% lower than those observed in the early 1980s. In the case of shorter and longer chained PFASs, quantification frequencies were between 0 and 60% and we found no indication of any temporal trends in human plasma concentrations.

Environmental surveys, specimen bank and health related environmental monitoring in Germany.

Production of chemicals, use of products and consumer goods, contamination of food as well as todays living conditions are related to a substantial exposure of humans to chemicals. Safety of human beings and the environment has to be safeguarded by producers and government. Human biomonitoring (HBM) has proven to be a useful and powerful tool to control human exposure and facilitate risk assessment. Therefore, the German Federal Environment Agency (Umweltbundesamt, UBA) employs two major HBM tools, the German Environmental Survey (GerES) and the German Environmental Specimen Bank (ESB). GerES is a nationwide population representative study on HBM and external human exposure, which has, inter alia, been used to identify lead in tap water, lead dustfall, time spent in traffic, and age of dwelling as exposure sources for lead and, thus, to derive risk reduction measures. The ESB is a permanent monitoring instrument and an archive for human specimens. Retrospective monitoring of phthalates and bisphenol A provides a continuous historical record of human exposure in Germany, over the last decades. Additionally it revealed that estimations of human exposure based on production and consumption data may supply misleading information on human exposure. HBM data demonstrated that (a) the use if the restricted isomer di-n-butylphthalat decreased while di-i-butylphthalate levels remained constant and (b) human bisphenol A exposure might be overestimated without monitoring data. The decrease of polycyclic aromatic hydrocarbon-exposure proves the success of German environmental policy after German re-unification. In addition to GerES and ESB UBA is involved in different co-operation networks, the two most prominent of which are (1) the harmonization of HBM in Europe (ESBIO; Expert Team to Support Biomonitoring in Europe, COPHES/DEMOCOPHES; Consortium to Perform Human Biomonitoring on a European Scale/Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) and (2) the co-operation between BMU and the German Chemical Industry Association (VCI). In the latter project emphasis will be placed on substances with a potential relevance for health and on substances to which the general population might potentially be exposed to a considerable extent and for which HBM methods are not available up to now.

Temporal trend (1988-2008) of hexabromocyclododecane enantiomers in herring gull eggs from the german coastal region

Levels of α-, β-, and γ-hexabromocyclododecane (HBCD) were determined in pooled eggs from herring gulls (Larus argentatus) sampled on three bird sanctuaries near the German North Sea coast between 1988 and 2008 (Mellum and Trischen) and the German Baltic Sea coast between 1998 and 2008 (Heuwiese) and archived by the German Environmental Specimen Bank. Pressurized fluid extraction, gel permeation chromatography, and LC-MS/MS using (13)C(12)-labelled isotope standards and a chiral column were applied. α-HBCD was the dominating diastereomer and ranged between 3.7 and 107 ng g(-1)lw while β- and γ-HBCD were throughout close to LOQ. The highest α-HBCD concentration was found in eggs from Mellum sampled in the year 2000. Interestingly, HBCD in eggs from the three islands displayed similar time courses with levels increasing to a peak contamination around 2000 and decreasing levels ever since. Chiral signatures of α-HBCD in eggs differed among the islands but indicated a preferential enrichment of the first eluting enantiomer (-)-α-HBCD.

Bis-(2-propylheptyl)phthalate (DPHP) metabolites emerging in 24h urine samples from the German Environmental Specimen Bank (1999-2012).

Bis-(2-propylheptyl)-phthalate (DPHP) has been introduced as a substitute for other high molecular weight phthalates primarily used in high temperature applications (e.g. cable wires, roofing membranes). The aim of this study was to investigate how the increased usage of DPHP is reflected in urine samples collected over the last 14 years and to evaluate the current extent of exposure. We analyzed 300 urine samples (24h voids) from the German Environmental Specimen Bank collected in the years 1999, 2003, 2006, 2009 and 2012, 60 samples per year, from 30 male and 30 female volunteers (age: 20-30 years) for three specific, secondary oxidized DPHP metabolites (with hydroxy, oxo and carboxy modifications of the alkyl side chain). We determined DPHP metabolites with a previously developed GC-HRMS method, enabling us to unambiguously distinguish DPHP metabolites from co-eluting, structurally isomeric di-iso-decyl phthalate (DIDP) metabolites. All samples were blinded before analysis. We detected no DPHP metabolites in urine samples from the years 1999, 2003 and 2006. Thereafter, detection rates increased from 3.3% in 2009 to 21.7% in 2012. Mono-oxo-propylheptylphthalate (oxo-MPHP) was the most abundant metabolite, with concentrations between <LOQ and 0.96μg/l. Extrapolating from oxo-MPHP concentrations in the 24h urine samples we calculated a maximum daily DPHP intake of 0.32μg/kg body weight. Our results show that the general German population is increasingly exposed to DPHP. However, exposure is considerably lower than for DIDP or other high molecular weight phthalates. Future measurements will enable us to monitor the development of DPHP exposure and advise risk management steps, if warranted.

Levels and trends of industrial chemicals (PCBs, PFCs, PBDEs) in archived herring gull eggs from German coastal regions

BackgroundPolychlorinated biphenyls [PCBs], perfluorinated compounds, and polybrominated diphenyl ethers [PBDEs] were retrospectively analyzed in archived herring gull (Larus argentatus) eggs from the North and the Baltic Sea over the last 20 years. The aim was to assess temporal trends and effects of regulatory measures.ResultsPCBs (sum of 7 congeners) were highest in eggs from the North Sea island Trischen, i.e., 3,710 to 20,760 ng/g lipid weight [lw] compared to 2,530 to 11,650 ng/g lw on the North Sea island Mellum and 4,840 to 9,190 ng/g lw on the Baltic Sea island Heuwiese. During the study period, PCBs decreased significantly. Concentrations of PFOS ranged between 46 and 170 ng/g wet weight [ww] at Trischen, 39 to 99 ng/g ww at Mellum, and 20 to 159 ng/g ww at Heuwiese. Since 2000 and 2003, concentration levels decreased in eggs from Mellum and Heuwiese, respectively. Perfluorooctanoic acid was the dominant perfluorinated carboxylic acid in the North Sea eggs (Trischen 2.0 to 74 ng/g ww; Mellum 2.6 to 118 ng/g ww), whereas perfluoroundecanoate [PFUnA] and perfluorodecanoate [PFDA] (means 3.9 ± 3.6 ng/g and 2.9 ± 2.3 ng/g ww, respectively) dominated in the Baltic Sea eggs. At all three locations, longer-chained perfluorinated carboxylic acids (perfluorononanoate, PFDA, PFUnA, perfluorododecanoate) increased during the monitoring period. PBDE concentrations (sum of 35 congeners) in eggs were in the ranges of 282 to 2,059 ng/g lw (Mellum), 116 to 1,722 ng/g (Trischen), and 232 to 2,021 ng/g lw (Heuwiese). Congeners associated with commercial Penta- and Octa-BDE formulations decreased during the study period. No decrease was observed for technical Deca-BDE.ConclusionEffects of regulatory measures were apparent for PCBs and Penta- and Octa-BDE, while no consistent trend is noticeable for PFOS.

Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide.

The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides.

Parabens in 24 h urine samples of the German Environmental Specimen Bank from 1995 to 2012

Parabens are widely used as antimicrobial preservatives in personal care and consumer products, food and pharmaceuticals. Due to their ubiquity, humans are constantly exposed to these chemicals. We assessed exposure to nine parabens (methyl-, ethyl-, n- and iso-propyl-, n- and iso-butyl-, benzyl-, pentyl- and heptyl paraben) in the German population from 1995 to 2012 based on 660 24h urine samples from the German Environmental Specimen Bank (ESB) using on-line HPLC coupled to isotope dilution tandem mass spectrometry. The limit of quantification (LOQ) was 0.5 μg/L for all parabens. We detected methyl-, ethyl- and n-propyl paraben in 79-99% of samples, followed by n-butyl paraben in 40% of samples. We infrequently detected iso-butyl-, iso-propyl- and benzyl paraben in 24%, 4% and 1.4% of samples, respectively. Urinary concentrations were highest for methyl paraben (median 39.8 μg/L; 95th percentile 319 μg/L) followed by n-propyl paraben (4.8 μg/L; 95th percentile 74.0 μg/L) and ethyl paraben (2.1 μg/L; 95th percentile 39.1 μg/L). Women had significantly higher urinary levels for all parabens than men, except for benzyl paraben. Samples from the ESB revealed that over the investigation period of nearly 20 years urinary paraben levels remained surprisingly constant; only methyl paraben had a significant increase, for both men and women. We found strong correlations between methyl- and n-propyl paraben and between n- and iso-butyl paraben. These results indicate that parabens are used in combination and arise from common sources of exposure. Urinary excretion factors are needed to extrapolate from individual urinary concentrations to actual doses.

Bioaccumulation in aquatic systems: methodological approaches, monitoring and assessment

Bioaccumulation, the accumulation of a chemical in an organism relative to its level in the ambient medium, is of major environmental concern. Thus, monitoring chemical concentrations in biota are widely and increasingly used for assessing the chemical status of aquatic ecosystems. In this paper, various scientific and regulatory aspects of bioaccumulation in aquatic systems and the relevant critical issues are discussed. Monitoring chemical concentrations in biota can be used for compliance checking with regulatory directives, for identification of chemical sources or event-related environmental risk assessment. Assessing bioaccumulation in the field is challenging since many factors have to be considered that can affect the accumulation of a chemical in an organism. Passive sampling can complement biota monitoring since samplers with standardised partition properties can be used over a wide temporal and geographical range. Bioaccumulation is also assessed for regulation of chemicals of environmental concern whereby mainly data from laboratory studies on fish bioaccumulation are used. Field data can, however, provide additional important information for regulators. Strategies for bioaccumulation assessment still need to be harmonised for different regulations and groups of chemicals. To create awareness for critical issues and to mutually benefit from technical expertise and scientific findings, communication between risk assessment and monitoring communities needs to be improved. Scientists can support the establishment of new monitoring programs for bioaccumulation, e.g. in the frame of the amended European Environmental Quality Standard Directive.