Publications by authors named "Thomas Göen"

130 Publications

The European human biomonitoring platform - Design and implementation of a laboratory quality assurance/quality control (QA/QC) programme for selected priority chemicals.

Int J Hyg Environ Health 2021 May 26;234:113740. Epub 2021 Mar 26.

National Centre for Environmental Health, Instituto de Salud Carlos III (ISCIII), Majadahonda, Spain. Electronic address:

A fundamental objective of the human biomonitoring for Europe initiative (HBM4EU) is to progress toward comparable and robust exposure data for a wide variety of prioritized chemicals in human samples. A programme for Quality Assurance/Quality Control (QA/QC) was designed in HBM4EU with the purpose of creating a network of European laboratories providing comparable analytical data of high quality. Two approaches were chosen for two sets of prioritized chemicals with different timelines: (i) Scheme 1, where interested candidate laboratories participated in multiple rounds of proficiency tests (ii) Scheme 2, where selected expert laboratories participated in three rounds of interlaboratory comparison investigations. In both cases, the results were used to identify laboratories capable of generating consistent and comparable results for sample analysis in the frame of HBM4EU. In total, 84 laboratories from 26 countries were invited to participate in Scheme 1 that covered up to 73 biomarkers from Hexamoll® DINCH, phthalates, bisphenols, per- and polyfluoroalkyl substances, halogenated flame retardants (HFRs), organophosporous flame retardants (OPFRs), polycyclic aromatic hydrocarbons (PAH), cadmium, chromium and aromatic amines. 74 of the participants were successful for at least one biomarker in Scheme 1. Scheme 2 involved 22 biomarkers and successful results were obtained by 2 expert laboratories for arsenic, 5 for acrylamide, 4 for mycotoxins, 2 for pesticides and 2 for UV-filters in skin care products. The QA/QC programme allowed the identification of major difficulties and needs in HBM analysis as well of gaining insight in the analytical capacities of European laboratories. Furthermore, it is the first step towards the establishment of a sustainable European network of HBM laboratories.
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http://dx.doi.org/10.1016/j.ijheh.2021.113740DOI Listing
May 2021

Sensitive monitoring of the main metabolites of tri-(2-ethylhexyl) trimellitate (TOTM) in urine by coupling of on-line SPE, UHPLC and tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 5;1171:122618. Epub 2021 Mar 5.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestr. 9-11, 91054 Erlangen, Germany. Electronic address:

Tri-(2-ethylhexyl) trimellitate (TOTM or TEHTM) is a substitute for the plasticizer di-(2-ethylhexyl) phthalate (DEHP). Here, a fast and sensitive UHPLC-MS/MS method is presented enabling the simultaneous quantification of the six main TOTM metabolites in urine. These include the primary metabolites 1-MEHTM and 2-MEHTM (1-/2-mono-(2-ethylhexyl) trimellitate) and two oxidized metabolites of each to ensure a precise determination and comparison of the regioselective pathways. The method is based on online enrichment of the analytes after enzymatic hydrolysis with subsequent UHPLC separation and tandem mass spectrometry using isotopically labeled internal standards. The method is distinguished by its high sensitivity with detection limits ranging from 0.01 to 0.04 µg/l and a proficient precision with relative standard deviations well below 10% for each analyte. The application of UHPLC-MS/MS analysis proved to significantly enhance the sensitivity of the method due to the efficient separation of the regioisomeric structures of the TOTM metabolites considered. Additionally, a proficient repeatability and recovery was achieved by the use of structurally identical isotopically labeled internal standard substances. The method was successfully applied to urine samples of infant patients indicating urinary levels of the TOTM metabolites examined in a very low concentration range.
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http://dx.doi.org/10.1016/j.jchromb.2021.122618DOI Listing
May 2021

Interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS) for cadmium in urine and blood: Results from the HBM4EU project.

Int J Hyg Environ Health 2021 May 10;234:113711. Epub 2021 Mar 10.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander Universität Erlangen-Nürnberg, Henkestraße 9-11, 91054, Erlangen, Germany. Electronic address:

Human biomonitoring (HBM) of cadmium is essential to assess and prevent toxic exposure. Generally, low cadmium levels in urine and blood of the general population place particularly high demands on quality assurance and control measures (QA/QC) for cadmium determination. One of the aims of the HBM4EU project is to harmonize and advance HBM in Europe. Cadmium is one of the chemicals selected as a priority substance for HBM implementation in the 30 European countries under HBM4EU. For this purpose, analytical comparability and accuracy of the analytical laboratories of participating countries was investigated in a QA/QC programme comprising interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS). This paper presents the evaluation process and discusses the results of four ICI/EQUAS rounds for the determination of cadmium in urine and blood. The majority of the 43 participating laboratories achieved satisfactory results, although low limits of quantification were required to quantify Cd concentrations at general population exposure levels. The relative standard deviation of the participants' results obtained from all ICI and EQUAS runs ranged from 8 to 36% for cadmium in urine and 8-28% for cadmium in blood. Applying inductively-coupled plasma mass spectrometry (ICP-MS), using an internal standard, and eliminating molybdenum oxide interferences was favourable for the accurate determination of cadmium in urine and blood. Furthermore, the analysis of cadmium in urine was found to have a critical point at approximately 0.05 μg/l, below which variability increased and laboratory proficiency decreased. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of cadmium across 20 European countries.
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http://dx.doi.org/10.1016/j.ijheh.2021.113711DOI Listing
May 2021

Pentachlorophenol and nine other chlorophenols in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Environ Res 2021 May 4;196:110958. Epub 2021 Mar 4.

German Environment Agency (UBA), Berlin, Germany.

Chlorophenols comprise of a large group of chemicals used inter alia for the production of biocides, pharmaceuticals, other industrial products and are used e.g. as antiseptics or wood preservatives due to their biocidal properties. Several of them are classified as toxic to aquatic life and harmful to humans by ingestion, inhalation, or dermal contact, causing skin and eye irritation. Moreover, chlorophenols are possibly carcinogenic to humans. The most prominent chlorophenol - pentachlorophenol - is carcinogenic to humans, was banned in Germany in 1989 and further regulated by the European Commission in 2006 and included in the Stockholm Convention in 2017. Some chlorophenols are persistent in the environment and are also biodegradation products of precursor substances. To evaluate the health-relevance of recent exposure and monitor the effectiveness of regulatory measures, chlorophenols were analysed in the population-representative German Environmental Survey on Children and Adolescents 2014-2017 (GerES V). First-morning void urine samples of 485 3-17-year-old children and adolescents were analysed for ten chlorophenols. Pentachlorophenol was still quantified in 87% of the children and adolescents with a geometric mean (GM) concentration of 0.19 μg/L (0.16 μg/g) and a maximum concentration of 6.7 μg/L (5.4 μg/g). The maximum concentration was well below the health-based guidance value HBM-I of 25 μg/L (20 μg/g). 4-Monochlorophenol was quantified in all samples with a GM concentration of 1.38 μg/L (1.14 μg/g). 2-Monochlorophenol, 2,4-dichlorophenol, and 2,5-dichlorophenol were quantified in 97%, 98%, and 95% of the samples, with GMs of 0.26 μg/L (0.21 μg/g), 0.24 μg/L (0.20 μg/g), and 0.26 μg/L (0.21 μg/g). 2,6-dichlorophenol, 2,3,4-trichlorophenol, and 2,4,5-trichlorophenol were quantified in 17-25% of the samples with GMs below the limit of quantification (LOQ) of 0.1 μg/L 2,4,6-trichlorophenol was quantified in 72% of the samples (GM: 0.13 μg/L, 0.11 μg/g), 2,3,4,6-tetrachlorophenol in 44% of the samples (GM < LOQ). Comparison to previous cycles of GerES revealed substantially lower exposure to most of the chlorophenols in GerES V. Exposure levels found in Germany were comparatively low in contrast to North American results.
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http://dx.doi.org/10.1016/j.envres.2021.110958DOI Listing
May 2021

From inequitable to sustainable e-waste processing for reduction of impact on human health and the environment.

Environ Res 2021 03 12;194:110728. Epub 2021 Jan 12.

The George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania. Electronic address:

Recycling of electric and electronic waste products (e-waste) which amounted to more than 50 million metric tonnes per year worldwide is a massive and global operation. Unfortunately, an estimated 70-80% of this waste has not been properly managed because the waste went from developed to low-income countries to be dumped into landfills or informally recycled. Such recycling has been carried out either directly on landfill sites or in small, often family-run recycling shops without much regulations or oversights. The process traditionally involved manual dismantling, cleaning with hazardous solvents, burning and melting on open fires, etc., which would generate a variety of toxic substances and exposure/hazards to applicators, family members, proximate residents and the environment. The situation clearly calls for global responsibility to reduce the impact on human health and the environment, especially in developing countries where poor residents have been shouldering the hazardous burden. On the other hand, formal e-waste recycling has been mainly conducted in small scales in industrialized countries. Whether the latter process would impose less risk to populations and environment has not been determined yet. Therefore, the main objectives of this review are: 1. to address current trends and emerging threats of not only informal but also formal e-waste management practices, and 2. to propose adequate measures and interventions. A major recommendation is to conduct independent surveillance of compliance with e-waste trading and processing according to the Basel Ban Amendment. The recycling industry needs to be carefully evaluated by joint effort from international agencies, producing industries and other stakeholders to develop better processes. Subsequent transition to more sustainable and equitable e-waste management solutions should result in more effective use of natural resources, and in prevention of adverse effects on health and the environment.
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http://dx.doi.org/10.1016/j.envres.2021.110728DOI Listing
March 2021

Dispersive liquid-liquid microextraction (DLLME) and external real matrix calibration for the determination of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) and its metabolites in human blood.

Talanta 2021 Feb 28;223(Pt 1):121699. Epub 2020 Sep 28.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Electronic address:

2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328; CAS: 25973-55-1) is a benzotriazole ultraviolet light (BUV) absorber which is applied to plastics and other organic substances to prevent discoloration and enhance product stability. Therefore, UV 328 is frequently used as a plastic additive and may lead to an exposure of consumers. For a reliable assessment of UV 328 metabolism, an analytical method applying dispersive liquid-liquid microextraction (DLLME) followed by gas chromatography tandem mass spectrometry and advanced electron ionization was developed which allows the determination of UV 328 and six of its metabolites in human whole blood. Sample preparation was optimized with respect to DLLME parameters. A critical aspect of the procedure was the application of spiked human blood for calibration, which proved to be essential for achieving accurate results. Validation of the method resulted in limits of detection of 0.1 μg/L for all analytes. Variation coefficients ranged from 2 to 9% for intraday precision and from 3 to 11% for interday precision. Furthermore, relative recovery rates between 80 and 100% were calculated. Afterwards, the procedure was successfully applied to blood samples collected from a volunteer orally exposed to a single dose of UV 328. The method proved to be highly sensitive, repeatable and robust for all compounds and may further be used for studies to elucidate the human metabolism and kinetics of UV 328 and for biomonitoring of specific, environmental and occupational exposure to this UV stabilizer.
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http://dx.doi.org/10.1016/j.talanta.2020.121699DOI Listing
February 2021

Calcium, magnesium and aluminium ions as decontaminating agents against dermal fluoride absorption following hydrofluoric acid exposure.

Toxicol In Vitro 2021 Mar 20;71:105055. Epub 2020 Nov 20.

Institute and Out- Patient Clinic of Occupational, Social and Environmental Medicine, Friedrich Alexander University Erlangen- Nürnberg (FAU), Germany. Electronic address:

The fluoride ions of the industrially largely irreplaceable, locally corrosive hydrofluoric acid (HF) can scavenge cations in biological tissues, which explains their high toxic potential, and also leads to local acidification through proton release. The influence of three complexing agents, calcium (Ca) gluconate (as 2.5% Cagel and individually (2.84%) or commercially (10%) formulated Casolution), magnesium (Mg) gluconate (2.84%) solution and aluminium (Al) solution (Hexafluorine®, pure and diluted) on the absorption of fluoride following HF exposure (1-3 min, 100 μl, 30%/0.64 cm) through human skin was investigated in an ex-vivo diffusion cell model. Fluoride absorption was assessed over 6-24 h and analysed with a fluoride electrode. Decreasing the contamination time reduced the fluoride absorption distinctly which was further reduced by the application of fluoride-binding decontamination agents (Ca, Mg, Al) or water alone without being significantly different. Ca appeared slightly more effective than Mg in reducing fluoride absorption. Moreover, the addition of pH adjusting buffer promoted the decontamination efficacy. Fluoride-binding agents can facilitate the decontamination of dermal HF exposure. However, prompt decontamination appeared to be the key to successful limitation of fluoride absorption and pushes the choice of decontamination agent almost into the background.
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http://dx.doi.org/10.1016/j.tiv.2020.105055DOI Listing
March 2021

Long-term time trend of lead exposure in young German adults - Evaluation of more than 35 Years of data of the German Environmental Specimen Bank.

Int J Hyg Environ Health 2021 Jan 19;231:113665. Epub 2020 Nov 19.

German Environment Agency (Umweltbundesamt), Berlin, Germany.

Lead is a ubiquitous pollutant with well-known effects on human health. As there is no lower toxicological threshold for lead in blood and since data gaps on lead exposure still exist in many European countries, HBM data on lead is of high importance. To address this, the European Human Biomonitoring Initiative HBM4EU classified lead as a priority substance. The German Environmental Specimen Bank (German ESB) has monitored lead exposure since more than 35 years. Using data from the early 1980s to 2019 we reveal and discuss long-term trends in blood lead levels (BLLs) and current internal exposure of young adults in Germany. BLLs in young adults decreased substantially in the investigated period. As results from the ESB sampling site Muenster demonstrate, the geometric mean of BLLs of young adults decreased from 1981 (78,7 μg/L) to 2019 (10.4 μg/L) by about 87%. Trends in human exposure closely correlate with air lead levels (ALLs) provided by the European Monitoring and Evaluation Programme (EMEP). Hence, the decrease of BLLs largely reflects the drop in air lead pollution. Known associations of sex, smoking, alcohol consumption, and housing situation with BLLs are confirmed with data of the German ESB. Although internal lead exposure in Germany decreased substantially, the situation might be different in other European countries. Since 2010, BLLs of young adults in Germany levelled out at approximately 10 μg/L. The toxicity of lead even at low levels is known to cause adverse health effects especially in children following exposure of the child or the mother during pregnancy. To identify current exposure sources and to minimize future lead exposure, continuous monitoring of lead intake and exposure levels is needed.
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http://dx.doi.org/10.1016/j.ijheh.2020.113665DOI Listing
January 2021

Metabolites of 4-methylbenzylidene camphor (4-MBC), butylated hydroxytoluene (BHT), and tris(2-ethylhexyl) trimellitate (TOTM) in urine of children and adolescents in Germany - human biomonitoring results of the German Environmental Survey GerES V (2014-2017).

Environ Res 2021 01 20;192:110345. Epub 2020 Oct 20.

German Environment Agency (UBA), Berlin, Germany.

The UV filter 4-methylbenzylidene camphor (4-MBC), used in cosmetics, the antioxidant butylated hydroxytoluene (BHT), used inter alia as a food additive and in cosmetics, and the plasticizer tris(2-ethylhexyl) trimellitate (TOTM), used mainly in medical devices as substitute for di-(2-ethylhexyl) phthalate (DEHP), are suspected to have endocrine disrupting effects. Human biomonitoring methods that allow for assessing the internal exposure of the general population to these substances were recently developed in a German cooperation to enhance the use of human biomonitoring. First-morning void urine samples from 3- to 17-year-old children and adolescents living in Germany were analysed for metabolites of 4-MBC (N = 447), BHT (N = 2091), and TOTM (N = 431) in the population-representative German Environmental Survey on Children and Adolescents 2014-2017 (GerES V). 4-MBC metabolites were found in quantifiable amounts only in single cases and exposure levels remained well below health-based guidance values. In contrast, ubiquitous exposure to BHT became evident with a geometric mean (GM) urinary concentration of the metabolite BHT acid of 2.346 μg/L (1.989 μg/g) and a maximum concentration of 248 μg/L (269 μg/g). The highest GM concentration was found in young children aged 3-5 years, yet no specific sources of exposure could be identified. Also, TOTM metabolites were found in quantifiable amounts only in very few samples. None of these findings could be related to previous hospital treatment or exposure via house dust. The presented results will be the basis to derive reference values for exposure of children and adolescents in Germany to BHT and will facilitate to identify changing exposure levels in the general population.
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http://dx.doi.org/10.1016/j.envres.2020.110345DOI Listing
January 2021

Corrigendum to "Effect of phospholipid coating on the migration of plasticizers from PVC tubes" [Chemosphere 202 (July 2018) 742-749].

Chemosphere 2020 Nov 11;258:127538. Epub 2020 Jul 11.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Henkestrasse 9-11, 91054, Erlangen, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.chemosphere.2020.127538DOI Listing
November 2020

Identification of in vitro phase I metabolites of benzotriazole UV stabilizer UV-327 using HPLC coupled with mass spectrometry.

Toxicol In Vitro 2020 Oct 8;68:104932. Epub 2020 Jul 8.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestraße 9-11, 91054 Erlangen, Germany. Electronic address:

The benzotriazole UV stabilizer (BUVS) 2-(5-chloro-benzotriazol-2-yl)-4,6-di-(tert-butyl)phenol (UV-327) is used in various plastic products to protect them against harmful UV radiation. Meanwhile, there are concerns about potential adverse health effects on humans, as residues of UV-327 and other BUVSs have already been detected in various environmental matrices. However, information on the metabolism of UV-327 is not yet available. Therefore, in vitro experiments with human liver microsomes (HLMs) were performed in order to identify phase I metabolites to be used as specific biomarkers of exposure in biomonitoring studies. The samples were analyzed by HPLC coupled with mass spectrometry (HPLC/MS). Potential metabolites, which were formed by hydroxylation and further oxidation to carboxylic acid, were tentatively identified. Special metabolite structures were suspected and custom-synthesized as reference substances for verification. In total, seven phase I metabolites, which may be suitable biomarkers for the assessment of exposure to UV-327, have been identified and quantified. The results of the present study provide initial insights into the metabolic pathway of UV-327, which is essential for further research on its human metabolism.
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http://dx.doi.org/10.1016/j.tiv.2020.104932DOI Listing
October 2020

Instability of urinary excreted methyl-2-acetamido-2-deoxy-1-seleno-β-d-galactopyranoside (selenosugar 1), the main elimination product of human selenium metabolism, and measures for its stabilization.

J Trace Elem Med Biol 2020 May 5;61:126538. Epub 2020 May 5.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestrasse 9-11, 91054, Erlangen, Germany. Electronic address:

Background: The urinary excreted selenium species selenosugar 1 (SeSug1) plays a key role for monitoring of supplemental selenium exposure, e.g. by occupational exposure. In order to reproduce its contents in the long term, the integrity of SeSug1 in the urine is essential. Studies on the stability of SeSug1 in urine samples stored at -20 °C have shown that degradation of SeSug 1 occurs, requiring adequate countermeasures.

Methods: Here, we explored the long-term stability of SeSug1 under usual storage conditions at -20 °C. For this purpose, the simultaneous determination of selenosugar 1 and methylselenic acid (MeSeA) was used to explore the stabilizing of the SeSug1 content by applying sodium azide (NaN) as a bactericide or/and 5 M ammonium acetate buffer for pH control.

Results: In untreated urine, conversion of SeSug1 to MeSeA was evident within days. Differences in urine matrices clearly showed different impact, which could be attributed to different buffer strengths by the urine itself. For durability, various concentrations of sodium azide were first applied, followed by pH buffering. A combination of 0.1% NaN and pH of 5.5 kept the SeSug1 content stable for over 3 months.

Conclusion: The formation of MeSeA as degradation product of SeSug1 could be confirmed. Based on the proportions, an oxidation-based decomposition pathway was proposed. The investigations revealed that the complex interaction of pH buffering and bactericidal activity must be taken into account in order to stabilize SeSug1 in the urine. The main effect was the addition of NaN. However, the alkaline nature of NaN required a sufficient buffering of the urinary matrix at a pH of 5.5.
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http://dx.doi.org/10.1016/j.jtemb.2020.126538DOI Listing
May 2020

Plasticizer exposure of infants during cardiac surgery.

Toxicol Lett 2020 May 6;330:7-13. Epub 2020 May 6.

Department of Pediatric Cardiac Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Loschgestr. 15, 91054 Erlangen, Germany.

In the present study we investigated the internal exposure situation of infant patients to the plasticizers TEHTM (tri-2-ethylhexyl trimellitate) and DEHP (di-2-ethylhexyl phthalate). The study collective included 21 infant patients aged 2-22 months that had to undergo cardiac surgery using cardio pulmonary bypass (CPB). Each patient, but one, received blood products during surgery. A special feature was that the used CPB tubings were exclusively plasticized with the alternative plasticizer TEHTM and were free of the standard plasticizer DEHP, that raises increasing toxicological concern. The blood products were stored in DEHP plasticized blood bags. Blood and urine samples of each infant patient were analysed before and after the surgery for the levels of the plasticizers DEHP and TEHTM and their metabolites. In general, the plasticizers were detected in the post-surgery blood samples only, with TEHTM in low levels (median 18.4 μg/L) and DEHP in rather elevated levels (median 1046 μg/L). With respect to the urine samples, TEHTM metabolites were not detected in any of the samples. DEHP metabolites were found in all urine samples, however, in significantly increased median levels in the post-surgery urine samples of the infants (increase factor 5-26). Thus, the present study clearly demonstrates the strong contribution of standard medical procedures to the internal plasticizer burden of patients. Particularly with regard to the suspected endocrine disrupting activities of the phthalate plasticizer DEHP, the elevated internal levels of this plasticizer and its metabolites in infants following cardiac surgery are alarming.
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http://dx.doi.org/10.1016/j.toxlet.2020.04.004DOI Listing
May 2020

Determination of eleven small selenium species in human urine by chromatographic-coupled ICP-MS methods.

J Trace Elem Med Biol 2020 Apr 11;61:126519. Epub 2020 Apr 11.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany. Electronic address:

Background: The determination of various selenium species in urine enables a specific biomonitoring of the exposure to different selenium compounds.

Methods: For this task a coupling of three chromatographic techniques with ICP-MS was developed for the separate quantification of eleven species in urine. The first procedure was based on reverse phase chromatography and was designed for the separate determination of methyl-2-acetamido-2-deoxy-1-seleno-b-d-galactopyranoside (SeSug1), methyl-2-acetamido-2-deoxy-1-seleno-b-d-glucopyranoside (SeSug2), selenomethionine (SeMet), methylselenocysteine (MeSeC), seleno-D,L-ethionine (SeEt), methylselenic acid (MeSeA) and methylselenoglutathione (MeSeG); the second procedure was based on anion exchange chromatography and measured selenate (Se (VI)) and selenite (Se (IV)); the third procedure was based on cationic exchange chromatography and determined methyl-2-amino-2-deoxy-1-seleno-b-d-galactopyranoside (SeSug3) and the trimethylselenium ion (TMSe). A fourth method for the more sensitive determination of TMSe was upgraded by an on-line after-column reaction process.

Results: The validation of the methods yielded sensitive detection limits of the species between 0.03 and 0.10 μg Se/L. For TMSe a detection limit of 0.02 μg Se/L resulted by the fourth method. An intra-day precision of 2.7-10.6% and a relative recovery between 87 % and 108 % confirm the robustness of the methods.

Conclusion: The developed procedures enable a separate and sensitive determination of eleven selenium species in urine and thus permit the exploring of metabolic factors in the general population and particularly exposed individuals.
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http://dx.doi.org/10.1016/j.jtemb.2020.126519DOI Listing
April 2020

Determination of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) and its oxidative metabolites in human urine by dispersive liquid-liquid microextraction and GC-MS/MS.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 May 19;1144:122071. Epub 2020 Mar 19.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander Universität Erlangen-Nürnberg, Henkestraße 9-11, 91054 Erlangen, Germany. Electronic address:

2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) is an ultraviolet light (UV) absorber which prolongs the stability of plastics and other organic compounds towards UV radiation. Therefore, it is frequently used as a preserving additive and may result in an exposure of consumers. Thus, an analytical method using dispersive liquid-liquid microextraction and subsequent gas chromatography tandem mass spectrometry analysis with advanced electron ionization was developed for a human biomonitoring of UV 328 exposure, which enabled the determination of UV 328 and six of its metabolites in human urine. Sample preparation and derivatization were optimized. Baseline separation of the analytes was assured by the application of a suitable temperature program. The validation resulted in limits of detection of 0.1 µg/L for all analytes, variation coefficients from 1 to 12% for precision in series and from 5 to 12% for interday precision. Furthermore, relative recovery rates between 80 and 120% were determined. Moreover, the procedure was successfully applied to urine samples of a volunteer exposed to UV 328. The method showed excellent sensitivity, repeatability and robustness for all parameters and may be applicable for studies to elucidate the metabolism and kinetics of the investigated UV absorber and for monitoring of individuals with specific exposure to UV 328.
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http://dx.doi.org/10.1016/j.jchromb.2020.122071DOI Listing
May 2020

Organophosphate pesticide exposure in children in Israel: Dietary associations and implications for risk assessment.

Environ Res 2020 03 13;182:108739. Epub 2019 Sep 13.

Public Health Services, Ministry of Health, 39 Yirmiyahu Street, Jerusalem, 9446724, Israel.

Background: Human biomonitoring (HBM) data is increasingly being compared to risk-based screening values to assess human health risk. However, as screening values have not been established for assessing biomarker concentrations of organophosphate (OP) pesticide metabolites, there are few studies using HBM data on urinary OP concentrations to assess human health risk. The purpose of the current study was to measure OP exposure in a sample of children in Israel; to explore associations between dietary patterns and OP exposure; and to assess risk of OP pesticides using urinary metabolite concentrations.

Methods: We recruited 103 children in Israel and collected demographic and dietary data and urinary samples, and measured creatinine and dialkyl phosphate (DAP) concentrations. We compared urinary DAP concentrations to international populations and analysed associations between fruit and vegetable consumption and urinary DAP concentrations. Using urinary DAP concentrations, we calculated estimated daily intakes (EDI) of OP pesticides in each child and compared those to the acceptable daily intake (ADI).

Results: Concentrations of several dialkyl phosphate metabolites (dimethylphosphate (DMP) and dimethylthiophosphate (DMTP)) were higher in our study population of Israeli children (geometric mean concentrations of DMP and DMTP were 6.6 μg/L and 7.6 μg/L, respectively) compared to children in the US, Canada, Spain, and Denmark. We found positive correlations between total fruit consumption and creatinine adjusted log transformed urinary DMP, DMTP, diethylthiophopshate (DETP), total dimethyl (DM) and total DAP concentrations (p < 0.05), positive correlations between cucumber consumption and diethylphosphate (DEP), DETP and diethyl (DE) concentrations (p < 0.05), and positive correlations between apple consumption and DETP concentrations (p = 0.02). Based on urinary DAP concentrations, we found that a portion of the children in our study had EDIs above the ADI, ranging from 2.9% to 79.4% of the children, depending on the active OP ingredient.

Conclusions: We found that Israeli children in our study are widely exposed to OP pesticides; that levels of dimethyl metabolites were high compared to other international populations; and that fruit consumption was associated with higher urinary DAP levels. Using urinary DAP concentration data, we found that a portion of the children in our study may be exposed to OP pesticides at levels above those considered safe.
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http://dx.doi.org/10.1016/j.envres.2019.108739DOI Listing
March 2020

Exposure of patients to di(2-ethylhexy)phthalate (DEHP) and its metabolite MEHP during extracorporeal membrane oxygenation (ECMO) therapy.

PLoS One 2020 30;15(1):e0224931. Epub 2020 Jan 30.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) is often used for PVC medical devices, that are also largely used for intensive care medical treatments, like extracorporeal membrane oxygenation (ECMO) therapy. Due to the toxicological potential of DEHP, the inner exposure of patients with this plasticizer is a strong matter of concern as many studies have shown a high leaching potential of DEHP into blood. In this study, the inner DEHP exposure of patients undergoing ECMO treatment was investigated. The determined DEHP blood levels of ECMO patients and the patients of the control group ranged from 31.5 to 1009 μg/L (median 156.0 μg/L) and from 19.4 to 75.3 μg/L (median 36.4 μg/L), respectively. MEHP blood levels were determined to range from < LOD to 475 μg/L (median 15.9 μg/L) in ECMO patients and from < LOD to 9.9 μg/L (median 3.7 μg/L) in the control group patients, respectively. Increased DEHP exposure was associated with the number of cannulas and membranes of the ECMO setting, whereas residual diuresis decreased the exposure. Due to the suspected toxicological potential of DEHP, its use in medical devices should be further investigated, in particular for ICU patients with long-term exposure to PVC, like in ECMO therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224931PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992201PMC
March 2020

Absorption, Biokinetics, and Metabolism of the Dopamine D2 Receptor Agonist Hordenine (,-Dimethyltyramine) after Beer Consumption in Humans.

J Agric Food Chem 2020 Feb 5;68(7):1998-2006. Epub 2020 Feb 5.

Department of Chemistry and Pharmacy, Food Chemistry , Friedrich-Alexander-Universität Erlangen-Nürnberg , Nikolaus-Fiebiger-Str. 10 , 91058 Erlangen , Germany.

Hordenine, a natural constituent of germinated barley, is a biased agonist of the dopamine D2 receptor. This pilot study investigated the biokinetics of hordenine and its metabolites in four volunteers consuming beer equal to 0.075 mg hordenine/kg body weight. A new ultrahigh-performance liquid chromatography method coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method determined maximum plasma concentrations of 12.0-17.3 nM free hordenine after 0-60 min. Hordenine phase-II metabolism was first dominated by sulfation, but later by glucuronidation. The elimination half-lives in plasma were 52.7-66.4 min for free hordenine and about 60/80 min longer for hordenine sulfate and hordenine glucuronide. Urinary excretion peaked 2-3.5 h after consumption and accumulated to 3.78 μmol within 24 h, corresponding to 9.9% of the ingested dose. The observed hordenine levels in plasma seem too low to provoke direct interaction with the dopamine D2 receptor related to food reward, but synergistic or additive effects with alcohol or -methyltyramine may occur.
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http://dx.doi.org/10.1021/acs.jafc.9b06029DOI Listing
February 2020

Inhalation and dermal exposure of workers during timber impregnation with creosote and subsequent processing of impregnated wood.

Environ Res 2020 02 1;181:108877. Epub 2019 Nov 1.

Federal Institute for Occupational Safety and Health (BAuA), Friedrich-Henkel-Weg 1-25, 44149 Dortmund, Germany.

Objectives: Coal tar creosote oils are used as highly effective wood protectants for, e.g., railway sleepers, utility poles and marine pilings. For impregnation of wood, the hot creosote oil is mostly applied in vacuum processes and by hot-and-cold dipping. From the perspective of an occupational hygienist, creosote tar oils are problematic because they have a number of hazardous properties, including carcinogenicity. We have studied inhalation and dermal exposure in six and four impregnation plants, respectively, in Germany. Some plants were visited repeatedly, for up to five measurement campaigns conducted over several years. Inhalation and dermal exposure resulting from vacuum impregnation and from hot-and-cold dipping, as well as secondary exposure resulting from assembly of impregnated railway sleepers have been measured. Accompanying, human biomonitoring of the employees has been performed.

Methods: Inhalation exposure was measured using personal air samplers, collecting particles and vapours simultaneously. Dermal exposure was investigated by whole body dosimetry using disposable chemical protective coveralls and split leather gloves. 18 polycyclic aromatic hydrocarbons (PAHs) have been determined separately by high performance liquid chromatography (HPLC) or gas chromatography-mass spectrometry (GC-MS), respectively. For human biomonitoring 1-hydroxypyrene (1-OHP) in urine related to creatinine has been measured using HPLC. Both, pre- and post-shift values have been determined for this metabolite.

Results: Dermal exposure towards pyrene and the sum of the determined 18 PAHs as well as inhalation exposure to naphthalene, pyrene and the sum of the determined 18 PAHs are presented in this paper. The plants performing vacuum impregnation have employed different constructive, technical and organisational measures, and some measures have also changed between the different measurement campaigns. We have found that cooling the vacuum impregnation vessel before unloading can reduce inhalation exposure to about one-third. However, our data shows that installation of structural or technical risk management measures (RMM) did not always reduce the exposure as intended, and can even lead to increased exposure in adverse constellations. Dermal exposure was strongly affected by differences in the working procedures. Measurements performed during assembly of impregnated railway sleepers indicate that secondary exposure leads to lower inhalation, but similar dermal exposure compared to the impregnation processes. Also 1-OHP excretion rates are similar after impregnation process and after assembly of impregnated railway sleepers.

Conclusion: Our recent data underlines that efficient reduction of the exposure resulting from impregnation with creosote requires sophisticated risk reduction strategies. Structural measures such as the enclosure of the loading area and technical measures like local exhaust ventilation shall be coordinated carefully with organisational measures and provision of personal protective equipment. The data presented here represents a broad bandwidth of current workplace situations in the creosote oil processing industry and is therefore suitable for risk assessment in related plants as well as under regulatory frameworks like the European Biocides Regulation. Each plant in this investigation was unique. Together they represent the whole width of this branch in Germany. Additionally, the number of plants and exposed workers is limited and relative low. Therefore, a comprehensive consideration and statistical analysis were not feasible.
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http://dx.doi.org/10.1016/j.envres.2019.108877DOI Listing
February 2020

Impact of Daily Antiperspirant Use on the Systemic Aluminum Exposure: An Experimental Intervention Study.

Skin Pharmacol Physiol 2020 25;33(1):1-8. Epub 2019 Sep 25.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany,

Background And Objectives: Adverse health effects such as neurotoxic and carcinogenic effects through aluminum from cosmetic products have been repeatedly discussed. The dermal uptake and impact on the systemic aluminum load is still poorly understood. Therefore, we investigated the effect of daily antiperspirant use on the systemic aluminum load under real-life conditions.

Methods: 21 healthy subjects meeting certain selection criteria to ensure a low systemic aluminum background load were asked to use a commercial aluminum-containing antiperspirant for 14 days. A questionnaire enquired about shaving habits and other sources of aluminum. Aluminum levels were measured before and after the exposure in 24-h urine and plasma using atomic absorption spectroscopy. Urine samples (n = 6) with <700 mg/day creatinine excretion or more than 30% difference in 24-h creatinine excretion were excluded from further analysis.

Results: No significant increase in plasma aluminum concentration or total excreted aluminum per day before and after exposure was measurable. No sample exceeded the reference values of the general population (maximum: 9.42 µg/g creatinine and 2.1 µg/L plasma). Shaving habits did not have a significant influence on the systemic aluminum load. Also, no correlation between the total amount of antiperspirant applied and the systemic aluminum level could be demonstrated.

Conclusions: No measurable contribution to the overall systemically available aluminum load due to daily use of an antiperspirant for 14 days could be shown, but real-life data concerning long-term use or higher concentrations are still lacking. Considering toxicological occupational exposure data, adverse neurotoxic changes are unlikely in the case of urinary excretion of <50 µg aluminum/g creatinine (= no observed adverse effect level), even following long-term exposure.
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http://dx.doi.org/10.1159/000502239DOI Listing
June 2020

Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats.

Arch Toxicol 2019 10 14;93(10):2787-2796. Epub 2019 Sep 14.

Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), Paul-Ehrlich-Straße 7, 63225, Langen, Germany.

Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC, mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.
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http://dx.doi.org/10.1007/s00204-019-02561-zDOI Listing
October 2019

Systemic availability of lipophilic organic UV filters through dermal sunscreen exposure.

Environ Int 2019 11 27;132:105068. Epub 2019 Aug 27.

Friedrich-Alexander Universität Erlangen-Nürnberg, Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Henkestr. 9-11, 91054 Erlangen, Germany. Electronic address:

Background: Chemical UV filters are common components in sunscreens and cosmetic products and used to protect the skin against harmful effects of sunlight like sunburn. However, the effectiveness of sunscreens in the prevention of skin cancer is in some parts still controversial. Meanwhile, questions about negative effects of the chemical UV filters on human health arise and request an effective risk assessment. Real-life exposure data in humans after application of these products are still rare. Thus, we explored whether and to what extent UV filters are absorbed through the skin into the human body.

Material And Methods: Plasma and urine samples from 20 healthy volunteers were collected before, during and after a real-life exposure scenario (1st application: 2 mg/cm; 2nd and 3rd (after 2 and 4 h): 1 mg/cm each) using a commercial sunscreen formulation for one day. These samples were analyzed for their content of the currently prominent UV filters octocrylene and avobenzone as well as 2-cyano-3,3-diphenylacrylic acid (CDAA) as the main octocrylene metabolite by using different liquid chromatography electrospray-ionization tandem mass spectrometric procedures.

Results: Following dermal sunscreen exposure, avobenzone, octocrylene and CDAA reached concentrations up to 11 μg/L, 25 μg/L and 1352 μg/L in plasma. In urine detection rates of avobenzone and octocrylene were low while CDAA showed a high detection rate and reached up to 5207 μg/g creatinine. Kinetic models could be fitted for octocrylene and CDAA in plasma and CDAA in urine. Concentration peaks were reached between 10 and 16 h after first application and half-life periods were in the range of 1.5 to 2 days. The lipophilic UV filter octocrylene and its metabolite CDAA showed a much slower elimination than other more hydrophilic UV filters. Concordantly, the metabolite CDAA in particular showed a markedly increased renal excretion over the whole sampling period and indicated high internal exposure to OC.

Discussion: Real-life sunscreen usage leads to considerable bioavailability of organic UV filters and their metabolites which is rarely seen for other environmental exposures. A combined monitoring of the parent compound and its metabolites is important to fully address internal exposure to the UV filter in humans. Considering the kinetic profiles a prolonged systemic release due to depot formation in skin and a potential accumulation through multi-day exposure is presumed. High in-vivo loads call for a critical toxicological assessment of the UV filters and their metabolites.
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http://dx.doi.org/10.1016/j.envint.2019.105068DOI Listing
November 2019

Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure.

Arch Toxicol 2019 09 22;93(9):2565-2574. Epub 2019 Aug 22.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestr. 9-11, 91054, Erlangen, Germany.

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9 h under real-life conditions (2 mg/cm body surface area; double re-application; corresponding to 3.8 g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray-ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525 µg/g and 213 µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8 h after first application. First-phase terminal half-lives were 8-9 h. For 5OH-EHS, a second-phase terminal half-life could be determined (87 h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24 h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24 h reached up to 334 µg EHS and 124 µg of 5OH-EHS. Simulated real-life sunscreen use for 1 day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.
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http://dx.doi.org/10.1007/s00204-019-02537-zDOI Listing
September 2019

Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium.

Environ Res 2019 10 10;177:108583. Epub 2019 Jul 10.

Public Health England, UK.

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.
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http://dx.doi.org/10.1016/j.envres.2019.108583DOI Listing
October 2019

Newborn infant urinary cotinine and birth outcomes in the Jerusalem Environment Mother and Child Cohort Study.

Int J Hyg Environ Health 2019 08 16;222(7):1054-1058. Epub 2019 Jul 16.

Hadassah-Hebrew University Braun School of Public Health, POB 12272, Jerusalem, 91120, Israel.

Background: Environmental tobacco smoke (ETS) exposure during pregnancy can cause preterm delivery and childhood cancer. The aim of this study was to measure ETS exposure in pregnant women and in newborn infants in Israel using urinary cotinine measurements, to assess predictors of ETS exposure in these vulnerable groups, and to assess associations with birth effects (birth weight, birth length, head circumference) in newborn infants.

Methods: We analyzed urinary cotinine and creatinine in 265 non-smoking pregnant women and 97 newborns, and analyzed associations with self-reported exposure to ETS, paternal smoking, sociodemographic variables and with birth outcomes (birth weight, birth length, head circumference).

Results: 37.7% of pregnant women and 29.0% of infants had urinary cotinine concentrations above the level of quantification (LOQ) of 1 μg/L, whereas 63.8% and 50.5%, respectively, had urinary cotinine concentrations above the level of detection (LOD) of 0.5 μg/L. Median unadjusted and creatinine adjusted urinary concentrations of cotinine in pregnant women were 0.7 μg/L, and 0.9 μg/g creatinine, respectively, and in newborn infants were 0.5 μg/L, and 1.3 μg/g creatinine, respectively. We did not find an association between maternal and infant urinary cotinine level. Maternal (but not infant) urinary cotinine was significantly associated with paternal smoking (p < 0.05). Infant (but not maternal) cotinine above the LOQ was negatively associated with birth weight (p < 0.05).

Conclusions: In this high socioeconomic cohort, almost a third of newborn infants born to non-smoking mothers had quantifiable levels of urinary cotinine. This is the first study showing that newborns with quantifiable urinary cotinine levels have lower birth weight.
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http://dx.doi.org/10.1016/j.ijheh.2019.07.006DOI Listing
August 2019

Aluminium from adjuvanted subcutaneous allergen immunotherapeutics in rats is mainly detected in bone.

Allergy 2020 01 1;75(1):215-217. Epub 2019 Aug 1.

Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), Langen, Germany.

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http://dx.doi.org/10.1111/all.13982DOI Listing
January 2020

Quantification of prominent organic UV filters and their metabolites in human urine and plasma samples.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Sep 28;1125:121706. Epub 2019 Jun 28.

Institute and Clinic of Occupational, Social and Environmental Medicine (IPASUM), University of Erlangen-Nürnberg, Henkestr. 9-11, 91054 Erlangen, Germany.

Monitoring human exposure to chemical UV filters is essential for an accurate assessment of the health risk caused by the resorbed compounds. We developed different procedures for the determination of the prominent UV filters octocrylene (OC), avobenzone (AVO) and 2-ethylhexyl salicylate (EHS) as well as for two OC and EHS metabolites in human urine and OC, AVO and 2-cyano-3,3-diphenylacrylic acid (CDAA) in plasma samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since the development of a multi-method for all analytes proved to be difficult, three different procedures were established for the determination of AVO, OC and its metabolite CDAA in urine and plasma as well as for EHS and its metabolite 5-hydroxy-EHS in urine. The methods have been validated with good sensitivity, precision and accuracy. The procedures were satisfactorily applied to the determination of the target compounds in human samples collected from volunteers after sunscreen application. These new analytical procedures can provide information on the internal exposure to the UV filters OC, AVO and EHS, which has been little studied.
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http://dx.doi.org/10.1016/j.jchromb.2019.06.033DOI Listing
September 2019

Validity of different biomonitoring parameters in human urine for the assessment of occupational exposure to naphthalene.

Arch Toxicol 2019 08 20;93(8):2185-2195. Epub 2019 Jun 20.

Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Henkestr. 9-11, 91054, Erlangen, Germany.

Up to date, information on the validity of human biomonitoring (HBM) parameters of naphthalene exposure is poor. This study was performed to reveal the relation between occupational exposure to naphthalene and biological exposure markers. Therefore, ten lowly and highly exposed workers from the abrasives industry were selected to characterise a broad exposure range. Naphthalene in air was determined by personal air monitoring during one shift. For biological monitoring, pre- and post-shift urine samples collected on 2 days of a working week were analysed for 1,2-dihydroxynaphthalene (1,2-DHN), 1- and 2-naphthol, 1- and 2-naphthylmercapturic acid (NMA). The naphthalene concentration in air was in the range of 0.5 to 11.6 mg/m. The biomarkers in urine showed post-shift concentration in the range of 114-51,809 µg/L for 1,2-DHN, 0.8-666 µg/L for 1-NMA, 2-2698 µg/L for 1-naphthol and 4-1135 µg/L for 2-naphthol, respectively. 2-NMA was not detected. The urinary levels increased significantly from pre- to post-shift for all analysed parameters and an accumulation over the working week was observed. Significant positive correlations were observed between 1,2-DHN, 1-NMA, 1- and 2-naphthol in post-shift urine samples and personal exposure to naphthalene in the air. 1-NMA and 1,2-DHN, 1- and 2-naphthol have been demonstrated as suitable biomarkers for naphthalene exposure monitoring. Of the determined biomarkers, 1,2-DHN is by far the metabolite with the highest concentration in the urine samples.
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http://dx.doi.org/10.1007/s00204-019-02468-9DOI Listing
August 2019

Oxidative phase I metabolism of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) in an in vitro model with human liver microsomes.

Toxicol In Vitro 2019 Oct 14;60:313-322. Epub 2019 Jun 14.

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander Universität Erlangen-Nürnberg, Henkestraße 9-11, 91054 Erlangen, Germany. Electronic address:

2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328, CAS: 25973-55-1) is an ultraviolet light (UV) absorber which is used as an additive for plastics and other polymeric substances to prevent the host material from light induced degradation reactions. However, no information about human exposure, metabolism and kinetics is available for this substance so far. Therefore, in vitro experiments with human liver microsomes were performed to derive oxidative phase I metabolites of UV 328 in an explorative approach using liquid-chromatography coupled with tandem mass spectrometry. Initially, a suspect screening mode was applied to the incubated samples. Six metabolites with hydroxy or oxo groups as well as a metabolite carrying both hydroxy and carbonyl moieties at the alkyl side chains were postulated and custom synthesized as reference standards. Afterwards, the results were verified in a target screening approach. Thereby, five of the six investigated analyte structures were confirmed. Quantitative estimations of the generated transformation products revealed 2-(2H-benzotriazol-2-yl)-6-(3-hydroxy-2-methylbutan-2-yl)-4-(tert-pentyl)phenol (UV 328-6/3-OH), 2-(2H-benzotriazol-2-yl)-4-(3-hydroxy-2-methylbutan-2-yl)-6-(tert-pentyl)phenol (UV 328-4/3-OH) and 2-(2H-benzotriazol-2-yl)-4-(2-methylbutan-3-on-2-yl)-6-(3-hydroxy-2-methylbutan-2-yl)phenol (UV 328-4/3-CO-6/3-OH) as most promising parameters. In summary, oxidation of both alkyl side chains at the phenol moiety was proven, but no metabolic transformations at the benzotriazole moiety were observed.
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http://dx.doi.org/10.1016/j.tiv.2019.06.012DOI Listing
October 2019

Reduction of exposure to plasticizers in stored red blood cell units.

Perfusion 2020 01 31;35(1):32-38. Epub 2019 May 31.

Department of Pediatric Cardiac Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Introduction: Plastic can be toxic and hazardous to an organism's health, but it is being widely used in our daily lives. Di-2-ethylhexyl-phthalate is the most common plasticizer in medical devices made of polyvinylchloride and is commonly found in soft bags storing red blood cell units. Di-2-ethylhexyl-phthalate and its degradation product mono-2-ethylhexyl-phthalate can migrate into human body fluids, for example, blood and tissues. The aim of the study was to assess the concentration of plasticizers in red blood cell units according to storage time and after mechanical rinsing using a cell salvage device.

Methods: Levels of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate were analysed in 50 unwashed red blood cell units using liquid chromatography coupled with tandem mass spectrometry. In addition, phthalate concentrations were measured before and after mechanical rinsing in six more washed red blood cell units with storage times ranging between 36 and 56 days. A linear regression model was determined by the daily increase of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate in the stored red blood cell units subject to their storage time (range = 4-38 days), and the effect of mechanical rinsing on their phthalate concentration was calculated.

Results: A linear correlation was found between storage time of unwashed red blood cell units and the concentration of di-2-ethylhexyl-phthalate (p < 0.001) or mono-2-ethylhexyl-phthalate (p < 0.001). Stored red blood cell units older than 14 days had significantly higher concentrations of both contaminants than red blood cell units of shorter storage time (p < 0.001). Mechanical rinsing in washed red blood cell units attained a reduction in the di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate concentration by a median of 53% (range = 18-68%; p = 0.031) and 87% (range = 68-96%; p = 0.031), respectively.

Conclusion: Leaching of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate into red blood cell units depends on the duration of storage time. Plasticizers can be significantly reduced by mechanical rinsing using cell salvage devices, and thus, red blood cell units can be regenerated with respect to chemical contamination.
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http://dx.doi.org/10.1177/0267659119851403DOI Listing
January 2020