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Toxics
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Analysis of Human Biomonitoring Data and Risk Assessment of Human...
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Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome Analysis and Risk Assessment".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 33862

Special Issue Editors

Prof. Dr. Greet Schoeters

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Guest Editor
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Interests: human biomonitoring; endocrine disruptors; molecular epidemiology; effect biomarkers; risk assessment
Dr. Tiina Santonen

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Guest Editor
Finnish Institute for Occupational Health (FIOH), Helsinki, Finland
Interests: biomonitoring; occupational exposure; metals; carcinogens
Dr. Eva Govarts

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Guest Editor
VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium
Interests: human biomonitoring; mixtures; exposure levels; health effects

Special Issue Information

Dear Colleagues,

Human biomonitoring offers a perspective to better understand the impact of human exposure to environmental chemicals. A diversity of initiatives at the national, European, and global level are bringing progress in this field. Human biomonitoring is a tool that is increasingly used to support policies around chemicals and as a basis for advice on how to better protect against human exposure to hazardous chemicals. It aggregates exposure by different exposure routes and as such offers unique insights into people’s body burden and possibilities to learn about exposure routes and sources that contribute to the body burden. By comparing biomonitoring data with health-based guideline values, interpretation in terms of health risks becomes possible. The combination of exposure biomarkers with effect biomarkers connects to the exposome and provides evidence for the causal pathways between external exposure and adverse health outcomes.

This Special Issue aims to capture knowledge from recent human biomonitoring studies but also from re-use and re-analysis of existing data to explore time trends and spatial trends of human exposure in a wider European or global context.

We look forward to manuscripts that result from the HBM4EUproject https://www.hbm4eu.eu/. HBM4EU is a joint effort of 30 countries, the European Environment Agency, and the European Commission, co-funded under Horizon 2020 and running from 2017 to 2022. HBM4EU coordinates and advances human biomonitoring in Europe to provide better evidence of the actual exposure of citizens to chemicals and to support policies around chemicals in Europe.

We also invite manuscripts from other human biomonitoring initiatives from outside Europe or national studies that provide insight into sources, exposure pathways, and interpretation of health risks based on human biomonitoring data.

The articles in this Special Issue are expected to provide recommendations on how to use human biomonitoring data and to gain insights into the need for further reduction in human chemical exposure to prevent adverse health effects. 

Prof. Dr. Greet Schoeters
Dr. Tiina Santonen
Dr. Eva Govarts
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human biomonitoring
  • risk assessment
  • exposure determinants
  • effect biomarkers
  • time trends
  • high exposure groups
  • chemicals of emerging concern

Published Papers (15 papers)

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23 pages, 3090 KiB  
Article
Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe
by Laura Rodriguez Martin, Liese Gilles, Emilie Helte, Agneta Åkesson, Jonas Tägt, Adrian Covaci, Amrit K. Sakhi, An Van Nieuwenhuyse, Andromachi Katsonouri, Anna-Maria Andersson, Arno C. Gutleb, Beata Janasik, Brice Appenzeller, Catherine Gabriel, Cathrine Thomsen, Darja Mazej, Denis Sarigiannis, Elena Anastasi, Fabio Barbone, Hanna Tolonen, Hanne Frederiksen, Jana Klanova, Jani Koponen, Janja Snoj Tratnik, Kim Pack, Koppen Gudrun, Kristin Ólafsdóttir, Lisbeth E. Knudsen, Loïc Rambaud, Loreta Strumylaite, Lubica Palkovicova Murinova, Lucia Fabelova, Margaux Riou, Marika Berglund, Maté Szabados, Medea Imboden, Michelle Laeremans, Milada Eštóková, Natasa Janev Holcer, Nicole Probst-Hensch, Nicole Vodrazkova, Nina Vogel, Pavel Piler, Phillipp Schmidt, Rosa Lange, Sónia Namorado, Szilvia Kozepesy, Tamás Szigeti, Thorhallur I. Halldorsson, Till Weber, Tina Kold Jensen, Valentina Rosolen, Vladimira Puklova, Wojciech Wasowicz, Ovnair Sepai, Lorraine Stewart, Marike Kolossa-Gehring, Marta Esteban-López, Argelia Castaño, Jos Bessems, Greet Schoeters and Eva Govartsadd Show full author list remove Hide full author list
Toxics 2023, 11(10), 819; https://doi.org/10.3390/toxics11100819 - 28 Sep 2023
Cited by 1 | Viewed by 1610
Abstract
Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a [...] Read more.
Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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16 pages, 2269 KiB  
Article
Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept
by Miranda M. Loh, Phillipp Schmidt, Yvette Christopher de Vries, Nina Vogel, Marike Kolossa-Gehring, Jelle Vlaanderen, Erik Lebret and Mirjam Luijten
Toxics 2023, 11(5), 408; https://doi.org/10.3390/toxics11050408 - 26 Apr 2023
Cited by 2 | Viewed by 1424
Abstract
Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human [...] Read more.
Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as ‘communities’, reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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23 pages, 2283 KiB  
Article
Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
by Nina Vogel, Rosa Lange, Phillipp Schmidt, Laura Rodriguez Martin, Sylvie Remy, Andrea Springer, Vladimíra Puklová, Milena Černá, Péter Rudnai, Szilvia Középesy, Beata Janasik, Danuta Ligocka, Lucia Fábelová, Branislav Kolena, Ida Petrovicova, Michal Jajcaj, Milada Eštóková, Marta Esteban-Lopez, Argelia Castaño, Janja Snoj Tratnik, Anja Stajnko, Lisbeth E. Knudsen, Jorma Toppari, Katharina M. Main, Anders Juul, Anna-Maria Andersson, Niels Jørgensen, Hanne Frederiksen, Cathrine Thomsen, Amrit Kaur Sakhi, Agneta Åkesson, Christina Hartmann, Marie Christine Dewolf, Gudrun Koppen, Pierre Biot, Elly Den Hond, Stefan Voorspoels, Liese Gilles, Eva Govarts, Aline Murawski, Antje Gerofke, Till Weber, Maria Rüther, Arno C. Gutleb, Cedric Guignard, Tamar Berman, Holger M. Koch and Marike Kolossa-Gehringadd Show full author list remove Hide full author list
Toxics 2023, 11(3), 241; https://doi.org/10.3390/toxics11030241 - 04 Mar 2023
Cited by 2 | Viewed by 1918
Abstract
Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from [...] Read more.
Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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15 pages, 612 KiB  
Article
Occupational Exposure and Health Impact Assessment of Diisocyanates in Finland
by Pasi Huuskonen, Simo P. Porras, Bernice Scholten, Lützen Portengen, Sanni Uuksulainen, Katriina Ylinen and Tiina Santonen
Toxics 2023, 11(3), 229; https://doi.org/10.3390/toxics11030229 - 27 Feb 2023
Cited by 4 | Viewed by 1542
Abstract
Diisocyanates are a group of chemicals widely used in different industrial applications. The critical health effects related to diisocyanate exposure are isocyanate sensitisation, occupational asthma and bronchial hyperresponsiveness (BHR). Industrial air measurements and human biomonitoring (HBM) samples were gathered in specific occupational sectors [...] Read more.
Diisocyanates are a group of chemicals widely used in different industrial applications. The critical health effects related to diisocyanate exposure are isocyanate sensitisation, occupational asthma and bronchial hyperresponsiveness (BHR). Industrial air measurements and human biomonitoring (HBM) samples were gathered in specific occupational sectors to examine MDI, TDI, HDI and IPDI and the respective metabolites from Finnish screening studies. HBM data can give a more accurate picture of diisocyanate exposure, especially if workers have been exposed dermally or used respiratory protection. The HBM data were used for conducting a health impact assessment (HIA) in specific Finnish occupational sectors. For this purpose, exposure reconstruction was performed on the basis of HBM measurements of TDI and MDI exposures using a PBPK model, and a correlation equation was made for HDI exposure. Subsequently, the exposure estimates were compared to a previously published dose–response curve for excess BHR risk. The results showed that the mean and median diisocyanate exposure levels and HBM concentrations were low for all diisocyanates. In HIA, the excess risk of BHR from MDI exposure over a working life period was highest in the construction and motor and vehicle industries and repair sectors, resulting in estimated excess risks of BHR of 2.0% and 2.6%, and 113 and 244 extra BHR cases in Finland, respectively. Occupational exposure to diisocyanates must be monitored because a clear threshold for DI sensitisation cannot be established. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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31 pages, 15369 KiB  
Article
Identification of Real-Life Mixtures Using Human Biomonitoring Data: A Proof of Concept Study
by Laura Rodriguez Martin, Ilse Ottenbros, Nina Vogel, Marike Kolossa-Gehring, Phillipp Schmidt, Katarína Řiháčková, Miguel Juliá Molina, Elena Varea-Jiménez, Eva Govarts, Susana Pedraza-Diaz, Erik Lebret, Jelle Vlaanderen and Mirjam Luijten
Toxics 2023, 11(3), 204; https://doi.org/10.3390/toxics11030204 - 22 Feb 2023
Cited by 3 | Viewed by 1699
Abstract
Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that [...] Read more.
Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that are in our body at one point in time. Network analysis applied to such data may provide insight into real-life mixtures by visualizing chemical exposure patterns. The identification of groups of more densely correlated biomarkers, so-called “communities”, within these networks highlights which combination of substances should be considered in terms of real-life mixtures to which a population is exposed. We applied network analyses to HBM datasets from Belgium, Czech Republic, Germany, and Spain, with the aim to explore its added value for exposure and risk assessment. The datasets varied in study population, study design, and chemicals analysed. Sensitivity analysis was performed to address the influence of different approaches to standardise for creatinine content of urine. Our approach demonstrates that network analysis applied to HBM data of highly varying origin provides useful information with regards to the existence of groups of biomarkers that are densely correlated. This information is relevant for regulatory risk assessment, as well as for the design of relevant mixture exposure experiments. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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11 pages, 1554 KiB  
Article
Glyphosate and AMPA in Human Urine of HBM4EU-Aligned Studies: Part B Adults
by Jurgen Buekers, Sylvie Remy, Jos Bessems, Eva Govarts, Loïc Rambaud, Margaux Riou, Thorhallur I Halldorsson, Kristin Ólafsdóttir, Nicole Probst-Hensch, Priska Ammann, Till Weber, Marike Kolossa-Gehring, Marta Esteban-López, Argelia Castaño, Helle Raun Andersen and Greet Schoeters
Toxics 2022, 10(10), 552; https://doi.org/10.3390/toxics10100552 - 21 Sep 2022
Cited by 10 | Viewed by 2382
Abstract
Within HBM4EU, human biomonitoring (HBM) studies measuring glyphosate (Gly) and aminomethylphosphonic acid (AMPA) in urine samples from the general adult population were aligned and quality-controlled/assured. Data from four studies (ESB Germany (2015–2020); Swiss HBM4EU study (2020); DIET-HBM Iceland (2019–2020); ESTEBAN France (2014–2016)) were [...] Read more.
Within HBM4EU, human biomonitoring (HBM) studies measuring glyphosate (Gly) and aminomethylphosphonic acid (AMPA) in urine samples from the general adult population were aligned and quality-controlled/assured. Data from four studies (ESB Germany (2015–2020); Swiss HBM4EU study (2020); DIET-HBM Iceland (2019–2020); ESTEBAN France (2014–2016)) were included representing Northern and Western Europe. Overall, median values were below the reported quantification limits (LOQs) (0.05–0.1 µg/L). The 95th percentiles (P95) ranged between 0.24 and 0.37 µg/L urine for Gly and between 0.21 and 0.38 µg/L for AMPA. Lower values were observed in adults compared to children. Indications exist for autonomous sources of AMPA in the environment. As for children, reversed dosimetry calculations based on HBM data in adults did not lead to exceedances of the ADI (proposed acceptable daily intake of EFSA for Gly 0.1 mg/kg bw/day based on histopathological findings in the salivary gland of rats) indicating no human health risks in the studied populations at the moment. However, the controversy on carcinogenicity, potential endocrine effects and the absence of a group ADI for Gly and AMPA induce uncertainty to the risk assessment. Exposure determinant analysis showed few significant associations. More data on specific subgroups, such as those occupationally exposed or living close to agricultural fields or with certain consumption patterns (vegetarian, vegan, organic food, high cereal consumer), are needed to evaluate major exposure sources. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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20 pages, 1318 KiB  
Article
Concurrent Assessment of Phthalates/HEXAMOLL® DINCH Exposure and Wechsler Intelligence Scale for Children Performance in Three European Cohorts of the HBM4EU Aligned Studies
by Valentina Rosolen, Elisa Giordani, Marika Mariuz, Maria Parpinel, Luca Ronfani, Liza Vecchi Brumatti, Maura Bin, Gemma Calamandrei, Vicente Mustieles, Liese Gilles, Eva Govarts, Kirsten Baken, Laura Rodriguez Martin, Greet Schoeters, Ovnair Sepai, Eva Sovcikova, Lucia Fabelova, Miroslava Šidlovská, Branislav Kolena, Tina Kold Jensen, Hanne Frederiksen, Marike Kolossa-Gehring, Rosa Lange, Petra Apel, Argelia Castano, Marta Esteban López, Griet Jacobs, Stefan Voorspoels, Helena Jurdáková, Renáta Górová and Fabio Barboneadd Show full author list remove Hide full author list
Toxics 2022, 10(9), 538; https://doi.org/10.3390/toxics10090538 - 16 Sep 2022
Cited by 3 | Viewed by 2215
Abstract
Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL® DINCH) on children’s neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL® DINCH exposure and child neurodevelopment in three European [...] Read more.
Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL® DINCH) on children’s neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children’s urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL® DINCH biomarkers. The relation between phthalates/HEXAMOLL® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 ± 11 (NAC-II), 98 ± 12 (OCC), and 81 ± 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP’s biomarkers were found: 5OH-MEHP+5oxo-MEHP (β = 2.56; 95% CI 0.58–4.55; N = 270), 5OH-MEHP+5cx-MEPP (β = 2.48; 95% CI 0.47–4.49; N = 270) and 5OH-MEHP (β = 2.58; 95% CI 0.65–4.51; N = 270). On the contrary, in the OCC the relation between DEHP’s biomarkers and FSIQ tended to be inverse but imprecise (p-value ≥ 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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26 pages, 1266 KiB  
Article
HBM4EU Chromates Study—Genotoxicity and Oxidative Stress Biomarkers in Workers Exposed to Hexavalent Chromium
by Ana Tavares, Kukka Aimonen, Sophie Ndaw, Aleksandra Fučić, Julia Catalán, Radu Corneliu Duca, Lode Godderis, Bruno C. Gomes, Beata Janasik, Carina Ladeira, Henriqueta Louro, Sónia Namorado, An Van Nieuwenhuyse, Hannu Norppa, Paul T. J. Scheepers, Célia Ventura, Jelle Verdonck, Susana Viegas, Wojciech Wasowicz, Tiina Santonen, Maria João Silva and on behalf of the HBM4EU Chromates Study Teamadd Show full author list remove Hide full author list
Toxics 2022, 10(8), 483; https://doi.org/10.3390/toxics10080483 - 18 Aug 2022
Cited by 8 | Viewed by 2260
Abstract
A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and [...] Read more.
A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2′-deoxyguanosine in urine. Workers from several Cr(VI)-related industrial activities and controls from industrial (within company) and non-industrial (outwith company) environments were included. The significantly increased genotoxicity (p = 0.03 for MN in lymphocytes and reticulocytes; p < 0.001 for comet assay data) and oxidative stress levels (p = 0.007 and p < 0.001 for MDA and 8-OHdG levels in pre-shift urine samples, respectively) that were detected in the exposed workers over the outwith company controls suggest that Cr(VI) exposure might still represent a health risk, particularly, for chrome painters and electrolytic bath platers, despite the low Cr exposure. The within-company controls displayed DNA and chromosomal damage levels that were comparable to those of the exposed group, highlighting the relevance of considering all industry workers as potentially exposed. The use of effect biomarkers proved their capacity to detect the early biological effects from low Cr(VI) exposure, and to contribute to identifying subgroups that are at higher risk. Overall, this study reinforces the need for further re-evaluation of the occupational exposure limit and better application of protection measures. However, it also raised some additional questions and unexplained inconsistencies that need follow-up studies to be clarified. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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24 pages, 2098 KiB  
Article
Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies
by Michael Poteser, Federica Laguzzi, Thomas Schettgen, Nina Vogel, Till Weber, Philipp Zimmermann, Domenica Hahn, Marike Kolossa-Gehring, Sónia Namorado, An Van Nieuwenhuyse, Brice Appenzeller, Thórhallur I. Halldórsson, Ása Eiríksdóttir, Line Småstuen Haug, Cathrine Thomsen, Fabio Barbone, Valentina Rosolen, Loïc Rambaud, Margaux Riou, Thomas Göen, Stefanie Nübler, Moritz Schäfer, Karin Haji Abbas Zarrabi, Liese Gilles, Laura Rodriguez Martin, Greet Schoeters, Ovnair Sepai, Eva Govarts and Hanns Moshammeradd Show full author list remove Hide full author list
Toxics 2022, 10(8), 481; https://doi.org/10.3390/toxics10080481 - 17 Aug 2022
Cited by 4 | Viewed by 1854
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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14 pages, 598 KiB  
Article
Glyphosate and AMPA in Human Urine of HBM4EU Aligned Studies: Part A Children
by Jurgen Buekers, Sylvie Remy, Jos Bessems, Eva Govarts, Loïc Rambaud, Margaux Riou, Janja Snoj Tratnik, Anja Stajnko, Andromachi Katsonouri, Konstantinos C. Makris, Annelies De Decker, Bert Morrens, Nina Vogel, Marike Kolossa-Gehring, Marta Esteban-López, Argelia Castaño, Helle Raun Andersen and Greet Schoeters
Toxics 2022, 10(8), 470; https://doi.org/10.3390/toxics10080470 - 12 Aug 2022
Cited by 12 | Viewed by 2735
Abstract
Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); [...] Read more.
Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); ESTEBAN (FR)). Median Gly concentrations in urine were below or around the detection limit (0.1 µg/L). The 95th percentiles ranged between 0.18 and 1.03 µg Gly/L. The ratio of AMPA (aminomethylphosphonic acid; main metabolite of Gly) to Gly at molar basis was on average 2.2 and the ratio decreased with higher Gly concentrations, suggesting that other sources of AMPA, independent of metabolism of Gly to AMPA in the monitored participants, may concurrently operate. Using reverse dosimetry and HBM exposure data from five European countries (east, west and south Europe) combined with the proposed ADI (acceptable daily intake) of EFSA for Gly of 0.1 mg/kg bw/day (based on histopathological findings in the salivary gland of rats) indicated no human health risks for Gly in the studied populations at the moment. However, the absence of a group ADI for Gly+AMPA and ongoing discussions on e.g., endocrine disrupting effects cast some uncertainty in relation to the current single substance ADI for Gly. The carcinogenic effects of Gly are still debated in the scientific community. These outcomes would influence the risk conclusions presented here. Finally, regression analyses did not find clear associations between urinary exposure biomarkers and analyzed potential exposure determinants. More information from questionnaires targeting exposure-related behavior just before the sampling is needed. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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22 pages, 1742 KiB  
Article
A Tiered Approach for Assessing Individual and Combined Risk of Pyrethroids Using Human Biomonitoring Data
by Jose V. Tarazona, Irene Cattaneo, Lars Niemann, Susana Pedraza-Diaz, Maria Carmen González-Caballero, Mercedes de Alba-Gonzalez, Ana Cañas, Noelia Dominguez-Morueco, Marta Esteban-López, Argelia Castaño, Teresa Borges, Andromachi Katsonouri, Konstantinos C. Makris, Ilse Ottenbros, Hans Mol, Annelies De Decker, Bert Morrens, Tamar Berman, Zohar Barnett-Itzhaki, Nicole Probst-Hensch, Samuel Fuhrimann, Janja Snoj Tratnik, Milena Horvat, Loic Rambaud, Margaux Riou, Greet Schoeters, Eva Govarts, Marike Kolossa-Gehring, Till Weber, Petra Apel, Sonia Namorado and Tiina Santonenadd Show full author list remove Hide full author list
Toxics 2022, 10(8), 451; https://doi.org/10.3390/toxics10080451 - 04 Aug 2022
Cited by 9 | Viewed by 2761
Abstract
Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall [...] Read more.
Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014–2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1–0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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14 pages, 1720 KiB  
Article
Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence
by Andreas-Marius Kaiser, Maryam Zare Jeddi, Maria Uhl, Florence Jornod, Mariana F. Fernandez and Karine Audouze
Toxics 2022, 10(8), 449; https://doi.org/10.3390/toxics10080449 - 04 Aug 2022
Cited by 6 | Viewed by 3097
Abstract
Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, [...] Read more.
Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, health status, and genetic predisposition). The biological mechanisms by which PFAS might affect systems are largely unknown. To support the risk assessment process, AOP-helpFinder, a new artificial intelligence tool, was used to rapidly and systematically explore all available published information in the PubMed database. The aim was to identify existing associations between PFAS and metabolic health outcomes that may be relevant to support building adverse outcome pathways (AOPs). The collected information was manually organized to investigate linkages between PFAS exposures and metabolic health outcomes, including dyslipidemia, hypertension, insulin resistance, and obesity. Links between PFAS exposure and events from the existing metabolic-related AOPs were also retrieved. In conclusion, by analyzing dispersed information from the literature, we could identify some associations between PFAS exposure and components of existing AOPs. Additionally, we identified some linkages between PFAS exposure and metabolic outcomes for which only sparse information is available or which are not yet present in the AOP-wiki database that could be addressed in future research. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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21 pages, 1629 KiB  
Article
Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)
by Michael Poteser, Federica Laguzzi, Thomas Schettgen, Nina Vogel, Till Weber, Aline Murawski, Phillipp Schmidt, Maria Rüther, Marike Kolossa-Gehring, Sónia Namorado, An Van Nieuwenhuyse, Brice Appenzeller, Edda Dufthaksdóttir, Kristín Olafsdóttir, Line Småstuen Haug, Cathrine Thomsen, Fabio Barbone, Valentina Rosolen, Loïc Rambaud, Margaux Riou, Thomas Göen, Stefanie Nübler, Moritz Schäfer, Karin H. A. Zarrabi, Liese Gilles, Laura Rodriguez Martin, Greet Schoeters, Ovnair Sepai, Eva Govarts and Hanns Moshammeradd Show full author list remove Hide full author list
Toxics 2022, 10(8), 443; https://doi.org/10.3390/toxics10080443 - 02 Aug 2022
Cited by 2 | Viewed by 2484
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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Review

Jump to: Research

37 pages, 410 KiB  
Review
Exposure Levels of Pyrethroids, Chlorpyrifos and Glyphosate in EU—An Overview of Human Biomonitoring Studies Published since 2000
by Helle Raun Andersen, Loïc Rambaud, Margaux Riou, Jurgen Buekers, Sylvie Remy, Tamar Berman and Eva Govarts
Toxics 2022, 10(12), 789; https://doi.org/10.3390/toxics10120789 - 15 Dec 2022
Cited by 11 | Viewed by 1567
Abstract
Currently used pesticides are rapidly metabolised and excreted, primarily in urine, and urinary concentrations of pesticides/metabolites are therefore useful biomarkers for the integrated exposure from all sources. Pyrethroid insecticides, the organophosphate insecticide chlorpyrifos, and the herbicide glyphosate, were among the prioritised substances in [...] Read more.
Currently used pesticides are rapidly metabolised and excreted, primarily in urine, and urinary concentrations of pesticides/metabolites are therefore useful biomarkers for the integrated exposure from all sources. Pyrethroid insecticides, the organophosphate insecticide chlorpyrifos, and the herbicide glyphosate, were among the prioritised substances in the HBM4EU project and comparable human biomonitoring (HBM)-data were obtained from the HBM4EU Aligned Studies. The aim of this review was to supplement these data by presenting additional HBM studies of the priority pesticides across the HBM4EU partner countries published since 2000. We identified relevant studies (44 for pyrethroids, 23 for chlorpyrifos, 24 for glyphosate) by literature search using PubMed and Web of Science. Most studies were from the Western and Southern part of the EU and data were lacking from more than half of the HBM4EU-partner countries. Many studies were regional with relatively small sample size and few studies address residential and occupational exposure. Variation in urine sampling, analytical methods, and reporting of the HBM-data hampered the comparability of the results across studies. Despite these shortcomings, a widespread exposure to these substances in the general EU population with marked geographical differences was indicated. The findings emphasise the need for harmonisation of methods and reporting in future studies as initiated during HBM4EU. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
42 pages, 2669 KiB  
Review
Reduced Birth Weight and Exposure to Per- and Polyfluoroalkyl Substances: A Review of Possible Underlying Mechanisms Using the AOP-HelpFinder
by Claudia Gundacker, Karine Audouze, Raimund Widhalm, Sebastian Granitzer, Martin Forsthuber, Florence Jornod, Maria Wielsøe, Manhai Long, Thórhallur Ingi Halldórsson, Maria Uhl and Eva Cecilie Bonefeld-Jørgensen
Toxics 2022, 10(11), 684; https://doi.org/10.3390/toxics10110684 - 12 Nov 2022
Cited by 9 | Viewed by 3071
Abstract
Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search PubMed for studies published until March 2021 that examined PFAS exposure in relation [...] Read more.
Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search PubMed for studies published until March 2021 that examined PFAS exposure in relation to birth weight, oxidative stress, hormones/hormone receptors, or growth signaling pathways. Of these 1880 articles, 106 experimental studies remained after abstract screening. One clear finding is that PFAS are associated with oxidative stress in in vivo animal studies and in vitro studies. It appears that PFAS-induced reactive-oxygen species (ROS) generation triggers increased peroxisome proliferator-activated receptor (PPAR)γ expression and activation of growth signaling pathways, leading to hyperdifferentiation of pre-adipocytes. Fewer proliferating pre-adipocytes result in lower adipose tissue weight and in this way may reduce birth weight. PFAS may also impair fetal growth through endocrine effects. Estrogenic effects have been noted in in vivo and in vitro studies. Overall, data suggest thyroid-damaging effects of PFAS affecting thyroid hormones, thyroid hormone gene expression, and histology that are associated in animal studies with decreased body and organ weight. The effects of PFAS on the complex relationships between oxidative stress, endocrine system function, adipogenesis, and fetal growth should be further explored. Full article
(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)
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