A large scale multi-laboratory suspect screening of pesticide metabolites in human biomonitoring: From tentative annotations to verified occurrences

Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides. For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure

From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined

A magyar lakosság vegyi anyagokkal és humán biomonitoringgal kapcsolatos ismereteinek, valamint hozzáállásának felmérése fókuszcsoportos beszélgetés és online kérdőíves felmérés alapján = Citizens’ perceptions and attitudes about chemicals and human biomonitoring based on focus group discussion and online questionnaire survey

A vegyi anyagok mára a mindennapi életünk elkerülhetetlen részévé váltak. Használatuk azonban számtalan előnyük mellett kockázatot is jelent az emberek egészségére és az ökológiai rendszerekre, amit folyamatosan vizsgálnunk és kezelnünk kell. Az utóbbi években a lakosság körében jól dokumentáltan nőtt a környezetszennyezéssel, illetve annak az egészségre gyakorolt hatásaival kapcsolatos közérdeklődés és aggodalom. A lakosság vegyi anyagoknak való kitettséggel kapcsolatos attitűdjének, valamint a humán biomonitoringra vonatkozó ismereteinek és elvárásainak felmérése céljából a HBM4EU projekt keretében, több résztvevő országhoz hasonlóan Magyarországon is fókuszcsoportos interjút, valamint online kérdőíves felmérést végeztünk 2020-ban. Az eredmények azt mutatják, hogy a megkérdezettek aggódnak az élelmiszerbiztonság és a vegyi anyagok okozta kitettség miatt. A kétféle közvélemény-kutatás résztvevői tisztában voltak a vegyi anyagok lehetséges felvételével az élelmiszerfogyasztás (pl. tartósítószerek, ízfokozók, színezékek, növényvédő szerek, fémek), illetve a szennyezett környezet (pl. levegő) révén. A kérdőíves felmérésben azonosított pozitív szempontok egyike, hogy a válaszadók nagy része támogatja a rendszeres humán biomonitoring vizsgálatok végzését és érdeklődést mutat a témával kapcsolatos újabb információk iránt, valamint bizonyos feltételek mellett hajlandó lenne meglévő szokásain változtatni. A személyes viselkedésbeli változások előmozdítása a teljes társadalom aktív részvételét igényli (pl. ingázási szokások, energiafelhasználás, hulladékgyűjtés, étkezési és fogyasztási szokások). Mivel a jelenlegi közvélemény-kutatásba csak a lakosság egy szűk rétegét sikerült bevonni, további kihívás a társadalom szélesebb rétegeinek elérése. A jövőben a lakosság tudatosságának növelésére, tudományosan megalapozott, új szakpolitikai intézkedések kidolgozására és végrehajtására, illetve a kapcsolódó témáknak az oktatási rendszerbe való beépítésére kell összpontosítani. A közvélemény tudatosságának növelése elősegítheti a polgárok elkötelezettségét, ami képessé teheti őket arra, hogy nyomást gyakoroljanak a politikai döntéshozókra az ártalmas vegyi anyagok okozta expozíció csökkentését célzó hatékony intézkedések meghozatalának érdekében

Citizens' Perception and Concerns on Chemical Exposures and Human Biomonitoring-Results from a Harmonized Qualitative Study in Seven European Countries.

Funding Information: Funding: This research was done within the HBM4EU project and funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032. The organization and collection of Danish data (including Norstat) was financed by the University of Copenhagen. Funding Information: This research was done within the HBM4EU project and funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032. The organization and collection of Danish data (including Norstat) was financed by the University of Copenhagen. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Exposure to different chemicals is an inevitable part of our everyday lives. Within HBM4EU, focus group discussions were conducted to gather data on citizens' perceptions of chemical exposure and human biomonitoring. These discussions were hosted in Cyprus, Denmark, Hungary, Israel, Latvia, the Netherlands, and North Macedonia following a protocol developed in the first round of discussions. Results indicate the very high concern of European citizens regarding food safety and the environment. Focus group participants were well aware of potential uptake of chemicals through food consumption (e.g., preservatives, flavor enhancers, coloring agents, pesticides, fertilizers, metals), drinking water, or from polluted air and water. One of the positive aspects identified here, is the high interest of citizens in awareness and education on personal measures to control exposure. The promotion of personal behavioral changes requires active involvement of society (e.g., commuting habits, energy choices, waste disposal, dietary habits). Activities should focus on raising awareness of the general public, implementation of policy measures, and mainstreaming of related topics into the education system. Raising awareness of the general public may promote engagement of citizens, which in turn may empower them to put pressure on politicians to take effective actions. There is also a need for further research which might focus on the impact of country-specific situations and of the COVID-19 pandemic on the exposure of citizens to chemicals.publishersversionPeer reviewe

Case study: Possible differences in phthalates exposure among the Czech, Hungarian, and Slovak populations identified based on the DEMOCOPHES pilot study results

Phthalates and their metabolites are classified as endocrine modulators. They affect the hormonal balance in both children and adults. The aim of this publication was to compare the urinary levels of phthalate metabolites in selected populations of the Czech Republic (CZ), Slovakia (SK), and Hungary (HU) in relation to the sources of phthalate exposure identified by means of questionnaire (personal care products, floor and wall coverings, plastic toys, and some kinds of foods).publisher: Elsevier articletitle: Case study: Possible differences in phthalates exposure among the Czech, Hungarian, and Slovak populations identified based on the DEMOCOPHES pilot study results journaltitle: Environmental Research articlelink: http://dx.doi.org/10.1016/j.envres.2014.10.025 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved.status: publishe

A large scale multi-laboratory suspect screening of pesticide metabolites in human biomonitoring: From tentative annotations to verified occurrences.

Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides. For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure

A large scale multi-laboratory suspect screening of pesticide metabolites in human biomonitoring: From tentative annotations to verified occurrences

International audienceWithin the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides.For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure

Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites). In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between adults and children. This survey demonstrates the feasibility of conducting a harmonized pan-European sample collection, combined with suspect screening to provide insight in the presence of exposure to pesticide mixtures in the European population, including agricultural areas. Future improvements could come from improved (harmonized) quantification of pesticide levels