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The prenatal environment may program health and disease susceptibility via epigenetic mechanisms. We evaluated associations of maternal trimester-specific intake of micronutrients with global DNA methylation (%5mC) and 5-hydroxymethylation (%5hmC) at birth in cord blood and tested for persistence into childhood. We quantified global %5mC and %5hmC in cord blood cells (n= 434) and in leukocytes collected in early (n= 108) and mid-childhood (n= 390) from children in Project Viva, a pre-birth cohort from Boston, MA. Validated food frequency questionnaires estimated maternal first- and second-trimester intakes of vitamin B2, vitamin B6, vitamin B12, folate, betaine, choline, methionine, iron, and zinc. Mean (SD) cord blood %5mC and %5hmC was 5.62% (2.04) and 0.25% (0.15), respectively. Each μg increase in first-trimester B12intake was associated with 0.002 lower %5hmC in cord blood (95% CI: −0.005, −0.0003), and this association persisted in early childhood (β= −0.007; 95% CI: −0.01, −0.001) but not mid-childhood. Second-trimester iron (mg) was associated with 0.01 lower %5mC (95% CI: −0.02, −0.002) and 0.001 lower %5hmC (95% CI: −0.01, −0.00001) in cord blood only. Increased second-trimester zinc (mg) intake was associated with 0.003 greater %5hmC in early childhood (β= 0.003; 95% CI: 0.0004, 0.006). Second-trimester folate was positively associated with %5hmC in early childhood only (β= 0.08, 95% CI: 0.003, 0.16). Associations did not survive multiple testing adjustment; future replication is needed. Trimester-specific nutrients may impact various sensitive windows of epigenetic programming some with lasting effects in childhood. Further research is needed to understand the role of gene-specific epigenetic changes and how global DNA methylation measures relate to child health.

Pesticide use has increased steadily over the years in both industrial farming and local agriculture. One of the most widely used pesticides at a global level, glyphosate, has been controversial for many years and many studies have focused on the effects of this compound on human health. Ethephon is also a controversial ripening agent used to ripen crops more quickly. A basic but crucial step in the study of the effects of their use on human health is the development of adequate analytical methodologies for the quantification of the compounds in relevant samples. For this study a quick, simple and selective method which uses LC-MS/MS was developed for the determination of ethephon, glyphosate and AMPA. The method uses selective fragment monitoring for each analyte and the internal standard, without prior analytical separation. Mobile phase used consisted of aqueous ammonium formate and methanol in isocratic elution and the sample cleanup was made using solid phase extraction (SPE). The method was validated with regards to selectivity, sensitivity, accuracy and precision in accordance with applicable guidelines. After validation the LC-MS/MS method was successfully used to determine ethephon, glyphosate and AMPA residues in ground and surface water, as well as vegetable samples.

Glyphosate, and the ever growing reliance on its use in agriculture, has been a point of contention for many years. There have been debates regarding the risk and safety of using glyphosate-based herbicides as well as the effects of occupational, accidental, or systematic. Although there have been a number of studies conducted, the biomonitoring of glyphosate poses a series of challenges. Researchers attempting to determine the occupational exposure face questions regarding the most appropriate analytical techniques and sampling procedures. The present review aims to summarize and synthetize the analytical methodologies available and suitable for the purpose of glyphosate biomonitoring studies as well as discuss the advantages and disadvantages of each analytical technique, from the most modern to more well-established and older ones. The most relevant publications that have described analytical methods and published within the last 12 years were studied. Methods were compared, and the advantages and disadvantages of each methods were discussed. A total of 35 manuscripts describing analytical methods for glyphosate determination were summarized and discussed, with the most relevant one being compared. For methods that were not intended for biological samples, we discussed if they could be used for biomonitoring and approaches to adapt these methods for this purpose. ispartof: Int J Environ Res Public Health vol:20 issue:4 pages:3314- ispartof: location:Switzerland status: Published online

Within the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has recently been subject to regulatory actions to improve its risk management in European workplaces. Analysis of the data obtained within the HBM4EU chromates study provides support both for the implementation of these regulatory actions and for national enforcement programs and may also contribute to the updating of occupational limit values (OELs) and biological limit values for Cr(VI). It also provides useful insights on the contribution of different risk management measures (RMMs) to further reduce the exposure to Cr(VI) and may support the evaluation of applications for authorisation under REACH. Findings on chrome platers’ additional per- and polyfluoroalkyl substances (PFAS) exposure highlight the need to also pay attention to this substance group in the metals sector. A survey performed to evaluate the policy relevance of the HBM4EU chromates study findings supports the usefulness of the study results. According to the responses received from the survey, the HBM4EU chromates study was able to demonstrate the added value of the human biomonitoring (HBM) approach in assessment and management of occupational exposure to Cr(VI). For future occupational studies, we emphasise the need for engagement of policy makers and regulators throughout the whole research process to ensure awareness, relevance and uptake of the results in future policies. Highlights: Potential policy impact of the HBM4EU chromates study is presented and discussed; Surveyed policy makers confirmed policy relevance of biomonitoring results; Study considered to support national enforcement and further lowering of OELs; Added value of HBM in the management of occupational exposure to Cr(VI) was demonstrated; Close co-operation with regulators to support policy uptake is emphasised. Funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. info:eu-repo/semantics/publishedVersion

Unsafe pesticide use is a significant concern in rural areas, resulting in serious threats to farmer and environmental health. This problem can be especially severe in developing countries, including Morocco. However, few studies have explored the factors influencing farmers’ safety behavior regarding pesticide use in this country. Hence, we conducted a cross-sectional survey of 232 arboricultural farmers in 12 counties of Morocco's Saïss Plain to assess farmers’ pesticide safety behavior. Farmers’ characteristics, knowledge of pesticides, perceived risk, health consequences, subjective norms, and safety behavior data were collected and analyzed using a structural equation model (SEM). The majority of farmers have long term experience with pesticide use, but they followed poor safety practices, including insufficient use of personal protective equipment during pesticide handling. As a result, farmers showed a high incidence of health problems related to pesticide use (e.g., skin irritation and headaches). Unsafe pesticide handling was mostly attributable to farmers’ low education levels and insufficient training. Consequently, farmers applied high amounts of pesticides to increase production quantities (an average of 12.02 kg/ha per growing season). Although banned in the country, considerable use of organochlorines (i.e., endosulfan) and organophosphorus (i.e., chlorpyrifos ethyl and chlorpyrifos methyl) were reported. Adherence to safety behaviors while handling pesticides significantly improved with high levels of pesticide knowledge (standardized path coefficient, SPC = 0.31) and the perceived severity of the associated health risks (SPC = 0.27). Conversely, uncertainty about the risks of pesticide use was associated with a lower likelihood of adopting safety measures (SPC = 0.24). Improved knowledge of safe pesticide handling and training courses on the risks posed by pesticide exposure to human and environmental health are urgently needed to improve farmers’ safety behavior in Morocco. ispartof: Sustainable Production and Consumption vol:25 pages:471-483 status: published

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values. Highlights: An international Human Biomonitoring Working Group (i-HBM) was formed in 2020; i-HBM working group is affiliated with the International Society of Exposure Science (ISES); i-HBM has developed the first curated database of HBM Health-Based Guidance Values or HB2GVs, The guidance values are freely available in the online HB2GV Dashboard. info:eu-repo/semantics/publishedVersion

This article belongs to the Section Occupational Safety and Health. Diisocyanates have long been a leading cause of occupational asthma in Europe, and recently, they have been subjected to a restriction under the REACH regulations. As part of the European Human Biomonitoring project (HBM4EU), we present a study protocol designed to assessoccupational exposure to diisocyanates in five European countries. The objectives of the study are to assess exposure in a number of sectors that have not been widely reported on in the past (for example, the manufacturing of large vehicles, such as in aerospace; the construction sector, where there are potentially several sources of exposure (e.g., sprayed insulation, floor screeds); the use of MDI-based glues, and the manufacture of spray adhesives or coatings) to test the usability of different biomarkers in the assessment of exposure to diisocyanates and to provide background data for regulatory purposes. The study will collect urine samples (analysed for diisocyanate-derived diamines and acetyl–MDI–lysine), blood samples (analysed for diisocyanate-specific IgE and IgG antibodies, inflammatory markers, and diisocyanate-specific Hb adducts for MDI), and buccal cells(micronucleus analysis) and measure fractional exhaled nitric oxide. In addition, occupational hygienemeasurements (air monitoring and skin wipe samples) and questionnaire data will be collected. The protocol is harmonised across the participating countries to enable pooling of data, leading to better and more robust insights and recommendations. This work has received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 and received co-funding from the author’s organizations and/or Ministries. info:eu-repo/semantics/publishedVersion

Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014-2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:19 issue:9 ispartof: location:Switzerland status: published

OBJECTIVES: Indirect dental restorations produced by computer-aided design and computer-aided manufacturing (CAD/CAM) are relatively new in daily dental practice. The aim of the present study was to compare the monomer release between direct composite restorations and indirect CAD/CAM produced restorations (composite, ceramic and hybrid). METHODS: Identical crown restorations were prepared from three indirect materials (Cerasmart, Vitablocs Mark II and Vita Enamic) and one composite material (Clearfil AP-X). For each restoration, eight crown restorations were luted onto tooth samples and immersed into 2.5mL of an aqueous extraction solvent. Additionally, three nonluted crowns of each restoration type were also immersed in the extraction solvent, and served as controls. Every week, the extraction solvent was collected and refreshed, during a period of 8 weeks. The released monomers were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Indirect restorations release significantly lower quantities of residual monomers than direct restorations, and the monomers released by the luted indirect restorations are mainly derived from the composite material used for cementation. The quantity of monomers released by direct restorations greatly depended on the time of light polymerization. SIGNIFICANCE: In terms of monomer release, indirect restorations are a good alternative to direct restorations to limit patient exposure to residual monomers. It is important to ideally design the fit of indirect restoration so that the cement layer is as thin as possible and the monomer release from this cement layer remains as low as possible. ispartof: DENTAL MATERIALS vol:36 issue:10 pages:1275-1281 ispartof: location:England status: published

Root canal sealers are commonly used to endodontically treat teeth with periapical infections. Some root canal sealers based on epoxy resin contain bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE). The presence of these chemicals is of concern due to the close contact to the blood stream at the apex and the long setting times of up to 24 h. These chemicals, or any of their degradation products or metabolites, can then exert their toxic effects before being excreted. This study aimed to identify the phase I in vitro biotransformation products of BADGE and BFDGE using human liver microsomes. During incubation with microsomal fractions, the epoxides were rapidly hydrolysed in a NADPH independent manner resulting in the formation of BADGE center dot 2H(2)O and BFDGE center dot 2H(2)O. Further, oxidative reactions, such as hydroxylation and carboxylation, generated other BADGE metabolites, such as BADGE center dot 2H(2)O-OH and BADGE center dot H2O center dot COOH, respectively. For BFDGE, further oxidation of BFDGE center dot 2H(2)O led to the newly reported carboxylic acid, BFDGE center dot H2O center dot COOH. In total, three specific metabolites have been identified which can serve in future human biomonitoring studies of BADGE and BFDGE.

Objectives Only little is known about degradation of methacrylate monomers. Therefore, using in vitro chemical and saliva degradation this study aimed to identify the degradation products of organic compounds present in resin-based dental materials. Methods Ten dental monomers and nine polymerized dental resin-based materials were immersed for 24 h in chemical media (0.1 M HCl, 0.1 M NaOH) and human pooled saliva in order to identify leached monomers and degradation products from chemical and saliva degradation. Samples were analyzed using liquid chromatography coupled to high-resolution mass spectrometry to identify previously unknown degradation products. Results During in vitro chemical degradation, uncured monomers were rapidly hydrolyzed into mono- and demethacrylated degradation products. During chemical degradation in alkaline conditions of polymerized materials, considered the worst-case scenario, only degradation products could be detected. In acidic conditions, monomers and their degradation products were detected. In addition, different additives such as EDMAB, DMPA and HMBP were present in acidic degradation samples. Degradation in human pooled saliva for 24 h to mimic the in vivo situation, resulted in the identification of both monomers and their degradation products. Clinical Significance Using state-of-the-art high-resolution mass spectrometry previously unknown degradation products of commonly used monomers were identified for the first time. Results show that patients may be exposed to monomers and their degradation products in the first 24 h after restorative procedures. The results provide a base for further research on the degradation of resin-based dental composites in order to assess their safety using elution and toxicity studies.

© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission's Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.

© 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.

Exposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals. This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. Luxembourg entered the study at a later stage and thus financed the study at its own means. Sí

Dental resin systems have been in use for several decades. (Meth)acrylic monomers are an important part of the matrix system and are either based on BPA while others lack the BPA core. The degree of conversion during restoration is in general between 50-70 % allowing leaching from unreacted monomers to the oral cavity where they can be taken up through the pulp or gastrointestinal tract after ingestion with subsequent hepatic metabolism. This study identified the in vitro Phase I and Phase II metabolism of the dental resin monomers BisGMA, UDMA, BisPMA and TCD-DI-HEA, using human liver microsomes (HLM) and human liver cytosols. During Phase I incubation with HLM, the (meth)acrylic acid in the monomers was rapidly removed followed by oxidative and hydroxylation pathways. For BisPMA an O-dealkylation pathway occurred resulting in the formation of BPA. The carbamates present in TCD-DI-HEA and UDMA were resistant to biotransformation reactions. Phase II biotransformation products were only observed for BisPMA and included conjugation reactions with sulphate and glucuronic acid. In total 4, 3, 12 and 3 biotransformation products were identified in this study for BisGMA, UDMA, BisPMA and TCD-DI-HEA respectively. Possible human health effects of these biotransformation products remain unclear due to limited data availability.

BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated. ispartof: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES vol:1205 ispartof: location:Netherlands status: published

Objective. There is still much debate about the release of bisphenol-A (BPA) from dental materials. Therefore, this study aimed to quantify BPA present as an impurity in both BPA-based and non-BPA-based monomers and to evaluate whether these monomers may degrade to BPA upon salivary, bacterial, and chemical challenges. Methods. BPA was determined in three different amounts (1, 2, and 3 mu mol) of each monomer (TEGDMA, UDMA, mUDMA, BisGMA, BisEMA-3, -6, -10, -30, BisPMA, EBPADMA urethane, BADGE, and BisDMA). Next, the monomers (3 similar to mol) were immersed in whole human pooled saliva collected from adults, Streptococcus mutans (2 x 10(7) CFU/mL), and acidic (0.1 M HCl), alkaline (0.1 M NaOH), and control media. The amount of BPA was quantified using a specific and highly sensitive UPLC-MS/MS method including derivatization of BPA by pyridine-3-sulfonyl chloride. Results. The monomers BisGMA and BisEMA-3 contained trace amounts (0.0006% and 0.0025%, respectively) of BPA as impurities of their synthesis process. BPA concentrations increased when the monomers BisGMA, BisEMA-3, BisEMA-6, BisEMA-10, BisPMA and BADGE were exposed to saliva and S. mutans, indicating degradation of a small amount of monomer into BPA. In addition, BisPMA and BADGE degraded into BPA under alkaline conditions. The conversion rate of the monomers into BPA ranged between 0.0003% and 0.0025%. Significance. Impurities and degradation of BPA-based monomers may account for the release of BPA from resin-based dental materials. Even though the detected amounts of BPA due to monomer impurity were small, manufacturers of dental materials can reduce the BPA content by using only monomers of the highest purity. Considering the overall current trend towards BPA-free materials, it may be recommendable to investigate whether non-BPA based monomers can be used in dental resin-based materials. (C) 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine (5mC) but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine (6mA) was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and fetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120 h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7-21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes. ispartof: FRONTIERS IN GENETICS vol:12 ispartof: location:Switzerland status: published

Glyphosate is one of the most frequently used organophosphorus plant protection products worldwide, and has recently been classified as probably carcinogenic to humans by the International Agency for Research and Cancer (IARC). We aimed to evaluate the urinary levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in Moroccan children, to identify the main predictors and to perform a risk assessment. Data was collected during a cross sectional study of 48 children from an intensive agricultural area. Measurements included a questionnaire on life-style, socio-demographic and herbicide exposures. Urinary glyphosate and AMPA were extracted using solid phase extraction (SPE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Overall, glyphosate and AMPA were detected in 73% and 75% of urine samples, respectively. The mean concentrations were 0.97 μg L

Objectives. BPA release from composites on the short term has been reported in several in-vitro and in-vivo studies. However, it remains unclear whether these materials also leach BPA on the long term. Even though composites may release various (BPA-based) methacrylate monomers up to one year, quantitative data about BPA have not been reported due to the lack of a sensitive method to accurately quantify low levels of BPA. In this context, the aim of the study was to quantify the one-year release of BPA with an optimized analytical method. Methods. Composite disks (n = 6, 6 mm diameter and 2 mm height) from four commercial materials (G-genial Posterior, Venus, Ceram.x mono and Filtek Supreme XTE) were immersed in 1 mL of water or ethanol as extraction solvent and stored in the dark at 37 degrees C. The extraction solvent was renewed weekly for a period of 52 weeks. Samples were derivatized with pyridine-3-sulfonyl chloride before analysis with ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results. Derivatizing BPA increased the sensitivity of the analytical method and allowed accurate quantification of very low levels of BPA (i.e. 0.78 pmol BPA). BPA eluted continuously in ethanol from all four tested composites over a period of one year. BPA elution was clearly higher when ethanol was used as extraction solution. In water, BPA eluted could be detected up to one year, but levels could not be accurately quantified anymore after several weeks. Significance. Composites can be considered as a potential long-term source of BPA, and thus should not be neglected when assessing the overall exposure to endocrine disrupting chemicals. (C) 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Objective The biocompatibility of resin based dental composites has not yet been fully characterized even though certain monomers used in these composites are synthesized from Bisphenol A (BPA), a well-known estrogenic endocrine disruptor. As a result, they show structural relationship to BPA and can contain it as an impurity. Therefore, the estrogenic activity of 9 monomers, 2 photoinitiators, one photostabilizer and leachates of 4 commercially available composites was determined. Methods The ERα-CALUX bioassay was used to determine both agonistic and antagonistic estrogenic activities of the pure compounds (BPA, BisDMA, BisGMA, BisEMA(3), BisEMA(6), BisEMA(10), TEGDMA, TCD-DI-HEA, BADGE, UDMA, HMBP, DMPA, CQ) and the leachates of cured composite disks. The leachates of 4 commercially available composites (Solitaire 2, Ceram.x Spectra ST, G-aenial Posterior and Filtek Supreme XTE) in water and 0.1 M NaOH (pH = 13, ‘worst-case scenario’) were tested for estrogenic activity (pooled leachates from 10 cured composite disks). Results Agonistic estrogenic activity was found for the monomer BisDMA, the photostabilizer HMBP and photoinitiator DMPA. All leachates from the 4 tested composites showed significant agonistic estrogenic activity higher than the DMSO control, and the highest activity (potency and efficacy) was found for Solitaire 2, followed by Ceram.x Spectra ST. Furthermore, antagonistic estrogenic activity was found in the leachates from G-aenial Posterior. Significance These results show that significant estrogenic activity was found in all leachates of the cured composite disks, and that this estrogenicity is most likely due to a mixture effect of multiple estrogenic compounds (including BPA, HMBP and DMPA). This indicates that further research into the endocrine activity of all the compounds that are present in these composites (even at low quantities) and their possible mixture effect is warranted to guarantee their safe use.

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 & ndash;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., Diagnosis, Monitoring and Prevention of Exposure-Related Noncommunicable Diseases (DiMoPEx) COST Action project [CA15129]; European UnionEuropean Commission, This work was supported by the Diagnosis, Monitoring and Prevention of Exposure-Related Noncommunicable Diseases (DiMoPEx) COST Action project (CA15129) and its Final Action Dissemination Grant from the European Union.

In Morocco, due to the lack of education and the presence of a counterfeit market, pesticides constitute a major problem to be addressed by occupational and environmental health agencies. This paper aims to introduce the PaPOE (Parental Pesticides and Offspring Epigenome) prospective study and its goals, to motivate the study rationale and design, and to examine comprehensively whether multi-residue exposure to commonly used pesticides could induce epigenetic alterations through the oxidative stress pathway. The PaPOE project includes a cross-sectional study assessing the occupational exposure among 300 farmworkers in Meknes, and initiates a birth cohort of 1000 pregnant women. Data and biological samples are collected among farmworkers, and throughout pregnancy, and at birth. Oxidative stress biomarkers include Glutathione, Malondialdehyde, and 8-OHdG. Global and gene-specific DNA methylation is assessed. The study began enrollment in 2019 and is ongoing. As of 30 June 2021, 300 farmworkers and 125 pregnant women have enrolled. The results are expected to showcase the importance of biomonitoring for understanding individual risks, and to identify a number of regions where DNA methylation status is altered in the pesticides-exposed population, paving the way for an integrated biomonitoring system in Morocco and Africa to assess environmental exposures and their long-term health consequences. This work was supported by the Institutional University Cooperation program with Moulay Ismail University, which is funded by the VLIR-UOS (Phase I: 2017-2021; Contract no MA2017IUC038A104) and by the Research and Development Project “SEBIO” (Morocco, 2017–2021), funded by the ARES-CCD of the Belgian Cooperation for Development.

Multicenter Study The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. As part of HBM4EU, we presented a protocol for a multicentre study to characterize occupational exposure to hexavalent chromium (Cr(VI)) in nine European countries (HBM4EU chromates study). This study intended to collect data on current occupational exposure and to test new indicators for chromium (Cr) biomonitoring (Cr(VI) in exhaled breath condensate and Cr in red blood cells), in addition to traditional urinary total Cr analyses. Also, data from occupational hygiene samples and biomarkers of early biological effects, including genetic and epigenetic effects, was obtained, complementing the biomonitoring information. Data collection and analysis was completed, with the project findings being made separately available. As HBM4EU prepares to embark on further European wide biomonitoring studies, we considered it important to reflect on the experiences gained through our harmonised approach. Several practical aspects are highlighted for improvement in future studies, e.g., more thorough/earlier training on the implementation of standard operating procedures for field researchers, training on the use of the data entry template, as well as improved company communications. The HBM4EU chromates study team considered that the study had successfully demonstrated the feasibility of conducting a harmonised multicentre investigation able to achieve the research aims and objectives. This was largely attributable to the engaged multidisciplinary network, committed to deliver clearly understood goals. Such networks take time and investment to develop, but are priceless in terms of their ability to deliver and facilitate knowledge sharing and collaboration. Highlights: Feasibility of conducting harmonised Pan-European biomonitoring study on occupational exposure demonstrated; Developing a successful network and implementation of systematic methodology takes significant dedication from all involved; Methodological improvements were identified which will benefit future large-scale occupational biomonitoring campaigns; Developed multicentre network allows and promotes further opportunities for future research, knowledge sharing and collaboration; Data produced supports science to policy interface in the scope of REACH and occupational safety and health regulations. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 and received co-funding from the author’s organizations and/or Ministries. info:eu-repo/semantics/publishedVersion

Previously, we have demonstrated the capability of activated charcoal cloth (ACC) to assess dermal exposure to VOCs. Here we investigated whether ACC patches can be used as an under-glove indicator to evaluate the ingress of toluene through disposable gloves in a controlled environment, and compared these results to the amount of toluene ingress determined from the standardized test methods for determining chemical permeation through PPE. In a test chamber, with plugs for air sampling, five to six ACC patches were placed on a mannequin hand underneath disposable gloves (latex, nitrile, neoprene, polymer laminate). Three work-exposure scenarios were simulated to assess toluene ingress through the different gloves: vapor exposure; spray exposure, and immersion. The standard permeation test, using a diffusion cell, was carried with glove material of the palm, with continuous contact conditions. In all of ACC test, the order of toluene ingress was latex > neoprene > nitrile > Barrier, but for the standardized testing, the order of the neoprene and nitrile was reversed, and nitrile had higher levels of toluene ingress. These results show the need to think beyond standard testing techniques for occupational exposure to hazardous substances, and the added value of "application style" testing. ispartof: JOURNAL OF HAZARDOUS MATERIALS vol:411 ispartof: location:Netherlands status: published

DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine but recently adenine methylation, through 6-methyl adenine (6mA), was also found to be present in eukaryotes. In mouse embryonic stem cells it was shown to be associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and foetal development. In somatic cells there are clear tissue specificity in 6mA levels, with, the highest 6mA levels being observed in the brain. In zebrafish, during the first 120h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7-21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period led to a decrease in the levels of this modification. Our identification of the periods during which 6mA epigenetic marks are put in place and how they dynamically change in response to an early environmental stress, may shed a light on our understanding of the mammalian epigenetic modifications, and, as outlined in the developmental origins of health and disease, mechanistically contribute how a deviation from normal development can trigger disease phenotypes later in life., This manuscript has now been accepted for publication in Frontiers in Genetics DOI: http://doi.org/10.3389/fgene.2021.657171

Recent advances in analytical chemistry have allowed a greater possibility of using quantitative approaches for measuring human exposure to chemicals. One of these approaches is biomonitoring (BM), which provides unequivocal evidence that both exposure and uptake of a chemical have taken place. BM has been a longstanding practice in occupational health for several reasons. BM integrates exposure from all routes. It can help identify unintentional and unexpected exposures and assess the effectiveness of existing risk-management measures. BM also provides relevant information to support policy development by delivering better evidence of workers' exposure to chemical substances, even within the framework of the present regulations. Thus, BM can allow for both the evaluation of the impact of regulation and identification of further needs for new or improved regulation. However, despite all these well-recognized advantages, BM is currently an underused exposure assessment tool. This paper provides an overview of the key aspects to be considered when using BM in the context of occupational health interventions. Additionally, this paper describes the potential of BM as an exposure assessment tool, distinguishing the role of BM in exposure assessment and health surveillance and clarifies ethical and communication aspects to guarantee that general data protection regulations are followed. In addition, actions and research needs are identified (particularly with reference to the European situation), which aim to encourage the increased use of BM as an exposure assessment tool. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:17 issue:16 ispartof: location:Switzerland status: published

Guidelines are in place to assure limited occupational exposure to cytostatic drugs. Even though this has led to a reduction in exposure, several studies reported quantifiable concentrations of these compounds in healthcare workers. In this study, we evaluated occupational exposure to cytostatic drugs in hospital workers from the University Hospital in Tlemcen, Algeria. Monitoring was performed by collecting wipe samples from surfaces, objects, personal protective equipment (gloves and masks) and from the skin of employees at an Algerian university hospital. Wipe samples were analyzed with ultra-performance liquid chromatography coupled to a mass spectrometer. Concentrations ranged from below the limit of quantification up to 208.85, 23.45, 10.49, and 22.22 ng/cm2 for cyclophosphamide, ifosfamide, methotrexate and 5-fluorouracil, respectively. The highest values were observed in the oncology department. Nowadays, there are still no safe threshold limit values for occupational exposure to cytostatic agents. Therefore, contamination levels should be kept as low as reasonably achievable. Yet, healthcare workers in this hospital are still exposed to cytostatic agents, despite the numerous guidelines, and recommendations. Consequently, actions should be taken to reduce the presence of harmful agents in the work environment. ispartof: FRONTIERS IN PUBLIC HEALTH vol:8 ispartof: location:Switzerland status: published

Review Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures. Highlights: Reliable effect biomarkers are available for most of the relevant MoAs; Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context; PBK/D models allow interpretation and simulation of biomarkers of effect; An inter-regulatory setting of effect-based trigger values is demanded; Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments. We would like to thank Dr, Michel Hauser from Swiss SECO, for providing the health based occupational background and Thomas Goen ¨ from German DFG and HBM Commission, Dave Marsh, Exxon Mobile UK (representing CEFIC) and Devika Poddalgoda from Health Canada for their discussions and suggestions in the OECD occupational biomonitoring subtask on effect biomarker. Moreover, we would like to thank Tiina Santonen from Finnish Institute for Occupational Health (FIOH). In addition, we specifically acknowledge the work package 14 (HBM4EU WP14) for their valuable work on the effect biomarkers. info:eu-repo/semantics/publishedVersion

Diisocyanates are a group of chemicals that are widely used in occupational settings. They are known to induce various health effects, including skin- and respiratory tract sensitization resulting in allergic dermatitis and asthma. Exposure to diisocyanates has been studied in the past decades by using different types of biomonitoring markers and matrices. The aim of this review as part of the HBM4EU project was to assess: (i) which biomarkers and matrices have been used for biomonitoring diisocyanates and what are their strengths and limitations; (ii) what are (current) biomonitoring levels of the major diisocyanates (and metabolites) in workers; and (iii) to characterize potential research gaps. For this purpose we conducted a systematic literature search for the time period 2000-end 2018, thereby focussing on three types of diisocyanates which account for the vast majority of the total isocyanate market volume: hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), and 4,4'-methylenediphenyl diisocyanate (MDI). A total of 28 publications were identified which fulfilled the review inclusion criteria. The majority of these studies (93%) investigated the corresponding diamines in either urine or plasma, but adducts have also been investigated by several research groups. Studies on HDI were mostly in the motor vehicle repair industry [with urinary hexamethylene diamine result ranging from 0.03 to 146.5 µmol mol-1 creatinine]. For TDI, there is mostly data on foam production [results for urinary toluene diamine ranging from ~0.01 to 97 µmol mol-1 creatinine] whereas the available MDI data are mainly from the polyurethane industry (results for methylenediphenyl diamine range from 0.01 to 32.7 µmol mol-1 creatinine). About half of the studies published were prior to 2010 hence might not reflect current workplace exposure. There is large variability within and between studies and across sectors which could be potentially explained by several factors including worker or workplace variability, short half-lives of biomarkers, and differences in sampling strategies and analytical techniques. We identified several research gaps which could further be taken into account when studying diisocyanates biomonitoring levels: (i) the development of specific biomarkers is promising (e.g. to study oligomers of HDI which have been largely neglected to date) but needs more research before they can be widely applied, (ii) since analytical methods differ between studies a more uniform approach would make comparisons between studies easier, and (iii) dermal absorption seems a possible exposure route and needs to be further investigated. The use of MDI, TDI, and HDI has been recently proposed to be restricted in the European Union unless specific conditions for workers' training and risk management measures apply. This review has highlighted the need for a harmonized approach to establishing a baseline against which the success of the restriction can be evaluated. ispartof: ANNALS OF WORK EXPOSURES AND HEALTH vol:64 issue:6 pages:569-585 ispartof: location:England status: published