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The article aims at starting a conversation around a 10-step checklist providing practical recommendations on how to facilitate community discussions around the creation of standards to implement FAIR.

Background A scientific framework on exposure science will boost the multiuse of exposure knowledge across EU chemicals-related policies and improve risk assessment, risk management and communication across EU safety, security and sustainability domains. Objective To stimulate public and private actors to align and strengthen the cross-policy adoption of exposure assessment data, methods and tools across EU legislation. Methods By mapping and analysing the EU regulatory landscape making use of exposure information, policy and research challenges and key areas of action are identified and translated into opportunities enhancing policy and scientific efficiency. Results Identified key areas of actions are to develop a common scientific exposure assessment framework, supported by baseline acceptance criteria and a shared knowledge base enhancing exchangeability and acceptability of exposure knowledge within and across EU chemicals-related policies. Furthermore, such framework will improve communication and management across EU chemical safety, security and sustainability policies comprising sourcing, manufacturing and global trade of goods and waste management. In support of building such a common framework and its effective use in policy and industry, exposure science innovation needs to be better embedded along the whole policymaking cycle, and be integrated into companies’ safety and sustainability management systems. This will help to systemically improve regulatory risk management practices. Significance This paper constitutes an important step towards the implementation of the EU Green Deal and its underlying policy strategies, such as the Chemicals Strategy for Sustainability.

Background: In this paper, the European chapter of the International Society for Exposure Science (ISES Europe) provides a vision on how dietary exposure sciences can contribute to address the challenges in the field of food safety and nutrition due to changes in food systems by answering the following question: How can we assess timely and accurately changes in dietary exposure to hazardous chemicals (and mixtures thereof) or intake of nutrients due to changes in food production, food consumption and food composition? Scope and approach: We first describe the current role of dietary exposure sciences and the instruments that are being used to assess dietary exposure in food safety and nutrition. This is followed by an analysis of current changes and developments, primarily at the European level, relevant for food safety and nutrition. This results in a list of identified challenges for dietary exposure sciences. Key findings and conclusions: We thus focus on the timely and accurate assessment of the impact of changes and developments on consumer's and public health, from the perspective of dietary exposure sciences. This includes making better use of chemical analysis, dietary exposure assessment and human biomonitoring, providing increased insight in food composition and nutrients, taking into account the impact of new technologies on human exposure, and making better use of risk-benefit assessment.

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters. Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20–64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals. Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47–4.71), HDL-C (β: 1.13, 95% CI: 0.92–1.33) and LDL-C (β: 3.14, 95% CI: 2.65–3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5–4.58), HDL-C (ψ: 1.07, 95% CI 20.87–1.27) and LDL-C (ψ: 2.71, 95% CI 2.23–3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender. Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.

Background: Evaluating and managing exposures to chemical, physical and biological stressors, which frequently interplay with psychological stressors as well as social and behavioural aspects, is crucial for protecting human and environmental health and transitioning towards a sustainable future. Advances in our understanding of exposure rely on input from well-trained exposure scientists. However, no education programmes in Europe are currently explicitly dedicated to cover the broader range of exposure science approaches, applications, stressors and receptors. Objective: To address this challenge, a curriculum is needed that yields credible, well-defined career pathways in exposure science. Methods: Needs and conditions for advancing exposure science education in Europe were identified. As a starting point for a way forward, harmonised learning outcomes for exposure science were defined at each level of the European Qualifications Framework. The course programme coordinators were recruited for three varying courses, with respect to the course level and the proportion of the curriculum dedicated to exposure science. These courses were assessed via our systematic course review procedure. Finally, strategic objectives and actions are proposed to build exposure science education programmes. Results: The ISES Europe ‘Education, Training and Communication’ expert working group developed a framework for creating a viable exposure science curriculum. Harmonised learning outcomes were structured under eight learning levels, categorised by knowledge, skills and competence. Illustrative case studies demonstrated how education providers integrated these learning outcomes for their educational context and aligned the overall exposure science curriculum. Conclusions: The international recognition and adoption of exposure science education will enable advances in addressing global exposure science challenges for various stressors, from behavioural aspects from individual to population scale, and effective communication between exposure scientists and relevant stakeholders and policy makers, as part of the European Exposure Science Strategy 2020–2030., Environment International, 168, ISSN:0160-4120, ISSN:1873-6750

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally., Journal of Exposure Science & Environmental Epidemiology, 32 (4), ISSN:1559-064X, ISSN:1559-0631

Exposure to per- and polyfluoroalkyl substances (PFAS), ubiquitous persistent environmental contaminants, has led to substantial global concern due to their potential environmental and human health effects. Several epidemiological studies have assessed the possible association between PFAS exposure and risk of metabolic syndrome (MetS), however, the results are ambiguous. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFAS and MetS. We performed a systematic search strategy using three electronic databases (PubMed, Scopus, and Web of Science) for relevant studies concerning the associations of PFAS with MetS and its clinical relevance from inception until January 2021. We undertook meta-analyses where there were five or more studies with exposure and outcomes assessments that were reasonably comparable. The pooled odd ratios (ORs) were calculated using random effects models and heterogeneity among studies was assessed by I2 index and Q test. A total of 12 cross-sectional studies (10 studies on the general population and two studies in the occupational settings) investigated the association between PFAS exposure and MetS. We pooled data from seven studies on the general population for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) and five studies for perfluorohexanesulfonate (PFHxS) and perfluorononanoic acid (PFNA). Predominately, most studies reported no statistically significant association between concentrations of PFAS and MetS. In the meta-analysis, the overall measure of effect was not statistically significant, showing no evidence of an association between concentrations of PFOA, PFOS, PFNA, and PFHxS and the risk of MetS. Based on the results of the meta-analysis, current small body of evidence does not support association between PFAS and MetS. However, due to limited number of studies and substantial heterogeneity, results should be interpreted with caution. Further scrutinizing cohort studies are needed to evaluate the association between various and less well-known PFAS substances and their mixture with MetS and its components in both adults and children in different settings.

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

Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health.We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect.The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers.A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16).Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

The use of aligned exposure science terminology is crucial for ease of comparison and appropriate interpretation of exposure information, regulatory reports, and scientific publications. Sometimes the use of different terminology in different contexts and areas of exposure science results in diverging interpretations of the same descriptor. During the development of the European strategy for exposure science, the need was identified to agree on a defined terminology requiring an evaluation of the commonly used terms, synonymous uses, and their relationships between each other. This paper presents the first steps in compiling the most important exposure-related terms from existing guidance documents and publications for exposure and risk assessment and adapting them to be useful for different contexts and areas. This initial step is intended to trigger discussion on terminology among exposure scientists around the globe and across regulatory and methodological silos. The glossary itself is intended as a living document to be hosted by the International Society for Exposure Science., Journal of Exposure Science & Environmental Epidemiology, 32 (4), ISSN:1559-064X, ISSN:1559-0631

EFSA's aim by 2030, is that the Agency and its partners will be equipped for the routine implementation of human health risk assessment to multiple chemicals, across EFSA's domains of activity. To facilitate this effort, a roadmap for action has been developed by mapping the methods, data and tools that are currently available for mixture risk assessment and identifying current scientific gaps including challenges and blockers. The results shows that extensive methods, data and tools are available for dietary mixture risk assessment for pesticides, but that several scientific gaps still exist for the non-dietary mixture exposure to pesticides. For food additives and for certain contaminants, the regulatory readiness for mixture risk assessment was also found to be fairly high compared to food contact materials and cross-silo mixture risk assessment. The scientific gaps identified were prioritised according to their impact on the implementation of mixture risk assessment and, as a result, ten multi-annual project proposals were defined to address these scientific gaps on the short-term, mid-term and long-term. The roadmap also proposes and prioritises a number of working areas in the regulatory domains of pesticides, food contact materials, contaminants, food additives, as well as in the overarching domain of chemicals. Besides the scientific proposals, recommendations to improve stakeholder engagement and communication on mixture risk assessment was investigated. These included, among others, creating an online catalogue of tools, methods and data for mixture risk assessment, as well as the organisation of regular webinars/workshop to promote exchange of information between stakeholders and making more efficient use of national communication hubs for food safety in communicating with the general public.

© 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.

A scientific framework on exposure science will boost the multiuse of exposure knowledge across EU chemicals-related policies and improve risk assessment, risk management and communication across EU safety, security and sustainability domains.To stimulate public and private actors to align and strengthen the cross-policy adoption of exposure assessment data, methods and tools across EU legislation.By mapping and analysing the EU regulatory landscape making use of exposure information, policy and research challenges and key areas of action are identified and translated into opportunities enhancing policy and scientific efficiency.Identified key areas of actions are to develop a common scientific exposure assessment framework, supported by baseline acceptance criteria and a shared knowledge base enhancing exchangeability and acceptability of exposure knowledge within and across EU chemicals-related policies. Furthermore, such framework will improve communication and management across EU chemical safety, security and sustainability policies comprising sourcing, manufacturing and global trade of goods and waste management. In support of building such a common framework and its effective use in policy and industry, exposure science innovation needs to be better embedded along the whole policymaking cycle, and be integrated into companies' safety and sustainability management systems. This will help to systemically improve regulatory risk management practices.This paper constitutes an important step towards the implementation of the EU Green Deal and its underlying policy strategies, such as the Chemicals Strategy for Sustainability.

Background Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. Methods A cross-sectional analysis was conducted in 319 pregnant women (age 14–48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. Results The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. Conclusions Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts.

Background: Studies on the association between perfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) are limited, and results are inconsistent. We aimed to examine the associations between PFAS serum levels and the prevalence of MetS among highly exposed young adults (ages 20&ndash, 39) residents of a large area of the Veneto Region (North-Eastern Italy) primarily stemming from PFAS water contamination before September 2013. A total of 15,876 eligible young adult residents living in the investigated municipalities were enrolled in the study from January 2017 to July 2019. Methods: MetS was defined by using a modified harmonized definition requiring the presence of 3 of the following: obesity (body mass index &ge, 30), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol, elevated blood pressure, and hemoglobin A1c &ge, 6.1% or self-reported diabetes mellitus or drug treatment for hyperglycemia. Multivariable generalized additive models were performed to identify the associations between four serum PFAS, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), and risk of MetS controlling for potential confounders. Results: A total of 1282 participants (8.1%) met the criteria of MetS with a higher prevalence among men. PFOA, PFHxS, and PFNA were not associated with the risk of MetS, whereas PFOS showed a consistent protective effect against the risk of MetS (OR 0.76, (95% CI: 0.69, 0.85) per ln-PFOS). However, we found statistically significant positive associations between PFAS serum levels and individual components of MetS, mainly elevated blood pressure and elevated TG. Conclusion: Our results did not support a consistent association between PFAS and MetS and conflicting findings were observed for individual components of MetS.

High-level toxic metal exposure has become rare in the recent years. Although, it has not known whether relatively lower exposure may adversely affect human reproductive system. Spontaneous abortion (SA) is a serious reproductive problem, which, in many cases, the cause(s) is not clearly understood. To assess the relationship between prenatal blood level of metals and SA risk, we compared blood concentration of some heavy metals in samples taken from mothers recruited in Tehran Environment and Neurodevelopmental Defects (TEND) study conducted on apparently healthy pregnant women in Tehran, Iran who subsequently experienced spontaneous abortion with mothers who their pregnancy ended to live births. During early gestation, 206 women were enrolled to the survey and followed up till fetal abortion or baby deliveries occur. Blood metal concentrations were measured using an inductively coupled plasma mass spectrometer. The mean blood levels of lead, antimony, and nickel were higher in SA than ongoing pregnancy; however, this difference was not statistically significant. When adjusted for covariates, the logistic regression analysis showed significant association between maternal age and the risk of SA in all models. Among toxic metals only antimony had a noticeable positive relation with the risk of SA (OR: 1.65, 95% CI:1.08–2.52, P value: 0.02). Pearson’s correlation coefficient showed significant (P < 0.05) positive correlations among prenatal blood metals levels, except for nickel. Although the present study failed to provide strong evidence for the effects of toxic metals on the occurrence of SA at the relatively low-levels, these metals should be avoided in women who plan pregnancy and/or during the early stages of gestation to prevent the chance of adverse effects.

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

This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11, 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.

Background: In spring 2013, groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by perfluoroalkyl substances (PFAS) from a PFAS manufacturing plant active since the late 1960s. Residents were exposed to high concentrations of PFAS, particularly perfluorooctanoic acid (PFOA), through drinking water until autumn 2013. A publicly funded health surveillance program is under way to aid in the prevention, early diagnosis, and treatment of chronic disorders possibly associated with PFAS exposure. Objectives: The objectives of this paper are: a) to describe the organization of the health surveillance program, b) to report serum PFAS concentrations in adolescents and young adults, and c) to identify predictors of serum PFAS concentrations in the studied population. Methods: The health surveillance program offered to residents of municipalities supplied by contaminated waterworks includes a structured interview, routine blood and urine tests, and measurement of 12 PFAS in serum by high-performance liquid chromatography–tandem mass spectrometry. We studied 18,345 participants born between 1978 and 2002, 14–39 years of age at recruitment. Multivariable linear regression was used to identify sociodemographic, lifestyle, dietary, and reproductive predictors of serum PFAS concentrations. Results: The PFAS with the highest serum concentrations were PFOA [median 44.4 ng/mL, interquartile range (IQR) 19.3–84.9], perfluorohexanesulfonic acid (PFHxS) (median 3.9 ng/mL, IQR 1.9–7.4), and perfluorooctanesulfonic acid (PFOS) (median 3.9 ng/mL, IQR 2.6–5.8). The major predictors of serum levels were gender, municipality, duration of residence in the affected area, and number of deliveries. Overall, the regression models explained 37%, 23%, and 43% of the variance of PFOA, PFOS, and PFHxS, respectively. Conclusions: Serum PFOA concentrations were high relative to concentrations in populations with background residential exposures only. Interindividual variation of serum PFAS levels was partially explained by the considered predictors. https://doi.org/10.1289/EHP5337

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

Many sources exist that contain valuable information on toxicology testing methods comprising in vivo (use of whole animals) and in vitro (use of artificial environment outside of living organisms) testing methods. The information resources presented below relate to chemical substances and are collected to pro-vide key guidance on available information on in vivo, in vitro, and other toxicological testing and assessment methods (e.g., in silico toxicological methods performed on computer or via computer simulation), on relevant databases, published literature, books and journals, teaching aids, and finally organizations, foundations, and testing laboratories involved in toxicity assessment. The current information is of relevance for research, applied sciences and policy implementation purposes, such as the implementation of the European Union’s (EU’s) chemicals policy REACH (Registration, Evaluation, Authorisation, and Restriction of CHemicals) or the GPSD (General Product Safety Directive) and many other regulations. The provided information resources are recommended starting points when searching for information on testing methods, alternative testing methods and computational assessment methods. The reader should take note, however, that the information provided is not a comprehensive listing given the ever-expanding number of Internet and Web resources that are becoming available.

Background Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study comprised 16,224 individuals aged 20–39 years. Pregnant women (n = 327), or individuals with missing information on the selected covariates (n = 111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP ≥ 140 mmHg)/diastolic blood pressure (DBP ≥ 90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61–2.47), 1.60 mmHg (95%CI 0.92–2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR = 1.06 (1.01–1.11), PFOS OR = 1.13 (1.03–1.23), PFHxS OR = 1.08 (1.02–1.15), PFNA OR = 1.20 (1.02–1.40). Conclusions Our findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

Many sources exist that contain valuable information on toxicology testing methods comprising in vivo (use of whole animals) and in vitro (use of artificial environment outside of living organisms) testing methods. The information resources presented below relate to chemical substances and are collected to provide key guidance on available information on in vivo, in vitro, and other toxicological testing and assessment methods (e.g., in silico toxicological methods performed on computer or via computer simulation), on relevant databases, published literature, books and journals, teaching aids, and finally organizations, foundations, and testing laboratories involved in toxicity assessment.

Background Acidic juices such as lemon juice, vinegar and Verjuice are popular beverages regularly consumed by both children and adults. Various brands of different acidic juices in Iran markets are packaged in disposable plastic bottles. Some evidence suggests that phthalates may immigrate from plastic bottles. Methods In this research the influence of sunlight, type of container and storage time on the leaching of phthalates from packaging materials into selected juices was investigated, by analyzing the samples kept in different conditions, before and throughout 2, 4 and 6 months storage time. Results The mean phthalate concentrations of the examined samples were determined to be between

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a European Exposure Science Strategy 2020 2030, which is aligned with advances in science and technology. We thank Claudia Cascio and Amelie Crépet for input to the initial manuscript. Open access was kindly provided by the German Federal Institute for Occupational Safety and Health (BAuA). peer-reviewed

Purpose: To advance knowledge about childhood neurodevelopmental disorders and study their environmental determinants, we conducted a study in Tehran, Iran to assess the feasibility of prospective birth cohort study. Methods: We evaluated participation of pregnant women, feasibility of sampling biological material, and health care services availability in Tehran in four steps: (1) first trimester of pregnancy; (2) third trimester of pregnancy; (3) at delivery; and (4) two to three months after delivery. We collected related data through questionnaires, also various biological samples were obtained from mothers (blood, urine, milk and nails—hands and feet) and newborns (umbilical cord blood, meconium, and urine samples) from February 2016 to October 2017. Results: overall 838 eligible pregnant women were approached. The participation rate was 206(25%) in our study and about 185(90%) of subjects were recruited in hospitals. Out of 206 participants in the first trimester, blood, urine, hand nail, and foot nail samples were collected from 206(100%),193(93%), 205(99%), and 205(99%), respectively. These values dropped to 65(54%), 83(69%), 84(70%), and 84(70%) for the remaining participants 120(58%) in the third trimester, respectively. Also, we gathered milk samples from 125(60%) of mothers at two to three months after delivery. Conclusion: Our findings suggest that hospitals were better places for recruitment of subjects in a birth cohort in Tehran. We further concluded that birth cohort study recruitment can be improved by choosing appropriate gestational ages. Obtaining the newborn’s urine, meconium, and umbilical cord blood were challenging procedures and require good collaboration between hospital staff and researchers.

Disinfection by-products are compounds occurring in drinking water as a result of reactions between disinfectants and impurities in raw water, and their occurrence has been a public health concern for the last four decades. Haloacetic acids (HAAs) are one of the major by-products of chlorination. The concentration and variation of HAAs was monitored in 540 samples taken from tap water in six water and wastewater districts of Tehran, Iran. Seasonal variation indicated that natural organic matter and HAA levels were much higher in the spring and fall seasons. The concentrations of HAAs in drinking water samples varied with water sources. They were higher in drinking water obtained from surface water. In this study, the analysis method of human health risk assessment with regard to exposure to HAAs by drinking water in Tehran was based on the United States Environmental Protection Agency (USEPA) guideline. It was found from these studies that the risk to human health appears to be negligible. © 2017 IWA Publishing.

Background Available evidence implicates environmental factors in the pathogenesis of autism spectrum disorders (ASD). However, the role of specific environmental chemicals such as phthalate esters that influence ASD risk remains elusive. This paper systematically reviews published evidences on association between prenatal and/or childhood exposure to phthalate and ASD. Methods Studies pertaining to systematic literature search from Scopus, PubMed, PsycInfo and Web of Science prior to December 2015 were identified. The authors included studies which assessed the effect of exposure to phthalates on occurrence of ASD. This comprehensive bibliographic search identified five independent studies. Each eligible paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment. Because of the heterogeneity in the type of included studies, different methods of assessing exposure to phthalates and the use of different statistics for summarizing the results, meta-analysis could not be used to combine the results of included studies. Results The results of this systematic review have revealed the limited number of studies conducted and assessed phthalate exposure. Seven studies were regarded as relevant to the objectives of this review. Two of them did not measure phthalate exposure directly and did not result in quantitative results. Out of the five studies in which phthalate exposure was mainly measured by the examining biomarkers in biological samples, two were cohort studies (one with positive results and another one with not clear association). Among the three case control studies, two of them showed a significant relation between exposure to phthalate and ASD and the last case control study had negative results. Indeed, this case control studies showed a compromised phthalate metabolite glucuronidation pathway, as a probable explanation of mechanism of the relation between phthalate exposure and ASD. Conclusions This review reveals evidence showing a connection between exposure to phthalates and ASD. Nevertheless, further research is needed with appropriate attention to exposure assessment and relevant pre and post-natal cofounders.

While progress in chemical safety research in recent years has been impressive, especially in the area of in-vitro and 3R approaches, an obvious gap between scientific ambition on the one hand and ...