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1.
Artigo em Inglês | MEDLINE | ID: mdl-37922338

RESUMO

A mixture risk assessment (MRA) for four metals relevant to chronic kidney disease (CKD) was performed. Dietary exposure to cadmium or lead alone exceeded the respective reference values in the majority of the 10 European countries included in our study. When the dietary exposure to those metals and inorganic mercury and inorganic arsenic was combined following a classical or personalised modified reference point index (mRPI) approach, not only high exposure (95th percentile) estimates but also the mean exceeded the tolerable intake of the mixture in all countries studied. Cadmium and lead contributed most to the combined exposure, followed by inorganic arsenic and inorganic mercury. The use of conversion factors for inorganic arsenic and inorganic mercury from total arsenic and total mercury concentration data was a source of uncertainty. Other uncertainties were related to the use of different principles to derive reference points. Yet, MRA at the target organ level, as performed in our study, could be used as a way to efficiently prioritise assessment groups for higher-tier MRA. Since the combined exposure to the four metals exceeded the tolerable intake, we recommend a refined MRA based on a common, specific nephrotoxic effect and relative potency factors (RPFs) based on a similar effect size.


Assuntos
Arsênio , Mercúrio , Cádmio/análise , Arsênio/análise , Exposição Dietética , Mercúrio/análise , Europa (Continente)
2.
Front Toxicol ; 5: 1116707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342468

RESUMO

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

3.
Int J Hyg Environ Health ; 251: 114167, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37149958

RESUMO

We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18-45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.


Assuntos
Arsênio , Dioxinas , Mercúrio , Compostos de Metilmercúrio , Bifenil Polibromatos , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Adolescente , Humanos , Feminino , Éteres Difenil Halogenados , Fluoretos , Chumbo
4.
Int J Hyg Environ Health ; 249: 114135, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36758443

RESUMO

Unintentional chemical mixtures that are present in the environment are of societal concern as the (environmental) chemicals contained therein, either singly or in combination, may possess properties that are hazardous (toxic) for human health. The current regulatory practice, however, is still largely based on evaluating single chemical substances one-by-one. Over the years various research efforts have delivered tools and approaches for risk assessment of chemical mixtures, but many of these were not considered sufficiently mature for regulatory implementation. This is (partly) due to mixture risk assessment (MRA) being very complex because of the large number of chemicals present in the environment. A key element in risk assessment is information on actual exposures in the population of interest. To date, information on actual personal (internal) mixture exposures is largely absent, severely limiting MRA. The use of human biomonitoring data may improve this situation. Therefore, we investigated within the European Human Biomonitoring Initiative (HBM4EU) various approaches to assess combined exposures and MRA. Based on the insights and lessons learnt in the context of the HBM4EU project, conclusions as well as recommendations for policy development regarding chemical mixtures and for further research were drafted. These conclusions and recommendations relate to both exposure and adverse health effects in humans. The recommendations were discussed with stakeholders in a workshop held in October 2021. There was considerable support and agreement with the spirit, scope and intention of the draft recommendations. Here we describe the lessons learnt on mixture risk assessment through the HBM4EU project and present the final recommendations. Overall, HBM4EU results demonstrated the potential of human biomonitoring as an instrument to obtain insight into the real-life mixtures the human population is exposed to. Also, HBM4EU results demonstrated that chemical mixtures are of public health concern. In the majority of the cases, it was possible to identify risk drivers, i.e. chemicals that contribute more strongly than others to the health risk. The novel approaches to identify co-occurrence patterns demonstrated clusters of co-occurring chemicals; chemicals in these mixture clusters are regulated independently under different legislative frameworks. Moreover, HBM4EU data and expertise can support a science-based derivation of a Mixture Assessment Factor and gauge potential impacts on the population's exposure to chemicals. While further expansion is needed on various aspects of the mixture activities carried out in the context of HBM4EU, application of available methodologies for mixture risk assessment should already be implemented to the degree possible.


Assuntos
Monitoramento Biológico , Exposição Ambiental , Humanos , Exposição Ambiental/análise , Medição de Risco , Formulação de Políticas
5.
Environ Int ; 168: 107476, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36067553

RESUMO

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.

6.
Environ Health Perspect ; 130(4): 47003, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35394809

RESUMO

BACKGROUND: Humans are exposed to combinations of chemicals. In cumulative risk assessment (CRA), regulatory bodies such as the European Food Safety Authority consider dose addition as a default and sufficiently conservative approach. The principle of dose addition was confirmed previously for inducing craniofacial malformations in zebrafish embryos in binary mixtures of chemicals with either similar or dissimilar modes of action (MOAs). OBJECTIVES: In this study, we explored a workflow to select and experimentally test multiple compounds as a complex mixture with each of the compounds at or below its no observed adverse effect level (NOAEL), in the same zebrafish embryo model. METHODS: Selection of candidate compounds that potentially induce craniofacial malformations was done using in silico methods-structural similarity, molecular docking, and quantitative structure-activity relationships-applied to a database of chemicals relevant for oral exposure in humans via food (EuroMix inventory, n=1,598). A final subselection was made manually to represent different regulatory fields (e.g., food additives, industrial chemicals, plant protection products), different chemical families, and different MOAs. RESULTS: A final selection of eight compounds was examined in the zebrafish embryo model, and craniofacial malformations were observed in embryos exposed to each of the compounds, thus confirming the developmental toxicity as predicted by the in silico methods. When exposed to a mixture of the eight compounds, each at its NOAEL, substantial craniofacial malformations were observed; according to a dose-response analysis, even embryos exposed to a 7-fold dilution of this mixture still exhibited a slight abnormal phenotype. The cumulative effect of the compounds in the mixture was in accordance with dose addition (added doses of the individual compounds after adjustment for relative potencies), despite different MOAs of the compounds involved. DISCUSSION: This case study of a complex mixture inducing craniofacial malformations in zebrafish embryos shows that dose addition can adequately predicted the cumulative effect of a mixture of multiple substances at low doses, irrespective of the (expected) MOA. The applied workflow may be useful as an approach for CRA in general. https://doi.org/10.1289/EHP9888.


Assuntos
Misturas Complexas , Peixe-Zebra , Animais , Alimentos , Humanos , Simulação de Acoplamento Molecular , Medição de Risco
7.
Environ Epidemiol ; 5(5): e166, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34934888

RESUMO

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE's results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward.

8.
Int J Hyg Environ Health ; 238: 113826, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34583227

RESUMO

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.


Assuntos
Monitoramento Biológico , Exposição Ambiental , Exposição Ambiental/análise , Monitoramento Ambiental , Humanos , Sistema de Registros , Estudos Retrospectivos
9.
Food Chem Toxicol ; 143: 111520, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32640355

RESUMO

Focus on risks to human health and the environment from combined exposure to multiple chemicals ("mixture risk assessment") has increased in the last couple of decades. There has been a rise in awareness and concern in the community, especially concerning unintentional environmental exposure to unknown chemical mixtures. The Horizon 2020 project EuroMix has developed methodologies and tools for mixture risk assessment with a focus on component-based approach where substances are grouped based on toxicological considerations. Dose addition is used as the model for calculating the combined toxicity of mixture components. The methodology is anchored in the Adverse Outcome Pathway (AOP) concept, which provides a structured basis for e.g. grouping substances into assessment groups and identifying and collecting relevant toxicity data. The aim of this paper is to describes development of the methodology for mixture risk assessment and to provide detailed methodology for problem formulation, use of AOP networks for development of tiered testing strategies and grouping of substances, as well as considerations for use of dose addition methodology.


Assuntos
Exposição Ambiental , Substâncias Perigosas/toxicidade , Modelos Biológicos , Simulação por Computador , Humanos , Medição de Risco
10.
Food Chem Toxicol ; 142: 111416, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439593

RESUMO

Risk assessment of chemicals occurring in our diet is commonly performed for single chemicals without considering exposure to other chemicals. We performed a case study on risk assessment of combined dietary exposure to chemicals from different regulatory silos, i.e. pesticides (PPRs), persistent organic pollutants (POPs) and food additives (FAs). Chemicals were grouped into the cumulative assessment group (CAG) liver steatosis using a component-based approach. Based on literature, the CAG included 144 PPRs, 49 POPS and 7 FAs for which concentration data were available. For each silo, chronic combined dietary exposure was assessed for adults and children of nine European countries following the most commonly used exposure methodologies in Europe and by using a relative potency factor approach. For risk characterization, a Margin of Exposure (MOE) was calculated. To overarch the risk across silos, a normalised combined margin of exposure (nMOET) approach was proposed. This case study demonstrated that risk assessment of combined exposure to chemicals can be performed within regulatory silos. It also highlighted important differences in the conservatism of exposure scenarios, the derivation of point of departures and the subsequent acceptable MOEs between the silos. To overarch the risk despite these differences, a nMOET approach can be used.


Assuntos
Exposição Dietética , Adulto , Criança , Poluentes Ambientais/toxicidade , Europa (Continente) , Humanos , Medição de Risco
11.
Food Chem Toxicol ; 138: 111223, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088251

RESUMO

Mixtures of substances to which humans are exposed may lead to cumulative exposure and health effects. To study their effects, it is first necessary to identify a cumulative assessment group (CAG) of substances for risk assessment or hazard testing. Excluding substances from consideration before there is sufficient evidence may underestimate the risk. Conversely, including everything and treating the inevitable uncertainties using conservative assumptions is inefficient and may overestimate the risk, with an unknown level of protection. An efficient, transparent strategy is described to retain a large group, quantifying the uncertainty of group membership and other uncertainties. Iterative refinement of the CAG then focuses on adding information for the substances with high probability of contributing significantly to the risk. Probabilities can be estimated using expert opinion or derived from data on substance properties. An example is presented with 100 pesticides, in which the retain step identified a single substance to target refinement. Using an updated hazard characterisation for this substance reduced the mean exposure estimate from 0.43 to 0.28 µg kg-bw-1 day-1 and reduced the 99.99th percentile exposure from 24.9 to 5.1 µg kg-bw-1 day-1. Other retained substances contributed little to the risk estimates, even after accounting for uncertainty.


Assuntos
Contaminação de Alimentos/análise , Praguicidas/análise , Exposição Ambiental , Monitoramento Ambiental , Humanos , Medição de Risco , Incerteza
12.
Food Chem Toxicol ; 138: 111185, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058012

RESUMO

A model and data toolbox is presented to assess risks from combined exposure to multiple chemicals using probabilistic methods. The Monte Carlo Risk Assessment (MCRA) toolbox, also known as the EuroMix toolbox, has more than 40 modules addressing all areas of risk assessment, and includes a data repository with data collected in the EuroMix project. This paper gives an introduction to the toolbox and illustrates its use with examples from the EuroMix project. The toolbox can be used for hazard identification, hazard characterisation, exposure assessment and risk characterisation. Examples for hazard identification are selection of substances relevant for a specific adverse outcome based on adverse outcome pathways and QSAR models. Examples for hazard characterisation are calculation of benchmark doses and relative potency factors with uncertainty from dose response data, and use of kinetic models to perform in vitro to in vivo extrapolation. Examples for exposure assessment are assessing cumulative exposure at external or internal level, where the latter option is needed when dietary and non-dietary routes have to be aggregated. Finally, risk characterisation is illustrated by calculation and display of the margin of exposure for single substances and for the cumulation, including uncertainties derived from exposure and hazard characterisation estimates.


Assuntos
Método de Monte Carlo , Medição de Risco , Rotas de Resultados Adversos , Animais , Benchmarking , Análise de Dados , Bases de Dados Factuais , Exposição Ambiental , Substâncias Perigosas , Humanos , Modelos Estatísticos , Nível de Efeito Adverso não Observado , Relação Quantitativa Estrutura-Atividade , Incerteza
13.
Environ Int ; 134: 105267, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704565

RESUMO

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages.


Assuntos
Medição de Risco , Misturas Complexas , Substâncias Perigosas , Humanos
14.
Artigo em Inglês | MEDLINE | ID: mdl-31021211

RESUMO

Pesticide residues in food can lead to harmful toxic effects when exposed. Some of these compounds have a common Mode of Action and thus elicit a similar biological response. This paper considers the triazoles, a class of widely used fungicides exhibiting the same short-term (acute) and long-term (chronic) response in humans. We examined Belgian pesticide residue data from 2011-2014 and coupled these with the results of the Belgian food consumption survey of 2004. Cumulative probabilistic risk assessment was done using the Monte Carlo Risk Assessment 8.0 web application. The European Food Safety Authority (EFSA) published a guidance document that proposes both optimistic and pessimistic scenarios for dietary exposure assessment. Other than those two, a third, more balanced, scenario was simulated and showed an exposure right in between the EFSA scenarios. In the optimistic scenario, the foods with the highest measured residues in the residue data contributed the most to the total health risk. In the balanced and pessimistic scenarios, the highest contribution to the total health risk was made by active ingredients with a high sampling rate and/or a high consumption rate. No significant trends were observed in the health risk through 2011 to 2014, and the exposure distribution showed no health risks for the extreme consumers, with one exception in 2012.


Assuntos
Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Medição de Risco/estatística & dados numéricos , Triazóis/análise , Bélgica , Inocuidade dos Alimentos , Humanos , Modelos Estatísticos
15.
Food Res Int ; 116: 859-869, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717016

RESUMO

Whilst risk management measures, including food policy, are developed for the protection of public health and the environment, they may also lead to a reduction in health benefits. Policy decisions require then consideration of these necessary trade-offs, which leads to an increasing need to apply formal risk-benefit assessment (RBA) of foods. In this context, the European Food Safety Authority sponsored a Risk-Benefit Assessment Workshop on "past, current and future developments within the risk-benefit assessment of foods (RBA)" held in May 2017. The overall aims of the RBA Workshop were to discuss existing methods, challenges and needs within RBA, and to draft a roadmap for future development of RBA. The specific objectives were to i) identify RBA activities in Europe and globally; ii) discuss how to further develop and optimize RBA methodology; iii) identify challenges and opportunities within RBA; and iv) increase collaboration internationally. The two-day workshop gathered 28 participants from 16 institutions in 11 countries. It included technical presentations of RBA methods and case studies, and two break-out sessions for group discussions. All participants agreed that RBA has substantial potential to inform risk-management decisions in the areas of food safety, nutrition and public health. Several activities to optimize further developments within RBA were suggested. This paper provides a summary of workshop presentations, a discussion of challenges that limit progress in this area, and suggestions of next steps for this promising approach supporting a science-based decision process in the area of risk-benefit management of foods.


Assuntos
Dieta Saudável , Inocuidade dos Alimentos , Alimentos , Comportamento de Redução do Risco , Animais , Congressos como Assunto , Dieta Saudável/efeitos adversos , Alimentos/efeitos adversos , Humanos , Cooperação Internacional , Valor Nutritivo , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco
16.
Int J Hyg Environ Health ; 222(2): 291-306, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30579770

RESUMO

Populations are exposed to mixtures of pesticides through their diet on a daily basis. The question of which substances should be assessed together remains a major challenge due to the complexity of the mixtures. In addition, the associated risk is difficult to characterise. The EuroMix project (European Test and Risk Assessment Strategies for Mixtures) has developed a strategy for mixture risk assessment. In particular, it has proposed a methodology that combines exposures and hazard information to identify relevant mixtures of chemicals belonging to any cumulative assessment group (CAG) to which the European population is exposed via food. For the purposes of this study, food consumption and pesticide residue data in food and drinking water were obtained from national surveys in nine European countries. Mixtures of pesticides were identified by a sparse non-negative matrix underestimation (SNMU) applied to the specific liver steatosis effect in children from 11 to 15 years of age, and in adults from 18 to 64 years of age in nine European countries. Exposures and mixtures of 144 pesticides were evaluated through four different scenarios: (1) chronic exposure with a merged concentration dataset in the adult population, (2) chronic exposure with country-specific concentration datasets in the adult population, (3) acute exposure with a merged concentration dataset in the adult population, and (4) chronic exposure with a merged concentration dataset in the paediatric population. The relative potency factors of each substance were calculated to express their potency relative to flusilazole, which was chosen as the reference compound. The selection of mixtures and the evaluation of exposures for each country were carried out using the Monte Carlo Risk Assessment (MCRA) software. Concerning chronic exposure, one mixture explained the largest proportion of the total variance for each country, while in acute exposure, several mixtures were often involved. The results showed that there were 15 main pesticides in the mixtures, with a high contribution of imazalil and dithiocarbamate. Since the concentrations provided by the different countries were merged in the scenario using merged concentration data, differences between countries result from differences in food consumption behaviours. These results support the approach that using merged concentration data to estimate exposures in Europe seems to be realistic, as foods are traded across European borders. The originality of the proposed approach was to start from a CAG and to integrate information from combined exposures to identify a refined list of mixtures with fewer components. As this approach was sensitive to the input data and required significant resources, efforts should continue regarding data collection and harmonisation among the different aspects within the pesticides regulatory framework, and to develop methods to group substances and mixtures to characterise the risk.


Assuntos
Dieta , Interações Medicamentosas , Exposição Ambiental/análise , Fígado Gorduroso/epidemiologia , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Medição de Risco/métodos , Adolescente , Adulto , Animais , Criança , Europa (Continente)/epidemiologia , Humanos , Pessoa de Meia-Idade , Nível de Efeito Adverso não Observado , Adulto Jovem
17.
Environ Int ; 120: 544-562, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30170309

RESUMO

Humans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns about their impact on public and environmental health. The risk assessment of chemicals for regulatory purposes mainly relies on the assessment of individual chemicals. If exposure to multiple chemicals is considered in a legislative framework, it is usually limited to chemicals falling within this framework and co-exposure to chemicals that are covered by a different regulatory framework is often neglected. Methodologies and guidance for assessing risks from combined exposure to multiple chemicals have been developed for different regulatory sectors, however, a harmonised, consistent approach for performing mixture risk assessments and management across different regulatory sectors is lacking. At the time of this publication, several EU research projects are running, funded by the current European Research and Innovation Programme Horizon 2020 or the Seventh Framework Programme. They aim at addressing knowledge gaps and developing methodologies to better assess chemical mixtures, by generating and making available internal and external exposure data, developing models for exposure assessment, developing tools for in silico and in vitro effect assessment to be applied in a tiered framework and for grouping of chemicals, as well as developing joint epidemiological-toxicological approaches for mixture risk assessment and for prioritising mixtures of concern. The projects EDC-MixRisk, EuroMix, EUToxRisk, HBM4EU and SOLUTIONS have started an exchange between the consortia, European Commission Services and EU Agencies, in order to identify where new methodologies have become available and where remaining gaps need to be further addressed. This paper maps how the different projects contribute to the data needs and assessment methodologies and identifies remaining challenges to be further addressed for the assessment of chemical mixtures.


Assuntos
Misturas Complexas , Exposição Ambiental , Substâncias Perigosas , Medição de Risco , Animais , União Europeia , Humanos , Pesquisa
19.
Food Chem Toxicol ; 79: 32-44, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25280924

RESUMO

Exposures to plant protection products (PPPs) are assessed using risk analysis methods to protect public health. Traditionally, single sources, such as food or individual occupational sources, have been addressed. In reality, individuals can be exposed simultaneously to multiple sources. Improved regulation therefore requires the development of new tools for estimating the population distribution of exposures aggregated within an individual. A new aggregate model is described, which allows individual users to include as much, or as little, information as is available or relevant for their particular scenario. Depending on the inputs provided by the user, the outputs can range from simple deterministic values through to probabilistic analyses including characterisations of variability and uncertainty. Exposures can be calculated for multiple compounds, routes and sources of exposure. The aggregate model links to the cumulative dietary exposure model developed in parallel and is implemented in the web-based software tool MCRA. Case studies are presented to illustrate the potential of this model, with inputs drawn from existing European data sources and models. These cover exposures to UK arable spray operators, Italian vineyard spray operators, Netherlands users of a consumer spray and UK bystanders/residents. The model could also be adapted to handle non-PPP compounds.


Assuntos
Dieta/efeitos adversos , Exposição Ambiental/efeitos adversos , Contaminação de Alimentos , Implementação de Plano de Saúde , Modelos Estatísticos , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Adulto , Criança , Pré-Escolar , Ecotoxicologia/métodos , União Europeia , Feminino , Guias como Assunto , Inquéritos Epidemiológicos , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Exposição Ocupacional/efeitos adversos , Medição de Risco/normas , Software , Adulto Jovem
20.
Food Chem Toxicol ; 79: 13-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25125392

RESUMO

The practicality was examined of performing a cumulative dietary exposure assessment according to the requirements of the EFSA guidance on probabilistic modelling. For this the acute and chronic cumulative exposure to triazole pesticides was estimated using national food consumption and monitoring data of eight European countries. Both the acute and chronic cumulative dietary exposures were calculated according to two model runs (optimistic and pessimistic) as recommended in the EFSA guidance. The exposures obtained with these model runs differed substantially for all countries, with the highest exposures obtained with the pessimistic model run. In this model run, animal commodities including cattle milk and different meat types, entered in the exposure calculations at the level of the maximum residue limit (MRL), contributed most to the exposure. We conclude that application of the optimistic model run on a routine basis for cumulative assessments is feasible. The pessimistic model run is laborious and the exposure results could be too far from reality. More experience with this approach is needed to stimulate the discussion of the feasibility of all the requirements, especially the inclusion of MRLs of animal commodities which seem to result in unrealistic conclusions regarding their contribution to the dietary exposure.


Assuntos
Dieta/efeitos adversos , Ecotoxicologia/métodos , Contaminação de Alimentos , Modelos Estatísticos , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Triazóis/toxicidade , Adolescente , Adulto , Animais , Bovinos , Criança , Inquéritos sobre Dietas , União Europeia , Estudos de Viabilidade , Feminino , Guias como Assunto , Humanos , Masculino , Carne/efeitos adversos , Carne/análise , Pessoa de Meia-Idade , Leite/efeitos adversos , Leite/química , Resíduos de Praguicidas/análise , Praguicidas/análise , Medição de Risco/normas , Triazóis/análise , Adulto Jovem
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