Browsing by Author "Borges, T."
Now showing 1 - 8 of 8
Results Per Page
Sort Options
- HBM4EU - Deliverable Report D 5.5: Human biomonitoring in risk assessment: 2nd set of examples on the use of HBM in risk assessments of HBM4EU priority chemicalsPublication . Santonen, Tiina; Mahiout, Selma; Bessems, J.; Buekers, J.; Baken, K.; Schoeters, G.; Woutersen, M.; Vermeire, T.; Bil, W.; Ougier, E.; Rousselle, C.; Šömen Joksić, A.; Kirinčič, S.; Louro, Henriqueta; Silva, Maria João; Assunção, Ricardo; Vinggaard, A. M.; Viegas, S.; Huuskonen, P.; Porras, S.; Kiilunen, M.; Uhl, M.; Hartmann, C.; Hauzenberger, I.; Losert, A.; Tratnik, J. Snoj; Horvat, M.; Schaddelee-Scholten, B.; Buist, H.; Westerhout, J.; Fletcher, T.; Rauscher-Gabernig, E.; Plichta, V.; Abraham, K.; Borges, T.; Kadikis, N.The aim of this work was to exemplify the inclusion of human biomonitoring (HBM) data in risk assessment (RA) and health impact assessment (HIA) strategies. RA was performed for six compound groups on HBM4EU’s first list of priority substances: anilines, cadmium/chromium, flame retardants, PAHs, PFAS and phthalates. In addition, burden of disease (BoD) calculations were made for cadmium. The general approach used included: 1) identification of an existing RA for the substance, 2) identification of possible existing biological limit or guidance values or biological equivalents (BEs), or if lacking, existing health based limit values for external exposure, 3) identification of relevant biomonitoring data to be used in the RA, 4) in case no existing biological limit or guidance values or BEs existed, identification of approaches for reverse/forward calculation, including the use of PBPK modelling or calculation of BE values based on one-compartment modelling, 5) RA or BoD calculation based on HBM data, 6) analysing the benefits and challenges of using HBM data in RA compared to the use of external exposure data. The overall result of the work was that HBM can be included in RA even when relatively few data are available, and its inclusion generally benefits the RA. Several methods exist, and a tiered approach is suggested, based on the amount and quality of data available. The recommended 1st tier method is a one-compartment modelling based derivation of BE values or reverse calculation of external exposure based on biomarker levels. This approach is simple and rough, and uses only very basic parameters. However, in many cases this approach can be considered sufficient, especially when conservative assumptions have been used for the FUE, and the calculated RCRs remain well below 1, indicating a low risk. Also, in cases in which risk assessment using this approach supports the RA made based on external exposure estimates, it is often a sufficient approach. Nevertheless, in some cases e.g. where the RCR is close to 1, a more detailed approach may be needed to refine the RA. For the 2nd tier, PBPK modelling is recommended. For the most robust, 3rd tier approach, measured data on correlations between external exposure and internal doses from well controlled studies would be needed. Certain cases were identified where inclusion of HBM would be particularly important for performing RA: for compounds, for which several exposure routes may contribute to the body burden and the health effects, as HBM reflects the total body burden, and cumulative compounds. For cumulative compounds, HBM could also be useful for hazard assessment in addition to exposure assessment. One of the major challenges for the inclusion of HBM into RA is the often limited data available on toxicokinetics. In addition, in some cases, there is an urgent need for more specific biomarkers or more sensitive analytic methods than currently available. It should be noted that these risk assessments were performed purely to determine how HBM data can contribute to the risk assessment of chemicals, and they have no regulatory implications. Overall for the substances on the HBM4EU’s first list of priority substances, more HBM data are needed. This work is ongoing in WP8, and the RAs presented here will be updated when new data become available.
- Human biomonitoring in risk assessment: analysis of the current practice and 1st examples HBM in risk assessments of HBM4EU priority chemicalsPublication . Santonen, T.; Heinälä, M.; Bessems, J.; Buekers, J.; Cornelis, C.; Vermeire, T.; Woutersen, M.; van Engelen, J.; Borges, T.; Rousselle, C.; Ougier, E.; Louro, Henriqueta; Alvito, Paula; Martins, Carla; Assunção, Ricardo; Silva, Maria João Silva; Krul, L.; Pronk, A.; Schaddelee-Scholten, B.; Gonzalez, M.C.; de Alba, M.; Díaz, G.; Castaño, A.; Viegas, S.; Humar-Juric, T.; Kononenko, L.; Abraham, K.; Vinggaard, A.M.In chemicals risk assessment frameworks, the default approach is to assess external intake from different sources of exposure and via different routes of exposure. They are often assessed separately. This approach includes various uncertainties and often overestimates the real uptake since default, conservative estimates are used e.g. for the absorption of the chemical. At the same time, actual (real life) exposure may be underestimated by not taking into account that exposure to a chemical substance may occur from different sources, which may fall under separate legislative frameworks. Examples are triclosan that is used in biocidal products as well as in consumer products and importantly, most if not all chemicals that are produced by workers where at the same time these workers may be exposed as part of the general population. In some cases, other tools to assess exposure via all possible routes may be insufficient; an example is occupational exposure via hand-to-mount exposure, which has been shown to occur for example in the case of many metals, like lead, through contaminated hands. Without biomonitoring, exposure in these cases could become severely underestimated. Human Biomonitoring (HBM) is an important tool to survey the real life body burden – or internal exposure – of humans resulting from ‘total’ exposure to chemicals via different routes (lung, skin, digestive tract) and ‘via’ different legislative frameworks on chemicals. By providing more accurate data on actual body burdens (internal exposure), inclusion of HBM data could improve human health risk assessment for both the general population (exposure via air, consumer products, drinking water and food) as well as for workers (exposure via inhalation and/or skin) separately or as part of the population.
- Improving risk assessment of chemicals by the use of human biomonitoring - HBM4EU project activitiesPublication . Santonen, T.; Alvito, Paula; Bessems, J.; Borges, T.; Brunet, D.; Buekers, J.; Cornelis, C.; van Engelen, J.; Gonzalez Caballero, M.C.; Humar-Juric, T.; Heinälä, M.; Klaus, A.; Kononenko, L.; Krul, L.; Lamkarkach, F.; Louro, Henriqueta; Pronk, A.; Ormsby, J-N.; Viegas, S.; Rousselle, C.; Schaddelee-Scholten, B.; Silva, Maria João; Stierum, R.; Vinggaard, S A.M.; Vermeire, T.; Woutersen, M.The default approach in the risk assessment (RA) of chemicals is to assess external exposure by combining different sources and routes of exposure. This kind of approach contains various uncertainties and may overestimate exposure, since conservative estimates are needed due to the limited data on, for example, the absorption of the chemical and interspecies and intraspecies differences. Human biomonitoring (HBM) can help improve RA by providing measured data on combined exposures. In some cases, biomonitoring data can even provide a direct link to health effects. In some cases, biomonitoring allows to link exposure to specific contexts such as occupational settings. Although recent years have seen good examples of the use of biomonitoring in the risk assessment of chemicals, much work is still needed to improve its use in regulatory RA and human impact assessment (HIA). The European Human Biomonitoring Initiative (HBM4EU) was recently launched for fulfilling the gap between the exposure to hazardous chemical agents and their impact on human health. One of the aims of the HBM4EU project is to enhance the use of HBM data in RA and HIA of chemicals in different regulatory contexts including legislations on chemicals, plant protection products and biocides, as well as legislation on cosmetics, food safety and occupational safety. RA models for mixtures are also considered. Firstly, current RA practices are evaluated: is the use of biomonitoring integrated in the available RA guidance, and do given RA schemes have good examples of the advanced use of biomonitoring? A survey is also conducted to gather information from national regulatory risk assessors (in the EU, but also in non-EU countries) on their risk assessment practices, the use of HBM, and the obstacles and challenges related to its use. The challenges of the use of HBM data in RA may include a lack of guidance in the use of biomonitoring, a lack of knowledge regarding the interpretation of biomonitoring results, or the inability to link biomonitoring data to different exposure sources. Using a selected group of priority chemicals as example, we can determine whether these challenges can be overcome by including the recent HBM data, collected during the HBM4EU project, in the existing RA schemes. Finally, proposals will be made for the better use of HBM in RA and HIA in different policy domains.
- Investigação e avaliação de risco: contributo do projeto MYCOMIXPublication . Alvito, Paula; Martins, Carla; Assunção, Ricardo; Silva, M.J.; Louro, H.; Borges, T.; Loureiro, S.; Leal, S.; Dupond, D.; Seljak, B.Sumário: 1. Misturas de micotoxinas nos alimentos – uma realidade 2. Avaliação de risco – alteração de paradigma 3. Desafios associados à avaliação de risco de misturas de micotoxinas em alimentos 4. Projeto MYCOMIX – um caso estudo
- MycoMix - Misturas de Micotoxinas em alimentos para crianças e potencial impacto na saúdePublication . Alvito, Paula; Assunção, Ricardo; Borges, T.; Leal, Sónia; Louro, Henriqueta; Martins, Carla; Martins, Vitor; Nunes, Baltazar; Silva, M.João; Tavares, Ana; Vasco, Elsa; Calhau, Maria AntóniaA ocorrência de micotoxinas constitui uma preocupação crescente em saúde pública, particularmente os síndromes associados à exposição das crianças a estas toxinas através da alimentação. A ocorrência simultânea de micotoxinas poderá constituir uma preocupação adicional dado que podem provocar maior toxicidade e carcinogenicidade do que individualmente. São escassos os estudos desenvolvidos nesta área e não existem, até ao momento, dados sobre a exposição das crianças Portuguesas a estas toxinas. Neste âmbito, o projeto Mycomix pretende avaliar o risco de exposição das crianças a estas misturas e os seus potenciais efeitos tóxicos. Considerando resultados anteriores da equipa, sugere-se que as crianças possam estar expostas a múltiplas micotoxinas através da sua alimentação. Esta possibilidade levou à constituição de uma equipa multidisciplinar que pretende responder às seguintes questões: 1) As crianças estão expostas diariamente a micotoxinas (isoladas e/ou em combinação) através da alimentação? 2) Qual a natureza e teor que caracterizam esta exposição? 3) Pode esta exposição trazer efeitos prejudiciais para as crianças? Para responder a estas perguntas a equipa está desenvolver novas abordagens, nomeadamente: 1) desenvolvimento de novos métodos analíticos para determinação de múltiplas micotoxinas, 2) compreensão dos efeitos tóxicos decorrentes da presença simultânea de micotoxinas e, 3) implementação de novas metodologias para a caracterização dos perigos e riscos decorrentes da exposição das crianças a micotoxinas. Os dados de ocorrência de micotoxinas nos alimentos adquiridos na região de Lisboa entre 2013 e 2015, combinados com os dados de consumo alimentar obtidos no estudo piloto efetuado a 100 crianças com idades até 3 anos, na Unidade de Saúde Familiar Cidadela, Cascais, permitirão estimar a ingestão de micotoxinas pelas crianças inquiridas, usando abordagens determinística e probabilística. A contribuição dos estudos toxicológicos sobre a biodisponibilidade destes contaminantes e os seus efeitos tóxicos interativos serão posteriormente abordados no âmbito de uma avaliação global de risco.
- MycoMix and risk assessment: a contribute to improve risk analysisPublication . Alvito, Paula; Assunção, Ricardo; Borges, T.; Dupont, D.; Leal, S.; Loureiro, S.; Louro, H.; Martins, Carla; Nunes, Baltazar; Pinhão, M.; Koroušic Seljak, B.; Silva, M.J.; Silva, E.; Vasco, Elsa; Calhau, Maria AntóniaRisk analysis, is a powerful tool for including science-based knowledge in a systematic approach to food safety problems. The use of risk analysis can promote ongoing improvements in public health and provide a basis for expanding international trade in foods. Within risk analysis, the risk assessment results are quantitative or qualitative expressions of the likelihood of harmful effects associated with exposure to a chemical (WHO, 2010). Human risk assessment of combined exposure to multiple chemicals (chemical mixtures) poses several challenges to scientists, risk assessors and risk managers, namely the complexity of the terminology and problem formulation, the diversity of chemical entities, and the toxicological profiles and exposure patterns in test species and humans (EFSA, 2013). Mycotoxins are natural contaminants produced by fungi and its frequent co-occurrence in food poses a threat to human health, mainly to vulnerable population groups as children. MycoMix is an ongoing national project (2013-15) that explores the toxic effects of mixtures of mycotoxins in infant food and its potential health impact. This project aims to study the occurrence of multiple mycotoxins and toxicity interactions in infant foods and cereals consumed by Portuguese children and try to answer several questions: 1) Are children exposed daily to mycotoxins through food? 2) What are the quality and quantity that characterize this exposure? 3) Can this exposure bring harm to children? Answering these questions will raise novel approaches to: 1) apply new techniques on mycotoxin multiple detection, 2) understand the toxicity responses upon multiple mycotoxin exposures, and 3) implement new methodologies to characterize hazard and risk for children exposure to mycotoxins. A multidisciplinary team has been developing, for the first time in Portugal, i) a liquid chromatography (LC) method coupled with tandem mass-spectrometry (LC-MS/MS) for multimycotoxin detection in infant food developed and applied to study infant food consumed by Portuguese children, ii) cito and genotoxic assays to assess the toxicity of binary mixtures of mycotoxins detected in analyzed infant foods associated with the MIXTOX tool to assess the interactive effects, iii) in vitro methodologies to simulate the digestive and intestinal absorption processes of binary mixtures of mycotoxins, iv) a web-based dietary assessment and diet planning platform, the “OPEN Portugal”, to record infant food consumption data allowing simultaneously the assessment of the nutritional profile of the inquired children, and v) a set of deterministic, probabilistic (@RISK) and cumulative risk assessment approaches that allow the exposure assessment and risk characterization of Portuguese children to multiple mycotoxins in food. An overview of the results obtained within the MycoMix project will be presented, showing the patterns of the exposure of Portuguese infant to multiple mycotoxins as well as the scientific evidence of the toxic effects of mycotoxin mixtures using in vitro models. Hence,MycoMix outputs contribute for hazard identification and characterization as well as to exposure characterization, contributing for risk analysis.
- Risk assessment of multiple mycotoxins in infant food consumed by Portuguese children – the contribute of the MYCOMIX projectPublication . Alvito, Paula; Assunção, Ricardo; Borges, T.; Leal, S.; Loureiro, S.; Louro, Henriqueta; Nunes, Baltazar; Silva, M.J.; Tavares, A.; Martins, Carla; Vasco, Elsa; Calhau, Maria AntóniaThere is a growing concern within public health about mycotoxin involvement in human diseases, namely those related to children. Scarce data are available in the literature concerning the occurrence of multiple mycotoxins in infant food and their combined toxicity, and no data exists in Portugal concerning this issue. In order to contribute to fill this gap, the MycoMix project, funded by the Portuguese Foundation for Science and Technology, gathered a multidisciplinary team aiming at answering several questions: 1) Are Portuguese children exposed daily to one or several mycotoxins through food? 2) Can this co-exposure affect children´s health? and 3) Are there interaction effect between mycotoxins? Within this project, Portuguese children (< 3 years old, n=103) food consumption data were obtained using a 3 days food diary in a pilot study performed at a Primary Health Care Unit. The main declared infant foods were purchased from the Lisbon market along 2014-15 and analyzed by means of HPLC and LC-MS/MS analytical techniques for multiple mycotoxins co-occurrence. Toxicological studies including bioaccessibility and cyto and genotoxic interactions between detected mycotoxins were also performed using in vitro approaches. Preliminary results showed that 96 % of the analyzed breakfast cereals (BC) were contaminated with one to six different mycotoxins in the same sample and children exposure to single mycotoxins present in BC were well below the tolerable daily intake (TDI) although the margin of exposure (MOS) values for multiple mycotoxins were near one. Bioaccessibility values for single mycotoxins ranged between 42-106% for patulin and aflatoxin M1 in cereal based foods and in infant formulae. Cito and genotoxicity studies on the detected mycotoxins provided evidence on the interaction effect between some binary mixtures of mycotoxins. The assessment of all data is expected to contribute to a more accurate risk assessment of multiple mycotoxins in infant foods consumed by Portuguese children, warranting the safety of infant health. Results obtained within MYCOMIX highlight the challenges posed by the occurrence of multiple chemicals co-occurring in foods.
- Towards a nanospecific approach for risk assessment.Publication . Dekkers, S.; Oomen, A.G.; Bleeker, E.A.; Vandebriel, RJ..; Micheletti, C.; Cabellos, J.; Janer, G.; Fuentes, N.; Vázquez-Campos, S.; Borges, T.; Silva, M.J.; Prina-Mello, A.; Movia, D.; Nesslany, F.; Ribeiro, A.R.; Leite, P.E.; Groenewold, M.; Cassee, F.R.; Sips, A.J.; Dijkzeul, A.; van Teunenbroek, T.; Wijnhoven, S.W.In the current paper, a new strategy for risk assessment of nanomaterials is described, which builds upon previous project outcomes and is developed within the FP7 NANoREG project. NANoREG has the aim to develop, for the long term, new testing strategies adapted to a high number of nanomaterials where many factors can affect their environmental and health impact. In the proposed risk assessment strategy, approaches for (Quantitative) Structure Activity Relationships ((Q)SARs), grouping and read-across are integrated and expanded to guide the user how to prioritise those nanomaterial applications that may lead to high risks for human health. Furthermore, those aspects of exposure, kinetics and hazard assessment that are most likely to be influenced by the nanospecific properties of the material under assessment are identified. These aspects are summarised in six elements, which play a key role in the strategy: exposure potential, dissolution, nanomaterial transformation, accumulation, genotoxicity and immunotoxicity. With the current approach it is possible to identify those situations where the use of nanospecific grouping, read-across and (Q)SAR tools is likely to become feasible in the future, and to point towards the generation of the type of data that is needed for scientific justification, which may lead to regulatory acceptance of nanospecific applications of these tools.