Browsing by Author "Santonen, T."
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- Improving risk assessment of chemicals by the use of human biomonitoring: HBM4EU project activitiesPublication . Santonen, T.; Alvito, P.; 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, H.; Pronk, A.; Ormsby, J. N.; Rousselle, C.; Schaddelee-Scholten, B.; Silva, M. J.; Stierum, R.; Viegas, Susana; Vinggaard, 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 legislation 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 with the available RA guidance, and do give 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 an 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.
- Occupational exposure to metals and PAHs: combining literature-based exposure and in vitro hazard data towards a mixture risk assessmentPublication . Tavares, A.M.; Alves, I.; Moreira, R.; Louro, H.; Ladeira, Carina; Viegas, Susana; Loureiro, S.; Santonen, T.; Göen, T.; Kortenkamp, A.; Luijten, M.; Silva, M.J.A.The environment within industrial settings is commonly characterized by the existence of a complex mixture of chemicals from different raw materials and transformation processes. Occupational co-exposure to chromium (Cr), Nickel (Ni), and Polycyclic Aromatic Hydrocarbons (PAHs) may occur in diverse workplaces, such as aeronautic and waste management, (e.g incineration) sectors. Such co-exposure raises concern in terms of occupational health, as these substances are recognized lung carcinogens and mainly act by genotoxic mechanisms, increasing the likelihood of interactive toxic effects. The fact that current regulatory practices are usually focused on single chemical substances, without integrating the possibility of combined or aggregated exposures and effects, may lead to a risk underestimation. This work, developed under the scope of HBM4EU Initiative (https://www.hbm4eu.eu), a literature-based mixture risk assessment (MRA) exercise for occupational exposure to metals and PAHs was performed. In addition, in vitro toxicity data was obtained for the same mixtures to provide support to its hazard assessment. Human biomonitoring (HBM) data on Cr(VI), Ni, and/or PAHs were extracted from occupational studies conducted in the European Union and searched in literature databases. Selected reference values were used to calculate risk quotients (RQ) for each substance based on the retrieved exposure data; the combined risk was given by the sum of the RQ, i.e., the Background Exposure Exceedance Score(BEES). In parallel, we evaluated the combined cyto- and genotoxicity of the same chemicals (assessed by the MTT and micronucleus assays) in the human alveolar A549 cell line. In most of the analyzed studies, we observed that BEES levels, estimated from the exposure to metals mixture or to metals and PAHs, exceeded RQ levels considered acceptable for the individual substances. Only two studies, conducted in hazard waste incinerator settings, presented urinary exposure levels for the three substances. They showed a value of BEES of concern (>1) for all exposure scenarios, even for workers performing activities considered of low exposure or no exposure, such as laboratory and administrative workers. In vitro assays supported that A549 cells' exposure to these substances resulted in interactive cytotoxic and genotoxic effects that may underlie health effects different from those predicted from single exposures. Our findings show the limitations of applying occupational exposure reference values defined on a single substance basis to workplaces where exposure to chemical mixtures occurs, highlighting the relevance of performing MRA as a more realistic approach to guide suitable risk management measures in occupational settings.