Fluorinated alkyl substances and technical mixtures used in food paper-packaging exhibit endocrine-related activity in vitro

International audienceMigration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can beused in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum andumbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters(PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs)and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects.Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs ofunknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, gluco-corticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. Ingeneral, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17b-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARaand PPARc. Collectively, this means that (i) PAPs,FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMsexhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate bothPPARaand PPARcwith similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicologicaltargets were identified for different groups of PFAS

Improving risk assessment of chemicals by the use of human biomonitoring - HBM4EU project activities

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.HBM4EU project, Grant agreement No: 733032info:eu-repo/semantics/publishedVersio

Human biomonitoring in risk assessment: analysis of the current practice and 1st examples HBM in risk assessments of HBM4EU priority chemicals

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.info:eu-repo/semantics/publishedVersio