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2020
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2006
2015
New advanced models (NAMs) for risk assessment of bisphenol A alternatives
The safety of bisphenol A (BPA) due to its adverse effects on the immune system has led to an increasing concern and a significant regulatory shift. The European Food Safety Authority (EFSA) proposed a reduction in the tolerable daily intake (TDI) of BPA in food in their 2023 scientific opinion, highlighting the need for stricter regulations compared to their previous assessment in 2015. This regulatory action has spurred the production of BPA alternatives, raising concerns about their safety due to insufficient toxicological data. Addressing this gap is crucial for ensuring human and environmental health. In this project, multiple genotoxicity endpoints were applied for testing of two regulatory relevant BPA alternatives, bisphenol E (BPE) and bisphenol P (BPP), in different human models: 2D HepG2 liver cells, 3D liver spheroids and primary human peripheral blood lymphocytes. DNA strand breaks and oxidised base lesions were evaluated by the enzyme-modified version of the comet assay, while clastogenicity and aneugenicity were analysed by the in vitro micronucleus assay (OECD TG 487, 2016), together with cytotoxicity. Development of new advanced models (NAMs), as 3D spheroids, are essential for next-generation risk assessment (NGRA) in line with the 3R's to replace, reduce or refine animal experiments. In this aspect, validation and standardisation of NAMs are needed to reach regulatory readiness level and development of OECD Test Guidelines. Therefore, a standardisation and pre-validation of the advanced 3D liver spheroid model was performed by using multiple genotoxicity endpoints and by comparing the obtained results with standard genotoxicity models.
2024
Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.
Frontiers Media S.A.
2023
2025
2014
Pergamon Press
2018
New brominated flame retardants in Arctic biota. Statlig program for forurensningsovervåking. Rapport 1070/2010. TA-2630/2010
2010
2002
2013
2014
2022
Per- and polyfluoroalkyl substances (PFAS) were analysed in a high number of terrestrial samples of soil, earthworm, bird eggs and liver from red fox and brown rat in an urban area in Norway from 2013 to 2020. PFOS and the long chain PFCAs were the most dominating compounds in all samples, proving their ubiquitous distribution. Other less studied compounds such as 6:2 FTS were first and foremost detected in earthworm. 8:2 FTS was found in many samples of fieldfare egg, sparrowhawk egg and earthworm, where the eggs had highest concentrations. Highest concentrations for both 6:2 FTS and 8:2 FTS were detected at present and former industry areas. FOSA was detected in many samples of the species with highest concentrations in red fox liver and brown rat liver of 3.3 and 5.5 ng/g ww.
PFAS concentrations from the urban area were significantly higher than from background areas indicating that some of the species can be suitable as markers for PFAS emissions in an urban environment. Fieldfare eggs had surprisingly high concentrations of PFOS and PFCA concentrations from areas known to be or have been influenced by industry. Biota-soil-accumulation factor and magnification calculations indicate accumulation and magnification potential for several PFAS.
Earthworm and fieldfare egg had average concentrations above the Canadian and European thresholds in diet for avian wildlife and predators. For earthworms, 18 % of the samples exceeded the European threshold (33 ng/g ww) of PFOS in prey for predators, and for fieldfare eggs, 35 % of the samples were above the same threshold. None of the soil samples exceeded a proposed PNEC of PFOS for soil living organisms of 373 ng/g dw.
Elsevier
2024
Munksgaard Forlag
2019
2003
2010
2020
2024