European Partnership for the Assessment of Risks from Chemicals (PARC)

Publications

Exploring BPA alternatives - Environmental levels and toxicity review

Publication . Adamovsky, Ondrej; Groh, Ksenia J.; Białk-Bielińska, Anna; Escher, Beate I.; Beaudouin, R.; Mora Lagares, Liadys; Tollefsen, Knut Erik; Fenske, Martina; Mulkiewicz, Ewa; Creusot, Nicolas; Sosnowska, Anita; Loureiro, Susana; Beyer, Jonny; Repetto, Guillermo; Štern, Alja; Lopes, Isabel; Monteiro, Marta; Zikova-Kloas, Andrea; Eleršek, Tina; Vračko, Marjan; Zdybel, Szymon; Puzyn, Tomasz; Koczur, Weronika; Ebsen Morthorst, Jane; Holbech, Henrik; Carlsson, Gunnar; Örn, Stefan; Herrero, Óscar; Siddique, Ayesha; Liess, Matthias; Braun, Georg; Srebny, Vanessa; Žegura, Bojana; Hinfray, Nathalie; Brion, François; Knapen, Dries; Vandeputte, Ellen; Stinckens, Evelyn; Vergauwen, Lucia; Behrendt, Lars; Silva, Maria João; Blaha, Ludek; Kyriakopoulou, Katerina

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

2024-05-23Journal article

Open access

A critical review to identify data gaps and improve risk assessment of bisphenol A alternatives for human health

Publication . Mhaouty-Kodja, Sakina; Zalko, Daniel; Tait, Sabrina; Testai, Emanuela; Viguié, Catherine; Corsini, Emanuela; Grova, Nathalie; Buratti, Franca Maria; Cabaton, Nicolas J.; Coppola, Lucia; De la Vieja, Antonio; Dusinska, Maria; El Yamani, Naouale; Galbiati, Valentina; Iglesias-Hernández, Patricia; Kohl, Yvonne; Maddalon, Ambra; Marcon, Francesca; Naulé, Lydie; Rundén-Pran, Elise; Salani, Francesca; Santori, Nicoletta; Torres-Ruiz, Mónica; Turner, Jonathan D.; Adamovsky, Ondrej; Aiello-Holden, Kiara; Dirven, Hubert; Louro, Henriqueta; Silva, Maria João

Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).

2024-10-22Journal article

Open access

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project

Publication . Snapkow, Igor; Smith, Nicola M.; Arnesdotter, Emma; Beekmann, Karsten; Blanc, Etienne B.; Braeuning, Albert; Corsini, Emanuela; Sollner Dolenc, Marija; Duivenvoorde, Loes P.M.; Sundstøl Eriksen, Gunnar; Franko, Nina; Galbiati, Valentina; Gostner, Johanna M.; Grova, Nathalie; Gutleb, Arno C.; Hargitai, Rita; Janssen, Aafke W.F.; Krapf, Solveig A.; Lindeman, Birgitte; Lumniczky, Katalin; Maddalon, Ambra; Mollerup, Steen; Parráková, Lucia; Pierzchalski, Arkadiusz; Pieters, Raymond H.H.; Silva, Maria Joao; Solhaug, Anita; Staal, Yvonne C.M.; Straumfors, Anne; Szatmári, Tünde; Turner, Jonathan D.; Vandebriel, Rob J.; Zenclussen, Ana Claudia; Barouki, Robert

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).

2024-04-09Research article

Open access

Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health

Publication . Behr, Anne-Cathrin; Fæste, Christiane Kruse; Azqueta, Amaya; Tavares, Ana M.; Spyropoulou, Anastasia; Solhaug, Anita; Olsen, Ann-Karin; Vettorazzi, Ariane; Mertens, Birgit; Zegura, Bojana; Streel, Camille; Ndiaye, Dieynaba; Spilioti, Eliana; Dubreil, Estelle; Buratti, Franca Maria; Crudo, Francesco; Eriksen, Gunnar Sundstøl; Snapkow, Igor; Teixeira, João Paulo; Rasinger, Josef D.; Sanders, Julie; Machera, Kyriaki; Ivanova, Lada; Gaté, Laurent; Le Hegarat, Ludovic; Novak, Matjaz; Smith, Nicola M.; Tait, Sabrina; Fraga, Sónia; Hager, Sonja; Marko, Doris; Braeuning, Albert; Louro, Henriqueta; Silva, Maria João; Dirven, Hubert; Dietrich, Jessica

Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.

2025-03-26Journal article

Open access

Regulatory practices on the genotoxicity testing of nanomaterials and outlook for the future

Publication . Andreoli, Cristina; Dusinska, Maria; Bossa, Cecilia; Battistelli, Chiara Laura; Silva, Maria João; Louro, Henriqueta

Highlights: - Genotoxicity testing of chemicals requires multiple tests to cover key endpoints; - NMs have distinct properties that require adaptations of conventional testing; - Approaches for genotoxicity testing of the NMs reviewed show challenges; - The level of harmonization between different frameworks is debated; - New approach methodologies are underlined to support NMs'regulation.

2025-06-06Journal article

Restricted access