Preventing regrettable substitutions : a proposal for a tiered testing approach for BPA alternatives under the PARC initiative

Aiello, Kiara (author), Bartmann, Kristina (author), Buratti, Franca Maria (author), Cabaton, Nicolas J. (author), Coppola, Lucia (author), Corsini, Emanuela (author), De La Vieja, Antonio (author), Franko, Nina (author), Kodila, Anja (author), Sollner Dolenc, Marija (author)

Bisphenol A (BPA) alternatives are increasingly used in the manufacture of industrial and consumer products, following regulatory restrictions on BPA. However, insufficient safety data on these substitutes raise concern as regards potential regrettable substitutions. Under the EU Partnership for the Assessment of Risks from Chemicals (PARC), Work Package 5 (WP5) addresses this challenge by applying a human-relevant tiered hazard assessment strategy grounded on OECD test guidelines as first tier and expanding the battery to include NAMs (New Approach Methodologies). Eight BPA alternatives were prioritized for studies addressing key toxicological endpoints, namely, endocrine disruption (ED), developmental neurotoxicity (DNT), immunotoxicity, genotoxicity and carcinogenicity and metabolic fate examination (detoxification vs. potential bioactivation), to enable early identification of biological activity and support cross-endpoint prioritization. This manuscript describes the structure and implementation of the testing framework. This integrated testing strategy proposes a structured approach to identify substances of potential concern, guide targeted higher-tier studies, and support regulatory prioritization. PARC WP5 framework is testing whether coordinated NAM-based methods may contribute to next-generation risk assessment and help prevent regrettable substitutions among BPA alternatives for rapid regulatory adoption. Detailed experimental results will be reported separately upon completion of the project.

• Language: English
• Keywords: bisphenol A alternatives, carcinogenicity, developmental neurotoxicity (DNT, endocrine disruption (ED), human hazard assessment, immunotoxicity, metabolism, new approach methodologies (NAMs)
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 9 str.
• Numbering: Vol. 8
• PID: 20.500.12556/RUL-184522
• UDC: 615.9+616.43-008.6
• ISSN on article: 2673-3080
• DOI: 10.3389/ftox.2026.1815869
• COBISS.SI-ID: 284130051
• Publication date in RUL: 09.07.2026

Record is a part of a journal

• Title: Frontiers in toxicology
• Shortened title: Front. toxicol.
• Publisher: Frontiers Media
• ISSN: 2673-3080
• COBISS.SI-ID: 68385795

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: alternative bisfenolu A, kancerogenost, razvojna nevrotoksičnost (DNT), endokrine motnje (ED), ocena nevarnosti za ljudi, imunotoksičnost, metabolizem, metodologije novega pristopa (NAMs), hormonske motnje, toksikologija

Projects

• Funder: EC - European Commission
• Project number: 101057014
• Name: Partnership for the Assessment of Risks from Chemicals
• Acronym: PARC