The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)

Frederick S Vom Saal¹, Michael Antoniou², Scott M Belcher³, Ake Bergman⁴, Ramji K Bhandari¹, Linda S Birnbaum^{5

6}, Aly Cohen⁷, Terrence J Collins⁸, Barbara Demeneix⁹, Anne Marie Fine¹⁰, Jodi A Flaws¹¹, Veronique Gayrard¹², William H Goodson 3rd¹³, Andrea C Gore¹⁴, Jerrold J Heindel¹⁵, Patricia A Hunt¹⁶, Taisen Iguchi¹⁷, Christopher D Kassotis^{18

19}, Andreas Kortenkamp²⁰, Robin Mesnage², Jane Muncke²¹, John Peterson Myers²², Angel Nadal²³, Retha R Newbold²⁴, Vasantha Padmanabhan^{25

26

27}, Paola Palanza²⁸, Zandra Palma²⁹, Stefano Parmigiani³⁰, Lyn Patrick¹⁰, Gail S Prins³¹, Cheryl S Rosenfeld^{32

33}, Niels E Skakkebaek³⁴, Carlos Sonnenschein³⁵, Ana M Soto³⁵, Shanna H Swan³⁶, Julia A Taylor¹, Pierre-Louis Toutain^{37

38}, Frank A von Hippel³⁹, Wade V Welshons⁴⁰, Daniel Zalko¹², R Thomas Zoeller⁴¹

Affiliations

¹ Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri, USA.
² Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
³ Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.
⁴ Department of Environmental Science (ACES), Stockholm University, Stockholm, Sweden.
⁵ Scientist Emeritus and Former Director, National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
⁶ Scholar in Residence, Duke University, Durham, North Carolina, USA.
⁷ Integrative Rheumatology Associates, Princeton, New Jersey, USA.
⁸ Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
⁹ Comparative Physiology Laboratory, Natural History Museum, Paris, France.
¹⁰ Environmental Medicine Education International, Mancos, Colorado, USA.
¹¹ Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana-Champaign, Illinois, USA.
¹² ToxAlim (Research Centre in Food Toxicology), University of Toulouse, Toulouse, France.
¹³ California Pacific Medical Center Research Institute, San Francisco, California, USA.
¹⁴ Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, Texas, USA.
¹⁵ Healthy Environment and Endocrine Disruptor Strategies, Raleigh, North Carolina, USA.
¹⁶ School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
¹⁷ Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
¹⁸ Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA.
¹⁹ Department of Pharmacology, Wayne State University, Detroit, Michigan, USA.
²⁰ Centre for Pollution Research and Policy, Brunel University London, Uxbridge, UK.
²¹ Food Packaging Forum Foundation, Zurich, Switzerland.
²² Environmental Health Sciences, Charlottesville, Virginia, USA.
²³ Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) and CIBERDEM, Miguel Hernandez University of Elche, Elche, Alicante, Spain.
²⁴ Scientist Emeritus, NTP, NIEHS, Research Triangle Park, North Carolina, USA.
²⁵ Department of Pediatrics, Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.
²⁶ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
²⁷ Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
²⁸ Unit of Neuroscience, Department of Medicine and Surgery, University of Parma, Parma, Italy.
²⁹ PalmaMD, Miami, Florida, USA.
³⁰ Unit of Evolutionary and Functional Biology, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
³¹ Department of Urology, University of Illinois at Chicago, Chicago, Illinois, USA.
³² Biomedical Sciences, Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri-Columbia, Columbia, Missouri, USA.
³³ MU Institute of Data Science and Informatics, University of Missouri-Columbia, Columbia, Missouri, USA.
³⁴ Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁵ Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.
³⁶ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³⁷ Royal Veterinary College, University of London, London, UK.
³⁸ NTHERES, INRAE, ENVT, Université de Toulouse, Toulouse, France.
³⁹ Department of Community, Environment & Policy, University of Arizona, Tucson, Arizona, USA.
⁴⁰ Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri, USA.
⁴¹ Department of Biology, University of Massachusetts, Amherst, Massachusetts, USA.

PMID: 38592230
PMCID: PMC11003459
DOI: 10.1289/EHP13812

The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)

Frederick S Vom Saal et al. Environ Health Perspect. 2024 Apr.

. 2024 Apr;132(4):45001.

doi: 10.1289/EHP13812. Epub 2024 Apr 9.

Authors

Affiliations

¹ Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri, USA.
² Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
³ Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.
⁴ Department of Environmental Science (ACES), Stockholm University, Stockholm, Sweden.
⁵ Scientist Emeritus and Former Director, National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
⁶ Scholar in Residence, Duke University, Durham, North Carolina, USA.
⁷ Integrative Rheumatology Associates, Princeton, New Jersey, USA.
⁸ Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
⁹ Comparative Physiology Laboratory, Natural History Museum, Paris, France.
¹⁰ Environmental Medicine Education International, Mancos, Colorado, USA.
¹¹ Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana-Champaign, Illinois, USA.
¹² ToxAlim (Research Centre in Food Toxicology), University of Toulouse, Toulouse, France.
¹³ California Pacific Medical Center Research Institute, San Francisco, California, USA.
¹⁴ Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, Texas, USA.
¹⁵ Healthy Environment and Endocrine Disruptor Strategies, Raleigh, North Carolina, USA.
¹⁶ School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
¹⁷ Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
¹⁸ Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA.
¹⁹ Department of Pharmacology, Wayne State University, Detroit, Michigan, USA.
²⁰ Centre for Pollution Research and Policy, Brunel University London, Uxbridge, UK.
²¹ Food Packaging Forum Foundation, Zurich, Switzerland.
²² Environmental Health Sciences, Charlottesville, Virginia, USA.
²³ Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) and CIBERDEM, Miguel Hernandez University of Elche, Elche, Alicante, Spain.
²⁴ Scientist Emeritus, NTP, NIEHS, Research Triangle Park, North Carolina, USA.
²⁵ Department of Pediatrics, Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.
²⁶ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
²⁷ Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
²⁸ Unit of Neuroscience, Department of Medicine and Surgery, University of Parma, Parma, Italy.
²⁹ PalmaMD, Miami, Florida, USA.
³⁰ Unit of Evolutionary and Functional Biology, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
³¹ Department of Urology, University of Illinois at Chicago, Chicago, Illinois, USA.
³² Biomedical Sciences, Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri-Columbia, Columbia, Missouri, USA.
³³ MU Institute of Data Science and Informatics, University of Missouri-Columbia, Columbia, Missouri, USA.
³⁴ Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁵ Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.
³⁶ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³⁷ Royal Veterinary College, University of London, London, UK.
³⁸ NTHERES, INRAE, ENVT, Université de Toulouse, Toulouse, France.
³⁹ Department of Community, Environment & Policy, University of Arizona, Tucson, Arizona, USA.
⁴⁰ Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri, USA.
⁴¹ Department of Biology, University of Massachusetts, Amherst, Massachusetts, USA.

PMID: 38592230
PMCID: PMC11003459
DOI: 10.1289/EHP13812

Abstract

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to $0.2 ng / kg body weight (BW) / day$ . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA's revision of the TDI for BPA.

Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model.

Discussion: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.

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References

1. Vom Saal FS, Vandenberg LN. 2021. Update on the health effects of bisphenol A: overwhelming evidence of harm. Endocrinology 162(3):bqaa171, 10.1210/endocr/bqaa171. - DOI - PMC - PubMed
1. Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. . 2012. Endocrine-disrupting chemicals and public health protection: a statement of principles from the Endocrine Society. Endocrinology 153(9):4097–4110, PMID: , 10.1210/en.2012-1422. - DOI - PMC - PubMed
1. EFSA (European Food Safety Authority). 2023. Re-evaluation of the Risks to Public Health Related to the Presence of Bisphenol A (BPA) in Foodstuffs - Immunotoxicity. https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2023.6857 [accessed 16 November 2023]. - DOI - PMC - PubMed
1. EFSA. 2017. Bisphenol A (BPA) Hazard Assessment Protocol. https://www.efsa.europa.eu/en/supporting/pub/en-1354 [accessed 19 July 2023].
1. BfR (German Federal Institute for Risk Assessment). 2023. Bisphenol A: BfR Proposes Health Based Guidance Value, Current Exposure Data are Needed for a Full Risk Assessment. German BfR Opinion No 018/2023. https://nam02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.bf... [accessed 12 November 2023].

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The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)

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The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)

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