Bisphenol-A (BPA) is a chemical compound primarily used to produce polycarbonate plastics and epoxy resins. These plastics are part of water bottles, toys, sports equipment, or medical devices. Epoxy resins are used as coatings inside food and drink cans to prevent corrosion and breaking and to protect food from bacterial contamination. Thermal papers, such as the ones used for parking and train tickets, are also a source of BPA.
BPA is an Endocrine-Disrupting Chemical (EDC), an exogenous chemical that affects hormone synthesis, metabolism, and function. BPA can bind several hormone receptors, including thyroid and steroid receptors (estrogen and androgen), having a substantial impact on human reproductive system.
BPA’s Journey into our Diet and its Effects on Human Health
Its migration from packaging to food has led to concern among the general public and prompted interest in the scientific community.
The routes of BPA exposure in humans are mainly diet and, to a lesser extent, through inhalation and dermal absorption. Since BPA is a constituent of food containers and packaging, it can leach into food, especially after heating. Once we ingest it, BPA is adsorbed by the gastrointestinal tract and metabolized by the liver. In the case of thermal papers, holding them can lead to BPA absorption through the skin.
BPA is an EDC due to its high affinity for the estrogen receptor, leading to estrogen-mimicking behavior and stimulating estrogen function. This EDCs can also inhibit androgen function by binding to the androgen receptor. These can be translated into several problems for the female reproductive system.
BPA could contribute to the pathogenesis of female infertility. Diverse studies have revealed that BPA levels are higher in infertile than fertile women. The interaction with the endocrine function can lead to the impairment of ovarian and uterine morphology and function. It has also even been linked to Polycystic Ovary Syndrome (PCOS) by some observational studies.
Timeline of BPA Regulation in Europe and the United States
BPA is one of the most investigated EDCs. The European Food Safety Authority (EFSA) published its first risk assessment of BPA in 2006. Since then, the measures against using BPA have been tightened.
New evidence against BPA and its risks to human health continued to accumulate, and in 2015, the EFSA decided to publish a new comprehensive assessment of BPA’s exposure and toxicity. EFSA’s experts reduced the tolerable daily intake level from the previously established tolerable daily intake (TDI) of 50 micrograms per kilogram of body weight per day (µg/kg of bw/day) to a temporary TDI of 4 µg/kg of bw/day.
In 2011, Regulation (EU) No 10/2011 stated BPA may not be used to manufacture polycarbonate infant feeding bottles or cups designed for infants and young children, such as spill-proof drinking containers. It may be used as a starting substance for other food contact materials, but migration into food must not exceed the specific migration limit (SML) of 0.05 mg/kg. In January 2020, the use of BPA in thermal paper was banned.
In November 2022, the EFSA met with the European Medicines Agency (EMA) to re-evaluate the risks to public health due to the presence of BPA in food ingredients. Finally, in April 2023, the EFSA published a report establishing a TDI of 0.2 ng/kg of bw/day, a TDI 20,000 times lower than before.
Food and Drug Administration's (FDA) position on BPA differs slightly from the EFSA's. FDA’s stance on BPA is that it is safe at levels commonly found in food. FDA’s National Center for Toxicological Research found no evidence to suggest that levels of BPA in food threaten human health. In 2013, using polycarbonate resins in products such as baby bottles and infant formula packaging was banned.
In 2014, after reviewing more than 300 scientific studies, the FDA found no inofrmation that prompted a revision of the FDA's safety assessment of BPA in food packing at the time. In February 2022, the FDA's issued a public comment on EFSA's draft opinion released two months prior, raising concern about the biological plausibility of the EFSA approach.
The emergence of Zebrafish for Endocrine Disruption assessment
The limits established by the EFSA on daily doses are based on toxicokinetic evidence of BPA harm in different species. Based on rodent studies, EFSA applies a conservative and prudent approach for the daily dose definition over the No Observed Adverse Effect Level (NOAEL).
The Zebrafish is a valuable alternative model for researching the effect of Bisphenol A and other EDCs. Furthermore, with new regulation policies advocating for the reduction of animal use in research, Zebrafish is the perfect New Alternative Model (NAM) to perform Endocrine Disruption Assays following the 3R Principle: Replacement, Reduction, and Refinement.
At Biobide, we are experts in Zebrafish, and our mission is to accelerate researchers' R&D process by minimizing risks and translating findings into potential benefits for humankind.
Biobide’s endocrine disruption assays in Zebrafish allow the detection of maximum tolerated concentrations, analysis of protein levels by image analysis, alterations in hormone levels by LC-Ms-Ms techniques, or gene expression of main genes related to EDCs, that affect the thyroid disruption or estrogen pathways. BPA's primary endocrine-disrupting activity mimics estrogen, but its exposure can also indirectly affect testosterone, androgens, and thyroid hormones.
Assessing the impact of endocrine disruptors like BPA is key to understanding their effects on human hormonal systems, vital for regulating body functions and overall health. This evaluation helps devise strategies to mitigate potential risks, ensuring public health safety by limiting exposure to these chemicals. Moreover, such assessments guide policy-making and foster the development of safer alternatives, contributing to long-term health and environmental sustainability.
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Bisphenol A (BPA): Use in Food Contact Application. Food and Drug Administration [Internet]. [updated 2023 Apr 20]; [cited 2024 Jan 29]. Available from: https://www.fda.gov/food/food-packaging-other-substances-come-contact-food-information-consumers/bisphenol-bpa-use-food-contact-application
EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Lambré C, Barat Baviera JM, Bolognesi C, Chesson A, Cocconcelli PS, et al. Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs. EFS2 [Internet]. [published 2022 Dec 6]; [cited 2024 Jan 29]. Available at: https://data.europa.eu/doi/10.2903/j.efsa.2023.6857
Pivonello C, Muscogiuri G, Nardone A, Garifalos F, Provvisiero DP, Verde N, et al. Bisphenol A: an emerging threat to female fertility. Reprod Biol Endocrinol. 2020;18(1):22.