Oral Systemic Bioavailability of Bisphenol A and Bisphenol S in Pigs

Abstract

Background:Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral availability and systemic persistency, were higher than those of BPA.Objectives:The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK.Methods:Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds.Results:The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds.Conclusion:Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599

Review: The Consumption of Ultra-Processed Foods and Non-communicable Diseases in Latin America

“…Synthetic compounds like bisphenol A (BPA) are omnipresent in food packaging, and BPA in particular has been shown to act as a xenohormone with the potential to impair reproductive function in men and increase cancer risk ( 19 ). While some manufacturers have responded to the public's concerns about BPA exposure by switching to bisphenol S (BPS), research indicates that this alternative may actually be more readily absorbed into the body ( 27 ). Phthalates are another class of synthetic chemicals commonly used in food packaging, and like BPA and BPS, they have the potential to act as xenohormones.…”

Perinatal oral exposure to low doses of bisphenol A, S or F impairs immune functions at intestinal and systemic levels in female offspring mice

“…In humans, BPA, BPS and BPF cross the placenta and represent a risk for the foetus [ 11 ]. BPA exposure during perinatal period is associated with non-communicable diseases (NCDs) at childhood and adulthood [ 12 – 14 ].…”

A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

“…Lastly, the bioavailability of BPS substitutes might be higher than for BPA. A recent study conducted in pigs, an ideal model for mimicking the human digestive tract, demonstrated the lower plasma clearance of BPS (3.5 lower) compared to BPA and an increased oral systemic exposure exceeding 250-fold [168]. These observations draw our attention and raise concerns about replacing BPA by BPS, as this may result in an increased internal exposure to EDCs.…”