Safety Concerns for BPA – Alternatives

Bisphenol A (BPA) is a common synthetic chemical used to manufacture epoxy-based resins that coat the interior of aluminum and steel food and beverage cans. The molecule acts as an inert barrier and protects the metal packaging surfaces from corrosion. Without BPA, small measurable amounts of metal from the container could seep into the food and cause harmful effects when consumed. But constant exposure to BPA is associated with adverse health effects such as cardiovascular disease, hormone irregularity and reproductive defects (Lang, 2008). 

Growing public concern over BPA in the past few years pressured many manufacturers to discontinue its use and label their products “BPA-free” to assure customers. But the industry has turned to other bisphenols such as bisphenol S (BPS) as replacements. These bisphenols are structurally similar to BPA (Fig. 1) and exhibit similarly hazardous properties, leaving the fundamental issue unaddressed. Even though the effects of BPS have been thoroughly documented in scientific literature across animal studies, epidemiological study populations, and mechanistic in-vitro work, its collective effects are still unknown. Its continued use in “BPA-free” products therefore presents issues regarding toxicity to human health and environmental impact. 

Figure 1. BPA and BPS structural similarities

Similar to BPA, BPS disrupts the endocrine system. The compound exhibits a nonlinear dose response behavior and remains biologically active even at very low concentrations (Chen, 2016). Since the severity of biological responses does not correlate well with the dosage administered, BPA and BPS exposure at low doses still poses a major public health concern. Chronic exposure to BPS is associated with developmental deformities in a number of organs including the heart (Gao, 2015). Zebrafish larvae populations that were administered BPS exhibited greater cardiac arrhythmic effects when compared to zebrafish larvae that had been given BPA, suggesting that BPS correlates with an increased risk of structural heart disease (Kinch, 2015). 

However, epidemiological data suggests that associations between BPS exposure and congenital heart defects are sex-specific (Yan, 2011). Another study published in the Naturesearch Journal used mouse studies to monitor the effects of BPS and BPA on heart muscle function (Ferguson, 2019). They found that the hearts of male mice were more resistant to the adverse cardiac effects of BPA than the hearts of female mice. And when perfused with BPS, the hearts of female mice suffered more from reduced phospholamban phosphorylation, a crucial regulator of cardiac contractility and relaxation, than the hearts of male mice did (Fig. 2). Phospholamban in its unphosphorylated state increases risk of stroke and heart failure (Chu 2006).  These results suggest that although “BPA-free” has become a lucrative marketing tool for manufacturers, BPS in reality may be just as dangerous, if not more so, than BPA exposure.

Figure 2. Both male and female hearts suffered reduced phospholamban phosphorylation when perfused with BPA for 15 minutes. However, BPS had no effect on phospholamban phosphorylation in male samples.

Additionally, exposure to BPA analogues affects male and female reproductive functions. By monitoring mice lineages, researchers can track how these chemicals alter the recombination and genetic diversity within a population (Fig. 3). They have found that BPS exposure has lasting effects that persist through generations of male mice. The exposure effects for subsequent female generations were not investigated in this study. Additionally,  descendents that face exposure themselves tend to manifest more pronounced and severe defects, suggesting that the effect can be magnified down the line (Horan, 2017). 

Figure 3. The effects of replacement bisphenols on male mice recombination rate persis for several generations. Increased levels of MLH1 indicated higher variation in meiotic recombination. In families 1 and 2, the F0 and F1 generations had significiantly lower MLH1 than the mean.

BPA use is still legal to this day (Ribeiro, 2017). Typically, research demonstrating the adverse health effects of a chemical will elicit a strong public awareness and promote better management and regulations. Unfortunately, the easiest solutions often involve the removal or ban of the chemical in question and increasing the use of an alternative with potentially worse health outcomes (Lakind, 2010). Evidently, such is the case with BPS which, being a structural analogue of BPA, results in similar exhibitions of metabolic syndromes, infertility, and neurodevelopmental effects. The superior, albeit more challenging, solution would be for manufacturers to work with regulators to actively seek safer alternatives instead of simply relying on another bisphenol.

Edited by Sarah Kim.

Placed by Albert Liu.

References

Chen, D., Kannan, K., Tan, H., Zheng, Z., Feng, Y.-L., Wu, Y., & Widelka, M. (2016, June 7). Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review. https://www.ncbi.nlm.nih.gov/pubmed/27143250

Chu, G., & Kranias, E. G. (2006). Phospholamban as a therapeutic modality in heart failure. Novartis Foundation symposium, 274, 156–276.

Ferguson, M., Lorenzen-Schmidt, I., & Pyle, W. G. (2019, November 4). Bisphenol S rapidly depresses heart function through estrogen receptor-β and decreases phospholamban phosphorylation in a sex-dependent manner. https://www.nature.com/articles/s41598-019-52350-y

Gao, X., Ma, J., Chen, Y., & Wang, H.-S. (2015, June). Rapid responses and mechanism of action for low-dose bisphenol S on ex vivo rat hearts and isolated myocytes: evidence of female-specific proarrhythmic effects. https://www.ncbi.nlm.nih.gov/pubmed/25723814

Horan, T. S., Marre, A., Hassold, T., Lawson, C., & Hunt, P. A. Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006885

Kinch, C. D., Kingsley Ibhazehiebo, J.-H. J., Habibi, H. R., & Kurrasch, D. M. (2015, February 3). Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish. https://www.pnas.org/content/112/5/1475

Lakind, J. S., & Birnbaum, L. S. (2010, February 17). Out of the frying pan and out of the fire: the indispensable role of exposure science in avoiding risks from replacement chemicals. Retrieved from https://www.nature.com/articles/jes200971

Lang, I. A., Galloway, T. S., Scarlett, A., Henley, W. E., Depledge, M., Wallace, R. B., & Melzer, D. (2008, September 17). Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. https://www.ncbi.nlm.nih.gov/pubmed/18799442

Ribeiro, E., Ladeira, C., & Viegas, S. (2017). Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled. Toxics, 5(3), 22. https://doi.org/10.3390/toxics5030022

Yan, S., Chen, Y., Dong, M., Song, W., Belcher, S. M., & Wang, H. S. (2011). Bisphenol A and 17β-estradiol promote arrhythmia in the female heart via alteration of calcium handling. PloS one, 6(9), e25455. https://doi.org/10.1371/journal.pone.0025455

Image References

BPS – What’s New in Eco. https://whatisnewinecomaterials.wordpress.com/tag/bps/

Ferguson, M., Lorenzen-Schmidt, I., & Pyle, W. G. (2019, November 4). Bisphenol S rapidly depresses heart function through estrogen receptor-β and decreases phospholamban phosphorylation in a sex-dependent manner. https://www.nature.com/articles/s41598-019-52350-y/figures/6

Horan, T.S., Pulcastro, H., Lawson, C., Gieske, M.C., Sartain, C.V., Hunt, P.A. (2018, September 13). Replacement bisphenols adversely affect mouse gametogenesis with consequences for subsequent generations. Current Biology, vol. 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156992/figure/F4/

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