Six popular BPA alternatives all mimic estrogen in breast cancer cells; three of them more so than BPA itself, according to new research.

Three chemicals used as BPA alternatives mimic estrogen and promote breast cancer cell growth more than the controversial compound they’re designed to replace, according to new research.

The study, preprinted online before it goes through the peer-review process, is the first study to test these six bisphenol-A (BPA) alternatives in various breast cancer cells and compare their level of estrogen mimicking against one another.

The findings suggest that “BPA-free” may mean very little for consumers trying to protect their health from endocrine disrupting chemicals.

These substitutions “are turning on gene pathways involved in cancer, and they’re doing that in a human cancer cell,” said Frederick vom Saal, a University of Missouri-Columbia professor who studies BPA but was not part of the new study.

Scientists for years have warned about the dangers of BPA—used in producing polycarbonate, epoxy and phenolic resins and largely used to make plastic hard and shatterproof, but also used in thermal receipt paper.

BPA is found widely in food packaging and just about everyone has it in his or her system, with diet as the most common culprit. It is a known endocrine disruptor.

These substitutions “are turning on gene pathways involved in cancer, and they’re doing that in a human cancer cell."
-Frederick vom Saal, University of Missouri-Columbia

Properly functioning hormones are crucial to reproduction, as well as development, brain function and immune systems.

Manufacturers have started using alternatives over the past decade, often using chemicals with a similar chemical structure. “The plastics manufacturing industry have turned to alternative bisphenols to produce their ‘BPA-free’ products, often with little toxicology testing,” wrote the authors of the new study.

In the current study, researchers tested six substitutes—all bisphenols—in three different human breast cancer cell lines. Two of the cell lines will only grow in the presence of estrogen or an estrogen mimic.

They found that all six of the substitutions mimicked estrogen. Three of the substitutes—bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol Z (BPZ)—were more potent than BPA at mimicking estrogen in the cancer cells.

While the findings do not mean BPA replacements cause breast cancer, the activation of estrogen receptors is behind roughly two-thirds of breast cancer cases. 

“Industry is working to replace BPA because of health concerns – but all these alternatives are also estrogenic,” said senior author Michael Antoniou, a researcher at the Gene Expression and Therapy Group at King’s College London.

While there isn’t as much information on the compounds as the heavily studied BPA, all six of the chemicals in the study have been detected in breast milk and urine, said Katie Pelch, a research associate at the non-profit organization The Endocrine Disruption Exchange.

One of the compounds, BPS, has been found in thermal paper used for receipts and raised red flags when researchers reported in 2013 that it interferes with the proper functioning of hormones.

For the other replacements, it’s not entirely clear what products they’re used in, Pelch said, but researchers’ “best guess” is that they’re in the same things BPA is used in such as thermal paper used in receipts and food packaging.

Pelch said the study was strong in that it tested the chemicals on different cell types, but was limited in that it only focused on estrogen. Such chemicals can behave in ways other than just mimicking estrogen—such as blocking estrogen, or androgen, she added.

Antoniou said people are more than likely exposed to multiple compounds, making such findings difficult to relate to the real world.

“We’ve studied each compound individually, but the reality is that people are exposed to a mixture of all of these substances,” Antoniou said, adding that he and others are currently studying these “synergistic” effects.

Preprinting a study is an unusual route for a scientific paper. The paper was published this month on an online archive called bioRxiv run by Cold Spring Harbor Laboratory, which touts the website as a way for authors to receive feedback from fellow scientists before submitting to journals.

Lead author of the study, Robin Mesnage, also of King’s College London, said that he and co authors decided to publish the study prior to peer-review because “public health data should be made public as soon as possible because it is of a critical interest for society.”