BPA replacements show hormone-mimicking issues in mice – Expert Reaction

Bisphenol A (BPA) replacements in plastics cause similar reproductive problems in lab mice that actual BPA does, according to a new study published in Current Biology.

Twenty years ago, researchers made the accidental discovery that plastics ingredient bisphenol A had inadvertently leached out of plastic cages used to house female mice in the lab, causing a sudden increase in chromosomally-abnormal eggs in the animals. Now, the same team says the array of alternative bisphenols now used to replace BPA in bottles, cups, cages, and other items appear to cause similar endocrine-disrupting problems in mice. They say more work is needed to determine whether some replacement bisphenols are safer than others.

The Science Media Centre gathered expert commentary on the paper. Please feel free to use these comments in your reporting. 

Lou Sherman, Technical and Service Leader, Biopolymers and Chemicals team, Scion, comments:

“This research highlights concerns about BPA alternatives. What is important to note is that not all plastics contain these alternatives. In general, plastics that are marked with the recycling codes 1 (PET, soft drink bottles), 2 (HDPE, milk bottles), 4 (LDPE, plastic bags), 5 (polypropylene), and 6 (polystyrene) are very unlikely to contain BPA or its alternatives.

“It is also important to note that even if a material does contain BPA or these alternatives, they will only pose a risk if they migrate from the packaging into the food at harmful levels. International food contact regulations require plastics to be tested for such migration and limits of migration have been designed to protect consumers from harm.

“To complete the picture, and fully understand the risk of packaging that contains these BPA alternatives, complementary research on the potential for these to migrate into food is needed. An example of this is a recent study conducted by Food Standards Australia New Zealand (FSANZ). The focus of this study was two phthalates and five other plasticisers that are also known endocrine disruptors. Results from this survey of 65 foods found that the estimated dietary exposure was below the tolerable daily intake for these substances, so they do not pose a public health concern.”

No conflict of interest.

Dr Alisyn Nedoma, Lecturer in Chemical and Materials Engineering at the University of Auckland, comments:

“While it is true that any polymer broken into its constituent bits could be toxic … in practice, most polymers simply do not break down. The plastic described in this article is exceptional in this respect.

“Recent work in Patricia Hunt’s laboratory at Washington State University has indicated that chemical leachates from damaged mouse cages have caused a biological effect on the mice living inside the cages. The mouse cages were made of a plastic called polysulfone that is manufactured from building blocks like bisphenol A. It is likely that the chemical degradation of the plastic cage resulted in the release of bisphenol A and similarly structured chemicals into the environment of the mice.

“The molecular structure of a chemical has a strong effect on how biological systems respond to that chemical, so it is unsurprising that chemicals shaped like bisphenol A have similar effects on mice. These researchers should be commended for identifying this unexpected phenomenon through the rigorous evaluation of their data.

“Plastics like polycarbonate and polysulfone are manufactured by chemically bonding thousands of individual bisphenol-type molecules, resulting in an inert plastic chain.

“Physical degradation of the plastic, like flaking into smaller particles, does not change the nontoxic inertness of the plastic; however, chemical degradation can cause the chain to break into smaller fragments, releasing potentially harmful degradation products like bisphenol A.

“Most plastics, like polyethylene and polystyrene, are extremely stable to chemical degradation and remain in the environment for hundreds of years. The potential danger of contaminants leaching from a damaged plastic must be considered on a case-by-case basis.”

No conflict of interest.

Professor James Wright, Director, Centre for Green Chemical Science University of Auckland, comments:

“In BPA-polymers such as polycarbonates, BPA is chemically bonded and it is not easily released. However, the action of heat, dishwashing, microwaving, and UV-light on these polymers all contribute to their slow break-down which can release molecular BPA.

“Leaching of molecular BPA from plastics that contain this compound as an additive, rather than chemically combined as part of the polymer, is much easier and gives much higher levels of released BPA.

“A number of replacements for BPA have been developed. However, the safety and toxicity of these have been much less studied than it has for BPA. Just because a plastic is ‘BPA free’, it does not necessarily mean the replacement used is less toxic. Most likely the toxicity of the replacement has not been intensely studied. Worryingly, a number of recent studies of some BPA replacements have shown they may have the same toxicity as BPA itself.”

No conflict of interest.

Our colleagues at the Australian Science Media Centre also asked experts to comment on the paper.

Associate Professor Oliver Jones, School of Science, RMIT University, comments:

“It is perhaps not surprising that chemical compounds that are structurally similar can act in a similar way and things that chemically ‘look like’ BPA may have similar effects, indeed this study is not the first to show this to be the case.

BPA itself has been around since the 1960s and is one of the most studied chemicals on earth, with thousands of scientific papers published on it. However, nobody has ever proven it causes harm at the levels to which people are normally exposed to it. Indeed, it is known to be metabolised and excreted by the body very quickly.

Public concern over BPA has led to the generation of a whole family of BPA replacers including BPF BPAF, BPE and BPS. These are chemically very similar to BPA but have not been as extensively tested for potential health effects, so further study in this area is welcome.

The present study is very interesting and conducted by well-known and respected researchers. However, the number of animals used in the work is very low and the animals themselves were very inbred. It should also be remembered that mice are not mini humans. Some chemicals that cause problems for them don’t affect us at all. For example, Aspirin causes birth defects in most rodents, but not in humans. While this is very clever work, I don’t think people need be alarmed about these results.”

Oliver has no conflicts of interest. He has provided images to for use, please contact the Aus SMC for access.

Associate Professor Samantha Richardson, School of Health and Biomedical Sciences, RMIT University, comments:

“The paper by Horan et al. highlights an extremely important issue that is not sufficiently recognised by the public. Chemical companies many no longer use BPA in plastics but they substitute very similar chemicals with different names, that have almost exactly the same function – in both manufacture of plastics and in harm to the environment and metabolism of animals, including humans. These are called ‘structural analogues’ which means that they have almost the identical molecular shape, so can have the same interactions with other synthetic or biological molecules.

Take for example morphine. This is a compound of the opioid family which was originally discovered in plants. However, it binds specific receptors in the human brain to alleviate pain. How can this be? Why would the human brain have receptors to a chemical made in plants? Morphine is a ‘structural analogue’ of naturally occurring chemicals in the brain called endorphins, which are released to reduce the perception of pain e.g. after extensive exercise.

Medicine exploits structural analogues in designing drugs to control metabolism and assist in prevention of disease progression. However, structural analogues can also be toxic to humans, other animals, plants and the environment. These include chemicals used in plastics, fire retardants etc. These chemicals are structural analogues of naturally-occurring compounds in the body that are very tightly regulated in the amounts made by the body and where they are released in the body. The structural analogues in plastics e.g. BPA disrupt the normal metabolism resulting in disease and long-term effects such as those described by Horan and colleagues. If chemical companies decide to make a structural analogue of BPA so they can label their plastics ‘BPA-free’, they are actually making the whole situation worse, because the structural analogues they use to replace BPA are still structural analogues of the naturally occurring compounds and the ‘BPA-free’ labelling is encouraging people to buy more of these products.”

Sam has not declared any conflicts of interest.