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By Pamela Ferdinand
Chemicals increasingly used to replace the toxic plastic additive bisphenol A (BPA) may disrupt fertility, fetal development and reproductive health through many of the same biological mechanisms, according to a narrative review of human, animal and laboratory studies.
Concerns about BPA have led some manufacturers to phase it out and replace it with structurally similar compounds, most commonly bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). While BPA exposure has declined, BPS and BPF use are rising, especially in North America and Asia.
The review, published this month in Archives of Medical Research, found that these BPA substitutes — widely used in plastics, processed food and food packaging, children’s toys and paper receipts — can interfere with the same hormone systems and gene-regulation pathways that control reproductive development in both males and females.
“Although these compounds were originally synthesized to be safe for human use, they have also exhibited endocrine-disrupting activity similar to BPA, which affects reproductive function,” the researchers wrote.
“These changes can lead to reproductive disorders and negative long-term and transgenerational consequences.”
They say analogues were introduced without sufficient evidence of their safety, and subsequent studies show they have adverse effects similar to BPA, warranting more scientific and regulatory scrutiny.
BPA has been associated with impaired memory and learning, infertility, heart disease, stroke, metabolic disease, Type 2 diabetes, preeclampsia, obesity and cancer, studies show.
At the molecular level, like BPA and other endocrine disruptors, the substitutes can mimic estrogen or block hormone activity, including testosterone signaling.
They also appear to induce epigenetic changes, altering the chemical signals that control how genes are turned on or off and affecting processes crucial for egg and sperm formation, hormone production and fetal growth.
The review analyzed findings from scores of studies, including laboratory experiments on cells or animals, biomonitoring studies measuring chemical exposure in humans and long-term cohort studies.
While data on the effects and mechanisms of these analogues is scarce, the authors say, some of these studies suggest that the effects of exposure may not only manifest in the immediate generation but also persist across generations.
In mice and zebrafish, for instance, exposure altered gene-regulation signals in developing sperm and egg cells, leading to reproductive and metabolic issues in their descendants.
In vivo and in vitro studies also linked exposure to BPA, BPS and BPAF with several ovarian disorders, such as polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age.
Other key findings show BPA analogues may:
- Disrupt gene activity. Studies of mouse egg cells exposed to BPS showed changes in DNA signals that control gene activity, potentially altering cell development.
- Damage cells. BPA substitutes increase oxidative stress and weaken mitochondria, the energy centers of cells.
- Harm egg cells and fertility. Bisphenol B (BPB) increased gene-silencing signals and reduced egg cell survival, while bisphenol AP (BPAP) caused DNA damage, interfered with DNA repair and disrupted chromosome separation during egg cell division.
- Disrupts hormone production in females and males. BPS suppressed genes needed for estrogen production, while studies in animals and humans suggest BPA analogues interfere with testosterone production and sperm development.
- Cross the placenta and affect fetal development. Animal studies show exposure to BPA and BPS before and during pregnancy can disrupt placenta formation and alter neurotransmitters such as serotonin and dopamine, affecting brain and reproductive development.
Most evidence comes from laboratory and animal studies, due to the ethics of human experiments, and epidemiological research on newer analogues remains limited. The researchers also caution that low doses of endocrine disruptors can have unexpected effects, and real-world exposure typically involves mixtures rather than single chemicals.
BPA is banned in baby bottles and sippy cups in both the European Union (EU) and in the U.S. because the chemical has been shown to leach from plastics into food or liquid.
No federal or state-level regulations address BPA analogues in the U.S., but regulatory responses for its analogues are emerging elsewhere: The EU has phased in a broad ban on BPA and certain bisphenols in food contact materials, and the U.K. is considering similar restrictions. BPS is under review in Europe as a substance of very high concern.
Stricter testing of plastics is needed, the authors said, including methods that account for low-dose effects, mixture exposure and sensitive life stages such as pregnancy, infancy and puberty, and menopause.
“The findings presented here provide evidence that highlight the need to develop new guidelines to protect human health from the harmful effects of BPA analogues,” they wrote.
“In addition, the experience with BPA and its substitutes must be considered before replacing materials intended for human use.”
To reduce your exposure to BPA and similar chemicals, avoid heating plastics and use safer alternatives such as glass, stainless steel or silicone.
Originally published by U.S. Right to Know.
Pamela Ferdinand is an award-winning journalist and former Massachusetts Institute of Technology Knight Science Journalism fellow who covers the commercial determinants of public health.
