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On March 7, 2024, the New England Journal of Medicine published a comprehensive review by Tracey J. Woodruff, PhD, professor of obstetrics and gynecology at the University of California, San Francisco, on the effects of endocrine-disrupting compounds (EDCs) derived from fossil fuels. This array of commonly used artificial compounds is enormous and diverse. The European Union lists 109 such compounds, but it is estimated that there are at least a thousand, according to the Endocrine Society. EDCs can interfere with every aspect of hormonal action.

The main message is clear: An overwhelming amount of data shows that EDCs are a constant, multifaceted, and pervasive health risk. Moreover, it is extremely difficult to avoid them, and the risk is exacerbated by environmental and social conditions. It is not possible to list all the health and biological consequences of exposure to EDCs, but numerous sources, including the aforementioned review, discuss them. Briefly, the main pathological conditions associated with EDCs include hormone-sensitive tumors, such as those of the breast, prostate, or testicles; fetal neurological development alterations with consequences such as ADHD or decreased intellectual abilities; infertility due to ovarian development disorders and reduced sperm quality; predisposition to metabolic syndrome; and immune system alterations that increase susceptibility to asthma and allergies.

On January 11, 2024, a study estimated the economic burden of EDCs on public health in the United States at $250 billion, which is 1% of the country's gross domestic product. Similar estimates have been circulating for almost a decade. In 2015, the cost of EDCs on European public health was calculated at €163 billion.

Defending Ourselves 

Avoiding EDCs seems virtually impossible. They are present in almost every object in our daily life, from plastics to building materials, from toys to fabrics, from cosmetics to detergents, and from cans to paints. Moreover, many EDCs are so persistent in the environment that, for example, per- and polyfluoroalkyl substances (PFAS) are called "forever chemicals." They also persist in the body, where they often accumulate in adipose tissue. The HBM4EU study found measurable amounts of bisphenol A in 92% of a sample of 2756 people in 11 European countries.

European agencies are taking action. In March 2023, the European Chemicals Agency (ECHA) published restriction proposals for flame retardants and PFAS. The latter proposals were discussed on March 15, 2024.

During the same period, the European Food Safety Authority (EFSA) reviewed scientific evidence on one of the best-known and dangerous EDCs, bisphenol-A, lowering the recommended exposure limits by twenty thousand times (ie, from 4 µg/kg of body weight per day to 0.2 ng/kg). This limit is practically always exceeded by everyone, the EFSA noted. This review has not been without controversy: The European Medicines Agency did not accept it, stating that there is a lack of direct evidence in humans justifying the downward revision, and the disagreement has not yet been resolved.

These considerations are technicalities, however. What seems clear is that exposure to EDCs is essentially an uncontrolled pharmacological experiment on a gigantic scale, concerning the exposed population and the diversity of substances to which we are simultaneously exposed. "We are continuously exposed, even if the amounts of individual compounds are low, to a cocktail of endocrine disruptors throughout the day. What happens when we are exposed to multiple substances simultaneously? What happens if there is a synergistic or additive effect, or if instead their combination nullifies each other? These issues are not yet fully understood. There is much to study regarding the combined effect of substances," Sabrina Tait, a researcher at the Istituto Superiore di Sanità (ISS), told Univadis Italy. 

"Conducting studies on mixtures of substances is complex," said Maria Elisabeth Street, MD, PhD, a pediatrician and lecturer at the University of Parma, Italy. "We do not know the exact number of endocrine disruptors. There are hundreds of chemicals found in umbilical cord serum. It has been observed that these substances can amplify or attenuate their effects when present together, without a clear dose-response relationship. Therefore, very low concentrations can have harmful effects, just as very high concentrations may not show effects, or the effects at intermediate concentrations may be less evident."

Ten years ago, the ISS published a guide for citizens on reducing exposure to EDCs, and similar suggestions are easily found (although further data are needed to characterize their effectiveness). Among the main recommendations are reducing fat consumption since many EDCs accumulate in fat; reducing consumption of canned or plastic-packaged foods; replacing torn or worn wrappings of objects with foam padding; keeping nonstick dishes intact and preferring other types of dishes; and avoiding heating plastics in contact with food. 

"Obviously, being researchers, we can only provide partial guidance. Ideally, this information should be provided by doctors," said Tait. "Over the years, we have seen increased awareness, especially among pediatricians. Participating in a project involving a national network of pediatricians, we noticed that they have taken this issue to heart and communicate it to families."

"In basic pediatrics, there still seems to be little awareness," according to Street. "However, scientific societies are beginning to move in this direction. The Italian Federation of Pediatricians, which, in addition to being a union, is dedicated to the cultural education of pediatricians, is also addressing the issue of endocrine disruptors. We are making efforts in this direction, but we clearly are still in an initial phase. Awareness, however, must also grow among the public."

Childhood is a critical phase for action and exposure to EDCs, said Street. "EDCs accumulate in the maternal body even before and during gestation. We inevitably have a passage of endocrine disruptors from the mother to the embryo and fetus. During intrauterine life, EDCs can interfere with epigenetics, hence the regulation of gene expression, in our future life. It is one of the mechanisms that can explain the development and incidence of noncommunicable diseases. Another critical exposure window is the first year of life. To understand its impact, the Life MILCH project, in which I participate, is evaluating the presence and effects of EDCs in breast milk, which remains the best food for early childhood."

More Substances, Always Together

The wide chemical variety of EDCs makes it difficult to quantify exposure. In general, standard chemical tests can only monitor 5% of the compounds of interest. "EFSA has been working for many years on the development of an approach for the evaluation of potential combined effects of chemical mixtures in food and feed," Cristina Croera, PhD, a scientific officer at EFSA, told Univadis Italy. "EFSA finalized its MixTox guidance document in 2019 following a public consultation. The guidance provides its scientists with methodologies and tools to assess combined exposure to multiple chemical substances. The priority now is to focus primarily on the assessment of pesticide mixtures before extending the approach to other substances. Toward the end of 2021, EFSA published a guidance document (MixTox 2) to group chemicals in the food safety sector and to prioritize groups of chemical substances for health risk assessment."

The industry responds to regulations by creating new compounds that can be equally dangerous. For example, if the limits on bisphenol A become stricter, it is replaced with other bisphenols on which there is less data, even though it is plausible that their biological effects are similar. The same script is repeated with PFAS, with new substances such as GenX and perfluorobutane sulfonate being introduced to replace toxic PFAS. Only recently have these substances gained the attention of regulators.

Things could change, however, according to Street. "I understand that the European Community is actively working on this front. The goal is to move toward much stricter regulatory controls, ensuring that packaging materials undergo rigorous approval before being marketed. These will be long processes, certainly, and much damage has already been done." 

"In 2020, a group of EFSA researchers, with the contribution of the Federal Public Service for Health, Food Chain Safety, and Environment of Belgium and ECHA, completed a project to evaluate two new studies on bisphenol S (BPS)," which is a substitute for bisphenol A, Croera told Univadis Italy. "At that time, they recommended data collection on the use of BPS in plastic materials in contact with food, as well as on its presence and migration in food, in the context of its possible use as an alternative to BPA."

Exposure Varies 

Not everyone is exposed to EDCs in the same way. The risk factors for EDC exposure are also related to various types of social and economic inequalities, said Woodruff. Workers employed in the plastic industry, cleaning services, construction, and agriculture inevitably are exposed to high levels of EDCs, with health consequences not only for the workers themselves, but also for their children, including at the neurocognitive level.

The industry has engaged in deliberate deception. For example, in 2023, numerous industrial documents that were revealed thanks to the legal action of lawyer Robert Bilott showed that PFAS-producing companies such as DuPont and 3M had begun to realize the health risks associated with these substances as early as the 1970s — 40 years before public research reached similar conclusions. Instead of alerting the public, however, they buried the data for decades, in the meantime sowing confusion about the risk associated with these substances. 

In Italy, a similar case, also related to PFAS, occurred with the environmental disaster of the Trissino chemical plant in the province of Vicenza, which has contaminated the drinking water of the Veneto since 1977. The responsible parties hid the situation until it emerged publicly in 2013.

Like many other global public health issues, and as recognized by the World Health Organization's One Health approach, EDCs are a node where health intersects with inequalities and the environment. EDCs are a consequence of technology based on fossil fuels, from which these substances are synthesized, Woodruff wrote. Their medical danger goes hand in hand with their environmental danger. In October 2023, the Organization for Economic Cooperation and Development published a report on freshwater contamination by EDCs, which not only affects ecosystems, but also allows these compounds to return to human food through water and fishing. The environmental pervasiveness of these compounds makes exposure even more difficult to avoid.

EDCs represent a public health challenge that is still relatively little discussed compared to its impact. Researchers suggest that the medical profession must acquire a guiding role and raise public awareness. In doing so, it must not hesitate to recognize its environmental, social, and political responsibility. Policy proposals have been made. 

"There is an urgent need for the clinical community to address the growing burden of exposure to EDCs," wrote Woodruff. "With the expected increases in fossil fuel production in the United States and worldwide...the problem will continue to grow. In addition to advising patients, doctors can be critical advocates for policy changes aimed at decarbonizing and detoxifying the economy to address the combined health threats posed by petrochemical-derived EDCs and climate change."

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.