Phthalates are substances that we can find in many everyday objects and products, from plastic to materials in contact with food. And one of these, DEHP, is now back in the spotlight of scientific research due to a possible link with breast cancer.
This is suggested by a new study conducted in Taiwan and published in the journal Proceedings of the National Academy of Sciences (PNAS)which followed a large cohort of women for about twenty years.
Let’s see what emerged but first let’s try to better understand what phthalates are.
What are phthalates
Phthalates are not a single substance, but a family of chemical compounds used mainly as plasticizers, i.e. useful for making some plastics softer, more flexible and resistant.
They have been used in many products and applications. According to the European Chemicals Agency (ECHA), they may be present, depending on the substance and use, in PVC plastics, adhesives, sealants, paints, rubber materials, cables, flooring, packaging, food contact materials, medical devices and sports equipment.
Among the best known is DEHP (di-2-ethylhexyl phthalate), used as a plasticizer especially in PVC.
The problem is that phthalates do not necessarily remain confined to the material that contains them. In fact, they can migrate into the environment and, under certain conditions, even into foods in contact with materials that contain them. Precisely for this reason, exposure can occur through various routes, including food.
In recent years the European Union has introduced numerous restrictions for the phthalates considered most problematic. DEHP, together with other substances of the same family, is also classified for its reproductive toxicity and its endocrine disrupting properties.
This does not mean, of course, that every plastic product contains DEHP or that every exposure automatically represents a hazard, much depends on the substance, material, use and exposure levels.
The new study
The new research starts from a longitudinal cohort of 11,923 women recruited in Taiwan between 1991 and 1992, followed until 2010. Within this population, the researchers identified 119 women who had developed invasive breast cancer and compared them with 245 women without cancer, used as a control group.
A particularly interesting aspect of the study is that the researchers did not limit themselves to reconstructing exposure through questionnaires: they analyzed urine samples collected during the visits, looking for 11 metabolites belonging to seven different phthalates. In this way they were able to estimate the participants’ exposure to these substances and, in the case of DEHP, also a parameter indicating how the body metabolises it.
The most important result is quite precise: among the seven phthalates analyzed, DEHP was the only one to show a statistically significant association with the risk of breast cancer.
Women with higher urinary levels of the sum of the five DEHP metabolites were at greater risk than women with lower levels. A similar result was observed considering MEHP, one of the main metabolites of DEHP.
In other words, in the specific sample studied, higher concentrations of DEHP and its metabolites were associated with a greater likelihood of having developed breast cancer.
But there is another interesting element. It’s not just how much DEHP is absorbed, but also how it is metabolized. The researchers also analyzed the percentage of MEHP compared to the total amount of DEHP metabolites. This parameter, called MEHP%, provides an indication of the individual’s ability to metabolize DEHP.
A higher percentage of MEHP was associated with a higher risk of breast cancer. According to the authors, this parameter could therefore represent a more informative biomarker of DEHP metabolism than just the overall quantity of metabolites present in the urine.
Previous research on the relationship between phthalates and breast cancer
The scientific community has been studying the possible relationship between endocrine disruptors and breast cancer for years, and phthalates are among the substances under observation.
A systematic review published in 2021 analyzed 37 studies and found that many papers reported an association between phthalate exposure and increased risk of breast cancer. The authors, however, stressed the need for further research to establish whether this association is indeed causal.
A 2018 review also focused specifically on dietary exposure to phthalates and their possible role in breast carcinogenesis. The authors had highlighted that some experimental studies suggested a possible involvement of estrogen-related mechanisms, but that the epidemiological evidence was still controversial.
But not all studies have reached the same conclusions. A meta-analysis published in 2021, which had collected nine studies totaling 7,820 cases and controls, had not found a statistically significant association between breast cancer and several phthalate metabolites, including MEHP. The authors therefore called for prospective and higher quality studies.
It is precisely in this context that the new Taiwanese work gains interest, in fact it offers data from a cohort followed for about two decades, with biological measurements of exposure.
Because DEHP is under observation
DEHP belongs to the best known and most studied phthalates. One of the reasons for the interest in it is its ability to interfere with the endocrine system. In fact, ECHA identifies it, together with other phthalates, as a substance with endocrine disrupting properties, in addition to the classification for reproductive toxicity.
This is also important because breast tissue is particularly sensitive to hormones. However, the fact that a substance has endocrine activity does not automatically mean that it causes a tumor; the transition from the biological activity observed in the laboratory to the actual increase in risk in the population must be demonstrated by epidemiological studies.
And it is precisely here that the necessary caution comes in when reading the new work.
The new study does not prove that DEHP causes breast cancer. Rather, it shows that, in the population analyzed, greater exposure to DEHP and some indicators of its metabolism were associated with a greater probability of developing breast cancer. It’s an important difference.
The same results must also be considered in light of the fact that exposure to phthalates is complex: we are generally exposed to multiple substances simultaneously and through different sources. Previous literature has also produced inconsistent results and highlighted the need for more robust longitudinal studies.
The new study, however, strengthens scientific interest in a class of substances to which we are exposed on a daily basis and which, precisely because of their diffusion, deserves to be studied even better.
In the meantime, the most concrete data is also what is already known on a regulatory level: in the European Union the use of DEHP is already subject to numerous restrictions, precisely due to its recognized risks.
And the fact that today research continues to study possible long-term effects, including on the risk of breast cancer, shows how important it is not to confuse an already regulated substance with a substance for which all scientific questions have been exhausted.
