Exposure of pregnant women to a variety of endocrine disruptors has been associated-in a cohort study published in Science (Caporale et al., 2022)-with adverse effects on children’s neurobehavioral development. With special regard to delays in the development of language skills. (1)
1) Endocrine disruptors
Endocrine disruptors are substances that affect the regular biosynthesis of hormones, metabolism and its homeostasis. They can also disrupt fetal development by interacting with a multitude of receptors (e.g., membrane receptors, neurotransmitters).
1.1) Sources and modes of exposure.
The sources and modes of exposure are multiple. Endocrine disruptors indeed abound in nonorganic foods-because of pesticide residues and other agrotoxics that pervade even homes in rural areas, as noted -and everyday goods.
From cosmetics to textiles and clothing(ISS, 2021), MOCAs (food contact materials and objects) and various plastic items. Among the most prevalent and dangerous endocrine disruptors are:
– pesticides, herbicides, fungicides and their
cocktails
. Ex. chlorpyrifos, diethylstilbestrol (DES), DDT,
– plastics and plasticizers. E.g. bisphenol(BPA), phthalates,
– industrial by-products. E.g., polychlorinated biphenyls (PCBs), dioxins, polybrominated biphenyls (PBBs). (2)
1.2) Food exposure
Foods, especially those of plant origin, are rich in micronutrients and bioactive substances with health-promoting properties (e.g., polyphenols and phenolic compounds). However, endocrine disruptors can remain there in the form of contaminants, especially on foodstuffs arriving from countries where controls are lacking, as seen in the case of the pesticide ethylene oxide.
Health risks are associated with non-organic foods. In particular:
– fruits and vegetables. Pesticide residues, polycyclic aromatic hydrocarbons (PAHs), heavy metals, and bisphenol A are some examples of endocrine disruptors that are associated with increased risk of cancer and development of gestational diabetes,
– eggs, meat, and fish can themselves be contaminated with PAHs, hexachlorobenzene (HCB), polychlorinated naphthalene (PCN), heavy metals, and flame retardants. As well as from pesticide residues used in animal feed. (3)
1.3) Non-organic teas, herbal teas and nutraceuticals, packaging
The paradox concerns foods whose consumption is often motivated by health expectations such as teas and herbal teas, as well as products designated as ‘nutraceuticals.’ Tea and herbal teas, as shown in the recent tests of 60 million de consommateurs, are among the products at greatest risk for pesticide residues even not allowed in the EU due to public health requirements. Same risks for nutraceutical products based on plant extracts. Unless, of course, they are organically certified products.
Packaging is another trouble. BPA and phthalates are major endocrine disruptors that can migrate into food, and their effect is enhanced by heavy metals. Lockdowns in recent years have accelerated the growth of food delivery and thus of the use of plastic containers, which, as a result of improper use (e.g., microwaves) has caused high exposures to these contaminants. (3)
2) Impact of endocrine disruptors on children’s neurobehavioral development.
The SELMA cohort study was the starting point for investigating possible correlations between fetal exposure to endocrine disruptors and abnormalities in children’s neurobehavioral development.
2.1) The research
Delay in speech development has been identified as the first marker of developmental deficits, as the same cohort study showed a correlation between delays in speech at 30 months and problems in cognitive function at 7 years.
The researchers thus conducted an analysis of phthalate, BPA, triclosane and perfluoro alkyl substances(PFAS) concentrations in 1,874 children. Identifying a specific mix of endocrine disruptors(Mix N) as responsible for the development of language delays in children.
2.2) In vitro and in vivo studies.
The properties of the mixture of endocrine disruptors, were then analyzed by special studies, in vitro and in vivo:
– Fetal stem cells at 11 and 19 months gestation were used for in vitro evaluation of Mix N. Which activated numerous genes imputed to the development of neurocognitive deficits, with influence on several hormonal pathways. The cocktail of endocrine disruptors proved to be even more dangerous than BPA alone, which was used as a comparison substance,
– In contrast, in vivo studies have identified the ability of Mix N to alter thyroid hormone (TH) activity, with a similar comparison to BPA. In addition, a negative effect on locomotion ability was observed, consistent with the effects seen on TH.
2.3) Conclusions
The application of a system of equivalence allowed for an overall analysis of the results that emerged in the two types of studies in order to make appropriate considerations on the starting question. Is there a correlation between pregnant women’s exposure to endocrine disruptors and their children’s neurobehavioral developmental delays and/or impairments?
The researchers’ findings unfortunately confirm the worst-case scenario. With the added concern related to the fact that as many as 54 percent of the women within the cohort had sufficient levels of endocrine disruptors in their bodies to instigate concerns about the future neurological and behavioral development of their offspring.
3) Risk analysis, new methods wanted
A serious gap exists to date on analytical methods for detecting endocrine disruptors. The most recent OECD guidelines are not comprehensive for all metabolic pathways, only the major ones. And several methods now in use, while scientifically validated, are not considered for issuance and renewal of authorization of substances with endocrine disrupting properties. (4)
3.1) Adagio in Brussels
The European Commission-after repeated reminders from the General Court and the EU Parliament, as well as the scientific community-has begun to introduce some changes to reg. EC 1107/2009 (phytosanitary) and reg. EU 528/2012 (biocidal products), for scientific requirements regarding the identification of endocrine disruptors in these products.
In Brussels and Strasbourg, paradoxically, the need to reduce in vivo testing on vertebrate animals as much as possible-and thus to identify alternative strategies and methods, especially in vitro (5)-seems even to take priority over the need to effectively protect the public health of humans. It is worth noting, among other things, the flaws in the EU database precisely on dietary endocrine disruptors. And inaction on microplastics, to which infants are particularly exposed (Zhang et al., 2021).
3.2) Pepper in France
Pepper
– the public-private platform for pre-validation of endocrine disruptor testing methods-is being organized in France starting in 2019. Thanks to the initiative of Ineris, Institut national de l’environnement industriel et des risques, a public body under the Ministry of the Environment.
Pepper’s experts are now developing a list of 17 pre-validated methods for submission to stakeholders (civil society, academia and research institutions, industry), the Maison de la Chimie foundation and relevant ministries involved in the national endocrine disruptor strategy. To facilitate replicability in different laboratories and consideration from a regulatory perspective.
4) Interim Conclusions
The hazards associated with endocrine disruptors are serious, and the risks of their exposure through numerous pathways are high. Indeed, these are ubiquitous substances that everyone comes into contact with every day, albeit with significant variations in relation to environment, consumption and lifestyles. As seen in the large EU Human Early-Life Exposome research project, which correlated organic diet with improved cognitive system development in children. (6)
Scientific research is essential to identify and demonstrate the effects of these substances and their cocktails on the body, also having regard to the microbiota (7,8). And it is equally crucial that European institutions effectively follow up on risks that emerge through progress on the various fronts of risk assessment. Adopting unsurpassable limits and not bland ‘recommendations,’ which have already proven to be totally unsuitable.
Dario Dongo and Andrea Adelmo Della Penna
Notes
(1) Nicolò Caporale et al. (2022) From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures. Science 375:735, https://doi.org/10.1126/science.abe8244
(2) Padmanabhan et al. (2021) Praegnatio Perturbatio – Impact of Endocrine-Disrupting Chemicals. Endocrine Reviews 42(3):295-353, https://doi.org/10.1210/endrev/bnaa035
(3) Mukherjee et al. (2021) Endocrine Disruptors – ‘Food’ for Thought. Proc. Zool. Soc. 74/4):432-442, https://doi.org/10.1007/s12595-021-00414-1
(4) Grignard et al. (2022) Regulatory Testing for Endocrine Disruptors; Need for Validated Methods and Integrated Approaches. Front. Toxicol. 3:821736, https://doi.org/10.3389/ftox.2021.821736
(5) Reg. EU 2017/2100 (criteria for determination of endocrine disrupting properties), reg. EU 2018/605 (phytosanitary), reg. EU 2021/525 (biocidal products)
(6) Elena Bosani. Organic diet and few pollutants to protect children’s cognitive system. The study Human Early-Life Exposome. FT (Food Times). 7/23/21, https://www.greatitalianfoodtrade.it/salute/dieta-bio-e-pochi-inquinanti-per-proteggere-il-sistema-cognitivo-dei-bambini-lo-studio-human-early-life-exposome
(7) Dario Dongo. Pesticides and the microbiome, interview with Prof. Alberto Mantovani. FT (Food Times). 5/22/19, https://www.greatitalianfoodtrade.it/sicurezza/pesticidi-e-microbioma-intervista-al-prof-alberto-mantovani
(8) Alberto Mantovani. Toxic cocktails? Risk assessment of multiple exposures to endocrine disruptors. FT (Food Times). 9/28/20, https://www.greatitalianfoodtrade.it/sicurezza/cocktail-tossici-valutazione-del-rischio-delle-esposizioni-multiple-a-interferenti-endocrini
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.
