Summary: Prenatal exposure to complex mixtures of endocrine-disrupting chemicals can alter brain development and is associated with delayed language acquisition in young children.
Source: Uppsala University
Researchers combining population data with laboratory experiments have demonstrated that real-life mixtures of endocrine-disrupting chemicals (EDCs) encountered during pregnancy can affect early brain development and language outcomes in children.
Using a novel integrative approach, the team found that experimentally defined levels of concern for these mixtures applied to a large proportion of pregnant women—up to 54 percent in the Swedish SELMA cohort. The study highlights a limitation of current regulatory practice, which assesses chemicals one by one, and argues for risk assessment methods that account for combined exposures.
There is growing evidence that many everyday environmental contaminants—particularly chemical substances used in plastics and consumer goods—can act as endocrine disruptors. These compounds enter the human body through food, water and air, and although individual compounds are often present at concentrations below existing safety thresholds, their combined action in mixtures can still pose developmental risks.
To address this gap, the EU-funded EDC-MixRisk project developed and tested an alternative strategy: identify real-life mixtures measured in pregnant women and evaluate those same mixtures across epidemiological analyses and experimental models. This combined strategy links human population observations with mechanistic laboratory work to better estimate health risks from mixed chemical exposures.
“The strength of this comprehensive project lies in connecting population findings with experimental studies and using those results to inform new methods for assessing risks from chemical mixtures,” says Carl-Gustaf Bornehag, Professor at Karlstad University and Project Manager of the SELMA study, who led the epidemiological component of EDC-MixRisk.
The study proceeded in three coordinated phases:
• First, researchers identified a specific mixture of chemicals present in the blood and urine of pregnant women in the Swedish SELMA cohort that was statistically associated with delayed language development at 30 months. This mixture included several phthalates, bisphenol A (BPA) and perfluorinated compounds.
• Second, laboratory experiments using human-relevant exposure levels revealed molecular targets and pathways through which the mixture disrupted endocrine signaling and the regulation of genes implicated in autism spectrum disorders and intellectual disability.
• Third, the experimental results were translated into improved principles for assessing the neurodevelopmental risk of chemical mixtures, suggesting how regulatory approaches could be updated to reflect combined exposures.
“It is notable that results from the experimental systems mirrored the epidemiological observations, and that effects were detectable at exposure levels typical for humans,” says Joëlle Rüegg, Professor of Environmental Toxicology at Uppsala University and Vice Coordinator of EDC-MixRisk.
Human brain organoids—advanced three-dimensional cell cultures that recapitulate key stages of human brain development—were used to probe how the mixture affects neural tissue at developmental time points equivalent to pregnancy. These in vitro models, together with animal studies and computational analyses, showed that the mixture can interfere with gene networks linked to autism and impede neuronal differentiation. Importantly, the mixture altered thyroid hormone signaling in neural tissue, a critical hormonal pathway for early brain development.
“Thyroid hormone is essential during early pregnancy for normal brain growth and maturation. Disruption of thyroid-related pathways by chemical mixtures provides a plausible mechanism for the observed association with language delay,” explains Barbara Demeneix, Professor of Physiology and Endocrinology at the Natural History Museum in Paris, who contributed to the mechanistic in vivo studies.
By integrating human cohort data with laboratory findings, the team estimated that 54 percent of children in the SELMA cohort were prenatally exposed to chemical mixtures at levels above those predicted to affect neurodevelopment, and these children showed an increased risk of delayed language at 30 months. This elevated risk was not apparent when applying current safety limits that consider individual chemicals in isolation.
The work reflects a collaborative effort across multiple universities and research centres in Sweden, Italy, France, Finland, Germany, Greece and the United States, combining epidemiology, molecular biology, toxicology, computational modeling and developmental neuroscience. The findings support the need to revise risk assessment frameworks so they reliably capture the effects of combined, low-level exposures that are typical in everyday life.
About this neuroscience and brain development research news
Author: Linda Koffmar
Source: Uppsala University
Contact: Linda Koffmar – Uppsala University
Image: The image is in the public domain
Original Research: The findings will appear in Science