Analysis of a Swedish study of pregnant mothers and their children has shown that more than half were exposed to unsafe levels of a mixture of endocrine disrupting chemicals (EDCs) associated with language delay. Researchers behind the analysis argue that risk assessments should consider the cumulative effects of such combinations to reflect real-life exposure. Integrating experimental and epidemiological evidence, they propose a methodology that could inform chemical regulations.
EDCs include, among others, chemicals commonly found in plastics such as phthalates and bisphenol-A (BPA). Exposure to EDCs may interfere with hormonal regulation and may cause a variety of health problems. When this exposure occurs early in life, it can cause neurodevelopmental disorders. Exposure to different EDCs may originate from various man-made sources – for example those found in paint, electronics or those present in some personal care and cosmetic products.
These combinations may cause problems even when concentrations of individual substances are very low; however, there is little relevant research to inform risk assessments. In this study researchers drew on the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study – involving 1 874 pregnant women – to identify common EDCs to which mothers and children had been exposed. These included 15 compounds such as phthalates, BPA, triclosan and perfluoroalkyl substances (PFAS).
Through statistical analysis, the researchers detected a particular set of chemicals associated with language delay– an early sign of risk for other neurodevelopmental problems such as cognitive
deficits and neuropsychiatric disorders (such as autism). They replicated this mixture and applied it to four experimental models at concentrations reflecting human exposure. Two models were based on human neural stem cells, including human brain organoids (i.e. miniaturised and simplified 3D versions of an organ produced in vitro) used for the first time in a neurotoxicology context, and two were based on aquatic organisms (Xenopus leavis and Danio rerio)
The models demonstrated that both acute and chronic exposure to the EDC mixture interfered with hormonal pathways and disrupted genes implicated in autism spectrum disorders. In the aquatic models, thyroid function was disrupted and mobility reduced. To validate the effects as being specific to the EDC mixture, the researchers also exposed the four models to a selection of other chemicals including a neutral control, the thyroid hormone T3 and BPA alone (in the same concentration as found in the mixture). These induced different patterns of effects, with BPA alone having a much less pronounced effect than the EDC mixture.
Blood and urine samples showed that nearly all the SELMA participants had been exposed to the combination of EDCs, but at different levels. Based on their experiments and concentrations of EDCs found in the SELMA mothers, the researchers discovered thresholds at which effects occurred in the experimental settings, and were able to estimate what proportion of the participants might be at risk. Children with the highest levels of prenatal (before birth) exposure were three times more likely to experience language delay at 30 months compared to those least exposed, found the researchers. Using a risk assessment framework incorporating a calculated safe threshold, they found that up to 54% of the SELMA children were at risk of increased likelihood of language delay due to prenatal exposure to this combination of EDCs.
Taking mixtures into account in chemical testing, regulation and risk assessment is vital to ensure realistic guidance and control measures, say the researchers, but suitable methods need to be developed. Revealing the gene networks altered by a previously identified EDC combination enabled this study to determine the proportion of a human population that had been exposed at levels of concern. The researchers propose that this methodology could offer a framework for mixture-based risk assessments and inform regulations that consider the combined effects of multiple substances. They recommend that further work prioritises identifying adverse health effects to study in relation to different mixtures in diverse populations.
Fuente: Comisión Europea