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Studying the effects of chemical mixtures on the developing brain – with cells and maths

Studying the effects of chemical mixtures on the developing brain – with cells and maths
Studying the effects of chemical mixtures on the developing brain – with cells and maths
Jun 08 2020

A JRC study shows that the effects of chemical mixtures on the developing brain can be assessed using human cells in vitro combined with mathematical modelling

JRC scientists found that chemicals at non-toxic concentrations combined in mixtures can cause adverse effects in developing human brain cells. The chemical mixtures altered significantly several cellular processes which are known to be indicators of developmental neurotoxicity (DNT), particularly those linked to cognitive deficits in children.

The JRC team exposed human developing brain cells to single chemicals and their mixtures at concentrations found in human samples, mimicking real life exposure.

“We have exposed the cells to single chemicals and chemical mixtures because it is well documented that so called mixture effects can be greater than the effects triggered by the most potent single chemical in a mixture, due to their additive or, in some cases, even synergistic effects” explains Francesca Pistollato, JRC scientist and lead author of the article.

This is potentially a matter of concern because different environmental chemicals have been found together in human biofluids such as breast milk and cord blood. Moreover, the developing brain is highly sensitive to the effects of these chemicals. “We are all exposed to more than one chemical at a time but more vulnerable individuals are pregnant women, infants and children, since these life stages are particularly sensitive to the effects of chemicals” continues Francesca.

After exposing the cells to the mixtures, the scientists evaluated whether key neurodevelopmental processes critical for learning and memory formation were impaired. Mathematical modelling confirmed that the combined effects of chemicals in a mixture can generally be predicted without testing the mixture itself, provided that the individual chemicals have been tested at relevant concentrations. Notably, these effects found in cell-based assays reproduce to a certain extent some autism-like cellular changes that are also observed in the brains of autistic children.

Overall, this study illustrates how mechanistic knowledge of DNT effects, captured as adverse outcome pathways, can guide the design and integration of in vitro methods and mathematical modelling to predict possible adverse effects that may result from exposure to chemical mixtures. It therefore represents a step forward towards more reliable DNT testing for protecting public health. 

Graphical abstract: Effects of chemical mixtures on the developing brain