17. October 2024
Effects of chemical mixtures: Neurotoxic effects add up
UFZ study demonstrates for the first time the toxicological relevance of chemical mixtures as they occur in humans

Chemicals are omnipresent today: they enter our bodies through food, air or the skin. But how do these complex mixtures of chemicals affect our health? In a study published in the journal Science, a research team from the Helmholtz Centre for Environmental Research (UFZ) has shown that chemicals that occur in complex mixtures and in concentration ratios as found in humans act together. Even if the concentrations of the individual substances were each below the effect threshold, the chemicals in the mixture showed a cumulative neurotoxic effect. For their investigations, they used blood samples from pregnant women from the LiNA mother-child study (lifestyle and environmental factors and their influence on the newborn allergy risk), which has been running at the UFZ since 2006.

"In our everyday lives, we are exposed to a wide variety of chemicals that are distributed and accumulate in our bodies. These are highly complex mixtures that can affect bodily functions and our health," says Prof Beate Escher, Head of the UFZ Department of Cell Toxicology and Professor at the University of Tübingen. "It is known from environmental and water studies that the effects of chemicals add up when they occur in low concentrations in complex mixtures. Whether this is also the case in the human body has not yet been sufficiently investigated - this is precisely where our study comes in."

The extensive research work was based on over 600 blood samples from pregnant women from the Leipzig mother-child cohort LiNA, which has been coordinated by the UFZ since 2006. The researchers first analysed the individual mixtures of chemicals present in these samples. "We wanted to find out which chemicals were contained in the blood plasma and in what concentrations. We used a two-step extraction process to isolate as diverse chemical mixtures as possible," says Georg Braun, postdoctoral researcher in Beate Escher's working group and first author of the study. "Using mass spectrometry analyses, we searched for 1,000 different chemicals that we knew could occur in the environment, could potentially be ingested by humans and could be relevant for adverse human health effects. Of these, we were able to quantify around 300 chemicals in several plasma samples." This provided the researchers with information on the composition and concentration ratios of the chemical mixtures present in the 600 individual plasma samples.

The researchers used a prediction model to calculate the neurotoxic effects of the chemical mixtures. To test the predictions of the mixture effects experimentally, they used an established cellular bioassay based on human cells that indicates neurotoxic effects. "We analysed individual chemicals as well as around 80 different, self-produced chemical mixtures in realistic concentration ratios. The extracts of the plasma samples were also tested," says Georg Braun. The results were clear. "The laboratory experiments confirmed the predictions from the model: the effects of the chemicals add up in complex mixtures," says environmental toxicologist Beate Escher. "Even if the individual concentrations of neurotoxic chemicals are so low that they are each below the effect threshold, there is still an effect on nerve-like cells in complex mixtures with many other chemicals."

…

Demonstration of the "something from nothing" phenomenon. The in majority low effects of the single chemicals that are found in one sample accumulate to measurable mixture effects.
Photo: UFZ

…