
A study by the Helmholtz Centre for Environmental Research (UFZ) has demonstrated for the first time that chemicals can have neurotoxic effects in the human body even when, individually, they are present in quantities below the threshold of effect. The scientists urgently call for a rethink of risk assessment. Instead of considering individual indicator substances, "we need to think in terms of chemical mixtures," says Prof. Beate Escher, head of the UFZ Department of Cell Toxicology and professor at the University of Tübingen.

Chemicals are ubiquitous today: They enter our bodies through food, air, or our skin. But how do these complex chemical mixtures affect our health? A research team at the Helmholtz Centre for Environmental Research (UFZ) has now demonstrated that chemicals interact in complex mixtures and at concentrations similar to those found in humans. Even when the concentrations of the individual substances were below the effective threshold, the chemicals in the mixture showed a cumulative effect: They damaged the nervous system. For their studies, the scientists used blood samples from pregnant women from the LiNA mother-child study, which has been running at the UFZ since 2006.
"In our everyday lives, we are exposed to a wide variety of chemicals that disperse and accumulate in our bodies. These are highly complex mixtures that can affect bodily functions and our health," says Escher. "Environmental and aquatic studies have shown 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 was based on over 600 blood samples from pregnant women in the Leipzig mother-child cohort LiNA, which has been coordinated by the UFZ since 2006. First, the researchers analyzed the individual chemical mixtures present in the samples. "We wanted to find out which chemicals were contained in the blood plasma and in what concentrations. We used a two-stage extraction method to isolate these different chemical mixtures," says Georg Braun, postdoctoral researcher in Beate Escher's research group and first author of the study. "Using mass spectrometry, we searched for 1.000 different chemicals that we knew could occur in the environment, could potentially be absorbed by humans, and might be relevant to human health. We were able to quantify around 300 of these chemicals in several plasma samples." This provided the researchers with information about the composition and concentration ratios of the chemical mixtures present in the 600 individual plasma samples.
Using a predictive model, the scientists calculated the neurotoxic effects of the chemical mixtures. To experimentally test the predictions of the mixture effects, they used an established cell-based test system from human cells that indicates neurotoxic effects. "We examined individual chemicals as well as around 80 different, self-prepared chemical mixtures in realistic concentration ratios. Extracts from plasma samples were also tested," says Georg Braun. The results were unequivocal. "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 threshold of effect, an effect on nerve-like cells becomes apparent in complex mixtures with many other chemicals."
But what exactly do these results mean? "With our study, we were able to prove for the first time that what is known about the effects of chemical mixtures in the environment also applies to humans," says Escher. UFZ environmental immunologist and head of the LiNA study, Dr. Gunda Herberth, adds: "It is becoming increasingly clear that many diseases such as allergies, immune system disorders, obesity, or nervous system development are linked to chemical exposure in the womb or early childhood."
The testing method presented in this study—the extraction of chemical mixtures from human samples and their characterization using chemical analysis combined with cell-based bioassay systems—opens up new possibilities for investigating the effects of complex chemical mixtures on human health. In future research projects, the scientists plan to refine their testing method and investigate the effects of chemical mixtures on other health-relevant endpoints, such as immunotoxicity. Furthermore, they hope to uncover possible links between chemical exposure and the development of developmental disorders in children.
original publication
Georg Braun, Gunda Herberth, Martin Krauss, Maria König, Niklas Wojtysiak, Ana C. Zenclussen, Beate I. Escher: Neurotoxic mixture effects of chemicals extracted from blood of pregnant women; Science (2024) DOI: 10.1126/science.adq0336
Background
No one knows exactly how many different chemicals are used in the EU. According to the German Federal Environment Agency (UBA), the European Chemicals Agency's (ECHA) Classification and Labelling Regulation (CLP) lists a total of 259.538 substances (as of August 2024). This figure does not include substances for which there is no obligation to register (in particular, substances not subject to REACH registration, provided they are not classified as hazardous under the CLP Regulation).
(REACH = Registration, Evaluation, Authorisation and Restriction of Chemicals. Derived from the English title of the European Chemicals Regulation: Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals. Source: Federal Environment Agency (UBA))
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