Neurotoxic effects are piling up, new research shows

Chemicals are ubiquitous these days. They enter our body through food, air or the skin. But how do these complex mixtures of chemicals affect our health? In a new study, a research team from the Helmholtz Center for Environmental Research (UFZ) has shown that chemicals that occur in complex mixtures and in concentration ratios such as those found in humans work 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 research, they used blood samples from pregnant women from the LiNA mother-child study (lifestyle and environmental factors and their influence on the allergy risk in newborns), which has been running at the UFZ since 2006.

The research is published in the news Science.

“In our daily lives we are exposed to a wide variety of chemicals that are distributed and accumulate in our body. These are very complex mixtures that can affect body 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 increase 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 exactly where our research comes from.”

The extensive research work was based on more than 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 analyzed the individual mixtures of chemicals present in these samples.

“We wanted to know which chemicals were 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 analysis, we looked for a thousand different chemicals that we knew could exist in the environment, could potentially be ingested by humans and could be relevant to adverse human health effects. Of these, we were able to quantify approximately 300 chemicals in different 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.

The researchers used a prediction model to calculate the neurotoxic effects of the chemical mixtures. To experimentally test the predictions of the mixture effects, they used an established cellular bioassay based on human cells that indicates neurotoxic effects.

“We analyzed individual chemicals and about 80 different self-produced chemical mixtures in realistic concentration ratios. The extracts of the plasma samples were also tested,” says Braun. The results were clear.

“The laboratory experiments confirmed the predictions from the model: the effects of the chemicals accumulate in complex mixtures,” says environmental toxicologist Escher. “Even if the individual concentrations of neurotoxic chemicals are so low that they are all below the effect threshold, there is still an effect on nervous cells in complex mixtures with many other chemicals.”

But what exactly do these results mean?

“With our research 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. “It is therefore imperative that we reconsider risk assessment. Indicator substances alone are far from sufficient. In the future, we must learn to think in terms of mixtures.”

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 exposure to chemicals in utero or in early childhood.”

The testing method presented in this study – the extraction of chemical mixtures from human samples and their characterization using chemical analysis in combination with cell-based bioassay systems – opens new possibilities for investigating the effects of complex chemical mixtures on human health.

In future research projects, the scientists want to refine their testing method and investigate the effects of chemical mixtures on other health-relevant endpoints such as immunotoxicity. In addition, they want to discover possible links between exposure to chemical substances and the development of developmental disorders in children.

As members of the German Center for the Health of Children and Adolescents, a Germany-wide research network of university hospitals, universities and non-university research institutions, the UFZ researchers will in the future collaborate with numerous experts from medicine and epidemiology to develop these methods of effect-based human biomonitoring into practice.