Summary: A new study has found that even low concentrations of chemicals, when mixed, can have cumulative neurotoxic effects on human cells. Using blood samples from a cohort of pregnant women, researchers identified and analyzed the presence of over 300 chemicals.
Testing these chemical mixtures revealed that they could impact nerve-like cells, supporting the concept that the combined effects of chemicals add up in complex bodily mixtures. This research suggests a need for revising chemical risk assessment, focusing on combined exposures instead of isolated chemicals.
Key Facts:
- Study found that low-level chemical mixtures can have cumulative neurotoxic effects.
- Over 300 chemicals were quantified in blood samples from pregnant women.
- Findings call for updated chemical risk assessments to consider mixture effects.
“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 valuable insights into the composition and concentration ratios of the chemical mixtures present in the 600 individual plasma samples.
The researchers utilized a prediction model to calculate the neurotoxic effects of the chemical mixtures. To experimentally support the model’s predictions, they employed 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 laboratory experiments confirmed the predictions from the model: the effects of the chemicals add up in complex mixtures.
“Even if the individual concentrations of neurotoxic chemicals are sufficiently low to be considered below the effect threshold, they still impact nerve-like cells when mixed with other chemicals,” explains environmental toxicologist Beate Escher.
What do these important results imply for public health?
“With our study, we are able to demonstrate for the first time that what is already known about the effects of chemical mixtures in the environment applies also to humans,” she continues. “It is therefore imperative that we rethink risk assessment. Indicator substances alone are far from sufficient. Moving forward, we must learn to consider mixtures.”
UFZ environmental immunologist Dr. Gunda Herberth, head of the LiNA study, reinforces this point: “An increasing body of evidence suggests that many diseases, including allergies, immune system disorders, obesity, and developmental issues, are linked to chemical exposure in the womb or early childhood.”
The test method presented in this study—extracting chemical mixtures from human samples and characterizing them using chemical analysis and cell-based biotest systems—opens new avenues for researching the effects of complex chemical mixtures on human health.
In future projects, the scientists aim to refine their testing methods and investigate how chemical mixtures impact other health-relevant endpoints, such as immunotoxicity. They also wish to explore potential links between chemical exposure and the emergence of developmental disorders in children.
As members of the German Centre for Child and Adolescent Health, a national research network of university hospitals and research institutions, the UFZ researchers are committed to collaborating with experts in medicine and epidemiology to implement these methods of effect-based human biomonitoring practically.
About this environmental neuroscience research news
Original Research: Open access.
“Neurotoxic mixture effects of chemicals extracted from blood of pregnant women” by Beate Escher et al. Science
Abstract:
Neurotoxic mixture effects of chemicals extracted from blood of pregnant women
Human biomonitoring studies typically capture only a small and unknown fraction of the entire chemical universe. We combined chemical analysis with a high-throughput in vitro assay for neurotoxicity to capture complex mixtures of organic chemicals in blood. Plasma samples of 624 pregnant women from the German LiNA cohort were extracted with a nonselective extraction method for organic chemicals. 294 of >1000 target analytes were detected and quantified. Many of the detected chemicals as well as the whole extracts interfered with neurite development. Experimental testing of simulated complex mixtures of detected chemicals in the neurotoxicity assay confirmed additive mixture effects at concentrations less than individual chemicals’ effect thresholds. The use of high-throughput target screening combined with bioassays has the potential to improve human biomonitoring and provide a new approach to including mixture effects in epidemiological studies.