How do complex mixtures of chemicals impact our health? Recent studies have demonstrated that when chemicals exist in complex mixtures and in the same concentrations found in humans, they interact with one another. This means that, even if each chemical’s concentration is below the threshold needed to provoke an effect on its own, their combination can still produce a cumulative neurotoxic impact.
Today, chemicals are everywhere; they enter our bodies through the food we eat, the air we breathe, and our skin. But what effect do these complex mixtures of chemicals have on our health? In a study published in the journal Science, researchers from the Helmholtz Centre for Environmental Research (UFZ) discovered that these chemical mixtures, at human-like concentration ratios, work together. Even when the individual substances are present in concentrations below their effect threshold, they can still lead to a cumulative neurotoxic effect. The researchers based their analysis on blood samples from pregnant women participating in the LiNA mother-child study, which has been ongoing at UFZ since 2006.
“In our daily lives, we come into contact with a multitude of chemicals that accumulate in our bodies over time. These complex mixtures can impact our bodily functions and overall health,” stated Prof. Beate Escher, who heads the UFZ Department of Cell Toxicology and teaches at the University of Tübingen. “Research has shown that low concentrations of chemicals can have additive effects in environmental settings. However, we have not thoroughly explored whether this also applies within the human body, which is the focus of our study.”
The study utilized over 600 blood samples from pregnant women involved in the Leipzig mother-child cohort LiNA, coordinated by UFZ since 2006. The research team first examined these samples to identify the chemical mixtures present. “We aimed to determine which chemicals were in the blood plasma and at what concentrations. A two-step extraction process allowed us to isolate a wide variety of chemical mixtures,” explained Georg Braun, a postdoctoral researcher and lead author of the study. “Using mass spectrometry, we sought to identify 1,000 different chemicals that are commonly found in the environment and could potentially affect human health. We successfully quantified around 300 of these chemicals across multiple plasma samples,” he added. This analysis yielded insights into the composition and concentration ratios of the chemical mixtures in the 600 individual plasma samples.
Researchers employed a prediction model to assess the neurotoxic effects of the identified chemical mixtures. To validate these predictions experimentally, they utilized a well-established biological assay involving human cells, which reveals neurotoxic effects. “We analyzed individual chemicals and approximately 80 different self-created mixtures at realistic concentration ratios. The plasma extracts were also tested,” Braun noted. The findings were compelling. “The experimental results corroborated the predictions of our model: the impacts of the chemicals indeed accumulate in complex mixtures,” stated environmental toxicologist Beate Escher. “Even when the individual neurotoxic chemicals are at such low concentrations that they fall below the effect threshold, complex mixtures with multiple other chemicals still affect nerve-like cells.”
But what do these results imply? “Our study demonstrates for the first time that the knowledge regarding the effects of chemical mixtures in the environment is also applicable to humans,” Escher said. “It’s crucial that we reevaluate our approach to risk assessment. Relying solely on indicator substances is insufficient. Moving forward, we must adopt a perspective that considers chemical mixtures.” Dr. Gunda Herberth, an environmental immunologist at UFZ and head of the LiNA study, added, “It’s increasingly evident that many health issues, including allergies, immune disorders, obesity, and nervous system development complications, are associated with chemical exposure during pregnancy or early childhood.”
The methodology established in this study — extracting chemical mixtures from human samples and characterizing these mixtures through chemical analysis in conjunction with cell-based assays — paves the way for new avenues in investigating how complex chemical mixtures affect human health. In future projects, the researchers intend to refine their testing methods and explore the effects of these chemical mixtures on other health-related outcomes, such as immunotoxicity. Moreover, they aim to uncover potential associations between chemical exposure and developmental disorders in children. As part of the German Centre for Child and Adolescent Health, a national research network encompassing university hospitals and other research entities, the UFZ team will collaborate with experts in medicine and epidemiology to implement these effect-based human biomonitoring techniques.
