Hunting Hidden Dangers

We live our lives surrounded by potentially harmful chemicals that are used for everything from washing our hands to building cars. As a one-off, they may be harmless, but some of these chemicals in the environment eventually accumulate in humans and can cause adverse health effects. Indeed, the latest statistics indicate that toxic compound exposure may be the leading cause of human morbidity and mortality in both the developing and developed world (1). However, the threat from toxic chemicals has not been sufficiently characterized. Not only is health data available on a very limited number of chemicals, but the important role of combined exposures to multiple chemicals has not been systematically studied.

Chemical exposure studies typically use targeted methods, such as gas or liquid chromatography combined with mass spectrometry, so most of the compounds are not even measured. Lists of target compounds largely consist of those with known toxicity, such as PCBs, brominated flame retardants, pesticides, and so on. However, our chemical exposure from food packing materials, cosmetics and other everyday products are much higher. Most of the compounds in these products have little or no toxicity in themselves, but the toxicity of combined exposure may be significantly higher.

The non-targeted methods applied in areas such as metabolomics are not sensitive enough for use in exposure profiling because of the low levels of many potentially toxic chemicals. Another challenge in exposome studies is the need to measure at more than a single time point to fully understand whole exposure, especially for chemicals with a short biological half-life. In any case, combining metabolomics with exposure analysis allows us to link chemical contact with specific biological changes – and thus link exposure to health outcomes. And even though it is impossible to measure all exposure all the time, the biological responses of past exposure represent a level of memory that reduces the need to capture historical exposure data.

It is obvious that advanced analytical methods are needed for exposome studies, including both GC and LC combined with high-resolution mass spectrometers. The key challenge is to find methods sensitive enough to both characterize and identify toxic compounds at low levels. As the number of chemicals that can be found in the human body is huge, it is critical to identify those compounds that are drivers of adverse effects. A very useful approach is effect-directed analysis, using specific fractionation procedures and in vitro functional assays for detection of the toxic fractions. Moreover, analyzing the metabolic profiles of the cell lines tested may also allow identification of specific metabolic biomarkers of even low-level toxicity. We are currently working with this type of workflow, in close collaboration with toxicologists and bioinformaticians. Currently, the identification of unknown compounds – both metabolic markers and environmental chemicals – is the most time-consuming and challenging task, typically requiring parallel mass spectrometry methods.

Exposome studies allow me to combine two research areas that deeply interest me, namely environmental research and metabolomics. Analytical methodologies play a starring role in this research, which gives me, as an analytical chemist, many interesting challenges to work with. However, it’s important to remember that novel analytical tools and non-targeted analyses produce a huge amount of data; often, the bottleneck of the analytical workflow is the preprocessing of data and data mining. Thus, one of the biggest priorities for the field must be developing better bioinformatics tools that allow us to fully exploit the data – and ultimately allow us to achieve our goal of improving global health.