Human Biomonitoring, a scientist’s opinion
Interview with Prof. Jana Klánová, professor of environmental chemistry at Masaryk University in Brno, Czech Republic, and a director of the RECETOX Centre of MU.
Establishing exposure-health relationships seems like an enormous task. How are the teams actually going about this?
This is not a task to be completed within one project. And definitely not this project which is primarily focused on building a European platform for a systematic collection of European exposure data that are needed to inform policy makers on how to better protect the health of citizens.
One of three pillars of the project addresses the links between exposures and human health from different angles. It looks for innovative approaches to assess the toxic mixtures and quantify exposures, employs mathematical models to predict behaviour of chemicals in the environmental and human body, investigates mechanisms through which the chemicals affect human health, identifies best biomarkers of potential health risks, and explores a potential of linking environmental data with data from the health registers. However, since we only have limited time and limited resources, these activities are restricted to pre-selected priority chemicals to help with interpretation of data from biomonitoring studies. There is not enough capacity within the project to build a system addressing all current gaps.
This system, however, is needed. The scientists globally are, for instance, trying to join forces and develop the adverse outcome pathway (AOP) model which allows for summing up contributions of multiple chemicals triggering the same mechanisms and predicting their combined health effects. This is a long-term effort where the international collaboration is a must. The same applies also to all the other areas of research described above. There is an on-going discussion on how to establish a sustainable European infrastructure supporting research collaboration and capacity building in this area in the long run. Currently we are preparing a project for such research infrastructure supporting Environment&Health research in Europe for consideration of the European Strategic Forum for research Infrastructures (ESFRI).
Are there any results so far that can be discussed?
Thanks to the rapid technological advances, toxicity testing has been shifting away from the traditional toxicological animal studies and focusing on the alternative (in vitro, in silico) approaches. We contribute to development and implementation of the novel AOPs describing the mechanisms leading from the effect in the cell to the organism and population. This mechanistic knowledge is further verified in the unique set of available human cohort studies providing information on both chemical exposures and health impacts. This is inevitable to improve our understanding of the causality between chemicals and health at the population scale.
So far we have identified, for instance, two AOPs by which Tetrabromobisphenol A (TBBPA), a flame retardant used to substitute previously banned substances, is likely to lead to impaired hearing or cognitive performance in humans through its effects on hormone (thyroid) regulation. For other novel flame retardants, we have for the first identified the time causal mechanisms by which they could decrease fertility in males through affecting a steroid hormone production in testicular cells. We have also established the links between Bisphenol-S and obesity. Bisphenol-S is used in various materials as a substitute for Bisphenol-A which is a known endocrine disruptor. The advanced text mining AOP-helpFinder tool led to the identification of a network of potential targets of bisphenol-S (so called nuclear receptors) that disrupt several lipid metabolism pathways behind the obesity development.
Exposure-health relationships were also studied in the mothers-child cohorts. The populations in the highly air-polluted districts seem to be affected by changes in their DNA with a potential impact on the metabolic processes (e.g. an ability of the organism to cope with PAHs through their transformation and excretion). It was revealed that the air quality can have significant long-lasting impacts including the shortened life expectancy.
What are ‘emerging’ substances, and can you give us some examples that are being examined?
I prefer the term “substances of emerging concern”. They may be truly “emerging” substances, i.e. substances new in the market which were only recently found in the environment and/or human tissues. They can be represented by novel flame retardants or plasticizers. However, sometimes a compound has been around for a long time but its increased production or application, significantly raising environmental or human tissue levels, or newly discovered adverse effects are a cause of an alert.
Can you explain to us the terms ‘exposure biomarkers’ and ‘effect biomarkers’?
They both refer to human tissues. Humans are in contact with various chemicals throughout their life course and/or their occupation. Exposure biomarkers are traces of anthropogenic chemicals or their metabolites found in the human tissues. They indicate that a person was exposed to these chemicals via outdoor and indoor air or dust, food, drinking water, personal care products or other consumer products. Effect markers are various human body parameters, fluctuations of which can indicate changes in the body’s health status. These can be simple parameters such as blood pressure, or levels of various signalling molecules – specific proteins, lipids, or metabolic markers. They can provide an early warning of some unbalances or initial stages of the development of chronic conditions. These two types of biomarkers should be analysed in parallel in order to access causality.