CHEM Trust recently sat down with Professor Andreas Kortenkamp from Brunel University London to discuss his recent research on the impact of exposure to chemical mixtures on male fertility. The new study, ‘Combined exposures to bisphenols, polychlorinated dioxins, paracetamol, and phthalates as drivers of deteriorating semen quality’, found that our exposures to mixtures of these chemicals are already at levels that could impact semen quality.
Read more about the study in our recent news story.
What inspired you to do research on chemical mixtures?
When I entered the field of endocrine disruptor research about 25 years ago, I became convinced that the extent of health risks from these chemicals would not be revealed by solely focussing on single chemicals, one by one. We found that in many cases the effects produced by one endocrine disruptor also materialised when we replaced the chemical with fractions of equally effective doses of many other substances. And the more chemicals we combined in such experiments, the lower the doses of each chemical became. We found that this was true even at doses below the thresholds of individual chemicals. We popularised this as the “something from nothing” principle.
What does the outcome of those experiments mean?
The outcome of these experiments means that it is not possible to conclude that chemicals are “safe” below dose thresholds, without considering the entire exposure scenario. In collaboration with Ulla Hass and her team at Denmark’s Technical University, Food Institute, we were later able to demonstrate this principle also in studies with anti-androgenic chemicals in one-generation studies in rats. This was a tremendous break-through. We also showed that these principles apply not only to endocrine disruptors, but to all types of toxicity.
Your research highlights very important issues, what concerns you most?
Our work challenges the predominant focus of chemical regulation on single chemicals. It is a worry that mixture risks may exist even when each chemical in the mixture stays below regulatory limits. These potential risks are simply missed when evaluating chemicals one-by-one. My interest is to translate these insights into concepts for better chemicals regulations that can cope with mixture risks.
What are the main challenges in researching exposure to chemical mixtures?
Mixture risk assessments rely on two types of data as input: We need exposure data about the chemicals to be assessed together, as well as data about their potency in relation to a common adverse effect. These data are often not available, or there are significant gaps. Ideally, we need information about co-exposure to multiple relevant chemicals in the same subject. Such data are as rare as gold dust. Human biomonitoring is just catching up with this challenge, but viable strategies for monitoring multiple chemicals in the same person need to be developed. The problems start with answering the most basic question: What chemicals should be measured together? That is often not clear, and many mixture risk assessments go the easy way by just considering chemicals with very similar structures (e.g. phthalates and nothing else). In addition, for many chemicals, toxicity data are missing, and these data gaps may lead to significant underestimations of risks, or make a meaningful mixture risk assessment impossible.
Why do you think chemical mixtures have been overlooked in chemicals regulations for so long?
The problem has not just been “overlooked”. For too long, it has been actively dismissed by the regulatory establishment. In certain quarters, this continues to this day. The science of mixture toxicology is rather old; the key concepts were developed in the 1920s and 1940s and have found entry into medicine (drug-drug interactions) and into pesticide research (exploiting synergisms in pesticide formulations). By the 1980s, sufficient evidence had accumulated to conclude that mixture effects pose problems in the aquatic environment. But nothing was done, due to inertia, a lack of political will and regulatory instruments.
The regulatory establishment has until recently refused to take the mixture issue seriously, with the argument that it is not necessary, and at the same time very difficult. But addressing mixtures is needed and overdue. Protection is not necessarily afforded by keeping all chemicals below their regulatory limits. Risks can arise when co-exposure is to sufficient numbers of chemicals at sufficiently high levels. The idea that there is automatically sufficient protection at regulatory limits for single chemicals also breaks down when we consider that there are tens of thousands of chemicals in use for which regulatory limits do not exist. The claim that mixture risk assessment is too difficult, can be countered with the recent advances in exposure science which show that there are patterns of mixture exposures, not unmanageable chaos. Thus, mixture risk assessment is both necessary and feasible.
What are your top 3 priorities for change for addressing concerns from mixture effects in EU policies?
First, the European Commission Chemical Strategy for Sustainability (CSS) proposes the introduction of so-called mixture assessment factors (MAF) into REACH. This is a step in the right direction and is to be welcomed. A discussion about the details of implementation has now begun, especially about the size of a MAF. I am concerned that such technical debates might get out of control and further delay implementation. It has taken more than 10 years to get from the 2009 decision of European Council environment ministers in which they encouraged the European Commission to assess mixtures, to the proposals now tabled as part of the CSS. Are we to spend another 10 years arguing about the size of a MAF?
Furthermore, MAFs will help, but much more is required. The legal mandates for assessing mixtures are currently limited to biocides and pesticides. We need specific legal obligations for mixture risk assessment and consideration of combined exposures in all relevant pieces of EU chemical regulation.
Finally, a legal mandate for assessing mixture risks from chemicals across regulatory domains is needed. Chemicals have the nasty habit of reaching our bodies, irrespective of the artificial boundaries of EU regulatory domains. But there is currently no mandate to assess the combined risks from pesticides, biocides, industrial chemicals, food contaminants, medicines, etc. Unless and until this is addressed, people and the environment are essentially unprotected from the risks of co-incidental mixtures.
Read more about chemical mixtures in CHEM Trust’s recent report on this topic, ‘Chemical Cocktails – The neglected threat of toxic mixtures and how to fix it.’