I want to open this blog with a proposition: “Everyone should understand the logic behind risk assessment of mixture toxicology, not just toxicologists.” Let’s see if I can convince you throughout the text.
Precisely three months ago, the people living in Dordrecht were horrified of their water. How can they not be? The same water that is used to water their vegetable gardens, and where their children swim in nature, has been contaminated with a cocktail of chemicals called per- and polyfluoroalkyl substances: PFAS has been and is now again becoming media highlight. One member of the group called PFOA is possibly carcinogenic to human, and its level was found to be way higher than what the Dutch RIVM considers as safe. Scary? I bet.
People tend to fear man-made chemicals such as PFAS, because artificial products are perceived to be less safe than what nature offers. But does natural mean safe? If all natural products are safe, I won’t be spending four years on a PhD studying plant toxins that make their way into our food chain. Although these plant toxins are less famous than PFAS, and not as easy to pronounce (I promise I will only mention it once: pyrrolizidine alkaloid N-oxides, there you go), they are also cocktail of chemicals that can cause liver tumor and cancer in the long run. As they are natural plant toxic metabolites found in 3% global flowering plants, they might contaminate crops such as wheat, barley, and even food products such as honey, tea, plant food supplements, salads, herbs and spices.
Imagine that you and I work at the regulatory agency; we are tasked to decide if the maximum level permitted of certain group of chemicals is still safe or must be changed. How do we precisely do that when there are 660 members in that group? On the one hand, adding everything up and assuming they are equally toxic is too conservative because some might be less toxic than the others. On the other hand, taking the “less-toxic” out of the equation might underestimate the real danger. That’s when they hired me to figure out this so-called relative potency for the purpose of risk assessment.
One of the goals of a toxicologist is to figure out whether a certain chemical is safe for most of the human population, and not just for 3-4 individual rats. Yet, testing chemicals directly on human is unethical, and monitoring exposure level often do not give clear link between occurrence, consumption and effects. So, we first built a computer model for rat, validated the model with rat data, built a model for human based on what we have for rat, and lastly a model for a population of human.
My initial task was to obtain a single number of relative potency, say 0.5 or 0.8, when comparing the toxicity of chemical A to chemical B. But science being science, it is full of surprises (which is one of my motivations to keep working in science even after I’m finished with this PhD!). This “single number” turns out to depend on dose, as depending on the dose level you’re looking at, the relative potency changes! My promotor and I certainly didn’t expect that. Not only dose, but the choice of endpoint also matters to the relative potency values. By the time I am writing this blog, I am still working on the extent of effect coming from individual donor – science is always in progress.
Now, coming back to my proposition, I am not saying that everyone should spend a four-years PhD assessing the risks of chemicals in a toxicology lab. It is our job as toxicologists to spread our research findings in a clear and relevant way: to make sure you understand why certain studies matter, and what we have learnt from it. But if you don’t understand how regulatory agency makes their decision (such as whether the water in Dordrecht is safe to swim in again, or whether we can drink certain tea and supplement products as often as we want), there will be no trust in the society and that doesn’t help anybody. Finally, quoting Dr. Angela Bearth from ETH Zurich: ”People should be aware of the risk. People should be knowledgeable and not be misled. People need to be motivated to protect their own health, health of others and the environment.”