Risk assessment of mixed exposures – takeaways from the 5th Eximious Symposium

The fifth EXIMIOUS Symposium was held online on Thursday, 28 September 2023, attracting 60 participants. Entitled “Risk assessment of mixed exposures: particles, carcinogens, and EU policies”, this event focused on the topic of combined exposure and featured three talks by Prof. Ulla Vogel (National Research Centre for the Working Environment), Prof. Tiina Santonen (Finnish Institute of Occupational Health), and Dr. Violaine Verougstraete (Eurometaux).

If you missed the event, read on for our key takeaways from the symposium. You can also watch the full video recording on the EXIMIOUS YouTube channel.

After a brief introduction to the EXIMIOUS project and the symposium by EXIMIOUS coordinator Prof. Peter Hoet (KU Leuven), the presentations kicked off with a talk by EXIMIOUS researcher Prof. Ulla Vogel from the National Research Centre for the Working Environment in Denmark.

Prof. Vogel’s research shows that inhalation of particles is a risk factor for the development of cardiovascular disease. More specifically, the key mechanism at work involves induction of the acute phase response in the lung and liver. Acute phase response is a systemic response to inflammatory states that can be caused by different factors. The acute phase response is causally related to atherosclerosis. In this case, it is triggered by the particles retained in the lung. This mechanism has been shown to apply to more than 100 different particles and nanomaterials tested. Prof. Vogel also shows that particle size matters when it comes to predicting the health effects of inhaling particles: the acute phase response is predicted by the total surface area of the particles retained in the lung.

The take-home message? Cardiovascular disease is a preventable particle-induced occupational disease, and there is a huge preventive potential. The association with particle-induced acute phase response may help us establish safe exposure limits in the future, for both single and mixed exposure.

“There is a huge preventive potential here, and there is evidence that reduction of particle exposure will reduce cardiovascular mortality.”

Prof. Ulla Vogel on cardiovascular disease​

From particles we moved to the risk assessment of combined exposure to carcinogenic metals, the topic of research conducted by Prof. Tiina Santonen and colleagues in the HBM4EU project. As Prof. Santonen explains, when considering the combined effects of exposure to multiple substances, an additive effect is usually assumed if it involves the same target organ and a similar mode of action. However, sometimes the given substances have different dose responses, as illustrated by an HBM4EU case study on hexavalent chromium, nickel, and PAHs using air monitoring. Nickel’s dose response, i.e. the relationship between the level of exposure and the magnitude of the risk effects, is different from that of the other two metals. For this reason, this mode of calculation cannot be considered as fully representative. In one of Prof. Santonen’s ongoing studies, biomonitoring data is taken into account in addition to air monitoring data. Measuring exposure levels in the body, e.g. in urine, means that the impact of respiratory protection worn by workers is also considered. Interestingly, the risk assessment picture resulting from this study is quite different from the one from the previous air monitoring study. Future research will further enhance these insights on different approaches to the risk assessment of combined exposure.

“Usually, additivity is assumed in the case of substances which have similar target and similar mode of action, unless there is information on potential synergistic effects.”

Prof. Santonen on  the  general assessment of combined exposure​

The final talk took yet another perspective on the topic of mixed exposure: Adding the “regulatory spices on the science” in her own words, Dr. Violaine Verougstraete looked at how the toxicological challenge of mixed exposure will be dealt with in EU policy, in the new REACH legislation in particular.

Over the past decades, there has been a growing recognition that exposure to a cocktail of chemicals may also generate risks that are not captured by a substance-by-substance risk assessment. REACH 2.0, currently under revision, will address the challenge of combined exposure by introducing a Mixture Allocation Factor (MAF). This is a default numerical value which adds an uncertainty factor to the risk calculation. As Dr. Verougstraete explained, this can be seen as a kind of shortcut, simplifying the assessment, but it is also very much a pragmatic tool which we have to rely on when we lack most of the data needed to make a more refined assessment.

For industry, this means that demonstrating the safety of their products will become more challenging with the required application of the MAF. In this context, Dr. Verougstraete briefly presented the scientific programme launched by Eurometaux to tackle these issues in the metals sector.

While the MAF in REACH 2.0 will be a practical basis for decision-making and risk management, she concludes, there are still “a lot of things that are still subject to the scientific community to see whether that concept is actually a valid one and whether we have to adapt it to really provide for safe assessments of substances in the environment.”

“There are […] a lot of things that are still subject to the scientific community to see whether that concept is actually a valid one and whether we have to adapt it to really provide for safe assessments of substances in the environment.”

Dr. Verougstraete on the Mixture Allocation Factor​

As the three lectures in this symposium have highlighted, the risk assessment of mixed exposures involves many interesting challenges, for scientists, regulators, and industry, not all of which we can solve today. At the same time, it has been encouraging and exciting to see the promising latest scientific progress presented by our three guest speakers. It is evident that their research will have a great impact on the environment and society we live in. The EXIMIOUS consortium would like to thank the speakers for sharing their latest work and valuable insights with the audience.

We are looking forward to bringing you more exposome research highlights at the next EXIMIOUS Symposium in 2024, so stay tuned! If you’d like to receive an invitation to the next symposia you can also subscribe to our events notifications here.

October 25, 2023