PhD Defence by Yanying Ma

Principal supervisor:

• Prof. Anne Marie Vinggaard

Co-supervisor:

• Postdoc Maria João Valente
• Postdoc Claudia Andrea Torero Gutierrez

Examiners:

• Senior Researcher, Morten Poulsen, DTU FOOD
• Prof. Wibke Busch, UFZ, DE
• Prof. Lisbeth E. Knudsen, KU, DK

Chairperson at defence:

• Ass. prof. Martin Frederik Laursen, DTU Food

Resume
Humans are exposed to countless chemicals every day. They come from the food we eat, the water we drink, the air we breathe, and the personal care products we use. Safety regulations usually evaluate these chemicals one at a time, asking whether each substance is harmful on its own. However, in real life, our bodies are exposed to these chemicals simultaneously. Thus, the risks that may come from these simultaneous exposures are not captured by single-chemical safety limits, which is of particular concern during pregnancy, when the developing fetus is vulnerable.

This PhD project explores how non-animal methods can help us better understand the health effects of chemical mixtures. By using in vitro bioassays and in silico approaches, the research focuses on how mixtures of chemicals can affect the hormone system and early human development.

In one part of the work, real-life samples collected from the environment, water and food items, as well as human blood and breast milk, were tested using cell-based assays that respond to hormonal activity. The results showed that mixtures from very different sources including human breast milk and cord blood can influence hormone signalling, highlighting that combined chemical exposure is a widespread issue.

Another part of the thesis examined mixtures of commonly used insecticides, the pyrethroids, using human-induced pluripotent stem cells that can develop into beating heart muscle cells for embryotoxicity testing. Even at low levels, these chemicals interfered with key steps in early development of the embryo. When combined, their effects followed predictable patterns, further supporting that chemical mixtures usually act additively.

Finally, we investigated the combined exposure to chemicals that interfere with male hormone signalling during pregnancy using human biomonitoring exposure data and in vitro hazard data. Results highlighted that human risk was driven by around 5 chemicals and that exposure levels were more important for driving the risk than the individual potency of the chemicals.

Overall, this work highlights the importance of considering the complex chemical environment we all live in. At the same time, the thesis contributes to the ongoing shift towards more human-relevant and animal-free approaches in toxicology, helping to improve how chemical risks are assessed in real-life conditions.

A copy of the PhD thesis is available for reading at the department.