PhD Defence by Mikala Melchiors

Principal supervisor:

• Professor Terje Svingen

Co-supervisor:

• Senior Researcher Anna Kjerstine Rosenmai

Examiners:

• Senior Scientist Gitte Ravn-Haren, DTU Food
• Professor Majorie van Duursen, Vrije Universiteit Amsterdam
• Associate Professor Line Mathiesen, University of Copenhagen

Chairperson at defence:

• Associate Professor Hanna Katarina Lilith Johansson

Resume
Endocrine disrupting chemicals (EDCs) are substances that interfere with the hormone system, potentially contributing to health issues such as developmental, reproductive, and metabolic disorders. From a regulatory perspective, identifying an EDC requires showing a link between how the chemical acts in the body and the harmful effects it causes. Traditionally, animal testing has been used to study these effects, but there is a growing push to replace such methods with more ethical and efficient alternatives.

This PhD project explores how modern toxicology can help predict endocrine disruption without relying on animal testing, including in vitro and in silico approaches. The project combined simple cell-based assays, more advanced tissue models, and a targeted animal study to evaluate how simpler models could predict real biological effects. We used chlorinated paraffins (CPs) - a group of industrial chemicals - as a case study, due to increased concern regarding their endocrine activity.

While several CPs showed potential endocrine disrupting effects in vitro, the follow-up animal study revealed limited effects, highlighting a key challenge: simple laboratory tests can detect chemical interactions with hormones, but they do not always reflect what happens in a living organism. To improve predictivity, the project incorporated advanced models that better mimic human tissue. Our findings suggest that CPs may not act directly on the thyroid gland, but could affect hormone levels indirectly through other systems, such as the liver.

Overall, the research supports the shift toward non-animal testing strategies, while emphasizing the need for integrated approaches that combine biological insight with an understanding of how chemicals behave in the body. This work contributes to the development of more accurate and human-relevant tools for chemical safety assessment.

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