Hormone alterations and adverse effects on human health
The interference of chemicals with hormone systems (endocrine disruption) and possible adverse health effects are receiving increasing regulatory, public and media attention. There is a tension between the growing public concern and the level of knowledge acquired so far on the link between exposure to endocrine disruptors and various health outcomes. The strategic planning of the SCAHT research programme with a focus on reproductive toxicology and steroid hormone alterations reflects the growing importance of these research fields and can contribute to improved risk assessment and public health protection.
Human health depends on a well-functioning endocrine system to regulate the release of certain hormones that are essential for functions such as metabolism, growth and development, sleep and mood. Some substances known as endocrine disruptors can alter the function(s) of this hormonal system, thereby increasing the risk of adverse health effects.
There is growing interest in the possible interference of EDCs with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction.
Some EDCs occur naturally, while synthetic varieties can be found in industrial production, consumer and personal care products, cosmetics and household items, as well as additives or contaminants in food such as pesticides and environmental pollutants. Human exposure can occur via the ingestion of food, dust and water, inhalation of gases and particles in the air, and skin contact.
The 2025 – 2028 SCAHT research programme supports core projects looking at steroid alteration and male fertility, occupational exposure to endocrine disruptors, and xenobiotics disrupting the corticosteroid-androgen balance.
P1 – CASA – Chemicals Altering Steroid Homone Action
We are daily exposed to hundreds of xenobiotics (environmental pollutants, industrial and occupationally relevant chemicals, body care products, food additives, supplements, recreational drugs, pharmaceuticals) that may contribute to the development and progression of diseases. Steroids essentially regulate endocrine, metabolic and immune functions, and their impaired actions are contributing to several major diseases. Thus, it is crucial to identify hazardous substances that can disrupt steroid hormone action and understand the underlying mechanisms.
This project focusses on generating experimental data that can serve as a basis to start filling existing knowledge gaps and to help establishing regulatory test systems for the characterization of EDCs. The currently available regulatory tests for EDCs mainly focus on effects on estrogen, androgen, and thyroid receptor signaling, and on sex steroid production. Therefore, we aim to address a knowledge gap and investigate whether such chemicals interfere with glucocorticoid and mineralocorticoid hormone action, in the context of immune and cardio-metabolic diseases, or whether they alter adrenal and/or gonadal steroidogenesis and might contribute to steroid modulated diseases. These represent so far neglected areas of research on endocrine active substances. For this purpose, we aim to develop and apply computational methods (WP1, led by Martin Smiesko, Uni Basel), enzyme- and cell-based models (WP2, led by Alex Odermatt, Uni Basel), steroid biosynthesis models (WP3, led by Jamal Bouitbir, Uni Basel), animal models (WP4, led by Claudia Cavelti-Weder, Uni Hospital Zürich), and analytical methods (led by Serge Rudaz, Isabel Meister and Julien Boccard). Furthermore, we aim to test certain steroid ratios as potential biomarkers for whether they can provide information on altered activities of specific enzymes and/or receptors by analyzing samples from exposed animals and/or humans. In our project, we will focus on chemicals that are also of interest for the regulators such as phthalates and bisphenol-A and their derivatives and substitutes, parabens, UV-filters, per- and polyfluorinated alkylates substances (PFAS), food additives and food contact materials, and other chemicals contained in body care and household products, and pesticides and fungicides.
P2 – Establish a Panel of Respiratory and Reproducitive Parameters of Phthalate and Phytocannabinoid Exposures by Inhalation in Women and Men
Inhalation is a route of chemical exposure in domestic, occupational, recreational settings, as well as in both accidental and intentional scenarios. There is growing concern regarding the contribution of inhaled endocrine-disrupting compounds, including some plastic additives and phytocannabinoids, to adverse health effects. These compounds have been associated with respiratory diseases, infertility, and metabolic effects. However, their toxicokinetics and toxicological mechanisms are not well understood to improve chemical risk assessment and public health protection.
This study focuses on plastic additives, unintentionally inhaled through environmental and occupational exposure, and phytocannabinoids, which are inhaled recreationally or medically. Their distinct physicochemical properties and exposure contexts make them relevant models for assessing toxicological responses via inhalation. By analyzing biological fluids (blood, urine, and semen) from exposed volunteers, we aim to characterize the absorption, distribution, metabolism, and elimination of these compounds during short and long exposure time and determine their internal dose—the amount that enters the body and interacts with biological systems. Using an in vitro to in vivo extrapolation approach, we will investigate biological effects of selected plastic additives and phytocannabinoids on lung function, hormone regulation, fertility, and global biochemical phenotype to understand the mode of action.
This research will provide critical insights into inhalation toxicology, enhancing risk assessments and public health strategies to reduce harmful exposures to plastic additives and phytocannabinoids. It will also support regulatory agencies by contributing to national and international efforts in understanding the mechanisms driving adverse health effects.
