The centre allocates a proportion of its research funding flexibly for short-term projects which represent a meaningful complement to its existing core research areas or support the scientific work in these areas.

For details about current projects see list and descriptions below.

Furthermore, SCAHT was coordinator of the EU-funded project HEROIC and participated as associated partner in the EU-project NanoReg2, receiving funding from the Swiss State Secretariat for Education, Research and Innovation SERI.

AP1 - Inhaled phthalate aerosols for long-term human toxicological studies

Project overview

This project aims at developing new methods for controlled human studies of chronic/sub-chronic inhalation exposure to semi-volatile organic compounds (SVOC) such as phthalates. Currently, no controlled exposure system exists for studying either acute or chronic respiratory effects from inhaling SVOC aerosols in humans. The new method is a specific and controlled aerosol delivery system that is portable and can give precise doses to volunteers over several weeks. This new system can be used in future studies to generate solid human toxicokinetic data from chronic inhalation exposure, which are often omitted in the health risk assessment of SVOCs. The improved risk assessment will account for both ingestion and inhalation routes of exposure.

Project description

The two focal points of the project are to (i) adapt and optimise aerosol delivery systems already available on the market for chronic/sub-chronic delivery of aerosolised SVOCs; and (ii) design a protocol for chronic exposure using this device for one test compound, the phthalate DEHP. This pilot study conducted with the developed aerosol delivery system will generate the first human controlled chronic inhalation exposure data, which is an important complement to the existing exposure data obtained from animal studies.

Partners: Nicole Charriere (Unisanté), Nancy Hopf (Unisanté), Serge Nef (Université de Genève), Rita Rahban (Université de Genève), Guillaume Suarez (Unisanté), David Vernez (Unisanté)

AP2 - Phthalate skin uptake in vitro and in vivo

Project overview

In this pilot study the metabolite composition as well as the internal exposure levels from dermal uptake of phthalates will be studied. This will pave the way for future cohort studies investigating the effects of occupational exposure to different endocrine disrupting agents and will also contribute to the development of new approaches for human biomonitoring.

Project description

Phthalates are widely used as formulating agents or as plasticisers and some of this large family of compounds are known to have endocrine disrupting or anti-androgenic properties. Due to these properties, phthalates, such as di(2-ethylexyl) phthalate (DEHP), have been subject to regulatory scrutiny and are increasingly being replaced by other non-ortho phthalates for which no tolerable daily intakes have been set. There is a clear knowledge gap in how skin permeation contributes to overall body-burden of these non-tested phthalates and this project will contribute to filling this gap.

Partner: Holger Koch (Ruhr University Bochum (IPA))

AP3 - Spatial and temporal trends in semen quality in Switzerland

Project overview

This study examines the temporal and geographical effects that influence sperm quality in Switzerland. Using existing epidemiological data and sophisticated computer tools, the project plans to investigate how sperm quality has deteriorated over the past four decades, while highlighting potential regional disparities within Switzerland.

Project description

A number of epidemiological studies have shown that sperm concentrations have fallen by about 50% over the last five decades in the western world. Epidemiological evidence suggests that this rapid decline may be due to environmental factors, although there are significant gaps in the understanding of the specific factors that influence male reproductive health. This project addresses these issues by applying high-resolution spatial techniques to identify potential underlying causes related to poor semen quality.

Partners: Idris Guessous (Université de Genève, HUG), Stéphane Joost (EPFL, HUG)

AP4 - Evaluation of multi-well electrode arrays for neurotoxicity screening

Project overview

This project addresses the need to develop human methods, more accurate and sensitive than current guidelines to screen for neurotoxicity of compounds, where disruption of the nervous systems’ functionality may occur in absence of biochemical or morphological changes. The project applies advanced 3D cell culturing techniques of induced pluripotent stem cell-derived human neural tissues where deleterious effects on neural network functionality can be assessed using multi-electrode assays (MEA). This state-of-the-art technology has proven to be a new venue to detect neuroactive chemicals that may act through a variety of different toxicity pathways.

Project description

Neurotoxicity data is particularly scarce as only pesticides and high-tonnage production requires neurotoxicity testing for market authorisation. A further problem is that current neurotoxicity test guidelines are based on cost and time-consuming animal experimentation, and primarily focus on biochemical and morphological readouts, whereas, in reality, major impact on the brains function may occur without impacting these endpoints. This project is conducted in close collaboration with the US Environmental Protection Agency and will use a set of compounds with different modes of action to test for the reliability and relevance of the MEA as a neurotoxicity screening tool.

Partners: Timothy Shafer (US Environmental Protection Agency), Giulio Zorzi (MaxWell Biosystems), Marie-Gabrielle Zurich (Université de Lausanne)

AP5 - Development of in silico screening tools and in vitro bioassays for 5α- and 5β-reductase

Project overview

This project focuses on developing in silico predictive models for screening compounds’ capacity to interact with the 5α-reductase (SRD5A1) and 5β-reductase (AKR1D1) enzymes. These two enzymes are key players in maintaining the androgen-glucocorticoid balance and thus, any undesired interaction of small molecules – may it be drugs, cosmetics, food additives or others – with these enzymes can potentially lead to disruption of the steroid homeostasis with major adverse health effects as a consequence. The models developed here would allow a rapid identification of such structural-based interactions.

Project description

Endocrine disruptors pose a major challenge to regulators as it is difficult to set thresholds of adversity for hormone alterations and the adverse health consequences are broad, from reproductive problems to diabetes. This project addresses a need in developing tools that allow rapid and reliable detection of interaction capacity with enzymes regulating steroid hormone homeostasis. An array of state-of-the-art modelling techniques are applied in order to elucidate enzyme-ligand interaction of an atomic level in silico. The models developed here will be integrated in the already existing portfolio of predictive models in the in silico screening platform named VirtualToxLab.

Partner: Alex Odermatt (University of Basel)