Extrapolating from acute to chronic toxicity in vitro
In vitro methods, as alternatives to animal testing, are key elements of new approach methodologies for toxicological hazard and risk assessment. Typical in vitro experiments are conducted over short durations with measurements of response at a single time point, with a focus on providing effect and concentration-response information as input to this assessment. This limits the usefulness of such data since potential chronic effects that cumulate over time are not usually considered. To address this, an experimental design is presented to characterise the toxicodynamics of a response not only in terms of concentration but also as a function of time. Generation of concentration-time-effect responses allows both the extrapolation of points of departure from an acute to chronic exposure and the determination of a chronicity index that provides a quantitative measure of a chemical's potential to cause cumulative effects over time. In addition, the approach provides a means to characterise the dynamics of key event relationships for the development of quantitative adverse outcome pathways.
Affiliation: European Commission, Joint Research Centre (JRC), Ispra, Italy EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) https://ec.europa.eu/jrc/en/
Presenter: Peter Macko
CV: Peter Macko graduated in physics from Comenius University in Bratislava, he completed his Ph.D. in laser spectroscopy at Joseph Fourier University in Grenoble. His early carrier research was in experimental and computational physics, focusing on highly sensitive spectroscopic techniques applied in atmospheric, interstellar, and plasma physics and chemistry. He gained extensive experience with laser detection techniques, optical systems, and microscopy, and computational skills with modelling optical systems, rate equations of photon-molecule interactions, and the dynamics and kinetics of chemical, transport, and diffusion processes. He later oriented his research towards biomolecular imaging and for more than 10 years has been working at EURL ECVAM with high content imaging platforms and in vitro methods, the alternatives to animal testing for toxicological hazard and risk assessment.