Chemical safety assessment requires information on both chronic and acute effects of toxicants. Traditionally, such information has been provided by a set of animal studies conducted over different durations, ranging from a single dose with observation of effects over a few days, to repeat daily dosing and observations made over many months. With the advent of modern mechanistic approaches to toxicology, the role of in vitro studies within alternative approaches has never been more prominent. 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 hazard and risk 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.
- Taina Palosaari
How to cite
Macko, Peter; Whelan, Maurice; Palosaari, Taina (2021): Time and Concentration Responses of HepaRG. European Commission, Joint Research Centre (JRC) [Dataset] PID: http://data.europa.eu/89h/79989ace-e09e-46c6-a8fc-2e076f23954f
The dataset contains the viability measurements of the liver HepaRG cells after exposure to the 5 different toxicants (Methylene bis(thiocyanate), Tamoxifen, Cadmium Chloride, Aflatoxin B1, and Rotenone). The viability was monitored with a non-invasive live-cell fluorescence imaging system, allowing time-concentration responses to be determined for each test chemical..
This database contains raw and processed data which were produced within our work concerning an in vitro exploratory study, in which concentration-time-effect responses were measured and used for 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.
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- European Commission, Joint Research Centre
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