Linking in vitro to in vivo toxicity of pharmaceuticals: an integrative approach


Since the early 90s, the continuous input of pharmaceuticals into the environment has brought environmental chemists and toxicologists to join forces in order to tackle obstacles and answer questions regarding the eventual risk posed by such compounds to human and environmental health. One of the main challenges in the area of analytical chemistry is the development of procedures for the identification, quantification and determination analysis of pharmaceuticals in environmental or biological samples. A major group of pharmaceuticals that consist a problem when it comes to ERA approaches concerning environmental impact, are antineoplastic agents (AAs) as they may represent specific risks to non-target species and eventually their mixtures, as little is known about their potential to e.g. fish. Besides, in terms of mechanistic knowledge, single exposures are little informative as they do not consider mixture exposure profiles and time-varying toxic effects. The VitroTox project goes beyond the state-of-the art and gathers expertise from different research areas highlighting the importance of using an integrative and multidisciplinary approach by i) developing chromatographic methodologies for AAs quantification in aquatic and biological samples, ii) combining different biological matrices (in vivo/in vitro) and creating a link between diverse endpoints, in order to iii) investigate the potential of cell lines to serve as proxy to in vivo for the single and joint toxicity assessment of AAs and finally, iv) to assist in the model development for single and joint toxicity of AAs predictions.
The VitroTox project is proposed by three research groups (CICECO, CESAM and iBiMED) from the University of Aveiro and the Institute of Biomedical Sciences, USP Brazil. The CICECO group has proven expertise in the development of different chromatographic protocols, allowing the quantification of different pharmaceuticals within the range of ng/L, thus tackling the first obstacle. The CESAM group has solid expertise in the single and joint effects of a vast range of contaminants (pharmaceuticals
included) in the aquatic environment (27,28), while the iBiMED group is one of the leading groups in signalling transduction and cell signalling proteins.The IBS, USP group involves the search for new AAs focusing on the Brazilian biodiversity, aiming at the sustainable development of new pharmaceuticals and has consolidated experience in the evaluation of the effects caused by AAS in both human and animal cell lines. Additionally, work within the CESAM, iBiMED and IBS, USP groups on the effects of several AAs of marine origin to the zebrafish (ZF) and ZFL cell line (hepatocytes), showed that the majority of the compounds cause toxicity (acute, geno-, cyto- and neurotoxicity) when found at concentrations as low as 0.05 nM (results from the ongoing EMPHASIS project). The present project proposed by three research groups of excellence (CICECO, CESAM and iBiMED) from the University of Aveiro and the Institute of Biomedical Sciences, USP Brazil, also one of the top universities in South America, can guarantee the successful implementation of the novel work herein presented.

Main Local Researcher

Susana Patrícia Mendes Loureiro (CESAM)


Universidade de Aveiro (UA)


Instituto de Ciências Biomédicas da USP Brasil


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