Published on October 25, 2013
Toxicological Risk Assessment An initiative of 24 October 2013 - UCL - Brussels (Woluwe) 1
Louvain Centre for Toxicology and Applied Pharmacology Université catholique de Louvain Pr Alfred Bernard Research Director FNRS
Potential of University Research Centres for Toxicological Risk Assessment • Academic and scientific independence • Commitment to high quality science (ethics, integrity, objectivity, transparency, confidentiality…) • Production of results that are applicable and publishable (peer-review journals) • Scientific knowledge rooted in basic research (e.g. translational medicine or from « bench to bedside ») 3
Potential of University Research Centres for Toxicological Risk Assessment • Development of advanced risk assessment methodologies (e.g. non-invasive biomarkers) • Critical and evidence-based reasoning (causal inference, statistical and analytical limitations,..) • Detection of emerging risks (e.g. nanoparticles and CBPs ) • Studies among patients or populations at risk in the industry or environment 4
Fields of expertise and industrial targets LTAP: an interdisciplinary expertise • • • • • • • • • • Development of non-invasive biomarkers to detect early effects of environmental pollutants (A. Bernard) Biological monitoring of exposure to chemicals (V. Haufroid) Physico-chemical properties and toxicity of nanoparticles (D. Lison) Experimental models of lung inflammation and fibrosis (F. Huaux) Evaluation of health hazards and risks of chemical substances (P. Hoet) Systematic review and meta-analysis (G. Van Maele-Fabry) Critical care toxicology: from the management of acute poisoning to the investigation of the mechanisms of toxicity (P. Hantson) Treatment of Cystic Fibrosis (T. Leal) Therapeutic drug monitoring and population pharmacokinetics (P. Wallemacq) Human pharmacogenomics (V. Haufroid) 5
Risks of low-level environmental Cd: toxicity or extrapolation fallacy ? In industrial workers, urinary Cd is a well-validated biomarker of the Cd body burden. What about the general population ? EFSA LTAP Toxicokinetic model developed by EFSA for assessing the risk of Cd in food (Amzal et al., , Environ Health Perspectives, 2009) Variations of urinary Cd over lifetime in the general population of Belgium (Chaumont et al., Environ Health Perspectives, 2013) 6
Biomarkers of kidney toxicity: LMW urinary proteins Derivation of the threshold of urinary Cd associated with an increased risk of renal dysfunction in an international cohort of Cd battery workers (n=599) Chaumont et al., Occup Environ Medicine, 2011
Biomarkers of lung toxicity: serum lung-specific proteins Persistent defects of airways epithelium in adolescents (n=800) with the highest attendance at chlorinated pools during childhood (top quintile). A, girls; B, boys. 8
Meta-analysis: pooling data from independent studies Risk of Parkinson disease associated with occupationnal exposure to pesticides (Van Maele-Fabry et al., 2012) Risk of childhood brain tumour associated with parental exposure to pesticides (Van Maele-Fabry et al,. 2013) Risk Risk 9
Emerging risks: indium (IT0) Pulmonary alveolar proteinosis induced by indium-tin oxide Industrial workers Cummings et al. 2010 Rat Lison et al., 2010 Biomonitoring of occupational exposure to indium-tin oxide Hoet et al., 2012 10
Emerging risks: lung toxicity of carbon nanotubes Experimental evidence of inflammatory and fibrotic reactions in rat two months after the intra-tracheal administration of multi-wall carbon nanotubes Muller et al.,Toxicol Appl Pharmacology, 2005 11
Special equipments Visit the LTAP after this session ! 12
Contacts Université catholique de Louvain Louvain Centre for Toxicology and Applied Pharmacology Tour Pasteur avenue E. Mounier, 53- box B1-52-12 1200 Brussels, Belgium http://www.toxi.ucl.ac.be/ Pr Alfred Bernard FNRS Research Director Alfred.firstname.lastname@example.org +32 2 764 53 34 Pr Dominique Lison Director of LTAP Dominique.email@example.com +32 2 764 53 31 13
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