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Standardization and validation of the in vitro use of respiratory epithelial cells for toxicity assessment of inhaled occupational and environmental agents

Objective


Foreseen Results

Development, by pooling research efforts, of standard methods for the preparation and culture of alveolar type II pneumocytes, nonciliated bronchiolar (Clara) cells and airway (bronchial, tracheal or nasal) epithelial cells from animals and humans.
Development of standard methods to expose respiratory cells in culture to inhalable agents (gaseous agents).
Validation of the use of respiratory epithelial cells in toxicology by assessing, in different laboratories, the effects of selected model compounds (gases) using sensitive tests of cell injury and dysfunction. A specific aspect is to assess irritant potential
Formulation and sound recommendations on the use of respiratory lung cells in culture for testing inhalable agents.
The proposed concerted action aims to contribute to the respiratory health protection of workers and citizens, exposed to agents that may be inhaled from the occupational or general environment.
The rationale for this approach is that :
the burden of respiratory diseases as a result of exposure to occupational and environmental pollutants is considerable in workers and citizens from Central and Eastern Europe;
research is needed to define occupational and environmental exposure standards on the basis of adequate scientific evidence and understanding of mechanisms, so as to protect the entire population against common and novel risks;
neither conventional in vivo toxicity testing in laboratory animals, nor epidemiology and clinical or occupational surveillance are sufficient to obtain rapid, adequate and relatively inexpensive information about mechanisms of toxicity, interactions of differents agents or newly introduced substances;
in vitro respiratory toxicology is a promising and scientifically valid alternative, which is, however, still in relatively early stage of development and application;
consequently, efforts are required, at international level, towards standardization and validation of the techniques used, both to obtain suitable cells (preferably of human origin) and to achieve adequate exposure systems;
it is important to maintain and enhance the research potential of high quality institutions from Central and Eastern Europe by having them join international research activities.
The methodology will consist in a research network of 6 laboratories and will practically consist in :
bringing together scientists from different laboratories for a one-week training course and three shorter workshops;
carrying out similar experiments in all laboratories using similar reference materials, working according to commonly agreed protocols and then comparing the results obtained in different laboratories;
exchanging samples of cellular material to carry out quality control of cellular purities and characteristics by electron microscopy and carrying out specialized analyses in single locations for one another.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Address
49,Herestraat 49
3000 Louvain / Leuven
Belgium

Participants (5)

Institute of Physiology - Bulgarian Academy of Sciences
Bulgaria
Address
23,Acad. Bonchev Street
1113 Sofia
Institute of Preventive and Clinical Medicine - Slovak Academy of Sciences
Slovakia
Address
14,Limbova
833 01 Bratislava
Medical University of Lodz
Poland
Address
22,Kopcinskiego
90153 Lodz
National Institute of Occupational Health
Hungary
Address
2,Xi Nagyvarad Ter
1450 Budapest
University of Wales Cardiff
United Kingdom
Address
Museum Avenue
CF1 3US Cardiff