Cel The objectives of this project improve our knowledge of nickel, cobalt and chromium allergies in the general population through: a. Evaluation of one or more indicators of exposure for each metal. b. Development of a strengthened scientific basis for risk assessment. c. Development of screening methods for risk assessment.Background Contact sensitisation to the metals nickel, cobalt and chromium (as chromate) is common in the general population. Sensitisation is often caused by skin contact with objects containing these metals. A recent study showed that 11% of the females of a Danish population were allergic to nickel. Smaller, but significant fractions of the population reacted to cobalt and chromate. The frequency may be higher in other EU countries. Sensitised individuals often get skin reactions (contact dermatitis), e.g. hand eczema, when exposed to the metals. The consequences of eczema are often long lasting sick leave or permanent disability. Thus metal contact dermatitis also has considerable socio-economic consequences. Methods for prediction of significant metal exposure and effective screening methods to be used for risk assessment are highly needed. Overview of the project work and expected achievements The project is a multi-disciplinary collaboration aiming at elucidating molecular and cellular responses resulting from exposure to the metals. The issues include: *Clinical studies for establishment of threshold concentrations of the metals for reaction in metal sensitised individuals as well as concentration of the metals in blood, urine and skin. *Development of in vitro-assay for early detection of sensitisation and for risk assessment of the general population. *Studies of responses on cellular level to metal exposure, including uptake of metals, cytotoxicity of metals, intracellular distribution of metals, the role of immune system hyperreactivity, and macrophage response to metal exposure. *Studies of responses on molecular level to metal exposure, including antibodies against metal-protein complexes and concentration of cytokines. Patient exposure to nickel will take place at Gentofte hospital (Denmark). It is foreseen to offer well needed information on threshold concentration of nickel for reaction in sensitised individuals useful for risk assessment. Samples will be taken and analysed by Partner 2, e.g. with lymphocyte transformation test and for cytokines, specific antibodies and metal binding protein complexes as well nickel concentration. Partner 1 will examine the proteins in samples from blood plasma and the cell cultures by gel electrophoresis. The proteins will be scanned by Partner 4 to allow detection of proteins that have different abundance caused by different exposure conditions. Thus candidates for markers of effect will be detected. The procedures to examine them is described in the Work Programme. Partner 1 will also cooperate with Partner 2 in the development of immunoassays of marker candidates using ELISA and chemiluminescence. Human skin keratinocytes will be cultivated and examined in respect to metal uptake in the laboratories of Partner 3. The cytokines will also be studied by partner 6, who will also test adhesion molecules. In short the project deals with evaluation of biomarkers for exposure and effect. Dziedzina nauki medical and health sciencesclinical medicinedermatologynatural scienceschemical sciencesinorganic chemistrytransition metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineallergology Program(-y) FP4-ENV 2C - Specific programme of research and technological development in the field of environment and climate, 1994-1998 Temat(-y) 02020101 - Risks to human health Zaproszenie do składania wniosków Data not available System finansowania CSC - Cost-sharing contracts Koordynator NATIONAL INSTITUTE FOR WORKING LIFE Wkład UE Brak danych Adres 16,Warfvinges vaeg, 25 11279 STOCKHOLM Szwecja Zobacz na mapie Koszt całkowity Brak danych Uczestnicy (2) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko COMMISSION OF THE EUROPEAN COMMUNITIES Włochy Wkład UE Brak danych Adres Via Enrico Fermi 1, TP 460 21020 BARASSO Zobacz na mapie Koszt całkowity Brak danych NATIONAL INSTITUTE OF OCCUPATIONAL HEALTH Dania Wkład UE Brak danych Adres Lersoe Parkalle 105 KOEPENHAGEN Zobacz na mapie Koszt całkowity Brak danych