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Content archived on 2024-05-14

Evaluation of early indicators for sensitisation to nickel, cobalt and chromium. Methods for risk assessment.

Objective

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.

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Coordinator

NATIONAL INSTITUTE FOR WORKING LIFE
EU contribution
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Address
16,Warfvinges vaeg, 25
11279 STOCKHOLM
Sweden

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Total cost

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Participants (2)

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