title: Exposure assessment of high molecular weight sensitisers: contribution to occupational epidemiology and disease prevention.
abstract: An important group of sensitising agents are so called high molecular weight sensitisers--proteins or glycoproteins with molecular weights in the 5-70 kDa range that can provoke a specific IgE response in workers exposed to these agents. Exposure to high molecular weight sensitisers could only be evaluated indirectly in the recent past. Few measurement techniques existed that made it possible to measure the allergens directly. As a result, few studies focused on establishing exposure-response relations, and exposure standards have not been established for high molecular weight sensitisers, or those that have are of doubtful scientific basis. Recent use of immunoassays changed this perspective dramatically. Antibodies used in the assays can originate from human serum (sensitized workers), serum from sensitised animals (rabbits producing polyclonal antibodies), or animal derived cell cultures producing monoclonal antibodies. Although few comparative studies exist, the available evidence suggests that although the correlation of allergen concentrations obtained with different assays is good, large systematic differences occur. The use of conversion factors to make data from previously performed allergen measurements comparable or exchangeable is limited and thorough standardization of assays is preferred. Validation and comparison of different assays by comparisons between laboratories seem important issues that have not received the attention needed. Epidemiological studies in several industries that used immunoassay for the exposure characterisation have shown that risk of sensitisation increases with increasing exposure to allergens. Several studies have also shown that clear differences in potency seem to exist. Sensitisation to rat urinary allergens and fungal alpha-amylase occurred in the pg/m3 and ng/m3 range. The main research questions of the near future have to focus on the prevention of occupational sensitisation. Standard setting seems possible for some allergenson the basis of the available scientific evidence for the existence of exposure response relations. However, assays for characterising exposure to allergens have to be rigorously standardised before they can be used under field conditions.
authors.affiliation: Environmental and Occupational Health Group, Wageningen, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Heederik
authors.forename: G
authors.initials: G
authors.lastname: Doekes
authors.forename: M J
authors.initials: MJ
authors.lastname: Nieuwenhuijsen
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D000485:Allergens / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004391:Dust / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007073:Immunoglobulin E / Q000276:immunology*; D008970:Molecular Weight; D016273:Occupational Exposure / Q000032:analysis* / Q000517:prevention & control; D011506:Proteins / Q000032:analysis / Q000276:immunology; D051381:Rats
chemical_list: D000395:Air Pollutants, Occupational; D000485:Allergens; D000906:Antibodies; D004391:Dust; D006023:Glycoproteins; D011506:Proteins; D007073:Immunoglobulin E