WORKSHOP ON STATUS OF TEST METHODS FOR ASSESSING POTENTIAL OF CHEMICALS TO INDUCE RESPIRATORY ALLERGIC REACTIONS

Because of the association between allergy and asthma and the increasi ng incidence of morbidity and mortality due to asthma, there is growin g concern over the potential of industrial chemicals to produce allerg ic reactions in the respiratory tract. Two classes of chemicals have b een well studied in this area: diisocyanates and acid anhydrides. The Environmental Protection Agency's Office of Pollution Prevention and T oxics (OPPT) encounters such chemicals in their premanufacturing notic e (PMN) program. This article is a summary of a workshop convened by O PPT in collaboration with EPA's Health Effects Research Laboratory to discuss presently available test methods that might be applied to pote ntial chemical allergens during the PMN process, the types of chemical s that should be considered suspect, and the kinds of research and val idation needed to improve our capability to make such predictions. For mal presentations by experts in the field summarized basic concepts as sociated with chemically mediated allergy (hypersensitivity), describe d several methods available in guinea pigs and mice to test for such a ctivity, and described regulatory problems associated with chemically induced hypersensitivity. Informal discussions followed and recommenda tions were developed, including the following: The presence of chemica l-specific cytophilic antibody in either guinea pig or mouse or an inc rease in total immunoglobulin E (IgE) in the mouse are useful markers for hazard identification of chemicals that might potentially cause re spiratory allergy, and the mouse IgE test provides a potentially usefu l and economical means for screening chemicals for this effect. Howeve r, further validation of this test as well as other tests discussed in this workshop is needed, and criteria need to be established for what constitutes a positive IgE test. Chemicals testing positive in this p reliminary screen would have to be further evaluated using an animal m odel of allergic bronchoconstriction in order to determine dose-respon se relationships and establish ''safe'' exposure levels. There was a g eneral consensus that the options currently available for testing chem icals for their potential to induce respiratory allergy are far from i deal and that more research and validation are needed.