Workshop on Status of Test Methods for Assessing Potential of Chemicals to Induce Respiratory Allergic Reactions

Abstract Because of the association between allergy and asthma and the increasing incidence of morbidity and mortality due to asthma, there is growing concern over the potential of industrial chemicals to produce allergic reactions in the respiratory tract. Two classes of chemicals have been well studied in this area: diisocyanates and acid anhydrides. The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) encounters such chemicals in their premanufacturing notice (PMN) program. This article is a summary of a workshop convened by OPPT in collaboration with EPA's Healtin Effects Research Laboratory to discuss presently available test methods that might be applied to potential chemical allergens during the PMN process, the types of chemicals that should be considered suspect, and the kinds of research and validation needed to improve our capability to make such predictions. Formal presentations by experts in the field summarized basic concepts associated with chemically mediated allergy (hypersensitivity), described several methods available in guinea pigs and mice to test for such activity, and described regulatory problems associated with chemically induced hypersensitivity. Informal discussions followed and recommendations were developed, including the following. The presence of chemical-specific cytophilic antibody in either guinea pig or mouse or an increase in total immunoglobuhnlin E (IgE) in the mouse are useful markers for hazard identification of chemicals that might potentially cause respiratory allergy, and the mouse IgE test provides a potentially useful and economical means for screening chemicals for this effect. However, further validation of this test 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 preliminary screen would have to be further evaluated using an animal model of allergic bronchoconstriction in order to determine dose-response relationships and establish "safe" exposure levels. There was a general consensus that the options currently available for testing chemicals for their potential to induce respiratory allergy are far from ideal and that more research and validation are needed.