You are here:
CURRENT STATE OF PREDICTING THE RESPIRATORY ALLERGY POTENTIAL OF CHEMICALS: WHAT ARE THE ISSUES?
Citation:
Gilmour, M I. AND S. E. Loveless. CURRENT STATE OF PREDICTING THE RESPIRATORY ALLERGY POTENTIAL OF CHEMICALS: WHAT ARE THE ISSUES? Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, Utah, March 9-13, 2003.
Description:
Current State of Predicting the Respiratory Allergy Potential of Chemicals: What Are the Issues? M I. Gilmour1 and S. E. Loveless2, 1USEPA, Research Triangle Park, NC and 2DuPont Haskell Laboratory, Newark, DE.
Many chemicals are clearly capable of eliciting immune responses in sensitized individuals, which, following re-exposure, can result in adverse allergic reactions. It is also generally agreed that contact sensitivity is the most common occupational health problem, and that respiratory sensitization occurs less frequently, and in a more restricted range of chemical classes. Various in vivo contact hypersensitivity tests, including the Buehler patch test, the mouse ear swelling test, and the local lymph node assay, have successfully identified contact sensitizers, although respiratory sensitizers also test positive in these assays. Guinea pig inhalation studies have been utilized to identify respiratory sensitizers, but these studies are expensive and labor-intensive and typically require protein conjugation of the chemical of interest in order to elicit a response. This workshop has highlighted pulmonary function testing, cytokine profiling and measurement of IgE as new, potential approaches for identifying respiratory sensitizers. While these techniques offer many advantages over the guinea pig models, further work is needed to validate these methodologies and to consider practical issues such as: which species and strain of animal to use; whether total IgE can be used as a surrogate for antigen specific reaginic antibody; and if measurement of IL4 after in vitro stimulation with mitogen is a reliable technique for identifying only respiratory sensitizers. Furthermore, timing and dose response curves for both the sensitization and challenge phases of the protocol need to be established to determine threshold and irritating concentrations of chemical, and to compare cytokine and antibody responses at doses which elicit the same level of immune-mediated hypersensitivity reactions. This abstract does not reflect EPA policy.