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PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES
Citation:
Selgrade, MJK, E H. Boykin, N. H. HaykalCoates, D L. Doerfler, AND S H. Gavett. PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES
M.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. Gavett
Experimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Development, U.S. EPA, Research Triangle Park, NC
Exposure to certain low molecular weight chemicals is associated with asthma. A simple test is needed to identify chemicals that pose this hazard. Increases in total serum IgE or a Th2 cytokines in draining lymph nodes following dermal exposure have been pursued as means to screen potential asthmagens. It would be useful to relate these responses to a respiratory effect. We hypothesized that dermal exposure to certain isocyanates would result in enhanced pulmonary hyperresponsiveness to methacholine challenge. We assessed 4 treatment groups including 2 chemicals associated with asthma, 2% diphenylmethane-4,4'-diisocyanate (MDI) and 2% dicyclohexylmethane-4,4'-diisocyanate (HMDI); a contact sensitizer not associated with asthma, 1% dinitrochlorobenzene (DNCB); and a vehicle control (4 acetone:1 olive oil). BALB/c mice received 5 dermal exposures over a period of 2 wks. Mice were then challenged with increasing doses of methacholine and responsiveness was assessed using whole body plethysmography (Buxco). Half of each group was killed and serum, bronchoalveolar lavage fluid (BALF), and lymph nodes were collected for total IgE, cell counts, and cytokine profiling. The remaining mice were exposed for an additional 2 wks and reassessed. There were no changes in total or differential cell counts for any of the exposure groups at any time compared to vehicle. Significant increases in serum IgE were apparent for the 3 exposure groups at 2 and 4 wks, with differences greater at 4 wks. Mice exposed to HMDI showed significant hyperresponsiveness at 2 wks; these differences were greater at 4 wks. Neither MDI nor DNCB produced significant hyperresponsiveness at either time. This data suggests a disconnect between the total serum IgE response and hyperresponsiveness. Also, using the current protocol hyperresponsiveness occurred after dermal exposure for only one of the two asthmagens. (This abstract does not reflect EPA policy).