Cross-reactivity of Halogenated Platinum Salts
Citation:
Lehmann, D., E. Boykin, C. Copeland, L. Copeland, S. Quell, AND W. Williams. Cross-reactivity of Halogenated Platinum Salts. Presented at Society of Toxicology, Phenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting, March 23-27, 2014, in Phoenix AZ
Description:
Halogenated platinum (Pt) salts are well-known respiratory sensitizers associated with the development of asthma. People may be exposed to a variety of platinum compounds in different contexts (e.g. occupationally, automobile exhaust). Published reports suggest that sensitization to one Pt compound may result in hypersensitivity reactions to other Pt compounds. We investigated the potential for this type of cross-reactivity using a mouse model of Pt hypersensitivity. Mice were sensitized through application of 100 µL 1% ammonium hexachloroplatinate (AHCP) in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, mice were challenged by intratracheal aspiration (IA) with saline or 100 µg AHCP or 100 g ammonium tetrachloroplatinate (ATCP) in saline. Before and immediately after dosing, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP. All mice dosed with AHCP demonstrated significant increases in total serum IgE, suggesting the animals were sensitized. An immediate airway response (IAR) was observed in mice sensitized and challenged with AHCP. Dose-dependent increases in Mch responsiveness occurred in mice sensitized and challenged with AHCP. Bronchoalveolar lavage fluid (BALF) harvested from mice sensitized and challenged with AHCP contained an average of 5% eosinophils compared to less than 0.5% in control mice (p < 0.05). When challenged with 100 g ATCP, AHCP sensitized mice also exhibited an IAR. Compared to control mice, BALF harvested from the lungs of ATCP challenged mice contained elevated numbers of eosinophils. These mice were also responsive to Mch aerosol. Our data demonstrate that ATCP can trigger pulmonary responses in AHCP sensitized mice. This abstract does not represent EPA policy.