The objectives of these studies were to investigate the potential acute pulmonary effects of World Trade Center dust (WTCD) on rats and to determine if pulmonary effects persisted or progressed after exposure. A range-finding study was conducted to characterize the dose-response of WTCD in male Fischer 344 rats and to determine an optimal dose to use in the 16-week study. Rats were administered 200 ul sterile saline (controls) or WTCD suspended in 200 ul sterile saline by intratracheal instillation. Rats (13/dose group) received WTCD at doses ranging from 20 to 1280 ug/day for 3 consecutive days. At 1 and 7 days after the last instillation, 5 rats/dose were euthanized and bronchoalveolar lavage (BAL) fluid collected and analyzed for cell differentials, LDH and protein. Deaths occurred at 320, 640, and 1280 ug WTCD and therefore these doses were not considered for the 16-week study. Cell differential data indicated that some pulmonary inflammation was still ongoing at 7 days after instillation of 160 ug, and not at lower doses. Based upon these results of the range-finding study, a dose of 160 ug WTCD was selected for the 16-week study. Male Fischer 344 rats received 160 ug of WTCD, TiO2 (control particulate), or sterile saline (controls) for 3 consecutive days by intratracheal instillation. At 2, 4, 8, and 16 weeks after the last instillation, 6 rats/dose group were euthanized, body and lung weights recorded, and the lungs processed for histopathology. At 4, 8, and 16 weeks after treatment, bronchoalveolar lavage fluid (BALF) was collected and evaluated (5 rats/dose). Lung 4-hydroxyproline (an indicator of fibrosis) was measured at 8 and 16 weeks after treatment. Pulmonary function (Buxco system) was measured in a subgroup (8 rats/treatment) of rats at 2, 4, 8, and 16 weeks after treatment with WTCD, TiO2, or saline. Instillation of 160 ug of WTCD or TiO2 had no significant effect on body and lung weights, BALF parameters, lung 4-hydroxyproline, pulmonary function or lung histopathology. Black pigmented macrophages were observed in lungs and BALN of TiO2 treated rats. A 13-week study is in progress to evaluate the potential immunotoxicity of WTC dust in B6C3F1 mice. Mice received a single intratracheal instillation of WTC dust (100 ug). At 1, 28, and 90 days after dosing a subgroup of mice were challenged by administration of influenza virus. BAL, viral titers, cytokine levels and cell subpopulations are being quantified in BAL fluid. Natural killer cell activity will be evaluated in spleen cells. At these same time points, another subgroup of mice will be assessed to determine whether they can mount an effective antibody response.
