Florida Red Tide: Inhalation Toxicity of Karenia brevis Extract in Rats

Abstract

Brevetoxins are neurotoxins produced by the marine dinoflagellate Karenia brevis. Histopathologic examination of marine mammals dying following repeated exposure of brevetoxins during red tide events suggests that the respiratory tract, nervous, hematopoietic, and immune systems are potential targets for toxicity in repeatedly exposed individuals. The purpose of this experiment was to evaluate the effects of repeated inhalation of K. brevis extract on these potential target systems in rats. Male Sprague-Dawley rats were exposed four hours/day, five days/week for up to four weeks to target concentrations of 200 and 1000 μg/L K. brevis extract (approximately 50 and 200 μg/L brevetoxin-like compounds; positive neurotoxicity in a fish bioassay). Control rats were sham exposed to air. Immunohistochemical staining of pulmonary macrophages indicated deposition of brevetoxin-like compound within the lung. However, exposure resulted in no clinical signs of toxicity or behavioral changes. There were no adverse effects on hematology or serum chemistry. No histopathological changes were observed in the nose, lung, liver, kidneys, lymph nodes, spleen, or brain of exposed rats. Immune suppression was suggested by reduced responses of spleen cells in the IgM-specific antibody-forming plaque cell response assay and reduced responses of lymphocytes to mitogen stimulation in vitro. Differences between responses observed in rats in this study and those observed in manatees may be a function of dose or species differences in sensitivity.

Figure 1

Immunohistochemical staining of alveolar macrophages from exposed animals (top left and right panel). Cells from control animals (bottom left panel) did not stain positive for brevetoxin. Color figure p. 575

Figure 2

Effect of K. brevis extract exposure on numbers of plaque-forming spleen lymphocytes. Error bars represent SEM. * indicates values are significantly different from control (analysis of variance, adjusted for multiple comparisons, P < 0.05).