INHALATION TOXICITY OF BREVETOXIN 3 IN RATS EXPOSED FOR 5 DAYS

Abstract

Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assesses possible adverse health effects associated with short-term inhalation exposure to brevetoxin 3. Male F344/Crl/Br rats were exposed to 500μg brevetoxin 3/m³ by nose-only inhalation for 0.5 or 2h/d for 5 consecutive days. Control rats were sham exposed for 2h to vehicle. Calculated deposited brevetoxin doses were 8.3 and 33μg/kg/d for the low- and high-dose groups, respectively. At the termination of exposures, only body weights of the high-dose group (Group B) were significantly below control values. By immunohistochemistry (IHC), small numbers of splenic and peribronchiolar lymphoid tissue macrophages stained positive for brevetoxin, while nasal mucosa, liver, and brain were IHC negative for brevetoxin. No gross or microscopic lesions were observed in any tissue examined. There was no biochemical evidence of cytotoxicity or inflammation in bronchoalveolar lavage fluid. Alveolar macrophages showed some evidence of activation following brevetoxin exposure. Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated by a >70% reduction in splenic plaque-forming cells in brevetoxin-exposed animals compared to controls. Results suggest that the immune system may be a target of toxicity following brevetoxin inhalation. Future studies will focus on identification of a no-effect level and mechanisms underlying brevetoxin-induced immune suppression.

This research was funded under National Institutes of Health (NIH) grant P01-ES10594ZES. The authors are grateful for the excellent technical assistance of Deborah Meyer, Carolyn Elliott, Amber Dison, Colleen Santistevan, Sarah Durr, Dean Kracko, and Brad Tibbetts.