title: 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 500 microg brevetoxin 3/m3 by nose-only inhalation for 0.5 or 2 h/d for 5 consecutive days. Control rats were sham exposed for 2 h to vehicle. Calculated deposited brevetoxin doses were 8.3 and 33 microg/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.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jbenson@Irri.org
authors.forename: Janet
authors.initials: J
authors.lastname: Benson
authors.forename: Fletcher
authors.initials: F
authors.lastname: Hahn
authors.forename: Thomas
authors.initials: T
authors.lastname: March
authors.forename: Jacob
authors.initials: J
authors.lastname: McDonald
authors.forename: Mohan
authors.initials: M
authors.lastname: Sopori
authors.forename: JeanClare
authors.initials: J
authors.lastname: Seagrave
authors.forename: Andrea
authors.initials: A
authors.lastname: Gomez
authors.forename: Andrea
authors.initials: A
authors.lastname: Bourdelais
authors.forename: Jerome
authors.initials: J
authors.lastname: Naar
authors.forename: Julia
authors.initials: J
authors.lastname: Zaias
authors.forename: Gregory
authors.initials: G
authors.lastname: Bossart
authors.forename: Daniel
authors.initials: D
authors.lastname: Baden
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D019570:Inhalation Exposure / Q000009:adverse effects / Q000032:analysis; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008387:Marine Toxins / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects / Q000276:immunology; D035964:Oxocins / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D000095702:Polyether Toxins
chemical_list: D000336:Aerosols; D008387:Marine Toxins; D035964:Oxocins; C053342:brevetoxin; D000095702:Polyether Toxins