Inhaled brevetoxins--Health effects & toxicokinetics

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Description (Taken from the Investigator's Abstract) Blooms of the dinoflagellate, Gymnodinium breve, have spread significantly along coastal waters over the past 25 years. G. breve produces a series of cyclic polyethers, known as brevetoxins (Polyether Breve Toxins; PbTxs). Brevetoxins are neurotoxic, causing membrane depolarization, and are responsible for the syndrome, Neurotoxic Shellfish Poisoning, in people who have eaten G. breve-contaminated shellfish. People can also be exposed to brevetoxins when G. breve blooms become aerosolized in surf. Because G. breve-induced red tides may last from days to several weeks, individuals working on, or living near, affected beaches may be repeatedly exposed to airborne brevetoxins. Acute exposure to brevetoxin-contaminated sea spray can cause irritation of the eyes, nose, and throat as well as bronchoconstriction. Evidence obtained from detailed examinations of marine mammals suggests in addition to the nervous system, the respiratory tract and hemopoietic and immune systems are potentially targets for chronic PbTx toxicity. The purpose of these studies is to evaluate the health effects associated with repeated inhalation of Florida red time toxins (brevetoxins) and to define the relationships among exposure concentration, duration, and effects. The project has five specific aims. 1) Determine the uptake, tissue distribution, and clearance of inhaled brevetoxin-3 (PbTx-3) in rats. Identify metabolites in lung, liver and brain, urine, bile, and feces. 2) Characterize metabolism of PbTx-3 by rat nasal epithelial and hepatic microsomes and human hepatic microsomes in vitro. Identify metabolites formed a compare rates of metabolism and metabolites formed as a function of species and tissue type. 3) Determine the respiratory tract and systemic toxicities resulting from repeated inhalation of aerosolized G. breve. Compare the observed toxicities with those produced by aerosolized G. breve. Compare the observed toxicities with those produced by aerosolized PbTx-containing G. breve extract and produced by individual PbTxs. 4) Evaluate the central theme and peripheral neurotoxic effects resulting from repeated inhalation of PbTx. 5) Determine the effects of repeated PbTx inhalation on humoral and cell- mediated immunity and on pulmonary and systemic immune function. This information is essential for estimating the risk associated with inhalation exposure on humans to Florida red tide aerosols.