Inhaled brevetoxins--Health effects & toxicokinetics

描述（摘自研究者摘要） 沟鞭藻短裸藻的开花 在过去的25年里，沿海沃茨的沿着有很大的变化。G. breve 产生一系列环状聚醚，称为短毒素（聚醚 短病毒毒素; PbTxs）。Brevetoxins具有神经毒性， 去极化，并负责综合征，神经毒性 贝类中毒，在人谁吃了G。短污 贝类。当G. breve 水华在海浪中雾化。因为G.赤潮 可能持续几天到几周，个人工作，或生活 附近受影响的海滩可能会反复暴露于空气中的短尾轮虫毒素。 急性暴露于短尾藻毒素污染的海水喷雾可引起刺激 以及支气管收缩。证据 对海洋哺乳动物的详细检查表明， 除了神经系统、呼吸道和造血系统外， 免疫系统是慢性PbTx毒性的潜在目标。的 这些研究的目的是评估与健康相关的影响， 反复吸入佛罗里达红色时间毒素（短毒素），并确定 暴露浓度、持续时间和效应之间的关系。 该项目有五个具体目标。1)确定摄取，组织 分布和清除的吸入短杆菌毒素-3（PbTx-3）。 鉴别肺、肝和脑、尿液、胆汁和粪便中的代谢物。（二） PbTx-3在大鼠鼻上皮和肝脏中的代谢特征 微粒体和体外人肝微粒体。鉴别代谢产物 形成了一个比较率的代谢和代谢物形成的， 物种和组织类型的功能。3)确定呼吸道， 反复吸入雾化G. 短音符。将观察到的毒性与 雾化G.短音符。将观察到的毒性与 由含PbTx的G.提取并生产 通过单独的PbTx。4)评价中心主题和外围 重复吸入PbTx导致的神经毒性作用。第五章） 确定反复吸入PbTx对体液和细胞的影响， 介导的免疫和肺和全身免疫功能。 这些信息对于估计与下列因素相关的风险至关重要： 人体吸入佛罗里达赤潮气溶胶。

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.