Inhaled brevetoxins--Health effects & toxicokinetics

吸入短毒素——对健康的影响

• 批准号: 6614504
• 负责人: JANET M. BENSON
• 金额: $ 17.91万
• 依托单位: UNIVERSITY OF NORTH CAROLINA WILMINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6614504
• 关键词: aerosols; cellular immunity; chemical kinetics; environmental exposure; environmental health; environmental toxicology; humoral immunity; laboratory rat; marine toxins; neurotoxins; respiratory disorder; respiratory function; respiratory toxin; aerosols; cellular immunity; chemical kinetics; environmental exposure; environmental health; environmental toxicology; humoral immunity; laboratory rat; marine toxins; neurotoxins; respiratory disorder; respiratory function; respiratory toxin

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.

描述（取自研究者的摘要） 鞭毛的绽放，裸子breve，已经蔓延开来 在过去的25年中，沿着沿海水域有着显着的意义。 G. Breve 产生一系列的环状聚乙烯，称为Brevetoxins（聚醚 Breve毒素； PBTXS）。 Brevetoxins是神经毒性的，导致膜 去极化，并负责综合征神经毒性 贝类中毒，在吃G. Breve污染的人中 贝类。当G. Breve时，人们也可以暴露于Brevetoxins 花朵在冲浪中被雾化。因为G. Breve引起的红潮 可能会持续几天到几周，从事或生活的人 在附近，受影响的海滩可能会反复暴露于空气中的布雷毒素。 急性暴露于Brevetoxin污染的海上喷雾会引起刺激 眼睛，鼻子和喉咙以及支气管收缩。证据 从海洋哺乳动物的详细检查中获得的 在神经系统中，呼吸道和肢体呼吸道和 免疫系统是慢性PBTX毒性的潜在靶标。这 这些研究的目的是评估与 重复吸入佛罗里达红时间毒素（Brevetoxin）并定义 暴露浓度，持续时间和影响之间的关系。 该项目具有五个特定的目标。 1）确定摄取，组织 大鼠吸入Brevetoxin-3（PBTX-3）的分布和清除。 鉴定肺，肝脏和大脑，尿液，胆汁和粪便中的代谢产物。 2） 由大鼠鼻上皮和肝的PBTX-3代谢表征 体外微粒体和人肝微粒体。识别代谢物 形成了形成的代谢和代谢率的比较。 物种和组织类型的功能。 3）确定呼吸道和 重复吸入雾化G.引起的全身毒性。 布雷夫。比较观察到的毒性与由 雾化的G. Breve。比较观察到的毒性 由含有PBTX的G. breve提取物生产并产生 由单个PBTXS。 4）评估中心主题和周围 由PBTX重复吸入引起的神经毒性作用。 5） 确定重复的PBTX吸入对体液和细胞的影响 介导的免疫力以及肺和全身免疫功能。 此信息对于估计与之相关的风险至关重要 吸入人类暴露于佛罗里达红潮气雾剂。