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

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（摘自研究者的摘要） 甲藻（Gymnodinium breve）的花朵已经蔓延 过去 25 年来，沿海水域发生了显着的变化。短 G. 短 产生一系列环状聚醚，称为短链毒素（Polyether 短毒素； PbTx）。短尾毒素具有神经毒性，可导致膜 去极化，并负责综合症，神经毒性 食用受短 G. breve 污染的人会发生贝类中毒 贝类。当短 G. breve 花朵在海浪中雾化。因为G. breve引起的赤潮 可能会持续几天到几周，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毒素。 急性接触受短尾藻毒素污染的海浪喷雾会引起刺激 眼睛、鼻子和喉咙以及支气管收缩。证据 从对海洋哺乳动物的详细检查中获得的结果表明 除了神经系统外，还有呼吸道和造血系统 免疫系统是慢性 PbTx 毒性的潜在目标。这 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时间毒素（短链毒素）并确定 暴露浓度、持续时间和影响之间的关系。 该项目有五个具体目标。 1) 确定组织的摄取量 大鼠吸入短尾毒素 3 (PbTx-3) 的分布和清除。 鉴定肺、肝、脑、尿液、胆汁和粪便中的代谢物。 2） 大鼠鼻上皮和肝脏 PbTx-3 代谢特征 体外微粒体和人肝微粒体。鉴定代谢物 形成了代谢率和代谢物形成的比较率 物种和组织类型的功能。 3) 确定呼吸道和 反复吸入雾化 G 引起的全身毒性。 短。将观察到的毒性与产生的毒性进行比较 雾化的G. breve。将观察到的毒性与实际结果进行比较 由雾化的含 PbTx 的短 G. breve 提取物产生并产生 由各个 PbTx 进行。 4）评估中心主题和外围主题 反复吸入 PbTx 造成的神经毒性作用。 5） 确定重复吸入 PbTx 对体液和细胞的影响 介导的免疫以及肺部和全身免疫功能。 此信息对于估计与以下相关的风险至关重要 人类吸入佛罗里达赤潮气溶胶。