TOXICOLOGY STUDIES OF LEAD

铅的毒理学研究

• 批准号: 3841023
• 负责人: M P DIETER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841023
• 关键词: biomarker; blood chemistry; bone; brain; dosage; environmental toxicology; enzyme activity; geographic site; histopathology; kidney; laboratory rat; lead; lead poisoning; minings; toxicant screening; toxin metabolism; urinalysis

A study was conducted to compare the toxicity and bioavailability of lead in male F344 rats exposed to pure lead salts or to lead ore from Skagway, AK. The chemicals were fed to rats for 30 days. At study termination lead concentrations in blood, bone, kidney, and brain, and urinary aminolevulinic acid were measured. The soluble lead salts, lead oxide and lead acetate, accumulated to a greater degree in bone and soft tissues than the insoluble lead sulfide or the lead ore from Skagway, AK. there was a strong correlation between dose and bone lead concentration for either soluble or insoluble lead samples when the data were graphed on a long- linear scale. Use of the aminolevulinic acid biomarker was ineffective at bone lead concentrations below 20 mug/g. Blood lead concentrations were ~ 80 mug/dl in rats fed the soluble lead salts, and ~ 10 mug/dl in rats fed lead sulfide or lead ore. The highest lead concentrations in soft tissue occurred in kidney, followed by brain. Rats fed soluble lead salts accumulated about 10-fold higher lead concentrations in the soft tissues compared to those fed lead sulfide or lead ore. However, detectable and potentially toxic concentrations of lead accumulated in a dose-related fashion in kidney and brain of rats fed the less soluble lead samples, and to a higher degree in rats fed lead ore compared to those fed lead sulfide. These data suggest that longer exposure periods might result in continual and greater accumulations of lead. Kidney lesions occurred in rats dosed with 30 or 100 ppm lead acetate but not in other treatment groups. Lead ore samples from three other mining sites, Alaska, Missouri, and Colorado, are being fed to rats for longer periods (90 days) to compare the bioavailability and toxicity or ores from different geographical areas. Assays of blood ?-aminolevulinic acid dehydratase enzyme activity, a sensitive and specific biomarker for lead toxicity, and determinations of lead in blood, kidney, and brain are being conducted at 30, 60, and 90d exposure. Data from the 30d samples indicate that at 100ppm in the feed two samples, Alaskan lead ore and Missouri lead ore, significantly inhibited blood ALAD enzyme activity.

进行了一项研究，以比较铅的毒性和生物利用度 在暴露于纯铅盐或来自Skagway的铅矿的雄性F344大鼠中， AK 这些化学物质被喂给老鼠30天。 在研究终止电极导线时 血液、骨骼、肾脏和大脑以及尿液中的浓度 测定氨基乙酰丙酸。 可溶性铅盐、氧化铅和 醋酸铅在骨和软组织中的累积程度大于 不溶性硫化铅或来自Skagway，AK的铅矿。 有一个 剂量与骨铅浓度之间存在强相关性， 可溶性或不溶性铅样品，当数据绘制在一个长- 线性比例尺 使用氨基乙酰丙酸生物标志物在以下情况下无效： 骨铅浓度低于20微克/克。 血铅浓度为~ 喂食可溶性铅盐的大鼠为80 mug/dl，喂食可溶性铅盐的大鼠为~ 10 mug/dl。 硫化铅或铅矿。 软组织中的最高铅浓度 发生在肾脏，其次是大脑。 用可溶性铅盐喂养大鼠 在软组织中积累了高出10倍的铅浓度 与喂入硫化铅或铅矿的那些相比。 然而，可检测和 潜在的有毒浓度的铅积累在一个剂量相关 以可溶性较低的铅样品喂养大鼠的肾脏和大脑， 与喂食硫化铅的大鼠相比，喂食铅矿的大鼠的这种情况更严重。 这些数据表明，较长的暴露时间可能会导致持续的 和更多的铅积累。 给药组大鼠出现肾脏病变 30或100 ppm醋酸铅，但其他处理组中没有。 铅 来自阿拉斯加、密苏里州和科罗拉多的其他三个矿区的矿石样本， 给大鼠喂食更长时间（90天），以比较 生物利用度和毒性。 血液化验？氨基乙酰丙酸脱氢酶活性，a 灵敏和特异的铅毒性生物标志物， 分别在30、60和90 d进行血铅、肾铅和脑铅测定 exposure. 30天的样品数据表明，在饲料中100 ppm 两个样品，阿拉斯加铅矿和密苏里州铅矿， 抑制血液ALAD酶活性。