TOXICOLOGY STUDIES OF LEAD

铅的毒理学研究

• 批准号: 3855860
• 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/3855860
• 关键词: Alaska; blood chemistry; environmental toxicology; histopathology; inhalation drug administration; laboratory rat; lead; lead poisoning; toxicant screening; toxin metabolism; urinalysis

A contract research project was conducted to compare the toxicity and bioavailability of lead oxide, lead sulfide, lead acetate, and a sample of lead ore concentrate from Alaska. The chemicals were fed to rats for 30 days at doses of 10, 30, and 100 ppm. The comparative bioavailability of the different types of lead materials were evaluated by measuring the accumulation of lead in the blood and bone. Urinary aminolevulinic acid was determined as a measure of lead toxicity that could be compared to lead-induced elevations of aminolevulinic acid reported in human urine samples. Lead from lead acetate and lead oxide accumulated rapidly in a dose-related fashion in the bone, such that peak concentrations of 200-30O micro-g/gm were attained in the 100 ppm dose group. A steady, dose-related, but much slower rate of accumulation of lead from lead sulfide and the Alaskan lead concentrate sample occurred in the bone, such that peak concentrations of 10-15 micro-g/gm were attained. There was a strong correlation between the elevations in bone lead and that of urinary aminolevulinic acid in rats fed the soluble lead acetate and lead oxide salts, but no correlation in rats fed the insoluble lead sulfide and the Alaskan lead concentrate. There was no elevation of urinary aminolevulinic acid in the latter animals, indicating accumulation of bone lead concentrations >15 pg/gm were necessary before inhibition of a marker enzyme for lead toxicity, aminolevulinic acid dehydratase, would result in excess excretion of urinary aminolevulinic acid. Analyses of lead in serial samples of blood, as well as evaluation of histopathology in the bone, kidney, liver, and brain are in progress. In addition, samples of selected target organs were archived from the study for potential future investigations on lead toxicity.

进行了一项合同研究项目，以比较毒性和 氧化铅、硫化铅、醋酸铅的生物利用度， 来自阿拉斯加的铅精矿。 这些化学物质被喂给老鼠30 在10、30和100 ppm剂量下持续30天。 的比较生物利用度 不同类型的铅材料通过测量 铅在血液和骨骼中的积累。 尿氨基乙酰丙酸 作为衡量铅毒性的指标， 铅诱导的人尿中氨基乙酰丙酸升高 样品 来自醋酸铅和氧化铅的铅在一个 剂量相关的方式在骨，这样的峰值浓度200- 30 O 在100 ppm剂量组中达到μ g/gm。 一个稳定， 剂量相关，但从铅中积累铅的速度要慢得多 硫化物和阿拉斯加的铅浓缩物样品发生在骨头上， 达到10-15微克/克的峰值浓度。 有一个 骨铅升高与尿铅升高之间有较强的相关性 可溶性醋酸铅和氧化铅对大鼠氨基乙酰丙酸的影响 盐，但在大鼠喂食不溶性硫化铅和 阿拉斯加铅精矿。 尿氨基乙酰丙酸无升高 在后一种动物中， 在抑制标记物之前需要>15 pg/gm的浓度 铅毒性的酶，氨基乙酰丙酸脱氢酶，会导致 尿氨基乙酰丙酸过量排泄。 铅含量分析 一系列血液样本，以及组织病理学评价， 骨、肾、肝和脑正在进行中。 此外， 将研究中选定的靶器官存档，以备将来使用。 铅毒性的研究。