EXPOSURE, DOSE, BODY BURDEN AND HEALTH EFFECTS OF LEAD

铅的暴露、剂量、身体负担和健康影响

• 批准号: 2018512
• 负责人: BRIAN Seth SCHWARTZ
• 金额: $ 50.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2018512
• 关键词: binding proteins; blood toxicology; bone; chemical binding; chemical kinetics; clearance rate; clinical research; cytotoxicity; environmental toxicology; epidemiology; hemotoxin; human subject; lead; lead poisoning; longitudinal human study; neurotoxicology; neurotoxins; outcomes research; porphobilinogen synthase; protein isoforms; renal toxin; succinates

Lead is a ubiquitous toxin and several biologic measures are available to assess its absorption, deposition, and health consequences. Blood lead (BLLs) and zinc protoporphyrin, commonly used measures, are poor predictors of health effects and are influenced by external exposure, internal lead stores, and interindividual differences in the toxicokinetics of lead. Other measures of lead absorption and burden have been developed (e.g., DMSA-chelatable lead, bone lead), but these have not been evaluated in prospective studies of health effects. Furthermore, there is little understanding of how individual factors may influence relations between these biologic measures and health effects. Increasingly, research has been directed at discovering interactions between individual factors and hazardous exposures. Interindividual differences in lead toxico-kinetics and toxicity are likely to be mediated, in part, by genetic factors, including polymorph-isms in proteins that differentially bind lead and affect its metabolism. Accumulating evidence suggests that delta-aminolevulinic acid dehydratase (ALAD), a polymorphic erythrocyte cytoplasmic enzyme, modifies lead~s toxicokinetics. We propose a prospective study of the relations among BLLs, DMSA-chelatable lead, bone lead, and health effects (heme synthesis, renal early biologic effects and function, blood pressure, and CNS and PNS function) in lead workers in South Korea. Effect modification of these relations by ALAD genotype will also be investigated. This population is uniquely suited to investigation of gene-environment interaction because of its broad range of lead exposures, covering the entire range observed in the U.S., and large numbers of new hires. All current workers will be enrolled in the first year (N=640) and new hires will be enrolled for 2 years (N=230); these two groups will be compared with 120 nonexposed controls. Study measures will be obtained longitudinally, 3 times during the 4 year study. This proposal offers an understanding of the composite roles of BLLs, bone lead, and DMSA-chelatable lead, and effect modification by ALAD genotype, in the prediction of important health outcomes.

铅是一种普遍存在的毒素，有几种生物措施可用 评估其吸收、沉积和健康后果。 血液 铅（BLL）和锌原卟啉，常用的措施， 对健康影响的预测较差，并受外部因素的影响 暴露，内部铅储存和个体间差异， 铅的毒性 铅吸收和负荷的其他测量方法 已经被开发（例如，DMSA-可螯合铅，骨铅），但 这些尚未在健康影响的前瞻性研究中进行评估。 此外，人们对个别因素如何影响 影响这些生物测量和健康影响之间的关系。 越来越多的研究已经指向发现相互作用 个体因素和危险暴露之间的关系。 个体间 铅毒性动力学和毒性的差异可能是 部分由遗传因素介导，包括 差异结合铅并影响其代谢的蛋白质。 越来越多的证据表明δ-氨基乙酰丙酸 α-淀粉酶（ALAD），一种多态性红细胞胞质酶， 改变铅的毒性。 我们提出了一项前瞻性研究， BLL、DMSA螯合铅、骨铅与健康的关系 影响（血红素合成，肾脏早期生物学效应和功能，血液 压力，以及CNS和PNS功能）。 ALAD基因型对这些关系的影响修饰也将被研究。 研究了 这个种群非常适合研究 基因与环境的相互作用，因为其广泛的铅 暴露，涵盖了在美国观察到的整个范围，和大型 新员工的数量。 所有现有的工人将参加第一次 年（N=640），新员工将入组2年（N=230）; 这两组将与120名未接触的对照组进行比较。 将纵向获得研究指标，在4个月内进行3次 年研究。 该建议提供了对复合材料的理解 BLL、骨铅和DMSA螯合铅的作用及其影响 ALAD基因型的修饰，在预测重要的健康 结果。