McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
J Toxicol Environ Health A. 2010;73(2):208-16. doi: 10.1080/15287390903340815.
While its precise form has not yet been defined, it is assumed that the exposure-response curve for copper (Cu) is U-shaped, as both Cu deficiency and excess can produce adverse health effects. Exposure-response relationships provide the foundation for setting recommended levels of exposure to essential and nonessential substances. A group of toxicologists, biologists, and epidemiologists formed a working group in 2002 to review the literature on Cu excess and deficiency as well as possible exposure-response modeling strategies. It was decided that in order to conduct more complex modeling exercises with studies on Cu, the information had to be organized into a database for application of emerging analytical approaches in exposure-response assessment. The database would support both current as well as proposed methods for exposure-response assessment and accommodate a variety of reporting methods found in the literature. As there are multiple studies looking at a wide range of adverse health effects attributed to excess and deficiency, data were organized into ordered categories of severity to create a common measure of response. The present study (1) outlines the approach used to identify studies for the Cu database based on their quality and usefulness for exposure-response analyses; (2) provides an overview of the process used to define a common dose metric; and (3) describes the process used to categorize a diverse number of responses from Cu excess and deficiency to an ordinal severity score. Efforts are underway to use this database to define the exposure-response curve for Cu excess and deficiency; however, the comprehensive database can be used to carry out other in-depth analyses on Cu toxicity.
虽然其确切形式尚未确定，但据推测铜 (Cu) 的暴露-反应曲线呈 U 型，因为 Cu 缺乏和过量都会对健康产生不良影响。暴露-反应关系为设定必需和非必需物质的推荐暴露水平提供了基础。一组毒理学家、生物学家和流行病学家于 2002 年组成一个工作组，审查关于 Cu 过量和缺乏以及可能的暴露-反应建模策略的文献。决定为了能够用 Cu 的研究进行更复杂的建模练习，必须将信息组织到数据库中，以便在暴露-反应评估中应用新出现的分析方法。该数据库将支持当前和拟议的暴露-反应评估方法，并适应文献中发现的各种报告方法。由于有多项研究探讨了归因于过量和缺乏的广泛的不良健康影响，因此将数据组织成严重程度的有序类别，以创建反应的通用衡量标准。本研究：（1）根据其对暴露-反应分析的质量和有用性，概述了用于确定 Cu 数据库研究的方法；（2）概述了定义通用剂量指标的过程；（3）描述了将过量和缺乏 Cu 引起的大量不同反应分类为有序严重程度评分的过程。目前正在努力使用该数据库来定义 Cu 过量和缺乏的暴露-反应曲线；然而，全面的数据库可用于对 Cu 毒性进行其他深入分析。
