Institute of Population Health, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada.
J Toxicol Environ Health B Crit Rev. 2010 Oct;13(7-8):546-78. doi: 10.1080/10937404.2010.538657.
There is a need to define exposure-response curves for both Cu excess and deficiency to assist in determining the acceptable range of oral intake. A comprehensive database has been developed where different health outcomes from elevated and deficient Cu intakes were assigned ordinal severity scores to create common measures of response. A generalized linear model for ordinal data was used to estimate the probability of response associated with dose, duration and severity. The model can account for differences in animal species, the exposure medium (drinking water and feed), age, sex, and solubility. Using this model, an optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against toxicity from Cu deficiency. It is also lower than the current tolerable upper intake level (UL; 10 mg/d) that protects against toxicity from Cu excess. Compared to traditional risk assessment approaches, categorical regression can provide risk managers with more information, including a range of intake levels associated with different levels of severity and probability of response. To weigh the relative harms of deficiency and excess, it is important that the results be interpreted along with the available information on the nature of the responses that were assigned to each severity score.
需要定义铜过量和缺乏的暴露-反应曲线，以帮助确定可接受的口服摄入量范围。已经开发了一个综合数据库，其中将不同的健康结果与摄入过量和不足的铜联系起来，并为其分配了等级严重程度评分，以创建共同的反应衡量标准。使用有序数据的广义线性模型来估计与剂量、持续时间和严重程度相关的反应概率。该模型可以考虑动物物种、暴露介质（饮用水和饲料）、年龄、性别和溶解度的差异。使用该模型，确定了 2.6 毫克/天的最佳铜摄入量。这个值高于目前美国推荐的膳食摄入量（RDI；0.9 毫克/天），该摄入量可以预防铜缺乏引起的毒性。它也低于目前可耐受的最高摄入量（UL；10 毫克/天），该摄入量可以预防铜过量引起的毒性。与传统的风险评估方法相比，分类回归可以为风险管理人员提供更多信息，包括与不同严重程度和反应概率相关的一系列摄入水平。为了权衡缺乏和过量的相对危害，重要的是要结合每个严重程度评分所分配的反应性质的现有信息来解释结果。
