Beyond the RfD: Broad Application of a Probabilistic Approach to Improve Chemical Dose-Response Assessments for Noncancer Effects.
Beyond the RfD: Broad Application of a Probabilistic Approach to Improve Chemical Dose-Response Assessments for Noncancer Effects.
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DOI：
10.1289/ehp3368
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发表时间：
2018-06
影响因子：
10.4
通讯作者：
Paoli G
中科院分区：
文献类型：
--
作者：
Chiu WA;Axelrad DA;Dalaijamts C;Dockins C;Shao K;Shapiro AJ;Paoli G
美国国家科学院建议风险评估将传统的非癌症参考剂量（RfD）重新定义为概率衍生的风险特异性剂量，这是世界卫生组织（WHO）最近制定的框架。我们的目的是评估用与效应量级M和人群发病率I相关的人体剂量的概率估计取代传统rfd的可行性和意义（）。我们从动物数据中创建了一个综合的、精心策划的射频识别数据库，并开发了一个标准化的、自动化的、可通过网络访问的、实施世卫组织框架的概率剂量反应工作流程。我们确定了1464个rfd和相关的端点，代表了608种化学物质在许多类型的影响。应用我们的标准化工作流程得到1,522个值。传统的rfd通常在通常用于基准剂量的和M值的较低置信范围的一个数量级内。造成不确定性的最大因素是缺乏基准剂量估计，其次是人类变异程度的不确定性。传统的RfD暴露通常意味着受影响人群中有几个百分点的95%置信上限。这种发生率是否被认为是可接受的，可能因化学和风险环境而异，特别是考虑到相关影响的严重程度范围很广，从临床化学到死亡率。总的来说，用估算代替rfd可以为风险管理决策提供更加一致、科学严谨和透明的基础，并支持额外的决策上下文，例如经济效益-成本分析、风险-风险权衡、生命周期影响分析和紧急响应。https://doi.org/10.1289/EHP3368
The National Academies recommended risk assessments redefine the traditional noncancer Reference Dose (RfD) as a probabilistically derived risk-specific dose, a framework for which was recently developed by the World Health Organization (WHO). Our aim was to assess the feasibility and implications of replacing traditional RfDs with probabilistic estimates of the human dose associated with an effect magnitude M and population incidence I (). We created a comprehensive, curated database of RfDs derived from animal data and developed a standardized, automated, web-accessible probabilistic dose–response workflow implementing the WHO framework. We identified 1,464 RfDs and associated endpoints, representing 608 chemicals across many types of effects. Applying our standardized workflow resulted in 1,522 values. Traditional RfDs are generally within an order of magnitude of the lower confidence bound for and M values commonly used for benchmark doses. The greatest contributor to uncertainty was lack of benchmark dose estimates, followed by uncertainty in the extent of human variability. Exposure at the traditional RfD frequently implies an upper 95% confidence bound of several percent of the population affected. Whether such incidences are considered acceptable is likely to vary by chemical and risk context, especially given the wide range of severity of the associated effects, from clinical chemistry to mortality. Overall, replacing RfDs with estimates can provide a more consistent, scientifically rigorous, and transparent basis for risk management decisions, as well as support additional decision contexts such as economic benefit–cost analysis, risk–risk tradeoffs, life-cycle impact analysis, and emergency response. https://doi.org/10.1289/EHP3368