Castorina Rosemary, Woodruff Tracey J
Center for Children's Environmental Health Research, School of Public Health, University of California, Berkeley, California, USA.
Environ Health Perspect. 2003 Aug;111(10):1318-25. doi: 10.1289/ehp.6185.
The U.S. Environmental Protection Agency (U.S. EPA) generally uses reference doses (RfDs) or reference concentrations (RfCs) to assess risks from exposure to toxic substances for noncancer health end points. RfDs and RfCs are supposed to represent lifetime inhalation or ingestion exposure with minimal appreciable risk, but they do not include information about the estimated risk from exposures equal to the RfD/RfC. We used results from benchmark dose modeling approaches recently adopted for use in developing RfDs/RfCs to estimate the risk levels associated with exposures at the RfD/RfC. We searched the U.S. EPA Integrated Risk Information System (IRIS) database and identified 11 chemicals with oral RfDs and 12 chemicals with inhalation RfCs that used benchmark dose modeling. For assessments with sufficient model information, we found that 16 of 21 (76%) of the dose-response models were linear or supralinear. We estimated the risk from exposures at the established RfDs and RfCs for these chemicals using a linear dose-response curve to characterize risk below the observed data. Risk estimates ranged from 1 in 10,000 to 5 in 1,000 for exposures at the RfDs, and from 1 in 10,000 to 3 in 1,000 for exposures at the RfCs. Risk estimates for exposures at the RfD/RfC values derived from sublinear dose-response curves ranged from 3 in 1,000,000,000 to 8 in 10,000. Twenty-four percent of reference values corresponded to estimated risk levels greater than 1 in 1,000; 10 of 14 assessments had points of departure greater than the no-observed-adverse-effect levels. For policy development regarding management of cancer risks, the U.S. EPA often uses 1 in 1,000,000 as a de minimis risk level. Although noncancer outcomes may in some instances be reversible and considered less severe than cancer, our findings call into question the assumption that established RfD and RfC values represent negligibly small risk levels.
美国环境保护局（U.S. EPA）通常使用参考剂量（RfDs）或参考浓度（RfCs）来评估非癌症健康终点接触有毒物质的风险。RfDs和RfCs理应代表终生吸入或摄入暴露且风险极小，但它们并未包含与等于RfD/RfC的暴露所估计风险相关的信息。我们利用最近在制定RfDs/RfCs时采用的基准剂量建模方法的结果，来估计与RfD/RfC暴露相关的风险水平。我们搜索了美国环境保护局综合风险信息系统（IRIS）数据库，确定了11种有口服RfDs的化学品和12种有吸入RfCs且采用基准剂量建模的化学品。对于有足够模型信息的评估，我们发现21个剂量反应模型中有16个（76%）是线性或超线性的。我们使用线性剂量反应曲线来描述低于观察数据的风险，估计了这些化学品在既定RfDs和RfCs下的暴露风险。RfDs暴露的风险估计范围为万分之一至千分之五，RfCs暴露的风险估计范围为万分之一至千分之三。源自次线性剂量反应曲线的RfD/RfC值暴露的风险估计范围为十亿分之三至万分之八。24%的参考值对应估计风险水平大于千分之一；14项评估中有10项的偏离点大于未观察到不良影响水平。对于癌症风险管理的政策制定，美国环境保护局通常将百万分之一作为可忽略不计的风险水平。尽管在某些情况下非癌症结果可能是可逆的且被认为不如癌症严重，但我们的研究结果对既定RfD和RfC值代表可忽略不计的小风险水平这一假设提出了质疑。
