A signal-to-noise crossover dose as the point of departure for health risk assessment.
A signal-to-noise crossover dose as the point of departure for health risk assessment.
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DOI：
10.1289/ehp.1003327
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发表时间：
2011-12
影响因子：
10.4
通讯作者：
Krewski D
中科院分区：
文献类型：
--
作者：
Sand S;Portier CJ;Krewski D
背景：美国国家毒理学计划 (NTP) 癌症生物测定数据库提供了一个机会来比较现有方法和新方法，以确定建立参考剂量 (RfD) 的出发点 (PoD)。目的：本研究的目的是 a) 调查与人类健康风险评估中使用的传统 PoD 相关的风险 [未观察到不良反应水平 (NOAEL)]； b) 提出一种基于信噪交叉剂量（SNCD）的新方法； c) 将 SNCD 和基于 SNCD 的 RfD 与基于 NOAEL 和基准剂量 (BMD) 方法的 PoD 和 RfD 进行比较。方法：完整的 NTP 数据库用作这些分析的基础，这些分析是使用 Hill 模型进行的。我们确定了 NOAEL 并估计了相应的额外风险。还估计了 BMD (BMDL) 的 95% 置信下限，对应于 1%、5% 和 10% 的额外风险（分别为 BMDL01、BMDL05 和 BMDL10）。我们引入SNCD作为新的PoD，定义为附加风险等于“背景噪声”（绝对风险两侧90%置信区间的上限和下限之间的差）或其指定分数的剂量。结果：NOAEL 的中位风险约为 10%，默认不确定性因子 (UF = 100) 被认为最适用于 BMDL10。因此，我们选择 1/1,000 (0.1/100) 的目标风险，通过线性外推法得出基于 SNCD 的 RfD。平均而言，该方法提供的 RfD 与 BMDL10 除以默认 UF 相同。结论：根据标准 BMD 方法，BMDL10 被认为是最合适的 PoD。 SNCD 方法基于能够可靠检测到信号的最低剂量，值得进一步开发为人类健康风险评估的 PoD。
Background: The U.S. National Toxicology Program (NTP) cancer bioassay database provides an opportunity to compare both existing and new approaches to determining points of departure (PoDs) for establishing reference doses (RfDs). Objectives: The aims of this study were a) to investigate the risk associated with the traditional PoD used in human health risk assessment [the no observed adverse effect level (NOAEL)]; b) to present a new approach based on the signal-to-noise crossover dose (SNCD); and c) to compare the SNCD and SNCD-based RfD with PoDs and RfDs based on the NOAEL and benchmark dose (BMD) approaches. Methods: The complete NTP database was used as the basis for these analyses, which were performed using the Hill model. We determined NOAELs and estimated corresponding extra risks. Lower 95% confidence bounds on the BMD (BMDLs) corresponding to extra risks of 1%, 5%, and 10% (BMDL01, BMDL05, and BMDL10, respectively) were also estimated. We introduce the SNCD as a new PoD, defined as the dose where the additional risk is equal to the “background noise” (the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute risk) or a specified fraction thereof. Results: The median risk at the NOAEL was approximately 10%, and the default uncertainty factor (UF = 100) was considered most applicable to the BMDL10. Therefore, we chose a target risk of 1/1,000 (0.1/100) to derive an SNCD-based RfD by linear extrapolation. At the median, this approach provided the same RfD as the BMDL10 divided by the default UF. Conclusions: Under a standard BMD approach, the BMDL10 is considered to be the most appropriate PoD. The SNCD approach, which is based on the lowest dose at which the signal can be reliably detected, warrants further development as a PoD for human health risk assessment.
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DOI：
10.1006/faat.1994.1134
发表时间：
1994-11-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
ALLEN, BC;KAVLOCK, RJ;FAUSTMAN, EM
通讯作者：
FAUSTMAN, EM
影响因子：
3.4
作者：
Gaylor, DW;Kodell, RL;Krewski, D
通讯作者：
Krewski, D
影响因子：
3.4
作者：
GAYLOR, DW
通讯作者：
GAYLOR, DW
影响因子：
3.8
作者：
Murrell, JA;Portier, CJ;Morris, RW
通讯作者：
Morris, RW
影响因子：
3.8
作者：
Sand, S;von Rosen, D;Filipsson, AF
通讯作者：
Filipsson, AF