Standardizing benchmark dose calculations to improve science-based decisions in human health assessments.
Standardizing benchmark dose calculations to improve science-based decisions in human health assessments.
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DOI：
10.1289/ehp.1307539
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发表时间：
2014-05
影响因子：
10.4
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Wignall JA;Shapiro AJ;Wright FA;Woodruff TJ;Chiu WA;Guyton KZ;Rusyn I
背景：基准剂量 (BMD) 模型计算与预先指定的反应水平相关的剂量。虽然 BMD 方法比传统出发点 (POD)（例如未观察到的不良影响水平 (NOAEL)）具有优势，但在化学品人类健康评估的应用、解释和报告方面缺乏一致性和透明度。目标：我们的目标是应用标准化流程进行 BMD 建模，以减少模型拟合和选择中的不一致情况。方法：我们利用现有的人类健康评估评估了 352 种环境化学品的 880 个剂量反应数据集。我们以标准化方式计算了每种化学品的基准剂量及其下限 [10% 额外风险，或平均值变化等于 1 SD (BMD/L10/1SD)]，并具有预先指定的模型拟合接受标准。我们确定了与可接受的模型拟合相关的研究设计特征。结果：我们得出了 255 种 (72%) 化学品的值。批量计算的 BMD/L10/1SD 值与先前用于人类健康评估的 POD 显着且高度相关（R2 分别为 0.95 和 0.83，n = 42），其值与报告的 NOAEL 相似。具体而言，BMDs10/1SD:NOAELs的中位比为1.96，BMDLs10/1SD:NOAELs的中位比为0.89。我们还观察到随着剂量组数量的增加，模型活力增加的显着趋势。结论：BMD/L10/1SD 值可以以标准化方式计算，用于对大量化学品和关键影响进行健康评估。这有助于探索特定化学品的多项研究对健康的影响，或者当需要比较化学品时，提供比当前方法更高的透明度和效率。引用：Wignall JA、Shapiro AJ、Wright FA、Woodruff TJ、Chiu WA、Guyton KZ、Rusyn I。2014 年。标准化基准剂量计算，以改进人类健康评估中基于科学的决策。环境健康视角 122：499–505； http://dx.doi.org/10.1289/ehp.1307539
Background: Benchmark dose (BMD) modeling computes the dose associated with a prespecified response level. While offering advantages over traditional points of departure (PODs), such as no-observed-adverse-effect-levels (NOAELs), BMD methods have lacked consistency and transparency in application, interpretation, and reporting in human health assessments of chemicals. Objectives: We aimed to apply a standardized process for conducting BMD modeling to reduce inconsistencies in model fitting and selection. Methods: We evaluated 880 dose–response data sets for 352 environmental chemicals with existing human health assessments. We calculated benchmark doses and their lower limits [10% extra risk, or change in the mean equal to 1 SD (BMD/L10/1SD)] for each chemical in a standardized way with prespecified criteria for model fit acceptance. We identified study design features associated with acceptable model fits. Results: We derived values for 255 (72%) of the chemicals. Batch-calculated BMD/L10/1SD values were significantly and highly correlated (R2 of 0.95 and 0.83, respectively, n = 42) with PODs previously used in human health assessments, with values similar to reported NOAELs. Specifically, the median ratio of BMDs10/1SD:NOAELs was 1.96, and the median ratio of BMDLs10/1SD:NOAELs was 0.89. We also observed a significant trend of increasing model viability with increasing number of dose groups. Conclusions: BMD/L10/1SD values can be calculated in a standardized way for use in health assessments on a large number of chemicals and critical effects. This facilitates the exploration of health effects across multiple studies of a given chemical or, when chemicals need to be compared, providing greater transparency and efficiency than current approaches. Citation: Wignall JA, Shapiro AJ, Wright FA, Woodruff TJ, Chiu WA, Guyton KZ, Rusyn I. 2014. Standardizing benchmark dose calculations to improve science-based decisions in human health assessments. Environ Health Perspect 122:499–505; http://dx.doi.org/10.1289/ehp.1307539
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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：
10.4
作者：
Sand S;Portier CJ;Krewski D
通讯作者：
Krewski D
影响因子：
10.4
作者：
Melnick, Ronald L.;Thayer, Kristina A.;Bucher, John R.
通讯作者：
Bucher, John R.
影响因子：
3.8
作者：
CRUMP, KS
通讯作者：
CRUMP, KS
影响因子：
3.8
作者：
Davis, J. Allen;Gift, Jeffrey S.;Zhao, Q. Jay
通讯作者：
Zhao, Q. Jay