Univ Lyon, Université Lyon 1, UMR CNRS 5558, Villeurbanne, France.
Bayer AG, Crop Science, Monheim, Germany.
PLoS One. 2021 Jan 7;16(1):e0245071. doi: 10.1371/journal.pone.0245071. eCollection 2021.
This research proposes new perspectives accounting for the uncertainty on 50% effective rates (ER50) as interval input for species sensitivity distribution (SSD) analyses and evaluating how to include this uncertainty may influence the 5% Hazard Rate (HR5) estimation. We explored various endpoints (survival, emergence, shoot-dry-weight) for non-target plants from seven standard greenhouse studies that used different experimental approaches (vegetative vigour vs. seedling emergence) and applied seven herbicides at different growth stages. Firstly, for each endpoint of each study, a three-parameter log-logistic model was fitted to experimental toxicity test data for each species under a Bayesian framework to get a posterior probability distribution for ER50. Then, in order to account for the uncertainty on the ER50, we explored two censoring criteria to automatically censor ER50 taking the ER50 probability distribution and the range of tested rates into account. Secondly, based on dose-response fitting results and censoring criteria, we considered input ER50 values for SSD analyses in three ways (only point estimates chosen as ER50 medians, interval-censored ER50 based on their 95% credible interval and censored ER50 according to one of the two criteria), by fitting a log-normal distribution under a frequentist framework to get the three corresponding HR5 estimates. We observed that SSD fitted reasonably well when there were at least six distinct intervals for the ER50 values. By comparing the three SSD curves and the three HR5 estimates, we shed new light on the fact that both propagating the uncertainty from the ER50 estimates and including censored data into SSD analyses often leads to smaller point estimates of HR5, which is more conservative in a risk assessment context. In addition, we recommend not to focus solely on the point estimate of the HR5, but also to look at the precision of this estimate as depicted by its 95% confidence interval.
本研究提出了新的观点,即将 50%有效率(ER50)的不确定性作为物种敏感度分布(SSD)分析的区间输入,并评估如何纳入这种不确定性可能会影响 5%危害率(HR5)的估计。我们探索了来自七个标准温室研究的非靶标植物的各种终点(存活、出现、茎干重量),这些研究使用了不同的实验方法(营养活力与幼苗出现),并在不同的生长阶段应用了七种除草剂。首先,对于每个研究的每个终点,在贝叶斯框架下,对每个物种的实验毒性测试数据拟合一个三参数对数逻辑模型,以获得 ER50 的后验概率分布。然后,为了考虑 ER50 的不确定性,我们探索了两种删失标准,以便根据 ER50 的概率分布和测试率的范围自动删失 ER50。其次,基于剂量-反应拟合结果和删失标准,我们考虑了三种方式将 ER50 值输入 SSD 分析(仅选择 ER50 中位数作为点估计值,基于其 95%可信区间的区间删失 ER50,以及根据两种标准之一的删失 ER50),通过在频率主义框架下拟合对数正态分布,得到三个相应的 HR5 估计值。我们观察到,当 ER50 值至少有六个不同的区间时,SSD 拟合得相当好。通过比较三个 SSD 曲线和三个 HR5 估计值,我们揭示了一个新的事实,即将 ER50 估计值的不确定性和将删失数据纳入 SSD 分析传播,通常会导致 HR5 的点估计值更小,这在风险评估中更为保守。此外,我们建议不要仅仅关注 HR5 的点估计值,还要关注其 95%置信区间所描绘的估计值的精度。