EPF Lausanne, School of Architecture, Civil and Environmental Engineering, Lausanne, Switzerland.
Eawag, Swiss Federal Institute of Aquatic Science and Technology, Dübendorf, Switzerland.
ALTEX. 2018;35(1):37-50. doi: 10.14573/altex.1701231. Epub 2017 Jun 26.
The maximal chemical concentration that causes an acceptably small or no effect in an organism or isolated cells is an often-sought-after value in toxicology. Existing approaches to derive this value have raised several concerns; thus, it is often chosen case-by-case based on personal experience. To overcome this ambiguity, we propose an approach for choosing the non-toxic concentration (NtC) of a chemical in a rational, tractable way. We developed an algorithm that identifies the highest chemical concentration that causes no more than 10% effect (= EC10) including the modeled 95% confidence intervals and considering each of the measured biological replicates; and whose toxicity is not significantly different from no effect. The developed algorithm was validated in two steps: by comparing its results with measured and modeled data for 91 dose-response experiments with fish cell lines and/or zebrafish embryos; and by measuring actual effects caused by NtCs in a separate set of experiments using a fish cell line and zebrafish embryos. The algorithm provided an NtC that is more protective than NOEC (no-observed-effect-concentration), NEC (modeled no-effect concentration), EC10 and BMD (benchmark dose). Despite focusing on small-scale bioassays here, this study indicates that the NtC algorithm could be used in various systems. Its application to the survival of zebrafish embryos and to metabolic activity in cell lines showed that NtCs can be applied to different effect measurements, time points, and levels of biological organization. The algorithm is available as Matlab and R source code, and as a free, user-friendly online application.
在毒理学中，引起可接受的小或无作用的最大化学浓度是经常被寻求的值。现有的推导该值的方法引起了一些关注；因此，它通常是根据个人经验逐个选择的。为了克服这种模糊性，我们提出了一种合理、可处理的选择化学物质无毒浓度（NtC）的方法。我们开发了一种算法，该算法确定了引起不超过 10%作用（= EC10）的最高化学浓度，包括建模的 95%置信区间，并考虑到每个测量的生物学重复；并且其毒性与无作用没有显著差异。该算法在两个步骤中进行了验证：通过将其结果与鱼类细胞系和/或斑马鱼胚胎的 91 个剂量反应实验的测量和建模数据进行比较；并通过在使用鱼类细胞系和斑马鱼胚胎的单独一组实验中测量 NtC 引起的实际作用来验证。该算法提供的 NtC 比 NOEC（无观察到的效应浓度）、NEC（建模的无效应浓度）、EC10 和 BMD（基准剂量）更具保护性。尽管这里重点是小规模生物测定，但这项研究表明，NtC 算法可用于各种系统。它在斑马鱼胚胎的存活和细胞系中的代谢活性中的应用表明，NtC 可用于不同的效应测量、时间点和生物组织水平。该算法以 Matlab 和 R 源代码以及免费的、用户友好的在线应用程序的形式提供。
