Verhaar H J, van Leeuwen C J, Bol J, Hermens J L
Research Institute of Toxicology, University of Utrecht, The Netherlands.
SAR QSAR Environ Res. 1994;2(1-2):39-58. doi: 10.1080/10629369408028839.
QSAR-estimates of aquatic toxicity of relatively unreactive (narcosis-type) organic chemicals for 19 species were used to predict "no-effect-levels" (NELs) at the ecosystem level by means of several extrapolation models which were recently discussed by the Organisation for Economic Cooperation and Development (OECD). It appeared that the differences between the numerical results of these extrapolation methods, despite their different statistical assumptions, were small. Equilibrium-partitioning theory for sediment and water as well as biota and water was used to derive NELs for aquatic sediments and whole-body residues. Simple equations are given, from which NELs for water, and subsequently for sediments and whole-body residues, can be predicted on the basis of only the octanol-water partition coefficient. Actual application of the models presented absolutely requires the availability of methods to recognize chemicals that act by the unspecific mechanism of narcosis. To this end, a classification scheme, based on molecular structure, was developed. This classification scheme was applied to the approximately 2000 so-called High Production Volume Chemicals (HPVCs) listed in Annex 1 of the Council Regulation on the Evaluation and the Control of the Environmental Risks of Existing Chemicals of the European Communities. From the classification of these 2000 HPVCs it is concluded that, for a large portion of all existing chemicals, reliable QSAR estimates of aquatic toxicity can be made; this considerably speeds up the process of priority setting and risk assessment of existing chemicals. The validity of this (dual) approach was tested by a comparison of estimated NELs with actual FCC values for all compounds from the US-EPA Water Quality Guidelines list that classify as narcosis-type compounds. This comparison shows that for many existing chemicals QSARs may be used to derive quality guidelines for water, aquatic sediments and residues in aquatic biota.
利用相对不活泼（麻醉型）有机化学品对19种物种的水生毒性的定量构效关系（QSAR）估计值，通过经济合作与发展组织（OECD）最近讨论的几种外推模型，预测生态系统水平的“无效应水平”（NELs）。结果表明，尽管这些外推方法的统计假设不同，但其数值结果之间的差异很小。利用沉积物与水以及生物群与水之间的平衡分配理论，得出了水生沉积物和全身残留的NELs。给出了简单的方程，仅根据正辛醇 - 水分配系数就可以预测水、进而沉积物和全身残留的NELs。所提出模型的实际应用绝对需要有方法来识别通过非特异性麻醉机制起作用的化学品。为此，开发了一种基于分子结构的分类方案。该分类方案应用于欧洲共同体关于现有化学品环境风险评估和控制的理事会条例附件1中列出的约2000种所谓的高产量化学品（HPVCs）。从这2000种HPVCs的分类中可以得出结论，对于所有现有化学品中的很大一部分，可以进行可靠的水生毒性QSAR估计；这大大加快了现有化学品的优先排序和风险评估过程。通过将估计的NELs与美国环境保护局水质指南清单中归类为麻醉型化合物的所有化合物的实际淡水标准（FCC）值进行比较，检验了这种（双重）方法的有效性。这种比较表明，对于许多现有化学品，QSAR可用于推导水、水生沉积物和水生生物群中残留的质量指南。
