National Institute for Public Health and Environment, Bilthoven, The Netherlands.
Altern Lab Anim. 2013 Mar;41(1):77-90. doi: 10.1177/026119291304100109.
Read-across as a non-animal testing alternative for the generation of risk assessment data can be useful in those cases where quantitative structure-activity relationship (QSAR) models are not available, or are less well developed. This paper provides read-across case studies for the estimation of the aquatic toxicity of five different fragrance substances, and proposes a pragmatic approach for expressing uncertainty in read-across estimates. The aquatic toxicity estimates and their uncertainties are subsequently used to estimate fresh water compartment Predicted No-Effect Concentrations (PNECs), with their two-sided 90% Confidence Intervals (CIs). These PNECs can be used directly in risk assessment. The results of the musk fragrance read-across cases (musk xylene, musk ketone and galaxolide) are compared to experimentally derived PNEC values. The read-across estimates made by using similarity in a hypothesised mechanism of action for (acute) toxicity of musk xylene gave a PNEC of 2μg/L (90% CI 0.0004-13.5μg/L) with the Species Sensitivity Distribution (SSD) approach. This estimated value is 1.8 times above the experimentally-based fresh water PNEC of 1.1μg/L. For musk ketone and galaxolide, the PNEC values based on the SSD approach and employing a toxicity mechanism-based read-across were 2.0 times greater, and 4.9 times below the experimentally derived PNEC values, respectively.
当定量构效关系 (QSAR) 模型不可用时，或者发展得不够完善时，可作为非动物测试替代方法的读值法在生成风险评估数据方面可能是有用的。本文提供了五个不同香料物质水生毒性估算的读值法案例研究，并提出了一种实用的方法来表示读值法估算中的不确定性。随后，将水生毒性估算及其不确定性用于估算淡水生物群落预测无效应浓度 (PNEC)，并给出了其双侧 90%置信区间 (CI)。这些 PNEC 可直接用于风险评估。本文还比较了麝香类香料读值法案例（二甲苯麝香、酮麝香和环十五内酯）的结果与实验得出的 PNEC 值。基于二甲苯麝香（急性）毒性作用机制相似性进行的读值法估算，使用物种敏感度分布 (SSD) 方法得出的 PNEC 为 2μg/L（90%CI 0.0004-13.5μg/L），该估算值比基于实验得出的淡水 PNEC 值 1.1μg/L 高出 1.8 倍。对于酮麝香和环十五内酯，基于 SSD 方法并采用基于毒性机制的读值法估算的 PNEC 值分别高出实验得出的 PNEC 值 2 倍和 4.9 倍。
