这项研究为阅读评估引入了一种新的概念方法,考虑结构相似的化合物组中磷酸盐化学物质之间的物种敏感性差异。二十五种有机化学物质,对数Kow为5或更小,根据乙酰胆碱酯酶(AChE)抑制作为特定的作用方式(MOA),分为三个功能组。鱼类的短期水生毒性数据(LC50),甲壳类动物,和昆虫是从美国EPA生态毒理学(ECOTOX)知识库中收集的。对多个毒性终点应用几何平均计算方法。新的跨读概念的性能指标,包括相关系数,偏见,精度,和准确性,被计算。总的来说,在两个病例研究中观察到毒性预测的高估(49.2%)略高于低估(48.4%).在案例研究I中,观察到目标化学品的预测和已知毒性值之间存在强正相关(r=0.93),而在案例研究II中,关于物种及其生态毒性的信息有限,呈中等相关性(r=0.75)。总的来说,案例研究I的偏倚和精度为0.32±0.01,而案例研究II显示为0.65±0.06;然而,相对偏差(%)从37.65%(案例研究I)增加到91.94%(案例研究II).Bland-Altman图突出了1.33(案例研究I)和1.24(案例研究II)的平均差异,分别。新的阅读概念,专注于AChE抑制和结构相似性,表现出良好的可靠性,适用性,和精度与最小的偏差。未来的研究需要评估各种类型的化学物质,不同的行动模式,功能组,毒性终点,和测试物种,以确保毒性预测的整体全面性和稳健性。
This study introduces a novel concept approach for a read-across assessment, considering species sensitivity differences among phosphate chemicals within structurally similar compound groups. Twenty-five organic chemicals, with a log Kow of 5 or less, were categorized into three functional groups based on acetylcholinesterase (AChE) inhibition as a specific mode of action (MOA). The short-term aquatic toxicity data (LC50) for fish, crustaceans, and insects were collected from the U.S. EPA Ecotoxicology (ECOTOX) Knowledgebase. A geometric mean calculation method was applied for multiple toxic endpoints. Performance metrics for the new read-across concept, including correlation coefficient, bias, precision, and accuracy, were calculated. Overall, a slightly higher overestimation (49.2%) than underestimation (48.4%) in toxicity predictions was observed in two case studies. In Case study I, a strong positive correlation (r = 0.93) between the predicted and known toxicity values of target chemicals was observed, while in Case study II, with limited information on species and their ecotoxicity, showed a moderate correlation (r = 0.75). Overall, the bias and precision for Case study I were 0.32 ± 0.01, while Case study II showed 0.65 ± 0.06; however, the relative bias (%) increased from 37.65% (Case study I) to 91.94% (Case study II). Bland-Altman plots highlight the mean differences of 1.33 (Case study I) and 1.24 (Case study II), respectively. The new read-across concept, focusing on AChE inhibition and structural similarity, demonstrated good reliability, applicability, and accuracy with minimal bias. Future studies are needed to evaluate various types of chemical substances, diverse modes of action, functional groups, toxic endpoints, and test species to ensure overall comprehensiveness and robustness in toxicity predictions.