Stevens An-Sofie, Pirotte Nicky, Plusquin Michelle, Willems Maxime, Neyens Thomas, Artois Tom, Smeets Karen
Zoology: Biodiversity and Toxicology, Centre for Environmental Sciences, Hasselt University, Agoralaan, building D, BE 3590, Diepenbeek, Belgium.
J Appl Toxicol. 2015 Mar;35(3):319-26. doi: 10.1002/jat.3011. Epub 2014 Jun 25.
To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent-toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short- (1 day) and long-term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l(-1) ) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long-term exposure set-up, a concentration of 500 µl l(-1) DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l(-1) DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l(-1) DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l(-1) in this organism. In the second part of our study, we propose a statistical approach to account for solvent-toxicant interactions and discuss full-scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea.
在毒理学研究中，使用二甲基亚砜（DMSO）等溶剂来研究疏水性测试化合物是不可避免的。然而，使用这些溶剂时，测试化合物诱导反应的解释可能会产生偏差。虽然有DMSO浓度指南，但大多基于涉及一个特定毒性终点的急性暴露。因此，为避免溶剂与毒物的干扰，我们使用多个慢性测试终点来进一步解释DMSO浓度，并提出一个统计模型来评估测试化合物及其溶剂可能的协同、拮抗或相加作用。在本研究中，我们研究了低浓度DMSO（高达1000 μl l⁻¹）短期（1天）和长期（2周）暴露对地中海涡虫的影响。我们测量了发育完全和发育中的动物的不同生物学水平。在长期暴露实验中，500 μl l⁻¹的DMSO浓度干扰了不同生物学水平的过程，如行为、干细胞增殖和基因表达谱。短期暴露后，500 μl l⁻¹的DMSO仅影响运动能力，而在1000 μl l⁻¹的DMSO浓度下观察到不同参数的最显著变化。由于不同生物学水平和发育阶段之间存在微小的敏感性差异，我们建议在该生物体中使用浓度低于500 μl l⁻¹的这种溶剂。在研究的第二部分，我们提出了一种统计方法来解释溶剂与毒物的相互作用，并讨论了全面的溶剂毒性研究。总之，我们重新评估了地中海涡虫不同实验终点的DMSO浓度限值。
