Fuselier S Grace, Ireland Danielle, Fu Nicholas, Rabeler Christina, Collins Eva-Maria S
Department of Biology, Swarthmore College, Swarthmore, PA, United States.
Department of Physics and Astronomy, Swarthmore College, Swarthmore, PA, United States.
Front Toxicol. 2023 Jun 26;5:1200881. doi: 10.3389/ftox.2023.1200881. eCollection 2023.
Glyphosate is a widely used, non-selective herbicide. Glyphosate and glyphosate-based herbicides (GBHs) are considered safe for non-target organisms and environmentally benign at currently allowed environmental exposure levels. However, their increased use in recent years has triggered questions about possible adverse outcomes due to low dose chronic exposure in animals and humans. While the toxicity of GBHs has primarily been attributed to glyphosate, other largely unstudied components of GBHs may be inherently toxic or could act synergistically with glyphosate. Thus, comparative studies of glyphosate and GBHs are needed to parse out their respective toxicity. We performed such a comparative screen using pure glyphosate and two popular GBHs at the same glyphosate acid equivalent concentrations in the freshwater planarian . This planarian has been shown to be a useful model for both ecotoxicology and neurotoxicity/developmental neurotoxicity studies. Effects on morphology and various behavioral readouts were obtained using an automated screening platform, with assessments on day 7 and day 12 of exposure. Adult and regenerating planarians were screened to allow for detection of developmentally selective effects. Both GBHs were more toxic than pure glyphosate. While pure glyphosate induced lethality at 1 mM and no other effects, both GBHs induced lethality at 316 μM and sublethal behavioral effects starting at 31.6 μM in adult planarians. These data suggest that glyphosate alone is not responsible for the observed toxicity of the GBHs. Because these two GBHs also include other active ingredients, namely diquat dibromide and pelargonic acid, respectively, we tested whether these compounds were responsible for the observed effects. Screening of the equivalent concentrations of pure diquat dibromide and pure pelargonic acid revealed that the toxicity of either GBH could not be explained by the active ingredients alone. Because all compounds induced toxicity at concentrations above allowed exposure levels, our data indicates that glyphosate/GBH exposure is not an ecotoxicological concern for planarians. Developmentally selective effects were not observed for all compounds. Together, these data demonstrate the usefulness of high throughput screening in planarians for assessing various types of toxicity, especially for comparative studies of several chemicals across different developmental stages.
草甘膦是一种广泛使用的非选择性除草剂。草甘膦和基于草甘膦的除草剂（GBHs）在目前允许的环境暴露水平下被认为对非靶标生物安全且对环境无害。然而，近年来它们使用量的增加引发了关于动物和人类低剂量长期暴露可能产生不良后果的疑问。虽然GBHs的毒性主要归因于草甘膦，但GBHs中其他大多未被研究的成分可能本身具有毒性，或者可能与草甘膦产生协同作用。因此，需要对草甘膦和GBHs进行比较研究以剖析它们各自的毒性。我们在淡水涡虫中使用纯草甘膦和两种常见的GBHs，以相同的草甘膦酸当量浓度进行了这样的比较筛选。这种涡虫已被证明是生态毒理学和神经毒性/发育神经毒性研究的有用模型。使用自动筛选平台获得了对形态和各种行为读数的影响，并在暴露的第7天和第12天进行评估。对成年和再生涡虫进行筛选以检测发育选择性效应。两种GBHs都比纯草甘膦毒性更大。虽然纯草甘膦在1 mM时诱导致死性且无其他影响，但两种GBHs在316 μM时诱导致死性，并且在成年涡虫中从31.6 μM开始产生亚致死行为效应。这些数据表明，观察到的GBHs的毒性并非仅由草甘膦导致。由于这两种GBHs还分别包含其他活性成分，即敌草快二溴化物和壬酸，我们测试了这些化合物是否对观察到的效应负责。对纯敌草快二溴化物和纯壬酸的等效浓度进行筛选发现，任何一种GBH的毒性都不能仅由活性成分来解释。因为所有化合物在高于允许暴露水平的浓度下都诱导了毒性，我们的数据表明草甘膦/GBH暴露对涡虫来说不是一个生态毒理学问题。并非所有化合物都观察到发育选择性效应。总之，这些数据证明了在涡虫中进行高通量筛选对于评估各种类型的毒性，特别是对不同发育阶段的几种化学物质进行比较研究的有用性。
