Daphnids Can Safeguard the Use of Alternative Bioassays to the Acute Fish Toxicity Test: A Focus on Neurotoxicity

Christoph Schuer, Martin Paparella, Christopher Fassbender, Gilly Stoddart, Marco Baity-Jesi, Kristin Schirmer
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Abstract

Assessment of potential impacts of chemicals on the environment traditionally involves regulatory standard data requirements for acute aquatic toxicity testing using algae, daphnids and fish (e.g., OECD test guidelines (TG) 201, 202, and 203, respectively), representing different trophic levels. In line with the societal goal to replace or reduce vertebrate animal testing, alternative bioassays were developed to replace testing with fish: the fish cell line RTgill-W1 acute toxicity assay (OECD TG249) and the zebrafish embryo acute toxicity test (zFET, OECD TG236). However, previous studies revealed the lower sensitivity of the RTgill-W1 cell line assay and zFET for some neurotoxic chemicals and allyl alcohol, which is presumably biotransformed in fish to the more toxic acrolein (which is predicted well through the cell line assay). To provide an additional alternative to acute fish toxicity, in this study, we analyzed historic ecotoxicity data for fish and daphnids from the EnviroTox Database. We found a considerable variability in acute fish LC50 and acute daphnids EC50 values, particularly for neurotoxic chemicals. Comparing sensitivity of these taxonomic groups according to different neurotoxicity classification schemes indicates that fish rarely represent the most sensitive trophic level of the two. Exceptions here most prominently include a few cyclodiene compounds, which are no longer marketed, and a chemical group that could be identified through structural alerts. Moreover, daphnids are more sensitive than fish to acrolein. This analysis highlights the potential of the Daphnia acute toxicity test, which is usually a standard regulatory data requirement, in safeguarding the environmental protection level provided by the RTgill-W1 cell line assay and the zFET. This research, rooted in decades of efforts to replace the fish acute toxicity test, shifts the focus from predicting fish toxicity 1-to-1 to emphasizing the protectiveness of alternative methods, paving the way for further eliminating vertebrate tests in environmental toxicology.
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水蚤可为使用急性鱼类毒性试验的替代生物测定提供保障:聚焦神经毒性
评估化学品对环境的潜在影响,传统上涉及使用藻类、水蚤和鱼类进行急性水生毒性 试验的监管标准数据要求(如经合组织试验准则(TG)201、202 和 203,分别代表不同 的营养级)。根据替代或减少脊椎动物试验的社会目标,开发了替代鱼类试验的生物测定方法:鱼细胞系 RTgill-W1 急性毒性试验(OECD TG249)和斑马鱼胚胎急性毒性试验(zFET,OECD TG236)。不过,先前的研究表明,RTgill-W1 细胞系试验和 zFET 对某些神经毒性化学品和烯丙基醇的灵敏度较低,而烯丙基醇在鱼体内可能会生物转化为毒性更强的丙烯醛(细胞系试验对丙烯醛的预测较好)。为了提供急性鱼类毒性的另一种替代方法,我们在本研究中分析了 EnviroTox 数据库中鱼类和水蚤的历史生态毒性数据。我们发现鱼类的急性半数致死浓度和水蚤的急性半数有效浓度存在很大差异,尤其是神经毒性化学品。根据不同的神经毒性分类方案对这些分类群体的敏感性进行比较后发现,鱼类很少是这两个营养级中最敏感的。最突出的例外情况包括几种已不再销售的环二烯化合物,以及一种可通过结构警报来识别的化学组。此外,水蚤比鱼类对丙烯醛更敏感。这项分析凸显了水蚤急性毒性测试在保障 RTgill-W1 细胞系测定和 zFET 所提供的环境保护水平方面的潜力,而水蚤急性毒性测试通常是标准监管数据要求。这项研究植根于几十年来为取代鱼类急性毒性试验所做的努力,将重点从预测鱼类毒性的1比1转移到强调替代方法的保护性,为进一步取消环境毒理学中的脊椎动物试验铺平了道路。
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