Jarema Kimberly A, Hunter Deborah L, Hill Bridgett N, Olin Jeanene K, Britton Katy N, Waalkes Matthew R, Padilla Stephanie
Center for Public Health and Environmental Assessment, Immediate Office, Program Operations Staff, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxics. 2022 May 17;10(5):256. doi: 10.3390/toxics10050256.
With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish () larvae using a behavioral Light/Dark assay. Larvae (n = 16-24 per concentration) were exposed to each chemical (0.0001-120 μM) during development and locomotor activity was assessed. Approximately half of the chemicals (n = 30) did not show any gross developmental toxicity (i.e., mortality, dysmorphology or non-hatching) at the highest concentration tested. Twelve of the 31 chemicals that did elicit developmental toxicity were toxic at the highest concentration only, and thirteen chemicals were developmentally toxic at concentrations of 10 µM or lower. Eleven chemicals caused behavioral effects; four chemicals (6-aminonicotinamide, cyclophosphamide, paraquat, phenobarbital) altered behavior in the absence of developmental toxicity. In addition to screening a library of chemicals for developmental neurotoxicity, we also compared our findings with previously published results for those chemicals. Our comparison revealed a general lack of standardized reporting of experimental details, and it also helped identify some chemicals that appear to be consistent positives and negatives across multiple laboratories.
鉴于环境中存在大量可能导致神经发育缺陷的化学物质，因此需要快速检测和化学筛选分析方法。本研究使用明暗行为分析评估了61种化学物质对斑马鱼幼体的发育毒性和行为影响。在发育期间，将幼体（每个浓度n = 16 - 24）暴露于每种化学物质（0.0001 - 120 μM）中，并评估其运动活性。在测试的最高浓度下，约一半的化学物质（n = 30）未表现出任何明显的发育毒性（即死亡率、畸形或不孵化）。在确实引发发育毒性的31种化学物质中，有12种仅在最高浓度下具有毒性，13种化学物质在10 μM或更低浓度下具有发育毒性。11种化学物质引起行为影响；4种化学物质（6 - 氨基烟酰胺、环磷酰胺、百草枯、苯巴比妥）在无发育毒性的情况下改变了行为。除了筛选化学物质库中的发育神经毒性外，我们还将我们的研究结果与之前发表的这些化学物质的结果进行了比较。我们的比较揭示了实验细节普遍缺乏标准化报告，并且还有助于识别一些在多个实验室中似乎一致表现为阳性和阴性的化学物质。
