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In Vitro Predictions of Acute Fish Toxicity for Development of Sustainable Crop Protection Products
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-12 , DOI: 10.1021/acs.jafc.4c01830 Tamara Lunsman 1 , Gyan Harwood 1 , Audrey Lehman 1 , Zachary Sutake 1 , Andrew Bowling 1 , Eric Sherer 1 , Heather Pence 1 , Wei Chen 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-12 , DOI: 10.1021/acs.jafc.4c01830 Tamara Lunsman 1 , Gyan Harwood 1 , Audrey Lehman 1 , Zachary Sutake 1 , Andrew Bowling 1 , Eric Sherer 1 , Heather Pence 1 , Wei Chen 1
Affiliation
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New agrochemicals must demonstrate safety to numerous ecological systems, including aquatic systems, and aquatic vertebrate toxicity is typically evaluated by using the in vivo acute fish toxicity (AFT) test. Here, we investigated two alternative in vitro assays using a cell line isolated from rainbow trout (Onchorhynchus mykiss) gill tissue: (i) adenosine triphosphate (ATP) luminescence and (ii) cell painting. The former assay measures cytotoxicity, while the latter measures changes in cellular morphology in response to chemical exposure. We assessed how well end points in these two assays predicted acute lethality (i.e., LC50 values) in independent in vivo AFT tests. When compared to results from OECD TG 249 (in vitro), we found that the ATP assay was not as predictive (R2 = 0.53) as the cell painting assay. Similarly, when compared to results from OECD TG 203 (in vivo), the cell painting was much more predictive (R2 = 0.67). Our results show that such in vitro assays are useful for fast and efficient screening alternatives to in vivo fish testing that can aid in the agrochemical discovery phase, where thousands of potential new actives are tested each year.
中文翻译：
用于开发可持续作物保护产品的急性鱼类毒性的体外预测
新农用化学品必须证明对包括水生系统在内的众多生态系统的安全性，并且通常通过使用体内急性鱼类毒性（AFT）测试来评估水生脊椎动物毒性。在这里，我们使用从虹鳟鱼 ( Onchorhynchus mykiss ) 鳃组织中分离的细胞系研究了两种替代体外测定：(i) 三磷酸腺苷 (ATP) 发光和 (ii) 细胞涂色。前一种测定测量细胞毒性，而后者测量细胞形态因化学暴露而发生的变化。我们评估了这两种测定中的终点在独立的体内 AFT 测试中预测急性致死率（即 LC 50值）的效果。与 OECD TG 249（体外）的结果相比，我们发现 ATP 测定的预测能力不如细胞涂色测定（ R 2 = 0.53）。同样，与 OECD TG 203（体内）的结果相比，细胞涂色更具预测性 ( R 2 = 0.67)。我们的结果表明，这种体外测定可用于快速有效地筛选体内鱼类测试的替代方案，有助于农用化学品的发现阶段，每年测试数千种潜在的新活性物质。
更新日期：2024-09-12
中文翻译：
用于开发可持续作物保护产品的急性鱼类毒性的体外预测
新农用化学品必须证明对包括水生系统在内的众多生态系统的安全性，并且通常通过使用体内急性鱼类毒性（AFT）测试来评估水生脊椎动物毒性。在这里，我们使用从虹鳟鱼 ( Onchorhynchus mykiss ) 鳃组织中分离的细胞系研究了两种替代体外测定：(i) 三磷酸腺苷 (ATP) 发光和 (ii) 细胞涂色。前一种测定测量细胞毒性，而后者测量细胞形态因化学暴露而发生的变化。我们评估了这两种测定中的终点在独立的体内 AFT 测试中预测急性致死率（即 LC 50值）的效果。与 OECD TG 249（体外）的结果相比，我们发现 ATP 测定的预测能力不如细胞涂色测定（ R 2 = 0.53）。同样，与 OECD TG 203（体内）的结果相比，细胞涂色更具预测性 ( R 2 = 0.67)。我们的结果表明，这种体外测定可用于快速有效地筛选体内鱼类测试的替代方案，有助于农用化学品的发现阶段，每年测试数千种潜在的新活性物质。
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