Toxicology Centre, University of Saskatchewan, Saskatoon, Canada.
Department of Soil Science, University of Saskatchewan, Saskatoon, Canada.
Food Chem Toxicol. 2022 Dec;170:113502. doi: 10.1016/j.fct.2022.113502. Epub 2022 Oct 29.
In vitro cell systems can support hazard characterization and identify mechanisms involved in toxicity; however, using in vitro data for risk assessment still is challenging. As part of an effort to develop approaches for a complex operating site used for biocide packaging and distribution, we evaluated in vitro assays that could be used in a site management format. Across 66 studies, 108 pesticides were assessed on ten human-derived cell types at four endpoints. In vitro IC50s were compared to in vivo guidelines, NOEL/NOAELs, and ADIs using Spearman correlation and linear regression models. While human neuroblastoma cells (SH-SY5Y) were the most sensitive, HepG2 was the most used cell line in evaluating the toxicity of pesticides. Amongst the ten human cell lines, the IC50s derived from SH-SY5Y cells, using MTT-24 & 48 h (the most used assay) correlated (rho = 0.56-0.79; p < 0.05) with ADIs and NOEL/NOAELs. Although in vitro cell systems have some limitations, the correlation between in vitro data derived from SH-SY5Y cells and in vivo safety guidelines can provide site investigators with a tool to survey and prioritize areas and media of concern at complex operating sites impacted by pesticide mixtures.
体外细胞系统可以支持危害特征描述，并确定毒性涉及的机制；然而，将体外数据用于风险评估仍然具有挑战性。作为为用于生物杀灭剂包装和分销的复杂操作现场开发方法的努力的一部分，我们评估了可用于现场管理格式的体外测定法。在 66 项研究中，评估了十种人体来源的细胞类型上的 108 种农药在四个终点的作用。使用 Spearman 相关性和线性回归模型，将体外 IC50s 与体内指南、NOEL/NOAELs 和 ADIs 进行了比较。虽然人神经母细胞瘤细胞（SH-SY5Y）是最敏感的，但 HepG2 是评估农药毒性时使用最多的细胞系。在十种人体细胞系中，使用 MTT-24 和 48 小时（使用最广泛的测定法）的 SH-SY5Y 细胞得出的 IC50s 与 ADIs 和 NOEL/NOAELs 相关（rho=0.56-0.79；p<0.05）。尽管体外细胞系统存在一些局限性，但源自 SH-SY5Y 细胞的体外数据与体内安全指南之间的相关性可为现场调查人员提供一种工具，用于调查和优先考虑受农药混合物影响的复杂操作现场的关注区域和介质。
