National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada.
Environ Toxicol Chem. 2018 Dec;37(12):3134-3144. doi: 10.1002/etc.4260. Epub 2018 Nov 15.
As the number of chemicals developed and used by industry increases, the inherent limitations of traditional toxicology approaches become an unavoidable issue. To help meet the demand for toxicity evaluation, new methods, such as high-throughput toxicity screening, are currently being developed to permit rapid determination of toxic, molecular, and/or biochemical effects of a wide range of chemicals. In the present study, we demonstrate the utility of an avian in vitro toxicogenomics screening approach to determine the cytotoxic and transcriptomic effects of 10 organic flame retardants (OFRs) currently of international priority for ecological risk evaluation to prioritize and inform future toxicological studies. Hepatocytes from 2 avian species, chicken and double-crested cormorant, were prepared and exposed for 24 h to various concentrations (0-300 μM) of the following 10 OFRs: Chemical Abstracts Service registration numbers 29761-21-5, 56803-37-3 (p-tert-butylphenyl diphenyl phosphate [BPDP]), 65652-41-7, 68937-41-7 (phenol, isopropylated, phosphate [3:1] [IPPP]), 95906-11-9, 19186-97-1, 26040-51-7, 35948-25-5, 21850-44-2, and 25713-60-4. Cell viability, the 7-ethoxyresorufin-O-deethylase assay, and transcriptomic analysis using species-specific ToxChip polymerase chain reaction arrays were performed to evaluate the in vitro effect of these OFRs. Of the 10 OFRs assessed, BPDP and IPPP elicited the strongest cytotoxic and transcriptomic responses in both chicken and double-crested cormorant hepatocytes and are therefore recommended as priority candidates for further wildlife toxicological investigations. Environ Toxicol Chem 2018;37:3134-3144. © 2018 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.
随着工业开发和使用的化学物质数量的增加，传统毒理学方法的固有局限性成为一个不可避免的问题。为了满足毒性评估的需求，目前正在开发新的方法，如高通量毒性筛选，以允许快速确定广泛化学物质的毒性、分子和/或生化效应。在本研究中，我们展示了一种禽类体外毒理学基因组学筛选方法的实用性，以确定 10 种目前国际优先进行生态风险评估的有机阻燃剂 (OFR) 的细胞毒性和转录组效应，以确定优先级并为未来的毒理学研究提供信息。从 2 种禽类物种（鸡和双冠鸬鹚）制备肝细胞，并暴露于 10 种以下 OFR 的各种浓度（0-300μM）24 小时：化学文摘社登记号 29761-21-5、56803-37-3（对叔丁基苯基二苯基磷酸酯 [BPDP]）、65652-41-7、68937-41-7（苯酚，异丙基化，磷酸酯 [3:1] [IPPP]）、95906-11-9、19186-97-1、26040-51-7、35948-25-5、21850-44-2 和 25713-60-4。使用物种特异性 ToxChip 聚合酶链反应阵列进行细胞活力、7-乙氧基resorufin-O-脱乙基酶测定和转录组分析，以评估这些 OFR 的体外效应。在评估的 10 种 OFR 中，BPDP 和 IPPP 在鸡和双冠鸬鹚肝细胞中引起最强的细胞毒性和转录组反应，因此被推荐为进一步进行野生动物毒理学研究的优先候选物。环境毒理化学 2018；37:3134-3144。©2018 加拿大王室。由 Wiley Periodicals Inc. 代表 SETAC 出版。
