Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, Quinta de Prados, Vila Real, Portugal.
Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production, Vila Real, Portugal.
Environ Toxicol Chem. 2022 Aug;41(8):1851-1864. doi: 10.1002/etc.5338. Epub 2022 Jun 6.
Venlafaxine is a chiral antidepressant detected in aquatic compartments. It was recently included in the 3rd Watch List from the European Union. The present study aimed to investigate venlafaxine toxicity effects, targeting possible enantioselective effects, using two aquatic organisms, daphnia (Daphnia magna) and zebrafish (Danio rerio). Specimens were exposed to both racemate, (R,S)-venlafaxine (VEN), and to pure enantiomers. Acute assays with daphnia showed that up to 50 000 μg/L of the (R,S)-VEN induced no toxicity. Organisms were also exposed to sublethal concentrations (25-400 μg/L) of (R,S)-, (R)- and (S)-VEN, for 21 days. No significant effects on mortality, age at first reproduction, and size of the first clutch were observed. However, a decrease in fecundity was observed for both enantiomers at the highest concentration. Regarding zebrafish, the effects of venlafaxine on mortality, embryo development, behavior, biochemistry, and melanin pigmentation were investigated after 96 h of exposure to the range of 0.3-3000 μg/L. (R)-VEN significantly increased the percentage of malformations in comparison with (S)-VEN. Behavior was also enantiomer dependent, with a decrease in the total distance moved and an increase in avoidance behavior observed in organisms exposed to (R)-VEN. Despite the biochemical variations, no changes in redox homeostasis were observed. (R)-VEN also led to an increase in zebrafish pigmentation. The different susceptibility to venlafaxine and enantioselective effects were observed in zebrafish. Our results suggest that at environmental levels (R,S)-VEN and pure enantiomers are not expected to induce harmful effects in both organisms, but (R)-VEN increased malformations in zebrafish larvae, even at reported environmental levels. These results highlight the importance of including enantioselective studies for an accurate risk assessment of chiral pollutants. Environ Toxicol Chem 2022;41:1851-1864. © 2022 SETAC.
文拉法辛是一种在水生环境中检测到的手性抗抑郁药。它最近被列入了欧盟的第三份观察名单。本研究旨在使用两种水生生物，即大型溞（Daphnia magna）和斑马鱼（Danio rerio），研究文拉法辛的毒性效应，针对可能的对映选择性效应。研究对象接触了外消旋体（R，S）-文拉法辛（VEN）和纯对映异构体。急性试验表明，高达 50,000μg/L 的（R，S）-VEN 没有毒性。还将生物体暴露于亚致死浓度（25-400μg/L）的（R，S）-、（R）-和（S）-VEN 中 21 天。没有观察到死亡率、首次繁殖年龄和第一窝卵的大小有显著影响。然而，在最高浓度下，两种对映体的繁殖力都有所下降。关于斑马鱼，在暴露于 0.3-3000μg/L 范围内的 96 小时后，研究了文拉法辛对死亡率、胚胎发育、行为、生物化学和黑色素沉着的影响。与（S）-VEN 相比，（R）-VEN 显著增加了畸形的百分比。行为也依赖于对映体，与（S）-VEN 相比，暴露于（R）-VEN 的生物体的总移动距离减少，回避行为增加。尽管生化发生了变化，但没有观察到氧化还原平衡的变化。（R）-VEN 还导致斑马鱼色素沉着增加。斑马鱼对文拉法辛的不同敏感性和对映选择性效应。我们的结果表明，在环境水平下，（R，S）-VEN 和纯对映异构体预计不会对两种生物造成有害影响，但（R）-VEN 甚至在报告的环境水平下也会增加斑马鱼幼虫的畸形。这些结果强调了进行对映选择性研究对于手性污染物准确风险评估的重要性。环境毒理化学 2022；41:1851-1864。 2022 年 SETAC 版权所有。
