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布洛芬:基于 OECD 229 扩展协议的斑马鱼(Danio rerio)短期鱼类繁殖试验。

Ibuprofen: Fish Short-Term Reproduction Assay with Zebrafish (Danio rerio) Based on an Extended OECD 229 Protocol.

机构信息

Pfizer Worldwide Research and Development, Groton, Connecticut, USA.

John W. Green Ecostatistical Consulting, Newark, Delaware, USA.

出版信息

Environ Toxicol Chem. 2020 Aug;39(8):1534-1545. doi: 10.1002/etc.4742. Epub 2020 Jul 8.

Abstract

A study was conducted to understand the potential for ibuprofen to impact the hypothalamus-pituitary-gonadal endocrine axis resulting in disruption of fish reproduction. The Good Laboratory Practice study was conducted according to the Organisation for Economic Co-operation and Development 229 Protocol, Fish Short-Term Reproduction Assay, and extended an additional 4 d to evaluate hatching success in the F1 generation. Test organisms were exposed to nominal test concentrations of 0.5, 2.4, 11.5, 55.3, and 265.4 µg ibuprofen/L and a negative control (dilution water). To strengthen the statistical power of the study, twice the number of replicates were used in the negative control versus individual treatment levels. A 21-d pre-exposure to identify groups of actively spawning fish was immediately followed by a 36-d exposure. Results for apical endpoints of survival, growth, and reproduction (fecundity and fertility), as well as the biomarker vitellogenin in the F0 generation and time to hatch and hatching success in the F1 generation are presented. Based on mean measured exposure concentrations and effects on fecundity in the F0 generation and hatching success in the F1 generation, overall no-observed-effect concentration and lowest-observed-effect concentration for the present study were 55.2 and 265.9 µg ibuprofen/L, respectively. Results from the present study indicate a lack of endocrine-mediated reproductive effects in zebrafish at environmentally relevant concentrations of ibuprofen. Environ Toxicol Chem 2020;39:1534-1545. © 2020 SETAC.

摘要

一项研究旨在了解布洛芬对下丘脑-垂体-性腺内分泌轴的潜在影响,从而破坏鱼类的生殖能力。该良好实验室规范研究是根据经济合作与发展组织的 229 号议定书进行的,即鱼类短期生殖试验,并延长了 4 天,以评估 F1 代的孵化成功率。受试生物暴露于名义测试浓度为 0.5、2.4、11.5、55.3 和 265.4 µg/L 的布洛芬和阴性对照(稀释水)中。为了增强研究的统计效力,阴性对照与各个处理水平相比,使用了两倍的重复次数。21 天的预暴露用于识别活跃产卵的鱼类群体,随后立即进行 36 天的暴露。呈现了 F0 代的顶端终点生存、生长和繁殖(生育力和育性)以及生物标志物卵黄蛋白原,以及 F1 代的孵化时间和孵化成功率的结果。基于平均测量的暴露浓度以及对 F0 代生育力和 F1 代孵化成功率的影响,本研究的总体无观察到效应浓度和最低观察到效应浓度分别为 55.2 和 265.9 µg/L 布洛芬。本研究的结果表明,在环境相关浓度的布洛芬作用下,斑马鱼没有表现出内分泌介导的生殖效应。环境毒理化学 2020;39:1534-1545。2020 年 SETAC 版权所有。

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