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卡马西平、双氯芬酸和美托洛尔对鱼类胚胎的毒性。

Fish embryo toxicity of carbamazepine, diclofenac and metoprolol.

机构信息

Laboratory for Ecological Risk Assessment, RIVM, PO Box 1, Bilthoven 3720 BA, The Netherlands.

出版信息

Ecotoxicol Environ Saf. 2010 Nov;73(8):1862-6. doi: 10.1016/j.ecoenv.2010.08.031. Epub 2010 Sep 15.

DOI:10.1016/j.ecoenv.2010.08.031
PMID:20832863
Abstract

Frequently measured pharmaceuticals in environmental samples were tested in fish embryo toxicity (FET) tests with Danio rerio, based on the draft OECD test protocol. In this FET test 2-h-old zebrafish embryos were exposed for 72 h to carbamazepine, diclofenac and metoprolol to observe effects on embryo mortality, gastrulation, somite formation, tail movement and detachment, pigmentation, heartbeat, malformation of head, otoliths and heart, scoliosis, deformity of yolk, and hatching success at 24, 48 and 72 h. We found specific effects on growth retardation above 30.6 mg/l for carbamazepine, on hatching, yolk sac and tail deformation above 1.5mg/l for diclofenac, and on scoliosis and growth retardation above 12.6 mg/l for metoprolol. Scoring all effect parameters, the 72-h-EC(50) values were: for carbamazepine 86.5mg/l, for diclofenac 5.3mg/l and for metoprolol 31.0mg/l (mean measured concentrations). In conclusion, our results for carbamazepine and metoprolol are in agreement with other findings for aquatic toxicity, and also fish embryos responded in much the same way as rat embryos did. For diclofenac, the FET test performs comparably to Early Life Stage testing.

摘要

在鱼类胚胎毒性(FET)测试中,通常会检测环境样本中的常用药物,这些测试是基于 OECD 测试草案进行的,使用斑马鱼(Danio rerio)作为受试生物。在这项 FET 测试中,将 2 小时龄的斑马鱼胚胎暴露于卡马西平、双氯芬酸和美托洛尔中 72 小时,以观察对胚胎死亡率、原肠胚形成、体节形成、尾部运动和分离、色素沉着、心跳、头部、耳石和心脏畸形、脊柱侧凸、卵黄变形以及孵化成功率的影响,分别在 24、48 和 72 小时进行观察。我们发现卡马西平在 30.6mg/L 以上时会导致生长迟缓,双氯芬酸在 1.5mg/L 以上时会导致孵化、卵黄囊和尾部畸形,美托洛尔在 12.6mg/L 以上时会导致脊柱侧凸和生长迟缓。对所有效应参数进行评分后,72 小时 EC50 值分别为:卡马西平 86.5mg/L、双氯芬酸 5.3mg/L 和美托洛尔 31.0mg/L(实测浓度平均值)。总之,我们对卡马西平和美托洛尔的研究结果与其他水生毒性研究结果一致,而且鱼类胚胎的反应方式与大鼠胚胎非常相似。对于双氯芬酸,FET 测试与早期生命阶段测试具有可比性。

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