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两种水蚤(大型蚤和双尾海蚤)对人类药物慢性影响的比较。

A comparison of the chronic effects of human pharmaceuticals on two cladocerans, Daphnia magna and Ceriodaphnia dubia.

机构信息

Pfizer, Environmental Sciences, Pharmacokinetics, Dynamics and Metabolism Pfizer Global Research and Development, Groton, CT 06423, USA.

出版信息

Chemosphere. 2010 Aug;80(9):1069-74. doi: 10.1016/j.chemosphere.2010.05.009. Epub 2010 Jun 14.

Abstract

Scientific researchers and regulators are focusing attention on trace quantities of pharmaceuticals in wastewater effluents and surface waters, resulting in an increased level of concern regarding the potential environmental impact of these compounds. The current European regulatory guideline requires evaluation of the chronic effects of active pharmaceutical ingredients on Daphniamagna. Based on the life cycle of D. magna, chronic studies to establish survival and reproductive endpoints require a 21 d exposure period. A similar organism, Ceriodaphniadubia, has a shorter life cycle and therefore survival and reproductive endpoints may be established following 7d of exposure. No observed effect concentrations and lowest observed effect concentrations for survival and reproduction were obtained for D. magna and C. dubia following exposure to six human pharmaceuticals and two metabolites (i.e. celecoxib, linezolid, varenicline, sunitinib, Compound A, ziprasidone and the M1 and M4 metabolites of torcetrapib). These data were evaluated to determine whether one organism may be considered more sensitive. Survival and reproduction data obtained from the C. dubia study provide similar outcomes to D. magna when determining the predicted environmental concentration/predicted no effect concentration (PEC/PNEC) ratios for surface water. Based on these data, C. dubia may be used as a cost-effective alternative and representative invertebrate species when assessing the potential risk of human pharmaceuticals.

摘要

科学研究人员和监管机构正在关注废水中痕量药物和地表水中的药物,这导致人们对这些化合物可能对环境产生的潜在影响的担忧日益增加。目前的欧洲监管指南要求评估活性药物成分对大型溞的慢性影响。基于大型溞的生命周期,为了建立生存和繁殖终点,慢性研究需要 21 天的暴露期。一种类似的生物——水蚤,其生命周期更短,因此在暴露 7 天后可能会建立生存和繁殖终点。在暴露于六种人类药物和两种代谢物(即塞来昔布、利奈唑胺、伐仑克林、舒尼替尼、化合物 A、齐拉西酮以及托伐普坦的 M1 和 M4 代谢物)后,获得了大型溞和水蚤的无观察效应浓度和最低观察效应浓度。对这些数据进行了评估,以确定是否可以认为一种生物更敏感。在确定地表水的预测环境浓度/无效应预测浓度(PEC/PNEC)比值时,水蚤研究中获得的生存和繁殖数据与大型溞提供的结果相似。基于这些数据,在评估人类药物的潜在风险时,水蚤可以作为一种具有成本效益的替代和代表性的无脊椎动物物种。

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