手性药物的水环境行为、毒性效应及生态风险

Chiral Pharmaceuticals in Aquatic Environments:Occurrence,Fate,Toxicity,and Ecological Risk

药物污染已经成为一个重要的环境问题,目前生产和使用的药物中大部分为手性药物,进入地表水环境后,2个对映异构体在生物降解和生态毒性等方面可能存在显著的差异。本文以8种手性药物为研究对象,系统综述了手性药物在水环境中的暴露特征和降解转化规律,分析其对不同生物靶点的毒性效应和机理,探讨了其对水生态系统的潜在风险。结果表明,8种手性药物在国内外地表水中的检出浓度达到μg·L^(-1)水平。手性药物在地表水环境中的对映体构成受药物种类、环境条件和时间的影响;布洛芬、普萘洛尔等差异显著的手性药物可以作为污染源示踪的特征污染物;不同污水处理工艺的对映体选择性也有较大差异,导致污水处理厂出水中手性药物对映体分数(enantiomer fraction,EF)值不同。由于手性药物在生物体内发生手性代谢和手性转化,导致体外毒性实验与体内毒性效果差异很大,手性药物在不同水生生物类群体内的受体或生物利用率有所差异,从而表现出不同的立体选择性。基于外消旋体的生态风险评估研究表明,目前布洛芬、卡马西平和萘普生等手性药物对水生生物具有潜在的风险,而不同对映体对水生生物的毒性存在一定差异。因此,有必要将手性药物的2种对映体当作2种独立的药品,进行更为精确的风险评估。

Pharmaceutical pollution has become an important environmental problem.Most of the currently produced and used pharmaceuticals are chiral,and there might be significant differences between the two enantiomers in terms of biodegradation and ecotoxicity when they enter the surface water environment.In this paper,the enantiomeric isomers were taken as the targets.We systematically reviewed the exposure characteristics and degradation transformation patterns of eight chiral pharmaceuticals in the aquatic environment,analyzed their toxic effects and mechanisms on different biological targets,and explored their potential risks to the aquatic ecosystem.The results showed that eight chiral pharmaceuticals were detected in surface water atμg·L^(-1)levels at home and abroad.The enantiomeric composition of chiral pharmaceuticals in surface water environment was influenced by pharmaceutical type,environmental conditions and time;significantly different chiral pharmaceuticals such as ibuprofen and propranolol could be used as characteristic pollutants for tracing pollution sources;the enantiomeric selectivity of different wastewater treatment processes also differed significantly,resulting in different enantiomer fraction(EF)values of chiral pharmaceuticals in wastewater treatment plant effluents.Chiral pharmaceuticals undergo chiral metabolism and chiral transformation in organisms,which could result in significant differences between in vitro toxicity assays and in vivo toxicity effects.Also,the receptors or bioavailability of chiral pharmaceuticals vary in different aquatic taxa,thus exhibit different stereoselectivity.Ecological risk assessment studies based on racemization have shown that chiral pharmaceuticals such as ibuprofen,carbamazepine and naproxen are currently a potential risk to aquatic organisms,while the toxicity of different enantiomers to aquatic organisms is different.Therefore,it is necessary to treat the two enantiomers of chiral pharmaceuticals as two separate pharmaceuticals for a more precise risk assessment.