Cancer is the second leading cause of death worldwide, with 9.6 million cancer-related deaths in 2018. Cancer incidence has increased over time, and so has the prescription rate of chemotherapeutic drugs. These pharmaceuticals, known as antineoplastic agents, enter the aquatic environment via human excretion and wastewater. The objectives of the present critical review were to investigate the risk of antineoplastics to aquatic species and to summarize the current state of knowledge regarding their levels in the environment, because many antineoplastics are not adequately removed during wastewater treatment. We conducted 2 separate literature reviews to synthesize data on the global environmental prevalence and toxicity of antineoplastics. The antineoplastics most frequently detected in the environment included cyclophosphamide, ifosfamide, tamoxifen, methotrexate, and 5-fluorouracil; all were detectable in multiple water sources, including effluent and surface waters. These antineoplastics span 3 different mechanistic classes, with cyclophosphamide and ifosfamide classified as alkylating agents, tamoxifen as a hormonal agent, and methotrexate and 5-fluorouracil as antimetabolites. Studies that characterize the risk of antineoplastics released into aquatic environments are scarce. We summarize the biological impacts of the most environmentally prevalent antineoplastics on aquatic organisms and propose an adverse outcome pathway for cyclophosphamide and ifosfamide, 2 widely prescribed drugs with a similar immunotoxic mode of action. Acute and chronic ecotoxicity studies using aquatic models are needed for risk characterization of antineoplastics. Environ Toxicol Chem 2020;39:967-985. © 2020 SETAC.

中文翻译：

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抗肿瘤药物：水生生物的环境流行率和不良后果。

癌症是全球第二大死亡原因，2018年有960万例与癌症相关的死亡。癌症的发生率随着时间的推移而增加，化学治疗药物的处方率也在增加。这些被称为抗肿瘤药的药物通过人类排泄物和废水进入水生环境。本批判性审查的目的是调查抗肿瘤药对水生物种的风险，并概述有关其在环境中水平的知识，因为在废水处理过程中许多抗肿瘤药没有被充分清除。我们进行了2次单独的文献综述，以合成有关抗肿瘤药的全球环境流行率和毒性的数据。在环境中最常检测到的抗肿瘤药包括环磷酰胺，异环磷酰胺，他莫昔芬，甲氨蝶呤和5-氟尿嘧啶；所有这些都可以在多种水源中检测到，包括废水和地表水。这些抗肿瘤药跨越3个不同的机理类别，其中环磷酰胺和异环磷酰胺被分类为烷基化剂，他莫昔芬被列为激素类药物，甲氨蝶呤和5-氟尿嘧啶被列为抗代谢物。缺乏表征抗肿瘤药释放到水生环境中的风险的研究。我们总结了环境上最普遍的抗肿瘤药对水生生物的生物学影响，并提出了环磷酰胺和异环磷酰胺这两种具有相似免疫毒性作用方式的广泛处方药物的不利结果途径。需要使用水生模型进行急性和慢性生态毒性研究，以表征抗肿瘤药的风险。Environ Toxicol Chem 2020； 39：967-985。