Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.
Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.
Environ Toxicol Chem. 2020 May;39(5):967-985. doi: 10.1002/etc.4687. Epub 2020 Apr 7.
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.
癌症是全球第二大死亡原因，2018 年有 960 万人因癌症死亡。随着时间的推移，癌症的发病率一直在上升，化疗药物的处方率也在上升。这些药物被称为抗肿瘤药物，通过人类排泄和废水进入水生环境。本批判性综述的目的是研究抗肿瘤药物对水生物种的风险，并总结其在环境中水平的现有知识状况，因为许多抗肿瘤药物在废水处理过程中没有被充分去除。我们进行了两次独立的文献综述，以综合全球环境中抗肿瘤药物的流行情况和毒性数据。环境中最常检测到的抗肿瘤药物包括环磷酰胺、异环磷酰胺、他莫昔芬、甲氨蝶呤和 5-氟尿嘧啶；所有这些药物都可以在多种水源中检测到，包括废水和地表水。这些抗肿瘤药物跨越了 3 种不同的作用机制类别，环磷酰胺和异环磷酰胺被归类为烷化剂，他莫昔芬是一种激素制剂，而甲氨蝶呤和 5-氟尿嘧啶是抗代谢物。描述释放到水生环境中的抗肿瘤药物风险的研究很少。我们总结了环境中最普遍的抗肿瘤药物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的不良结局途径，这两种药物都是广泛使用的具有类似免疫毒性作用模式的药物。需要使用水生模型进行急性和慢性生态毒性研究，以对抗肿瘤药物进行风险特征描述。环境毒物化学 2020；39：967-985。©2020 SETAC。
