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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\u2013985. \u00a9 2020 SETAC<\/jats:p>\n               <jats:p>Abstract<\/jats:p>\n               <jats:p>The world population is aging and there is a higher prevalence of cancer and therefore, antineoplastic drugs. These drugs are a challenge for wastewater treatment plants and are present in the environment. The prevalence and biological impacts of antineoplastics in aquatic systems are summarized in the present review.<\/jats:p>","DOI":"10.1002\/etc.4687","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T04:05:49Z","timestamp":1586318749000},"page":"967-985","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Antineoplastic Agents: Environmental Prevalence and Adverse Outcomes in Aquatic Organisms"],"prefix":"10.1093","volume":"39","author":[{"given":"Alexis M.","family":"Wormington","sequence":"first","affiliation":[{"name":"Department of Environmental and Global Health, College of Public Health and Health Professions University of Florida Gainesville Florida USA"},{"name":"Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-4869","authenticated-orcid":false,"given":"Maite","family":"De Mar\u00eda","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine University of Florida Gainesville Florida USA"},{"name":"Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2621-0482","authenticated-orcid":false,"given":"Hajime G.","family":"Kurita","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine University of Florida Gainesville Florida USA"},{"name":"Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Joseph H.","family":"Bisesi","sequence":"additional","affiliation":[{"name":"Department of Environmental and Global Health, College of Public Health and Health Professions University of Florida Gainesville Florida USA"},{"name":"Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy D.","family":"Denslow","sequence":"additional","affiliation":[{"name":"University of Florida Genetics Institute Gainesville Florida USA"},{"name":"Department of Physiological Sciences, College of Veterinary Medicine University of Florida Gainesville Florida USA"},{"name":"Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Martyniuk","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Biomedical Sciences Neuroscience Gainesville Florida 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