Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms

Abstract

Pharmaceutical compounds represent a class of emerging contaminants present in the environment. Their intense (and increasing) use in human and veterinary medicine leads to their discharge, mainly via human excretion, into wastewater treatment plants where their removal is inefficient. A specific class of pharmaceuticals used to fight cancer, known as antineoplastic or anticancer drugs, has gained increased attention regarding their possible environmental hazard due to their pharmacological properties, which include the nonselective targeting of DNA replication mechanisms and cell division processes, potentially inducing cell apoptosis. To date, there is limited information concerning the effects of anticancer drugs and/or their metabolites in species inhabiting freshwater environments, let alone marine and estuarine compartments. In the present review, we aimed to assemble information regarding the impact that anticancer drugs have on biological traits of marine species, to identify gaps in the current environmental hazard assessment, and to make recommendations to promote an efficient environmental hazard assessment of anticancer drugs in the marine environment. Environ Toxicol Chem 2022;41:1793–1807. © 2022 SETAC

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“…128 The presence of APs in the environment is a well-known phenomenon however, information about their biological effects on organisms is scarce. 126,127 Anticancer agents are cytotoxic and cytostatic drugs that target cancerous and noncancerous cells thus, eukaryotic organisms are prone to the side effects. 127 With the global incidence of cancer on the rise, several AP agents have been detected in the aquatic environment with the five most widely studied being: CP, IF, methotrexate, tamoxifen and 5-fluorouracil (5-FU).…”

“…126,127 Anticancer agents are cytotoxic and cytostatic drugs that target cancerous and noncancerous cells thus, eukaryotic organisms are prone to the side effects. 127 With the global incidence of cancer on the rise, several AP agents have been detected in the aquatic environment with the five most widely studied being: CP, IF, methotrexate, tamoxifen and 5-fluorouracil (5-FU). 125 Tamoxifen, an oestrogen receptor antagonist, is used individually or in combination with other drugs to treat hormone receptor-positive breast cancer.…”

“…125,127 A study performed by Pagano and colleagues observed the effects of tamoxifen on fertilization, embryogenesis and mitotic effects in the sea urchin. 127 Researchers observed the effects of tamoxifen on developmental toxicity resulting in early embryonic death.…”

“…126 Elevated concentrations of AP agents, 125 reaching levels on the order of micrograms per liter (µg/L), have been identified in in hospital effluents. 127 Despite this, there are limited environmental regulations overseeing their safety thresholds and wastewater treatment options for these compounds. 125 The presence of APs in untreated wastewater may result in acute and chronic effects in vulnerable aquatic species such as zebrafish and crustaceans.…”

“…125 The presence of APs in untreated wastewater may result in acute and chronic effects in vulnerable aquatic species such as zebrafish and crustaceans. 127 Chronic exposure to APs alters the genetic composition and cellcycle of aquatic flora and fauna with researchers deeming them as pseudo-resistant pollutants. 128 Individual APs are present at low concentrations with limited aquatic effects however, their combined effect results in additive and synergistic effects.…”