Detection of anti-cancer drugs and metabolites in the effluents from a large Brazilian cancer hospital and an evaluation of ecotoxicology.

Abstract

The use of chemotherapy agents has been growing worldwide, due to the increase number of cancer cases. In several countries, mainly in Europe countries, these drugs have been detected in hospitals and municipal wastewaters. In Brazil this issue is poorly explored. The main goal of this study was to assess the presence of three anti-cancer drugs, 5-fluorouracil (5-FU), gemcitabine (GEM) and cyclophosphamide (CP), and two metabolites, alpha-fluoro-beta-alanine (3-NH2-F) and 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF), in effluents from a large cancer hospital, in the municipal wastewater treatment plant (WWTP) influent and effluent, and also to evaluate toxicity of the mixtures of these compounds by ecotoxicological testing in zebrafish. The sample collections were performed in Barretos Cancer Hospital of the large cancer center in Brazil. After each collection, the samples were filtered for subsequent Liquid Chromatography Mass Spectrometry analysis. The presence of CP, GEM, and both metabolites (3-NH2-F and 2-DOH-DiF) were detected in the hospital wastewater and the WWTP influent. Three drugs, GEM, 2-DOH-DiF and CP, were detected in the WWTP effluent. Two drugs were detected below the limit of quantification, 2-DOH-DiF: <LOQ (above 1400ngL-1) and CP: <LOQ (above 300ngL-1), and GEM was quantified at 420ngL-1. Furthermore, 2-DOH-DiF (116,000ngL-1) was detected at the highest level in the hospital wastewater. There were no zebrafish deaths at any of the concentrations of the compounds used. However, we observed histological changes, including aneurysms and edema in the gills and areas of necrosis of the liver. In summary, we found higher concentrations of CP, GEM and both metabolites (3-NH2-F and 2-DOH-DiF) were detected for the first time. There is currently no legislation regarding the discharge of anti-cancer drugs in effluents in Brazil. This study is first to focus on effluents from specific treatments from a large cancer hospital located in small city in Brazil.