Do cytotoxic chemotherapy drugs discharged into rivers pose a risk to the environment and human health? An overview and UK case study (original) (raw)
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Environmental Toxicology and Chemistry, 2009
Cytotoxic, also known as antineoplastic, drugs remain an important weapon in the fight against cancer. This study considers the water quality implications for the Thames catchment (United Kingdom) arising from the routine discharge of these drugs after use, down the drain and into the river. The review focuses on 13 different cytotoxic drugs from the alkylating agent, antimetabolite, and anthracycline antibiotic families. A geographic-information-system-based water quality model was used in the present study. The model was informed by literature values on consumption, excretion, and fate data to predict raw drinking water concentrations at the River Thames abstraction points at Farmoor, near Oxford, and Walton, in West London. To discover the highest plausible values, upper boundary values for consumption and excretion together with lower removal values for sewage treatment were used. The raw drinking water cytotoxic drug maximum concentrations at Walton (the higher of the two) representative of mean and low flow conditions were predicted to be 11 and 20 ng/L for the five combined alkylating agents, 2 and 4 ng/L for the three combined antimetabolites, and 0.05 and 0.10 ng/L the for two combined anthracycline antibiotics, respectively. If they were to escape into tap water, then the highest predicted concentrations would still be a factor of between 25 and 40 below the current recommended daily doses of concern. Although the risks may be negligible for healthy adults, more concern may be associated with special subgroup populations, such as pregnant women, their fetuses, and breast-feeding infants, due to their developmental vulnerability.
Molecules, 2020
Potential risks associated with releases of human pharmaceuticals into the environment have become an increasingly important issue in environmental health. This concern has been driven by the widespread detection of pharmaceuticals in all aquatic compartments. Therefore, 22 pharmaceuticals, 6 metabolites and transformation products, belonging to 7 therapeutic groups, were selected to perform a review on their toxicity and environmental risk assessment (ERA) in different aquatic compartments, important issues to tackle the water framework directive (WFD). The toxicity data collected reported, with the exception of anxiolytics, at least one toxicity value for concentrations below 1 µg L −1. The results obtained for the ERA revealed risk quotients (RQs) higher than 1 in all the aquatic bodies and for the three trophic levels, algae, invertebrates and fish, posing ecotoxicological pressure in all of these compartments. The therapeutic groups with higher RQs were hormones, antiepileptics, anti-inflammatories and antibiotics. Unsurprisingly, RQs values were highest in wastewaters, however, less contaminated water bodies such as groundwaters still presented maximum values up to 91,150 regarding 17α-ethinylestradiol in fish. Overall, these results present an important input for setting prioritizing measures and sustainable strategies, minimizing their impact in the aquatic environment.
Occurrence of anticancer drugs in the aquatic environment: a systematic review
Environmental Science and Pollution Research
Water contamination with pharmaceutical products is a well-studied problem. Numerous studies have demonstrated the presence of anticancer drugs in different water resources that failed to be eliminated by conventional wastewater treatment plants. The purpose of this report was to conduct a systematic review of anticancer drugs in the aquatic environment. The methodology adopted was carried out in compliance with the PRISMA guidelines. From the 75 studies that met the specific requirements for inclusion, data extracted showed that the most common anticancer drugs studied are cyclophosphamide, tamoxifen, ifosfamide and methotrexate with concentrations measured ranging between 0.01 and 86,200 ng/L. There was significant variation in the methodologies employed due to lack of available guidelines to address sampling techniques, seasonal variability and analytical strategy. The most routinely used technique for quantitative determination was found to be solid-phase extraction followed by ...
Prioritising anticancer drugs for environmental monitoring and risk assessment purposes
Science of The Total Environment, 2014
Anticancer drugs routinely used in chemotherapy enter wastewater through the excretion of the nonmetabolised drug following administration to patients. This study considers the consumption and subsequent behaviour and occurrence of these chemicals in aquatic systems, with the aim of prioritising a selection of these drugs which are likely to persist in the environment and hence be considered for environmental screening programmes. Accurate consumption data were compiled from a hospital survey in NW England and combined with urinary excretion rates derived from clinical studies. Physical-chemical property data were compiled along with likely chemical fate and persistence during and after wastewater treatment. A shortlist of 15 chemicals (from 65) was prioritised based on their consumption, persistency and likelihood of occurrence in surface waters and supported by observational studies where possible. The ecological impact of these 'prioritised' chemicals is uncertain as the measured concentrations in surface waters generally fall below standard toxicity thresholds. Nonetheless, this prioritised sub-list should prove useful for developing environmental screening programmes.
Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment
Journal of Hazardous Materials, 2010
Pharmaceuticals are biologically active and persistent substances which have been recognized as a continuing threat to environmental stability. Chronic ecotoxicity data as well as information on the current distribution levels in different environmental compartments continue to be sparse and are focused on those therapeutic classes that are more frequently prescribed and consumed. Nevertheless, they indicate the negative impact that these chemical contaminants may have on living organisms, ecosystems and ultimately, public health. This article reviews the different contamination sources as well as fate and both acute and chronic effects on non-target organisms. An extensive review of existing data in the form of tables, encompassing many therapeutic classes is presented.
Occurrence and ecological risks of pharmaceuticals in a Mediterranean river in Eastern Spain
Environment International, 2020
Pharmaceuticals are biologically active molecules that may exert toxic effects to a wide range of aquatic organisms. They are considered contaminants of emerging concern due to their common presence in wastewaters and in the receiving surface waters, and the lack of specific regulations to monitor their environmental occurrence and risks. In this work, the environmental exposure and risks of pharmaceuticals have been studied in the Mijares River, Eastern Mediterranean coast (Spain). A total of 57 surface water samples from 19 sampling points were collected in three monitoring campaigns between June 2018 and February 2019. A list of 40 compounds was investigated using a quantitative target UHPLC-MS/MS method. In order to complement the data obtained, a wide-scope screening of pharmaceuticals and metabolites was also performed by UHPLC-HRMS. The ecological risks posed by the pharmaceutical mixtures were evaluated using species sensitivity distributions built with chronic toxicity data for aquatic organisms. In this study, up to 69 pharmaceuticals and 9 metabolites were identified, out of which 35 compounds were assessed using the quantitative method. The highest concentrations in water corresponded to acetaminophen, gabapentin, venlafaxine, valsartan, ciprofloxacin and diclofenac. The compounds that were found to exert the highest toxic pressure on the aquatic ecosystems were principally analgesic/anti-inflammatory drugs and antibiotics. These were: phenazone > azithromycin > diclofenac, and to a lower extent norfloxacin > ciprofloxacin > clarithromycin. The monitored pharmaceutical mixtures are expected to exert severe ecological risks in areas downstream of WWTP discharges, with the percentage of aquatic species affected ranging between 65% and 82% in 3 out of the 19 evaluated sites. In addition, five antibiotics were found to exceed antibiotic resistance thresholds, thus potentially contributing to resistance gene enrichment in environmental bacteria. This work illustrates the wide use and impact of pharmaceuticals in the area under study, and the vulnerability of surface waters if only conventional wastewater treatments are applied. Several compounds included in this study should be incorporated in future water monitoring programs to help in the development of future regulations, due to their potential risk to the aquatic environment.
Antineoplastic Agents: Environmental Prevalence and Adverse Outcomes in Aquatic Organisms
Antineoplastic Agents: Environmental Prevalence and Adverse Outcomes in Aquatic Organisms, 2020
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;00:1-19. © 2020 SETAC
Aquatic environmental assessment of the top 25 English prescription pharmaceuticals
2001
An environmental assessment is presented for the 25 most used pharmaceuticals in the National Health Service (NHS) in England in 2000. Predicted environmental concentrations (PECs) for the aquatic environment were calculated using conservative assumptions and all PECs exceeded 1 ng l À1 . The calculation of predicted no-effect concentration (PNEC) based on aquatic toxicity data from the literature was possible for eleven of the pharmaceuticals. PNECs were predicted with ECOSAR for 12 of the remaining 14 but no data was available for two of the compounds. The PEC/ PNEC ratio exceeded one for Paracetamol, Amoxycillin, Oxytetracycline and Mefenamic acid. Comparisons of the predicted concentrations of the compounds in sewage sludge based on either calculated sludge-water coefficients ðK d Þ; octanol water coefficients ðK ow Þ; acid base constants ðpKaÞ or environmental modelling revealed large variations. No toxicity data was available for the terrestrial environment and no assessment was made. r
Environmental research, 2015
Cytostatic drugs, used in chemotherapy, are excreted unchanged by urine and feces or modified as metabolites. Elimination of these drugs in wastewater treatment plants (WWTPs) is often incomplete and residues reach surface water. Their presence in the natural environment depends on consumption patterns, excretion fraction and the effectiveness of the wastewater treatment. This study compiled the total consumption of cytostatic drugs in Catalonia (NE Spain) and provides data on the occurrence and risk of anticancer drugs in the aquatic environment by calculating predicted environmental concentrations (PECs). PECs were estimated using publicly available consumption data in the period of 2010-2012, published or calculated excretion values and wastewater elimination rates for a suite of 132 compounds. This allows predicting the range of concentrations in effluent wastewaters and receiving waters. Out of the 132 cytostatics, mycophenolic acid and hydroxycarbamide had a PEC value higher than 10 ng L À 1 . PECs were compared with MECs (measured environmental concentrations) to evaluate the reliability of the estimation. A risk assessment was conducted to determine the potential adverse effects of cytostatics in the environment. All the risk quotients calculated using EC 50 in Daphnia magna were below 1, showing no significant risk.
Annals of the ”Dunarea de Jos” University of Galati. Fascicle II, Mathematics, Physics, Theoretical Mechanics, 2019
Currently, there is an urgent need to strengthen the scientific knowledge and to adopt the most appropriate means to monitor the emerging pollutants in different water and wastewater sources and at the same time to evaluate their actions and risks on human health. Emerging contaminants (ECs) or pollutants (EPs) are, in the widest sense, any synthetic or natural compound or any microorganism that is not ussualy found or monitored in the environment, with potentially known or suspected ecotoxicological and negative effects on human health. Among the EPs, pharmaceuticals and personal care products are well-known for their adverse reactions. Among pharmaceutical compounds, antibiotics such as amoxicillin, cefuroxime, ciprofloxacin etc. are recognized as a class of emerging contaminants due to the fact that these compounds have been massively administered to humans and animals and usually persist in the environment through a complex vicious cycle of biotransformation and bioaccumulation. Two other classes of emerging pollutants-endocrine disruptors and contraceptives-are compounds that can mimic or interfere with the normal function of hormones in the body. These substances can turn on, stop or alter the signals that hormones carry, which can in turn affect the normal functions of the body. As regards of pharmaceuticals, a set of programs has been launched in EU Member States to reduce the risks that they pose to human health and the environment, here including several comprehensive monitoring programs. In the light of the new regulations and the concerns regarding the presence of pharmaceuticals in the aquatic environment, the experimental design is a very important step in achieving the detection of selected compounds, such as antibiotics, anti-inflammatory, endocrine disruptors and contraceptives, in the Romanian aquatic natural ecosystems. In this paper we highlighted the ecotoxicological effects of selected ECs and EPs, as well as the proposed methodology for their analysis.