Toxicity toward freshwater and marine water organisms of the cytostatic drugs bleomycin and vincristine and their binary mixture.

Antineoplastic drugs are not effectively removed by wastewater treatment plants, ending up in surface waters. Since these drugs can interfere with the structure and functions of DNA, they pose a potential threat to aquatic biota. Unfortunately, many chemotherapeutic agents have not been studied in an environmental context. Additionally, there is a significant lack of information about the impact of anticancer drugs on marine organisms compared to freshwater species, and most studies only focus on the toxicity of single compounds rather than considering their occurrence as complex mixtures in the environment. Therefore, the aim of this study was to evaluate the ecotoxicity of two commonly used cytostatics, bleomycin and vincristine, toward six biomodels: Pseudokirchneriella subcapitata, Phaeodactylum tricornutum, Brachionus plicatilis, Brachionus calyciflorus, Thamnocephalus platyurus, and Artemia franciscana. These selected aquatic organisms are representatives of both freshwater and marine environments and belong to different trophic levels. The pharmaceuticals were investigated both individually and in combination. Binary mixture toxicity predictions were performed according to the Response Additivity and Independent Action models. Additionally, the toxicity data obtained from these experiments were utilized for risk assessment in the context of the drugs' environmental occurrence. The results indicated that freshwater species were generally more sensitive to both tested compounds than marine organisms, with T. platyurus being the most sensitive. Based on the tests performed on this biomodel, bleomycin was categorized as extremely toxic, while vincristine was considered moderately toxic. Neither of the applied models suitably predicted binary mixture toxicity, as the combination of drugs showed additive, synergistic, and antagonistic effects, suggesting that single compound toxicity data are insufficient for predicting the aquatic toxicities of cytostatics mixtures. The environmental risk of vincristine ranged from low to high, and for bleomycin varied from moderate to high, depending on the matrices examined. Therefore, further research on drug removal is recommended.

Removal of two cytostatic drugs: bleomycin and vincristine by white-rot fungi - a sorption study.

PURPOSE: Cytostatic drugs cannot be easily removed by conventional sewage treatment plants, resulting in their ultimate release into aquatic systems where they become a threat. Thus, new technologies which can be used to eliminate these drugs more effectively before they enter the environment are increasingly important. Fungal treatment of wastewaters is a promising and environmentally friendly technology for pharmaceutical remediation. The aim of this work is to examine the biosorption of two cytostatics, bleomycin and vincristine, in the aqueous solution by fungal biomass. METHODS: Five white-rot fungi were used in this study: Fomes fomentarius (CB13), Hypholoma fasciculare (CB15), Phyllotopsis nidulans (CB14), Pleurotus ostreatus (BWPH), and Trametes versicolor (CB8). Tests were conducted on different types of biomass (alive and dead - autoclaved) and in various physico-chemical conditions: varied drug concentrations (5, 10 and 15 mg/L), temperatures (from 15.4 to 29.6 °C), and pH (from 3.2 to 8.8). RESULTS: The results showed that among alive biomass, T. versicolor (CB8) had the greatest sorption ability for bleomycin and P. nidulans (CB14) worked best for vincristine. The tested sorption process could be described by a pseudo-second order kinetics model. Sorption equilibrium studies demonstrated that for bleomycin Redlich-Peterson, while for vincristine Langmuir model fitted best. The thermodynamic studies showed that the sorption process was endothermic chemisorption for bleomycin, and exothermic physisorption for vincristine. For both drugs the sorption ability increased with an increase of the pH value. CONCLUSION: The biosorption on fungal biomass is a favorable alternative to conventional wastewater treatment processes for anticancer drug removal.

White-rot fungi-mediated biodegradation of cytostatic drugs - bleomycin and vincristine.

The contamination of the environment with anticancer drugs, which show recalcitrance to conventional wastewater treatment, has become a significant ecological threat. Fungi represent a promising non-conventional biological alternative for water conditioning. The aim of this work was to evaluate the efficacy of five white-rot fungi (Fomes fomentarius (CB13), Hypholoma fasciculare (CB15), Phyllotopsis nidulans (CB14), Pleurotus ostreatus (BWPH) and Trametes versicolor (CB8)) in the removal of bleomycin and vincristine. The removal capacity was measured at 0, 4, 9, and 14 days of incubation using SPE-UPLC-MS. The enzymatic profiles of laccase, manganese, and lignin peroxidases and wide range of eco- and cytotoxicity, assays of the post-process samples were also conducted. We observed >94% vincristine elimination by F. fomentarius, H. fasciculare and T. versicolor after only 4 days. Bleomycin removal occurred after a minimum of 9 days and only when the drug was incubated with T. versicolor (36%) and H. fasciculare (25%). The removal of both cytostatics was associated with laccase production, and the loss of eco- and cytotoxicity, especially in regard to viability of Lemna minor and Daphnia magna, as well as fibroblasts morphology.

Is Biochar from the Torrefaction of Sewage Sludge Hazardous Waste?

Improved technologies are needed for sustainable management of sewage sludge (SS). The torrefaction (also known as biomass "roasting") is considered a pretreatment of SS before use in agriculture. However, it is not known whether the torrefaction has the potential to decrease heavy metals' (HMs) leachability and the SS toxicity. Thus, the aim of the study was to evaluate the influences of the SS torrefaction parameters (temperature and process time) on HM contents in biochar, HM leachability, and biochar toxicity, and compare them with raw SS. The experiments were designed in 18 combinations (six temperatures, 200, 220, 240, 260, 280, and 300 °C; and three process times-20, 40, 60 min). Standard tests were used to determine HMs content, leachability, and toxicity. Results indicated that the torrefaction did not increase (p < 0.05) the HM content in comparison to the raw SS. The leachability of Zn, Ni, Cu, Cr, and Mn from SS biochars was similar to raw SS. However, the degree of leachability varied significantly (p < 0.05) from as low as 0.1% for Cu to high as 16.7% for Cd. The leachability of Cd (<16.7%) and Pb (<11.9%) from biochars was higher than from raw SS (<6.1% and <2.4%, respectively). The leachability of Cd from SS biochar, in five torrefaction combinations, was higher than the threshold value for hazardous waste. It is recommended that site-specific decisions are made for torrefaction of SS with respect to its HM content, as the resulting biochar could be considered as hazardous waste, depending on the feedstock. Moreover, the biochar produced under the whole range of temperatures during 20 min retention time significantly (p < 0.05) increased the Daphnia magna Straus mobility inhibition by up to 100% in comparison to the biochar obtained during 40 and 60 min torrefaction. Taking into account the increased leachability of specific HMs and D. magna Straus mobility inhibition, biochar should be considered a potentially hazardous material. Future research should focus on biochar dosage as a fertilizer in relation to its toxicity. Additional research is warranted to focus on the optimization of SS torrefaction process parameters affecting the toxicity.

Cytostatic pharmaceuticals as water contaminants.

Due to the growing problem of cancer diseases, cytostatic drugs have become a great environmental threat. Their main sources are hospital effluents, household discharge and drug manufacturers. As these compounds are not removed during wastewater treatment with sufficient efficiency, they are found in the surface, ground and drinking water in quantities up to 2.12 × 10-4 mg/l. The current knowledge about their harmful influence on humans does not indicate a significant risk to the health of water consumers, although it points to certain groups of risk (children and lactating women) in particular. In aquatic organisms, anticancer drugs in detected concentrations can cause chronic toxicity and have a detrimental impact on their genetic material. The acute toxicity effect is less likely. The HC5 value calculated by us (the concentration at which 5% of the species is potentially affected) equalling 2.1 × 10-4 mg/l shows that anticancer drugs are real hazardous contaminants for the environment. It indicates that effective elimination of cytostatics from water still requires intensive research.

Ecotoxicity risk of presence of two cytostatic drugs: Bleomycin and vincristine and their binary mixture in aquatic environment.

Cytostatic drugs have become one of the greatest environmental threats. They occur in surface, ground and even drinking water. Their key emission sources are hospital effluents, municipal wastewater, as well as drug manufacturers and their effluents. These compounds are extremely stable in natural waters and they are not significantly removed during wastewater treatment, because they are resistant to biodegradation. The aim of this work was to establish possible negative effects of chosen cytostatics: bleomycin and vincristine on the three trophic levels of surface waters. A single agent acute toxicity test was conducted on representatives of the producer - an aquatic freshwater plant Lemna minor, the consumer - crustaceans Daphnia magna, and the decomposer - bacteria Pseudomonas putida. Binary mixture tests were performed according to the Concentration Addition, Response Additivity, and Independent Action models. Both substances had a different effect on the tested organisms; bleomycin could be classified as a very toxic, while vincristine as a toxic water pollutant. Half maximal effective concentration (EC50) values designed in the presented single agent acute toxicity studies are < 10 mg/L in all the tests with bleomycin as well as vincristine conducted on L. minor. In tests with vincristine performed on D. magna and P. putida EC50 > 100 mg/L. The highest toxicity is demonstrated by bleomycin towards the aquatic freshwater plant (EC50 = 0.2 mg/L). The binary mixture of the tested chemicals showed antagonistic effects of environmental concern.