FLAVIO KIYOSHI TOMINAGA

FLAVIO KIYOSHI TOMINAGA

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Application of electron beam irradiation for remediation of pharmaceutical compounds in water
2022 - TOMINAGA, F.K.; BOIANI, N.F.; SILVA, T.T.; LEO, P.; BORRELY, S.I.
A significant number of pharmaceutical active compounds have been released in the aquatic environment. These compounds are not fully removed from water and wastewater treatment plants. Furthermore, these contaminants are not commonly monitored, and they possess the potential to cause adverse ecological and human health effects. Electron Beam Irradiation (EBI) have been applied as an alternatively green method in water management, being efficient for removing organic recalcitrant pollutants at low doses. This work aims to assess the effect of EBI on toxicity of four pharmaceuticals from distinct class (anti-inflammatory, antidepressant, antibiotic, and antidiabetic) using organism from different trophic levels. Acetylsalicylic acid and fluoxetine hydrochloride were obtained from Labsynth (>99.5%) and Divis Pharmaceuticals Pvt. Ltd (98.8%), respectively. Metformin hydrochloride (97%) and ciprofloxacin (>98%) were purchased from Sigma- Aldrich. All aqueous solution were diluted using ultra-pure water. Acute toxicity assays with Daphnia similis and Vibrio fischeri were based on ABNT/NBR standard methods. The evaluated endpoint was immobility and bioluminescence inhibition, respectively. The yeast assays were carried by monitoring of changes in the specific conductivity of suspensions of S. cerevisiae. All the assays were performed in triplicate. The toxicity results of the microcrustacean and the bacteria were expressed in Toxicity Factor. For the yeast, data were analyzed by F-test and t-test using a significance level of 0.05. The UV-Vis spectrum showed changes in all pharmaceutical’s spectrum after irradiation at 2.5 kGy. The toxicity results indicated that the effects varied depending on the organism and the studied pharmaceutical. For acetylsalicylic acid, increase of toxicity was observed for all three the organism. In contrast, for fluoxetine, a great toxicity removal was achieved for D. similis while and for the bacteria and the yeast no changes of toxicity were noted. Regarding metformin, the radiolytic byproducts were only toxic to the microcrustacean, possibly including residual hydrogen peroxide. Finally, for ciprofloxacin, toxicity increase was verified for D. similis and V. fischeri, while detoxification was observed for S. cerevisiae. In conclusion, the present work demonstrated EBI is effective for removing pharmaceuticals and showed the importance of using different organism for toxicity assessment.
Assessment of binary mixture toxicity of pharmaceuticals of environmental concern to aquatic organisms
2022 - BOIANI, N.F.; TOMINAGA, F.K.; SILVA, T.T.; REDÍGOLO, M.M.; BORRELY, S.I.
Pharmaceutical products have been frequently detected in aquatic environments as mixtures. They may cause direct toxic effects to aquatic organisms and indirect effects on ecosystems, due to interactions which induce additive, synergistic or antagonistic effects. The classical mathematical models of concentration addition and independent action of pollutants have been extensively used for predicting the mixture effects of chemicals of environmental relevance. The objective of this study was to assess the binary mixture toxicity of pharmaceuticals: fluoxetine and propranolol; fluoxetine and sulfadiazine; fluoxetine and caffeine, in acute tests with Daphnia similis carried out based on ABNT/NBR standard methods. The prediction of the acute effects to binary mixture was performed considering the mentioned mathematical models and deviations of them (synergism/antagonism; concentration level-dependent or concentration ratio-dependent), using an automated Excel spreadsheet. For the mixture of propranolol + fluoxetine, the concentration addition model best described the mixture effects, which explained most of the variability of acute toxic responses. Through the concentration level-dependent, synergism at low doses and antagonism at high doses was pointed out. The concentration addition model better described the effects of the binary mixture of sulfadiazine + fluoxetine. Synergism related to the independent action model and an antagonism related to the concentration ratio-depend were identified. For caffeine + fluoxetine mixture, the concentration addition model described slightly better the effects of this binary mixture, synergism concentration level-dependent and dose ratio-dependent were identified. We can conclude that the nature of the interaction between the compounds of a mixture depends on effect level and on the ratio in which each one is applied. Major effects of the binary mixture were detected in the zone between the effects predicted by the evaluated models. The synergism/antagonism or additivity do not depend on the similarity/dissimilarity of the mode of action of the compounds of a mixture, showing a different behaviour respect to the theoretical assumptions.
Avaliação da toxicidade de surfactantes não iônico e aniônico submetidos a tratamento por feixe de elétrons
2021 - GARCIA, VANESSA S.G.; TOMINAGA, FLAVIO K.; BOIANI, NATHALIA F.; SILVA, THALITA T.; ROSA, JORGE M.; BORRELY, SUELI I.
Toxicity assessment of acetylsalicylic acid using Saccharomyces cerevisiae
2021 - TOMINAGA, F.; LEO, P.; BORRELY, S.I.
Urban and industrial growth has triggered the release of toxic compounds into the environment, causing negative impacts on the population and ecosystems. Among the pollutants, pharmaceuticals have drawn attention due to potential of impacting the environment at ecological relevant concentrations. Aspirin is widely used in human medicine as an analgesic, antipyretic and in actively preventing platelet aggregation, and it is frequently detected in influent samples at relatively high concentrations. The yeast Saccharomyces cerevisiae consists in simple eukaryotic model, widely used for toxicity assessment. The current study aims to evaluate the toxicity of the anti-inflammatory acetylsalicylic acid (aspirin) using viability and conductometric assays. The viability assays were based on the evaluation of the number of viable cells present in a cell suspension after 1 hour exposure, while the conductometric tests were done by monitoring of changes in the specific conductivity of suspensions of S. cerevisiae due to inhibition of fermentation in toxic conditions after 30 minutes of exposure. The viability tests showed no reduction of viability at the evaluated concentrations (up to 100 mg L-1). The conductometric assays demonstrated low sensibility of the yeast to aspirin with EC5030min of 815 mg L-1. The results also indicated that there was no increase in the sensitivity of conductometric assays even at 6 hours of exposure. Furthermore, the acute toxicity data was compared with data obtained from in silico toxicity models (ECOSAR). Toxicity data collated from the software from different trophic levels showed EC5096h, LC5048h and LC96h of 867, 1774 and 777 mg L-1 for green algae, daphnid and fish, respectively, indicating low toxicity of aspirin.
Acute toxicity assessment for binary and tertiary mixtures containing fluoxetine, propranolol and diclofenac to microcrustacean and zebrafish embryos
2019 - TOMINAGA, F.; BOIANI, N.F.; SANTANA, N.D.; BORRELY, S.I.
Pharmaceuticals are essential for treatment and prevention of several diseases and for the maintenance of human and animal’s life quality. Due to the increasing use of pharmaceuticals worldwide, many actives substances are currently detected in μg.L-1 and ng.L-1 in different environmentals matrices such as surface water, ground water, soil and sediment. Many of these emerging pollutants are recalcitrant to biological treatment process in WWTPs and they may cause ecotoxicological effects on organisms and also possible to reach the human food chain. Pharmaceuticals are frequently detected as mixtures and may induce toxic effects to aquatic organisms, producing synergistic, additive or antagonistic toxic effects. Fluoxetine hydrochloride (FXT) is a selective serotonin reuptake inhibitor, prescribed as an antidepressant. Propranolol (PRP) is a beta-adrenergic blocker widely prescribed for the treatment of cardiovascular diseases and diclofenac sodium (DIC) is a non-steroidal anti-inflammatory drug, often recognized as the “world’s most popular pain killer”. These compounds are worldwide used for healthy treatment and also often detected in aquatic environments. This work aims to assess the toxicity of three pharmaceutical individually and in a mixture for both Daphnia similis and zebrafish embryos. The results of individual acute toxicity showed that the microcrustacean was more sensitive to FXT (EC50 = 1.08 mg/L), PRP (EC50 = 5.92 mg/L) and DIC (EC50 = 25.0 mg/L), respectively, while for zebrafish embryos, it was only calculated LC50 of 30.5 mg/L for DIC, after 48h exposure. Antagonistic effects of binary mixtures of FLX + PRP (EC50 = 9.38%) and FXT + DIC (EC50 = 24.2%) were observed to D. similis. For Danio rerio embryos, binary mixture of FLX + DIC (LC50 = 82.1%) presented antagonistic effects, while no acute toxicity was observed for the of FXT + PRP mixture. Tertiary mixture of the three compounds showed an antagonist effect (EC50 = 5.57%) for the microcrustacean and additive effect for zebrafish embryos (LC50 = 87.5%). In conclusion, most of the binary mixture resulted in antagonistic effects, in which the response of acute toxicity depended on the organism and type of pharmaceutical mixture. Therefore, it is necessary further studies to assess the toxicity of different mixtures.
Effect of electron beam irradiation on mineralization and toxicity of aspirin
2019 - TOMINAGA, F.K.; SILVA, T.T.; JESUS, J.M.S. de; BOIANI, N.F.; TEIXEIRA, A.C.S.C.; BORRELY, S.I.
Electron Beam Irradiation (EBI) is an important technology for degradation, mineralization and detoxification of pollutants. In this work, total organic carbon (TOC) and toxicity was evaluated for aspirin after Electron Beam Irradiation at doses of 1.0, 2.5 and 5.0 kGy. Low mineralization was achieved at all applied doses. Toxicity increase and hydrogen peroxide formation was observed with the increase of absorbed dose. EBI can be an interesting alternative process applied as a pre-treatment for alternatives AOPs.
Toxicidade do Propranolol (comercial versus manipulado), e de sua mistura com o cloridrato de fluoxetina, quando tratado por radiação ionizante
2018 - BOIANI, NATHALIA F.; GARCIA, VANESSA S.G.; TOMINAGA, FLAVIO K.; BORRELY, SUELI I.
Synthesis and characterization of magnetic graphene oxide nanocomposites
2018 - TOMINAGA, F.K.; SAKATA, S.K.; SOARES, J.J.S.; JACOVONE, R.M.S.
Graphene oxide (GO) is a unique material that can be described as a single monomolecular layer of graphite containing various oxygen functionalities such as epoxide, carbonyl, carboxyl and hydroxyl groups. Chemical modifications at the surface of the graphene oxide through the incorporation of magnetite can provide magnetic properties to these nanomaterials. This work aims to synthesize and characterize graphene oxide/magnetite (GO/M) nanocomposites, evaluating the different proportions of incorporated magnetite. The synthesis of graphene oxide/magnetite nanocomposites was performed by co-precipitation of iron salts on the graphene oxide (GO) particles in alkaline medium. The characterization of the nanocomposites was performed by thermogravimetric analysis (TGA), infrared spectroscopy (FTIR), X-ray diffraction (XRD), nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). The thermogravimetric results showed the incorporation of approximately 20, 50, 70 and 80% of magnetite to the graphene oxide. Regarding the hydrodynamic size, for the magnetite, mode values of 31.3 ± 1.3 nm were determined, whereas for the GO/M, the mode values of size ranged from 72.8 to 194 nm. The results of XRD and FTIR showed the respective characteristic diffraction and absorption peaks only for graphene oxide, magnetite and GO/M(20%). It was not observed characteristic peaks for the other samples of graphene oxide that have higher loads of magnetite incorporated.
Sustainable synthesis of transition metals/graphene oxide nanocomposites by electron beam irradiation
2017 - SAKATA, S.K.; SOBRINHO, L.F.; JACOVONE, R.M.S.; SOARES, J.J.S.; TOMINAGA, F.K.; ANGNES, L.; GARCIA, R.H.L.
Graphene is nanomaterial with unique physical and chemical properties that makes it a precursor for the synthesis of new materials, such as conductive nanocomposites. Graphene can be obtained by the reduction of graphene oxide, but when it is incomplete, reduced graphene oxide (rGO) is produced with both graphene and graphene oxide properties: it is electrical and thermal conductor, it can be exfoliated in several polar solvents and moreover, the oxygen groups can later be functionalized, affording nanocomposites for electrochemical applications and also in biomaterials. A method of increasing the electrical conductivity of graphene-based compounds is by the incorporation of metallic nanoparticles. When these nanomaterials are joined together the surface area increases for the passage of electric current and the electrical conductivity. The chemical reduction method for the incorporation of metallic nanoparticle on GO involves toxic reagents or it is a time-consuming and it also requires high costs for the removal of excess reagents and by-products. The general synthesis of transition Metal/graphene-based nanocomposites by the electron beam in a sustainable process will be presented. The experiments were performed in a 1.5 MeV electron accelerator at room temperature and no hazardous wastes were generated. The nanocomposites were characterized by FT-IR, DRX and TEM/EDS as metallic nanoparticle at the average size of 5-20 nm incorporated into reduced graphene oxide layers. The electrochemical behavior of these nanocomposites was evaluated by cyclic voltammetry.
Efeito da irradiação com feixe de elétrons na degradação e toxicidade de fármacos em solução aquosa: cloridrato de fluoxetina, diclofenaco de sódio e mistura de ambos
2016 - TOMINAGA, F.K.; BOIANI, N.F.; SOLE, S.V.D.; BORRELY, S.I.