Recalcitrant Pharmaceuticals in the Aquatic Environment: A Comparative Screening Study of Their Occurrence, Formation of Phototransformation Products and Their in Vitro Toxicity

Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio- and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill data gaps and to help prioritise them for further testing. Twelve out of the fourteen compounds investigated were found to be neither readily nor inherently biodegradable in the Organisation of Economic Cooperation and Development-biodegradability tests. The study further demonstrates that the photo-induced transformation of the pharmaceuticals was faster upon irradiation with a Hg lamp (UV light) than with a Xe lamp emitting a spectrum that mimics sunlight. Comparing the non-irradiated with the respective irradiated solutions, a higher acute and chronic toxicity against bacteria was found for the irradiated solutions of seven compounds (cetirizine, cimetidine, hydrochlorothiazide, ranitidine, sulpiride, tramadol and valsartane). No cyto- and genotoxic effects were found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their phototransformation products. This comparative study documents that phototransformation products can arise as a result of UV treatment of wastewater containing these pharmaceuticals. It further demonstrates that some phototransformation products may have a higher environmental risk potential than the respective parent compounds because some phototransformation products exhibited a higher bacterial toxicity

Determinación de daño genético en comerciantes de plaguicidas en el departamento de Matagalpa

EL DAÑO CITOGENÉTICO ASOCIADO CON PLAGUICIDAS POR PARTE de comerciantes de agroquímicos fue evaluado en el departamento de Matagalpa analizando micronúcleos en células bucales (MNBC). Así mismo, fue evaluada la exposición crónica a plaguicidas usando la prueba de acetilcolinesterasa y adicionalmente se identificaron mutaciones de manera exploratoria en el gen CYP2D6, implicado en el metabolismo de plaguicidas. La comparación entre comerciantes de plaguicidas y controles reveló diferencias significativas en las frecuencias de MNBC (6.23±2.2 vs. 3.63±1.3 MN/2000 MNBC, P<0.001, t de student). Niveles de colinesterasa indican efecto neurotóxico crónico en los comerciantes de plaguicidas. Estos comerciantes utilizan poco o ningún equipo de protección personal así como medidas de seguridad. Este es el primer estudio a nivel nacional que reporta efecto citogenético de exposición crónica a plaguicidas en comerciantes expuestos

Impact of Nanocomposite Combustion Aerosols on A549 Cells and a 3D Airway Model

The use of nanomaterials incorporated into plastic products is increasing steadily. By using nano-scaled filling materials, thermoplastics, such as polyethylene (PE), take advantage of the unique properties of nanomaterials (NM). The life cycle of these so-called nanocomposites (NC) usually ends with energetic recovery. However, the toxicity of these aerosols, which may consist of released NM as well as combustion-generated volatile compounds, is not fully understood. Within this study, model nanocomposites consisting of a PE matrix and nano-scaled filling material (TiO$_{2}$, CuO, carbon nano tubes (CNT)) were produced and subsequently incinerated using a lab-scale model burner. The combustion-generated aerosols were characterized with regard to particle release as well as compound composition. Subsequently, A549 cells and a reconstituted 3D lung cell culture model (MucilAir™, Epithelix) were exposed for 4 h to the respective aerosols. This approach enabled the parallel application of a complete aerosol, an aerosol under conditions of enhanced particle deposition using high voltage, and a filtered aerosol resulting in the sole gaseous phase. After 20 h post-incubation, cytotoxicity, inflammatory response (IL-8), transcriptional toxicity profiling, and genotoxicity were determined. Only the exposure toward combustion aerosols originated from PE-based materials induced cytotoxicity, genotoxicity, and transcriptional alterations in both cell models. In contrast, an inflammatory response in A549 cells was more evident after exposure toward aerosols of nano-scaled filler combustion, whereas the thermal decomposition of PE-based materials revealed an impaired IL-8 secretion. MucilAir™ tissue showed a pronounced inflammatory response after exposure to either combustion aerosols, except for nanocomposite combustion. In conclusion, this study supports the present knowledge on the release of nanomaterials after incineration of nano-enabled thermoplastics. Since in the case of PE-based combustion aerosols no major differences were evident between exposure to the complete aerosol and to the gaseous phase, adverse cellular effects could be deduced to the volatile organic compounds that are generated during incomplete combustion of NC

Determinación de daño genético en comerciantes de plaguicidas en el departamento de Matagalpa

El daño citogenético asociado con plaguicidas por PARTE de comerciantes de agroquímicos fue evaluado en el departamento de Matagalpa analizando micronúcleos en células bucales (MNBC). Así mismo, fue evaluada la exposición crónica a plaguicidas usando la prueba de acetilcolinesterasa y adicionalmente se identificaron mutaciones de manera exploratoria en el gen CYP2D6, implicado en el metabolismo de plaguicidas. La comparación entre comerciantes de plaguicidas y controles reveló diferencias significativas en las frecuencias de MNBC (6.23±2.2 vs. 3.63±1.3 MN/2000 MNBC, P<0.001, t de student). Niveles de colinesterasa indican efecto neurotóxico crónico en los comerciantes de plaguicidas. Estos comerciantes utilizan poco o ningún equipo de protección personal así como medidas de seguridad. Este es el primer estudio a nivel nacional que reporta efecto citogenético de exposición crónica a plaguicidas en comerciantes expuestos

Genotoxic effects of three selected black toner powders and their dimethyl sulfoxide extracts in cultured human epithelial A549 lung cells in vitro

Until now, the adverse effects of toner powders on humans have been considered to be minimal. However, several recent reports have suggested possible significant adverse health effects from toner dust inhalation. The aim of this study was to evaluate the genotoxic potential of black toner powders in vitro. For the study of DNA damage, A549 cells were exposed to toner-powder suspensions and to their DMSO extracts, and then subjected to the comet assay and to the in-vitro cytokinesis block micronucleus test (CB-MNvit). Cytotoxic effects of the toner samples were assessed by the erythrosin B assay. Furthermore, size, shape, and composition of the toner powders were investigated. None of the three toner powders or their DMSO extracts reduced cell viability; however, they did induce DNA damage and formed micronuclei at concentrations from 80 to 400 μg cm⁻², although to a varying extent. All toner powders contain considerable amounts of the pigments carbon black and magnetite (Fe₃O₄) as well as small amounts of polycyclic aromatic hydrocarbons (PAHs). The overall results of our in-vitro study suggest that the investigated toner-powder samples are not cytotoxic but genotoxic. From the results of the physical and chemical characterization, we conclude that metals and metalloids as components of magnetite, or PAHs as components of the carbon-bearing material, are responsible for the genotoxic effects. Further research is necessary to determine the relevance of these in-vitro observations for private and occupational toner powder exposure

Cellular uptake and toxic effects of fine and ultrafine metal-sulfate particles in human A549 lung epithelial cells

Ambient airborne particulate matter is known to cause various adverse health effects in humans. In a recent study on the environmental impacts of coal and tire combustion in a thermal power station fine crystals of PbSO4 (anglesite), ZnSO4•H2O (gunningite), and CaSO4 (anhydrite) were identified in the stack emissions. Here, we have studied the toxic potential of these sulfate phases as particulates and their uptake in human alveolar epithelial cells (A549). Both PbSO4 and CaSO4 yielded no loss of cell viability, as determined by the WST-1 and NR assays. In contrast, a concentration-dependent increase in cytotoxicity was observed for Zn sulfate. For all analyzed sulfates, an increase in the production of reactive oxygen species (ROS), assessed by the DCFH-DA assay and Electron Paramagnetic Resonance (EPR), was observed, although to a varying extent. Again, Zn sulfate was the most active compound. Genotoxicity assays revealed concentration-dependent DNA damage and induction of micronuclei for Zn sulfate and, to a lower extent, for CaSO4, whereas only slight effects could be found for PbSO4. Moreover, changes of cell cycle were observed for Zn sulfate and PbSO4. It could be shown further that Zn sulfate increased the nuclear factor kappa-B (NF-κB) DNA binding activity and activated c-Jun N-terminal kinases (JNK). During our TEM investigations, no effect on the appearance of the A549 cells exposed to CaSO4 compared to the non-exposed cells was observed, and in our experiments only one CaSO4 particle was detected in the cytoplasm. In the case of exposure to Zn sulfate, no particles were found in the cytoplasm of A549 cells, but we observed a concentration-dependent increase in the number and size of dark vesicles (presumably zincosomes). After exposure to PbSO4, the A549 cells contained isolated particles as well as agglomerates both in vesicles and in the cytoplasm. Since these metal-sulfate particles are emitted into the atmosphere via the flue gas of coal-fired power stations, they may be globally abundant. Therefore, our study is of direct relevance to the population living near such power plants

Antibiotics and sweeteners in the aquatic environment : biodegradability, formation of phototransformation products, and in vitro toxicity

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option.publishe

Antibiotics and sweeteners in the aquatic environment: biodegradability, formation of phototransformation products, and in vitro toxicity

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option.publishe