Myriam Catalá

Detection of pharmaceutically active compounds in the rivers and tap water of the Madrid Region (Spain) and potential ecotoxicological risk

Concentrations of pharmaceutically active compounds (PhACs) in the order of ng L(-1) to μg L(-1) have been reported worldwide in waste, fluvial and even drinking water, raising concern about the efficacy of the currently employed waste water treatments in the elimination of this kind of compounds. Despite ranking 29th in terms of population, Spain is currently the 8th country on pharmaceutical prescription with an expense of 14×10(9) euros in 2008. In this context, the aim of this study was to determine the presence of 33 pharmaceutically active compounds in specific points of the main rivers of the Madrid Region (MR) as well as tap water samples from the metropolitan area of Madrid. Additionally, a screening level risk characterization by means of the Hazard Quotient (HQ) method was applied. A total of 25 pharmaceutical compounds and metabolites were detected in the 10 sampling points downstream the outlet of the major STPs of the MR. The highest concentrations were detected for the anticonvulsant carbamazepine and the stimulant caffeine. Concentrations for most of the analyzed compounds exceed levels previously reported in the literature. Moreover, we report the highest concentration of the cytostatic ifosfamide, detected for the first time in Spain in surface water. Preliminary risk characterization shows that a total of 16 compounds represent at least a low potential hazard based on their scored HQs, with five of them present in a concentration that exceeds the predicted no effect concentration (PNEC). Toxic Units calculation indicates that for all the selected sampling points high hazard is anticipated from the presence of the analyzed compounds in the measured concentrations (TUs>10). Caffeine and cotinine were detected in all (10) the analyzed tap water samples. Carbamazepine and nicotine were detected in six and venlafaxine in two samples. No studies venlafaxine in drinking water have been reported. These results clearly pinpoint the need for water quality monitoring and research in urban rivers, as well as the need for improved water treatment techniques able to eliminate this kind of compounds from the effluent waters as well as from drinking water sources.

Pollution by psychoactive pharmaceuticals in the Rivers of Madrid metropolitan area (Spain)

There are a number of reports in the literature which describe the occurrence of so-called emerging pollutants, such as pharmaceuticals, in surface water. Few of these studies have reported values from large cities in relatively arid areas, such as in Spain. The persistence of some pharmaceuticals to usual wastewater treatments allows their discharge into surface waters. It is increasingly evident that mental health problems are of special concern for public health since psychiatric drugs are used in large amounts. Compared to other countries, Spain has a high pharmaceutical consumption rate, and Madrid metropolitan area is one of the most densely populated areas in Europe. The aim of the present study was to determine the presence of different psychoactive pharmaceuticals and metabolites in the main rivers of Madrid metropolitan area: Jarama, Manzanares, Guadarrama, Henares and Tajo. Sampling was done downstream of ten sewage treatment plants (STP) discharging into these rivers. Control points upstream of STPs discharge points were also sampled. Pharmaceutical compounds and metabolites for analysis were selected according to human consumption and prescription rates in Madrid, and the availability of valid techniques for detection. We observed residues of the antidepressants fluoxetine (80% of the sampling sites), citalopram (60%) and venlafaxine (100%), the anxiolytics nordiazepam (90%), oxazepam (80%) and 7-aminoflunitrazepam (10%) and the anticonvulsant carabamazepine (70%). Measured concentrations equalled or exceeded those reported for other geographical areas, although there is a pronounced lack of information for the anxiolytics and venlafaxine. This is of special concern given that Wyeth-Ayersts venlafaxine, Effexor, was the 10th greatest selling pharmaceutical worldwide in 2006. We conclude that the origin of pharmaceutical pollution in the rivers of Madrid is mainly the discharge of sewage treatment plants in Madrids metropolitan area and a comprehensive monitoring program should be implemented.

Heterogeneous photo-Fenton treatment for the reduction of pharmaceutical contamination in Madrid rivers and ecotoxicological evaluation by a miniaturized fern spores bioassay.

Fifty-six pharmaceuticals of various chemical groups, such as anti-inflammatory, antibacterial and cardiovascular drugs, were detected in four selected river waters receiving sewage effluents in the Community of Madrid (Spain). A promising approach for the degradation of those residues is the application of a photo-Fenton treatment. Several new bioassays using fern spores were employed for the evaluation of acute and chronic toxicity based on mitochondrial activity, DNA and chlorophyll quantifications of as-received river water and photo-Fenton-treated samples. photo-Fenton treatment provided a high degree of total organic carbon mineralization with up to 70% reduction for river water samples. In addition, the elimination of most of the studied pharmaceutical compounds was confirmed. A few compounds, however (salicylic acid, ofloxacin, caffeine, cotinine and nicotine), seemed more resistant, with after-treatment concentrations between 4 and 44ngL(-1). Nicotine showed the most refractory behaviour with concentrations ranging from 29 to 224ngL(-1) for treated samples. Photo-Fenton treatment yielded a significant decrease in acute and chronic toxicity, even though some residual toxicity remained after treatment. This fact seemed to be related to the presence of toxicants in the water matrix, probably of inorganic nature, rather than the toxic effect of the studied pharmaceutical compounds, as revealed by the effective removal of these compounds and high TOC mineralization of photo-Fenton treatments.

Drugs of abuse in surface and tap waters of the Tagus River basin: Heterogeneous photo-Fenton process is effective in their degradation

This work investigates for the first time the occurrence of drugs of abuse and metabolites in surface waters from the Tagus River on its way through the province of Toledo (downstream Madrid metropolitan area) and in drinking waters in two nearby cities. Some of the studied drugs are used for therapeutic purposes but they can also be consumed as illicit drugs. The results of this preliminary study have revealed the presence of 12 out of 22 drugs of abuse analyzed in fluvial water at concentrations ranging from 1.14 to 40.9 ng/L. The largest concentrations corresponded to the anxiolytics diazepam and lorazepam, the cocaine metabolite benzoilecgonine, the amphetamine-like compound ephedrine, and the methadone metabolite EDDP. All these substances, except for lorazepam, were detected in all the sampling points. Traces of methadone and ephedrine were detected in some samples of tap water. Despite the low concentrations of these pollutants, effects on wildlife or human health cannot be disregarded, especially on vulnerable population. Thus, the treatment of these substances using a heterogeneous photo-Fenton process has been evaluated, rendering a remarkable effectiveness for their degradation.

The impact of dehydration rate on the production and cellular location of reactive oxygen species in an aquatic moss

BACKGROUND AND AIMS The aquatic moss Fontinalis antipyretica requires a slow rate of dehydration to survive a desiccation event. The present work examined whether differences in the dehydration rate resulted in corresponding differences in the production of reactive oxygen species (ROS) and therefore in the amount of cell damage. METHODS Intracellular ROS production by the aquatic moss was assessed with confocal laser microscopy and the ROS-specific chemical probe 2,7-dichlorodihydrofluorescein diacetate. The production of hydrogen peroxide was also quantified and its cellular location was assessed. KEY RESULTS The rehydration of slowly dried cells was associated with lower ROS production, thereby reducing the amount of cellular damage and increasing cell survival. A high oxygen consumption burst accompanied the initial stages of rehydration, perhaps due to the burst of ROS production. CONCLUSIONS A slow dehydration rate may induce cell protection mechanisms that serve to limit ROS production and reduce the oxidative burst, decreasing the number of damaged and dead cells due upon rehydration.

Fungal-associated NO is involved in the regulation of oxidative stress during rehydration in lichen symbiosis

BackgroundReactive oxygen species (ROS) are normally produced in respiratory and photosynthetic electron chains and their production is enhanced during desiccation/rehydration. Nitric oxide (NO) is a ubiquitous and multifaceted molecule involved in cell signaling and abiotic stress. Lichens are poikilohydrous organisms that can survive continuous cycles of desiccation and rehydration. Although the production of ROS and NO was recently demonstrated during lichen rehydration, the functions of these compounds are unknown. The aim of this study was to analyze the role of NO during rehydration of the lichen Ramalina farinacea (L.) Ach., its isolated photobiont partner Trebouxia sp. and Asterochloris erici (Ahmadjian) Skaloud et Peksa (SAG 32.85 = UTEX 911).ResultsRehydration of R. farinacea caused the release of ROS and NO evidenced by the fluorescent probes DCFH2-DA and DAN respectively. However, a minimum in lipid peroxidation (MDA) was observed 2 h post-rehydration. The inhibition of NO in lichen thalli with c-PTIO resulted in increases in both ROS production and lipid peroxidation, which now peaked at 3 h, together with decreases in chlorophyll autofluorescence and algal photobleaching upon confocal laser incidence. Trebouxia sp. photobionts generate peaks of NO-endproducts in suspension and show high rates of photobleaching and ROS production under NO inhibition which also caused a significant decrease in photosynthetic activity of A. erici axenic cultures, probably due to the higher levels of photo-oxidative stress.ConclusionsMycobiont derived NO has an important role in the regulation of oxidative stress and in the photo-oxidative protection of photobionts in lichen thalli. The results point to the importance of NO in the early stages of lichen rehydration.

Seasonal variation of pharmaceutically active compounds in surface (Tagus River) and tap water (Central Spain)

Numerous studies have shown the presence of pharmaceutically active compounds (PhACs) in different environmental compartments, for example, in surface water or wastewater ranging from nanograms per litre to micrograms per litre. Likewise, some recent studies have pointed to seasonal variability, thus indicating that PhAcs concentrations in the aquatic environment may depend on the time of year. This work intended to find out (1) whether Tagus fluvial and drinking water were polluted with different groups of PhACs and (2) if their concentrations differed between winter and summer seasons. From the 58 substances analysed, 41 were found belonging to the main therapeutic groups. Statistical differences were seen for antibacterials, antidepressants, anxiolytics, antiepileptics, and cardiovascular drugs, with higher concentrations being detected in winter than in summer. These results might indicate that the PhACs analysed in this study undergo lower environmental degradation in winter than in summer. In order to confirm these initial results, a continuous monitoring should be performed especially on those PhACs that either because of an elevated consumption or an intrinsic chemical persistence are poorly degraded during winter months due to low temperatures and solar irradiation. It is especially important to identify which of these specific PhACs are in order to recommend their substitution by equally effective and safe substances but also environmentally friendly.

Elimination of drugs of abuse and their toxicity from natural waters by photo-Fenton treatment

This paper investigates the elimination of drugs of abuse from six different chemical classes and their metabolites in natural fluvial waters (nearby the output of a sewage system). Mineralization of these substances and toxicological characterization before and after treatment by a heterogeneous photo-Fenton system has been evaluated. This advanced oxidation technology was able to significantly reduce the concentration of the drugs of abuse in all the tested conditions (different hydrogen peroxide and catalyst loadings). However, toxicological analyses measured as inhibition of fern spore mitochondrial activity, showed only a complete elimination of acute and chronic toxicity when a higher solid catalyst loading was used (0.6 g/L). A lower catalyst loading of 0.2 g/L was not enough for toxicity elimination. These results evidence the need for combining toxicological tests and chemical analyses in order to establish the effectiveness of the water treatment technologies based on advanced oxidation processes.

Nicotine occurrence in bottled mineral water: Analysis of 10 brands of water in Spain

The presence of pharmaceuticals in surface and drinking water has been evidenced in numerous studies. Despite representing one of the most common consumption sources, to the best of our knowledge, this is the first report on the presence of pharmaceutical compounds in bottled mineral water. Pollution of these sources not only could pose a serious human health risk, but would also warn about the quality of the water in our aquifers, a vital and vulnerable source of water, essential for the future water supply. Fifty eight pharmaceutically active compounds (PhACs) belonging to the 12 main therapeutic groups were analyzed in 10 bottled mineral water brands produced in Spain. Nicotine was detected in concentrations ranging from 7ngL(-1) to 15ngL(-1) in 5 of 10 bottled mineral waters. Despite the low nicotine concentration measured, the presence of this compound in bottled water still raises concern. Health risk assessment researchers have postulated that the risk to adult healthy humans from oral intake of nicotine at low levels is negligible. However, no studies have been conducted to assess the human health risk of vulnerable populations such as pregnant women and newborns. This population is the target of advertising on the purity and quality characteristics of bottled mineral water.

Preliminary data suggest that venlafaxine environmental concentrations could be toxic to plants

Venlafaxine hydrochloride is a structurally novel antidepressant. Its occurrence in surface waters and drinking water has only been reported in recent works. The aim of this work is to assess the acute and chronic sublethal toxicity of venlafaxine in relevant taxa of riparian ecosystems. We used the fern Polystichum setiferum during the critical life stage of development. Reliable biomarkers of cell viability (mitochondrial activity), plant physiology (chlorophyll), and growth (DNA content) were assessed as sensitive endpoints of toxicity. About DNA quantification, our results show that venlafaxine induces acute lethal phytotoxicity at 24 and 48 h (LOECs 1 μg L(-1) and 0.1 μg L(-1), respectively). At 24 h, hormetic effects in spores of P. setiferum mitochondrial activity mask lethality and adverse effects are observed (LOEC 1 μg L(-1)). At 48 h a reduction in the mitochondrial activity happens (LOEC 10 μg L(-1)). In chronic exposure of 1 week, LOEC for DNA is 0.1 μg L(-1). Mitochondrial activity showed a strong hormetic stimulation of a surviving spore population (LOEC 10 μg L(-1)). Changes were not observed in chlorophyll autofluorescence. Environmental concentrations of venlafaxine can be deleterious for the development of significant populations of sensitive individuals in riparian ecosystems.