Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region.

The increasing human presence in Antarctica and the waste it generates is causing an impact on the environment at local and border scale. The main sources of anthropic pollution have a mainly local effect, and include the burning of fossil fuels, waste incineration, accidental spillage and wastewater effluents, even when treated. The aim of this work is to determine the presence and origin of 30 substances of anthropogenic origin considered to be, or suspected of being, endocrine disruptors in the continental waters of the Antarctic Peninsula region. We also studied a group of toxic metals, metalloids and other elements with possible endocrine activity. Ten water samples were analyzed from a wide range of sources, including streams, ponds, glacier drain, and an urban wastewater discharge into the sea. Surprisingly, the concentrations detected are generally similar to those found in other studies on continental waters in other parts of the world. The highest concentrations of micropollutants found correspond to the group of organophosphate flame retardants (19.60-9209ngL(-1)) and alkylphenols (1.14-7225ngL(-1)); and among toxic elements the presence of aluminum (a possible hormonal modifier) (1.7-127µgL(-1)) is significant. The concentrations detected are very low and insufficient to cause acute or subacute toxicity in aquatic organisms. However, little is known as yet of the potential sublethal and chronic effects of this type of pollutants and their capacity for bioaccumulation. These results point to the need for an ongoing system of environmental monitoring of these substances in Antarctic continental waters, and the advisability of regulating at least the most environmentally hazardous of these in the Antarctic legislation.

Pharmaceuticals and iodinated contrast media in a hospital wastewater: A case study to analyse their presence and characterise their environmental risk and hazard.

This work analyses the presence of twenty-five pharmaceutical compounds belonging to seven different therapeutic groups and one iodinated contrast media (ICM) in a Spanish medium-size hospital located in the Valencia Region. Analysis of the target compounds in the hospital wastewater was performed by means of solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry analysis (HPLC-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on Predicted No Effect Concentration (PNEC) was also applied to estimate Hazard Quotients (HQs) for the compounds investigated. Additionally, the environmental hazard associated to the various compounds measured was assessed through the calculation of the Persistence, Bioaccumulation and Toxicity (PBT) Index, which categorizes compounds according to their environmentally damaging characteristics. The results of the study showed the presence of twenty-four out of the twenty-six compounds analysed at individual concentrations ranging from 5 ng L(-1) to 2 mg L(-1). The highest concentrations corresponded to the ICM iomeprol, found at levels between 424 and 2093 µg L(-1), the analgesic acetaminophen (15-44 µg L(-1)), the diuretic (DIU) furosemide (6-15 µg L(-1)), and the antibiotics (ABIs) ofloxacin and trimethoprim (2-5 µg L(-1)). The lowest levels corresponded to the anti-inflammatory propyphenazone, found at concentrations between 5 and 44 ng L(-1). Differences in terms of concentrations of the analysed compounds have been observed in all the therapeutic groups when comparing the results obtained in this and other recent studies carried out in hospitals with different characteristics from different geographical areas and in different seasons. The screening level risk assessment performed in raw water from the hospital effluent showed that the analgesics and anti-inflammatories (AAFs) acetaminophen, diclofenac, ibuprofen and naproxen, the antibiotics (ABIs) clarithromycin, ofloxacin and trimethoprim, and the ß-blocker (BBL) propranolol were present at concentrations leading to HQ values higher than 10, thus indicating high risk. When applying a factor to take into account potential dilution and degradation processes, only the compound ibuprofen showed a HQ higher than 1. Likewise, the cumulative HQ or Toxic Units (TUs) calculated in the raw water for each of the therapeutic groups studied showed that these three classes of drugs were at concentrations high enough to potentially generate high risk to aquatic organisms while taking into account possible dilution and degradation processes only one of them, the AAFs can be considered to represent high risk. Finally, the environmental hazard assessment performed showed that the AAFs diclofenac and ibuprofen and the ABI clarithromycin have the highest, maximum value of 9 of PBT Index due to their inherent environmentally damaging characteristics of persistence, bioaccumulation and toxicity. The methodology followed in the present case study can be taken as a novel approach to classify and categorize pharmaceuticals on the basis of their occurrence in hospital effluents, their derived environmental risks, and their associated environmental hazard. This classification becomes important because it can be used as a model or orientation for hospitals in the process of developing environmentally sustainable policies and as an argument to justify the adoption of advanced, specific treatments for hospital effluents before being discharged into the public sewage system.

New microbioassays based on biomarkers are more sensitive to fluvial water micropollution than standard testing methods.

Recent investigations suggest that, despite lack of lethality in validated bioassays, micropollutants in surface waters could induce sublethal toxicity in sensitive taxa, jeopardizing their biological performance and eventually leading to populations' extinction. A broader array of testing species, the miniaturization of bioassays and the development of reliable biomarkers of damage are sought in order to improve ecological relevance and cost efficiency of environmental monitoring. Our aim is to assess the different sensitivity of validated bioassays and new approaches using biomarkers as sensitive endpoints of toxicity in spores of Polystichum setiferum and Danio rerio embryos. Six water samples were collected in Tagus basin in summer and winter. Samples tested induce no acute toxicity in validated methods (algae growth inhibition and daphnia mobility inhibition). Summer water samples induced acute membrane damage (lipid peroxidation) in Danio rerio embryos and hormetic increases in fern spore mitochondrial activity. One of the samples dramatically reduced mitochondrial activity indicating severe acute sublethal phytotoxicity. All the winter samples induced significant decreases in fern spore mitochondrial activity and membrane damage increases in Danio rerio embryo. Furthermore, three samples induced lethal phytotoxicity in fern spores. We conclude that the new microbioassays show a better sensitivity to fluvial water micropollution and confirm the necessity to test critical life stages such as development and provide cost-efficient methods for environmental monitoring.

Analyzing the potential environmental impact of NIOSH list of hazardous drugs (group 2).

For the first time, several pharmaceuticals have been defined as priority substances in the new proposal of the revision of the Water Framework Directive (WFD). Consequently, environmental quality standards have been determined for several drugs. This is the case with the antiepileptic carbamazepine, which is considered as hazardous in healthcare settings by The National Institute for Occupational Safety and Health (NIOSH). This organism considers as such drugs that have shown teratogenicity, carcinogenicity, genotoxicity or other developmental, reproductive, or organ toxicity at low doses in studies with animals or humans. This study has been focused on the non-carcinogenic drugs classified in group 2, and their presence in the environment. This group contains many different therapeutic agents such as antineoplastics, psychoactive drugs, immunosuppressants and antivirals, among others. Of the 116 drugs included in the list, 26 have been found in aquatic environmental matrices. Certain drugs have received most attention (e.g., the antiepileptic carbamazepine, progesterone and the antidepressant paroxetine) while others completely lack environmental monitoring. Carbamazepine, fluconazole, paroxetine and warfarin have been found in invertebrates' tissues, whereas carbamazepine, oxazepam and paroxetine have been found in fish tissues. The main aim of the NIOSH's hazardous drug list is to inform healthcare professionals about adequate protection measures to prevent occupational exposure to these pharmaceuticals. However, this list contains useful information for other professionals and researchers such as environmental scientists. The paucity of relevant environmental data of certain hazardous pharmaceuticals might be important to help in the prioritization of compounds that may demand further research.

Hazardous drugs (NIOSH's list-group 1) in healthcare settings: Also a hazard for the environment?

Healthcare workers can be exposed to dangerous drugs during their daily practice. The National Institute for Occupational Safety and Health (NIOSH) considers "hazardous drugs" as those that had shown one or more of the following characteristic in studies with animals, humans or in vitro systems: carcinogenicity, teratogenicity or other toxicity for development, reproductive toxicity, organ toxicity at low doses, or genotoxicity. In the actual list (draft list 2020), drugs classified in group 1 are those with carcinogenic effects. Moreover, the global human and veterinary cancer is expected to grow, so antineoplastic drug consumption may consequently grow, leading to an increase of anticancer pharmaceuticals in the environment. Not all drugs pertaining to group 1 can be classified as "antineoplastic" or "cytostatic". Since most of the research on environment presence and ecotoxicological effects of pharmaceuticals has been focused on this therapeutic class, other carcinogenic drugs belonging to different therapeutic groups may have been omitted in previous studies. In this study we aim to review the presence in the environment of the hazardous drugs (NIOSH group 1) and their possible environmental impact. Of the 90 drugs considered, there is evidence of presence in the environment for 19. Drugs with more studies reporting positive detections are: the antibiotic chloramphenicol (55), the alkylating agents cyclophosphamide (39) and ifosfamide (30), and the estrogen receptor modulator tamoxifen (18). Although the original purpose of the NIOSH list and related documents is to provide guidance to healthcare professionals in order to adequately protect them from the hazards posed by these drugs in healthcare settings, we believe they can be useful for environmentalists too. Absence of data regarding the potential of environmental risk of certain hazardous drugs might tell us which drugs ought to be prioritized in the future.

Removal efficiency for emerging contaminants in a WWTP from Madrid (Spain) after secondary and tertiary treatment and environmental impact on the Manzanares River.

The effluents from wastewater treatment plants (WWTPs) can be an important contamination source for receiving waters. In this work, a comprehensive study on the impact of a WWTP from Madrid on the aquatic environment has been performed, including a wide number of pharmaceuticals and pesticides, among them those included in the European Watch List. 24-h composite samples of influent (IWW) and effluent wastewater after secondary (EWW2) and after secondary + tertiary treatment (EWW3) were monitored along two campaigns. Average weekly concentrations in IWW and EWW2 and EWW3 allowed estimating the removal efficiency of the WWTP for pharmaceutical active substances (PhACs). In addition, the impact of EWW3 on the water quality of the Manzanares River was assessed, in terms of PhAC and pesticide concentrations, through analysis of the river water collected upstream and downstream of the discharge point. After a preliminary risk assessment, a detailed evaluation of the impact on the aquatic environment, including a toxicological study and screening of pharmaceutical metabolites, was made for the seven most relevant PhACs: sulfamethoxazole, azithromycin and clarithromycin (antibiotics), metoprolol (antihypertensive), diclofenac (anti-inflammatory/analgesic), irbesartan (antihypertensive), and the antidepressant venlafaxine. Among selected PhACs, irbesartan, clarithromycin and venlafaxine presented moderate or high risk in the river water downstream of the discharge. Albeit no acute toxicity was detected, more detailed studies should be carried out for these substances, including additional toxicological studies, to set up potential sublethal and chronic effects on aquatic organisms.

Prioritisation of emerging contaminants in the northern Antarctic Peninsula based on their environmental risk.

Although Antarctica is protected and human activity is restricted exclusively to scientific research, with numerous restrictions on tourism, the steadily increasing human presence appears to be having a marked impact on terrestrial and aquatic, especially marine, ecosystems. Evidence of this excessive presence can be seen from the recent detection of contaminants linked to human activity in locations that should be considered to be untouched. The aim of this study is to determine the environmental risk present on the Antarctic Peninsula due to the 54 emerging contaminants linked to human presence previously detected and reported in previous studies published in leading scientific journals. The substances analysed belong to the group of drugs/medicines of abuse, endocrine disruptors, pyrethroids, perfluorinated compounds and sunscreens. The environmental risk was determined for all substances detected by calculating the hazard quotient (HQ) following the guidelines established by the European Union. An HQ value higher than 10 was taken to represent a high environmental risk. In the group of drugs/medicines of abuse, a high risk was detected for two analgesics, namely acetaminophen and diclofenac, and the anti-inflammatory ibuprofen. Although the risk detected was considered to be medium, the presence of the antibiotic clarithromycin, one of the substances included in the EU's current watch list for emerging contaminants, should be noted. In the group of endocrine disruptors, the high risk posed by the metabolite nonylphenol diethoxylate, which is higher than that for its parent compound nonylphenol, should be noted. In the group of pyrethroids/sunscreens/perfluorinated compounds, two pyrethroids, namely bifenthrin and cyhalothrin, were found to pose a high environmental risk. We propose the need to establish a monitoring system for emerging contaminants linked to human presence on the Antarctic Peninsula similar to the watch list found in the EU Water Framework Directive. Subsequently, an environmental monitoring plan based on individual ecotoxicological studies with the substances concerned, and analysing their possible synergic effects, should be implemented.

Comparative study of esterase activities in different tissues of marine fish species Trachurus trachurus, Merluccius merluccius and Trisopterus luscus.

Pesticides are one of the most frequently anthropogenic xenobiotics detected in water. Among these, the organophosphorus pesticides (OPs) are very widely used in agriculture due to their broad spectrum of activity and their low price, but they also have high potent effects as neurotoxic compounds in non-target organisms. The aim of this study was to evaluate biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), propionylcholinesterase (PChE) and carboxylesterase (CbE) in the representative Atlantic fish species Trachurus trachurus, Merluccius merluccius and Trisopterus luscus from "Rías Gallegas", a traditional Spanish fishing area. These esterase activities were evaluated in the brain, muscle and liver to determine the most adequate tissue to measure such enzymatic activities. The sensitivity of AChE and CbE activities from different tissues the widely used organophosphorus insecticide chlorpyrifos (CP), and its toxic metabolite (CP-oxon) was also tested. AChE activity was predominant in all tissues of the analysed species (particularly in brain constituting from 78.33%, 89.83% and 88.43% of total ChEs in Trachurus trachurus, Merluccius merluccius and Trisopterus luscus, respectively). Under in vitro exposure, esterases were shown to be highly sensitive to CP and especially to CP-oxon. Moreover, a similar effect observed on AChE and CbE activities could suggest that CbE activity might contribute efficiently against the toxic effects of CP, especially in muscle and the liver. The presence of BChE, PChE and upper CbE activities in muscle and the liver and their OP-sensibilities can be used to study their function in the pesticide biochemical detoxification pathways with a prominent role as a safeguarding mechanism against pesticide toxicity.

Caffeine and paraxanthine in aquatic systems: Global exposure distributions and probabilistic risk assessment.

This study presents one of the most complete applications of probabilistic methodologies to the risk assessment of emerging contaminants. Perhaps the most data-rich of these compounds, caffeine, as well as its main metabolite (paraxanthine), were selected for this study. Information for a total of 29,132 individual caffeine and 7442 paraxanthine samples was compiled, including samples where the compounds were not detected. The inclusion of non-detect samples (as censored data) in the estimation of environmental exposure distributions (EEDs) allowed for a realistic characterization of the global presence of these compounds in aquatic systems. EEDs were compared to species sensitivity distributions (SSDs), when possible, in order to calculate joint probability curves (JPCs) to describe the risk to aquatic organisms. This way, it was determined that unacceptable environmental risk (defined as 5% of the species being potentially exposed to concentrations able to cause effects in>5% of the cases) could be expected from chronic exposure to caffeine from effluent (28.4% of the cases), surface water (6.7% of the cases) and estuary water (5.4% of the cases). Probability of exceedance of acute predicted no-effect concentrations (PNECs) for paraxanthine were higher than 5% for all assessed matrices except for drinking water and ground water, however no experimental effects data was available for paraxanthine, resulting in a precautionary deterministic hazard assessment for this compound. Given the chemical similarities between both compounds, real effect thresholds, and thus risk, for paraxanthine, would be expected to be close to those observed for caffeine. Negligible Human health risk from exposure to caffeine via drinking or groundwater is expected from the compiled data.

A case study to identify priority cytostatic contaminants in hospital effluents.

This study analyses the presence of 17 cytostatic agents from seven different groups, based on their different mechanisms of action, in the effluent from a medium-sized hospital located in eastern Spain. Analysis of the compounds found in the effluents studied involved solidphase extraction (SPE) coupled on-line to a high performance liquid chromatograph tandem mass spectrometer (HPLC-MS/MS). The environmental risk of the compounds studied was then assessed by calculating the hazard quotient (HQ), combining the measured environmental concentrations (MECs) with dose-response data based on the predicted no effect concentrations (PNECs). In addition, the environmental hazard associated was evaluated in accordance with their intrinsic characteristics by calculating the PBT (Persistence Bioaccumulation Toxicity) index. The results of this study showed the presence of seven of the 17 compounds analysed in a range of between 25 and 4761 ng/L. The highest concentrations corresponded to ifosfamide (58-4761 ng/L), methotrexate (394-4756 ng/L) and cyclophosphamide (46-3000 ng/L). Assessment of the environmental hazard showed that the three hormonal agents (tamoxifen and its metabolites endoxifen and hydroxytamoxifen) exhibited a maximum PBT value of 9 due to their inherent harm to the environment resulting from their characteristics of persistence, bioaccumulation and toxicity. A combined evaluation of the risk and environmental hazard showed that three of the 17 compounds studied, namely, ifosfamide, imatinib and irinotecan, all of which exhibited HQ values higher than 10 and PBT indices of 6, indicative of a particularly high potential to harm the environment, deserve special attention.

Determining the presence of chemicals with suspected endocrine activity in drinking water from the Madrid region (Spain) and assessment of their estrogenic, androgenic and thyroidal activities.

Endocrine disruptors (EDs) are natural or man-made chemicals that can affect the health of organisms by interfering with their normal hormonal functions. Many of these substances can cause their effects at very low doses and, considering the key role played by the endocrine system on development, organisms in early phases of growth (foetal, childhood, puberty) are especially sensitive to the action of EDs. In addition, when combined, they can show additive, antagonistic and synergistic activities. Taking all this into account it is essential to determine the presence of this kind of compounds in drinking water. Thus the main aim of the present study was to monitor the presence of substances with suspected or known endocrine activity in drinking water of the Madrid Region (MR) (Central Spain) and determine possible estrogenic, androgenic, or thyroidal activities. Water samples were collected at different times from a number of supply points that received water from reservoirs or rivers. The sampling point with the highest concentration of the analysed substances (up to 30 compounds) was DW1 (1203 ng L-1). This sampling point receives water from a drinking water treatment plant (DWTP) that serves the population from the south of the MR with treated water from the Tajuña River. DW2 was the second point with the highest concentration of the analysed substances (1021 ng L-1). DW2 receives water from one of the reservoirs in the north of the MR. The highest daily concentrations detected corresponded to the flame retardant Tris (2-chloroethyl)phosphate (TCEP) (266.55 ng L-1) and to the nonylphenol diethoxylate (188.57 ng L-1) at points DW1 and DW4, respectively, both of which are supplied with treated river water. None of the water samples exhibited androgenic, oestrogenic, or thyroidal activities in in vitro assays based on cells stably transfected with the receptors of interest and luciferase as reporter gene. These results demonstrate that water quality in the MR is high and does not present a health risk for the population, although the concentrations of some substances justify the need for local authorities to continually monitor the presence of these contaminants in order to implement any corrective measures if necessary.

Efficacy and safety of amlodipine: a comparative study of hypertensive patients treated at primary- and specialised-care centres.

BACKGROUND: This study set out to assess the safety and efficacy of amlodipine in two cohorts of patients who were attended in primary- and specialised-care centres, respectively. METHODS: Prospective, observational, multicentre pharmacovigilance study including patients aged >18 years who presented with a diagnosis of hypertension (systolic blood pressure [SBP] >or=140 mm Hg and diastolic blood pressure [DBP] >or=90 mm Hg) of >6 months' duration, which was either untreated or uncontrolled, and who were followed up by general practitioners and specialists over a period of 4-6 months. RESULTS: Of the total of 4277 patients included in the study, 2520 (58.9%) were attended in primary care and 1757 (41.1%) in specialised care. 2982 patients (69.7%) were receiving monotherapy, the rest were receiving combined therapy. Over the course of the study, 308 patients (7.2%) experienced adverse events related to the study drug, mostly mild to moderate in nature. There were 20 serious events, although none was related to the study drug. By the end of the study, 1617 patients (37.8%) had achieved the therapeutic goal (SBP <140 mm Hg and DBP <90 mm Hg), with the greatest degree of control being registered among patients receiving combined therapy compared with monotherapy (38.7% vs 35.7%), and in those treated in a specialised-care setting versus a primary-care setting (43.5% vs 33.8%; p < 0.005). CONCLUSIONS: Amlodipine was shown to be a well tolerated and effective drug in one in three patients, and achieved the therapeutic goal in a higher proportion of patients at specialised-care centres compared with those in primary care, and in those receiving combined therapy compared with monotherapy.

Ozonation of hospital raw wastewaters for cytostatic compounds removal. Kinetic modelling and economic assessment of the process.

The kinetics of the ozone consumption for the pretreatment of hospital wastewater has been analysed in order to determine the reaction rate coefficients between the ozone and the readily oxidisabled organic matter and cytostatic compounds. The wastewater from a medium size hospital was treated with ozone and peroxone methodologies, varying the ozone concentration, the reaction time and the hydrogen peroxide doses. The analysis shows that there are four cytostatic compounds, i.e. irinotecan, ifosfamide, cyclophosphamide and capecitabine, detected in the wastewaters and they are completely removed with reasonably short times after the ozone treatment. Considering the reactor geometry, the gas hydrodynamics, the mass transfer of ozone from gas to liquid and the reaction of all oxidisable compounds of the wastewater it is possible to determine the chemical ozone demand, COzD, of the sample as 256mgO3L(-1) and the kinetic rate coefficient with the dissolved organic matter as 8.4M(-1)s(-1). The kinetic rate coefficient between the ozone and the cyclophosphamide is in the order of 34.7M(-1)s(-1) and higher for the other cytostatics. The direct economic cost of the treatment was evaluated considering this reaction kinetics and it is below 0.3€/m(3) under given circumstances.

Drugs of abuse, cytostatic drugs and iodinated contrast media in tap water from the Madrid region (central Spain):A case study to analyse their occurrence and human health risk characterization.

This work analyses the presence of forty-eight emerging pollutants, including twenty-five drugs of abuse and metabolites, seventeen cytostatic drugs and six iodinated contrast media, in tap water from the Madrid Region. Analysis of the target compounds in the tap water was performed by means of (on-line or off-line) solid-phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry. A preliminary human health risk characterization was undertaken for each individual compound and for different groups of compounds with a common mechanism of action found in tap water. The results of the study showed the presence of eight out of the twenty-five drugs of abuse and metabolites analysed, namely, the cocainics cocaine and benzoylecgonine, the amphetamine-type stimulants ephedrine, 3,4-methylenedioxymethamphetamine and methamphetamine, the opioid methadone and its metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine and, finally caffeine at concentrations ranging from 0.11 to 502 ng L(-1). Four out of the six analysed iodinated contrast media, namely, diatrizoate, iohexol, iomeprol and iopromide, were detected in at least one sample, with concentration values varying between 0.4 and 5 ng L(-1). Cytostatic compounds were not detected in any sample. Caffeine was the substance showing the highest concentrations, up to 502 ng L(-1), mainly in the drinking water sampling point located in Madrid city. Among the other drugs of abuse, the most abundant compounds were cocaine and benzoylecgonine, detected at concentrations ranging from 0.11 to 86 ng L(-1) and from 0.11 to 53 ng L(-1), respectively. Regarding iodinated contrast media, iohexol was the most ubiquitous and abundant compound, with a frequency of detection of 100% and concentrations from 0.5 to 5.0 ng L(-1) in basically the same range in all sampling points. Taking into account the results and types of treatment applied, ozonisation plus granular activated carbon filtration appears to be efficient in the removal of cocaine and benzoylecgonine. For the amphetamine-type stimulants, opioids and caffeine, ozonisation plus granular activated carbon filtration and ultrafiltration plus reverse osmosis showed higher removal efficiency than sand filtration. The human health risk characterization performed indicates that the lifetime consumption of the tap waters analysed has associated a negligible human health concern.

Environmental concentrations of the cocaine metabolite benzoylecgonine induced sublethal toxicity in the development of plants but not in a zebrafish embryo-larval model.

Several studies have found cocaine and its main active metabolite benzoylecgonine (BE) in the aquatic environment and drinking water, derived from its consumption by humans as well as the inability of water treatment processes to eliminate it. A few studies have already investigated the ecotoxicology of BE to aquatic invertebrates, but none has still addressed the effects of BE on aquatic vertebrates or vascular plants. The goal of this publication is to provide information on the toxicity of environmental concentrations of BE during animal and vascular plant development, in order to contribute to a better understanding of the potential risk of this substance for the environment. BE induced alterations in mitochondrial activity and DNA levels of fern spores at environmental concentrations (1 ng L(-1)), which could disrupt gametophyte germination. However, BE at concentrations ranging from 1 ng L(-1) to 1 mg L(-1) did not disturb morphogenesis, hatching, heartbeat rate or larval motility in a zebrafish embryo-larval model. Adverse effects on ferns agree with the allelophathic role described for alkaloids and their unspecific interference with plant germination. Therefore, the anthropogenic dispersion of alkaloid allelochemicals may pose a risk for biodiversity and irrigated food production that should be further investigated.

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.

El análisis de aguas residuales con fines epidemiológicos: presente y futuro en España / Wastewater-based epidemiology: present and future in Spain

El análisis de aguas residuales con fines epidemiológicos es actualmente una herramienta fiable y complementaria a las metodologías basadas en indicadores tradicionales para el control de diferentes sustancias entre las que cabe destacar las drogas. Si bien varios países europeos la utilizan como herramienta de trabajo para la monitorización de drogas de abuso, en España su uso se limita principalmente a estudios realizados por diferentes grupos de investigación, tal y como se describe en el caso práctico puesto de ejemplo en el artículo. Sin embargo, el potencial de la metodología ha quedado evidenciado en los estudios científicos llevados a cabo tanto a nivel español como internacional y, aunque son necesarios más estudios para llegar a conocer todo su potencial, se prevé pueda ser incorporada como herramienta de trabajo complementaria a las que habitualmente se utilizan. En este sentido, la Red Española de Análisis de Aguas Residuales (ESAR-Net), creada en 2017 y formada por diferentes grupos de investigación españoles, pretende contribuir al conocimiento y aplicación de esta metodología en España a través de actividades científicas y de divulgación

Wastewater-Based Epidemiology is currently a reliable and complementary tool to methodologies based on traditional indicators for the control of various substances such as drugs. Although several European countries use it as a working tool for the monitoring of drugs of abuse, in Spain its use is mainly limited to studies carried out by different research groups, as described in the case study used as an example in the article. However, the potential of the methodology has been demonstrated in the scientific studies carried out both at the Spanish and international level and, although more studies are necessary to get to know its full potential, it is expected that it could be incorporated as a complementary work tool to those that are usually used. In this sense, the Red Española de Análisis de Aguas Residuales (ESAR-Net), created in 2017 and formed by different Spanish research groups, aims to contribute to the knowledge and application of this methodology in Spain through scientific and outreach activities

Effectiveness and Safety of Amlodipine in Newly Diagnosed Hypertensive Patients and in Previously Diagnosed Hypertensive Patients not Controlled with their Usual Treatment (NOTA Study).

OBJECTIVE: To evaluate the effectiveness and safety of amlodipine in two cohorts of hypertensive patients, one newly diagnosed and the other previously diagnosed but not controlled with drug therapy, and to assess the risk factors for the entire sample at the outset of the study. PATIENTS AND DESIGN: We designed a postmarketing, multicentre, open-label, prospective, observational surveillance study with a 6-month follow-up, which included hypertensive patients (systolic blood pressure [SBP] >/=140mm Hg and/or diastolic blood pressure [DBP] >/=90mm Hg) who attended specialised units and had either newly diagnosed or previously diagnosed pharmacologically uncontrolled arterial hypertension. RESULTS: Of the total of 1797 patients eligible for evaluation, 760 (42.3%) were newly and 1037 (57.7%) were previously diagnosed. Of these, 22.9% were classified as being in the high-risk and 43.2% in the very high-risk groups at the outset of the study (WHO-ISH [International Society of Hypertension]). On conclusion of the 6-month follow-up, 54.3% of newly diagnosed and 44.4% of previously treated patients had attained the BP therapy targets defined as SBP <140mm Hg and DBP <90mm Hg, representing a statistically significant difference (p < 0.0001). A total of 8% of patients experienced some adverse event during the course of the study, with this percentage being somewhat higher in the previously treated than in the newly diagnosed group (10.8% vs 5.1%, p < 0.0001). Only 0.3% experienced some severe adverse event, although in no case was this linked to the drug under evaluation. CONCLUSIONS: We conclude that amlodipine has shown itself to be an effective and safe drug for the control of hypertension, whether isolated or associated with other cardiovascular risk factors, both in patients without a previous diagnosis of arterial hypertension and in those previously diagnosed although not controlled under a prior treatment regimen.

Phthalate occurrence in rivers and tap water from central Spain.

The aim of this study is to evaluate the presence and concentrations of the main phthalates in water from the Jarama and Manzanares rivers in the region of Madrid (RM, Central Spain), the most densely populated region of Spain, and to determine the possible oestrogenic activity based on found phthalate concentration. The presence of phthalates in major supply drinking water areas of the RM was also analysed, thus allowing a preliminary assessment of the health risks resulting from the concentrations obtained. The results of this study show the presence of the three (dimethyl phthalate (DMP), diethyl phthalate (DEP) di-n-butyl phthalate (DBP)) of five phthalates studied (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-(2-ethylhexyl) phthalate (DEHP), benzyl-butyl phthalate (BBP) and di-n-butyl phthalate (DBP)). The DBP was found in both river and tap water samplers, whereas DMP and DEP were found in only drinking water samples. The DBP was found to make the highest average contribution to pollution in both river and tap water. The DEHP was not found in both the river and tap water because it is one of the most regulated phthalates. The highest phthalate contamination was found in the Manzanares river and in those areas that receive treated water from the Tagus river. The phthalates found in river and tap water in the RM do not represent a potential oestrogenic risk for the aquatic environment or humans. A preliminary risk assessment suggested that the risk of exposure to phthalates from tap water in this study is acceptable, although continuous monitoring of the presence of these substances in both drinking and river water should be undertaken to detect possible increases in their concentrations. This is the first study to analyse the presence of phthalates in both rivers and drinking water of the centre of Spain.

Monitoring endocrine disrupting compounds and estrogenic activity in tap water from Central Spain.

The aims of this study are to investigate the presence of 30 substances known or thought to act as endocrine disrupting compounds in tap water from the main water supply areas for region of Madrid, to determine the total estrogenic activity of the samples analysed and to estimate the health risk for the population resulting from those compounds found at detectable concentrations. To this end, a one-off composite sampling was performed in August 2012 in which six tap water samples were collected from private residences in the drinking water supply network of the region of Madrid. A total of 14 of the 30 endocrine disruptors analysed were found at concentrations ranging from 0.3 to 165 ng/L. The organophosphorus flame retardants were detected at the highest concentrations followed by the plasticizer bisphenol A, alkylphenols, anticorrosion agents and preservatives. Tap water in the region of Madrid is contaminated with traces (ng/L) of compounds with endocrine disrupting properties. Although the concentrations of endocrine disrupting compounds obtained are too low to be able to confirm a public health risk, and no risk has been detected upon evaluation, it should be remembered that these compounds act at very low doses and that their effects may only appear in the long term.