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.

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.

Drugs of abuse and benzodiazepines in the Madrid Region (Central Spain): seasonal variation in river waters, occurrence in tap water and potential environmental and human risk.

This work analyzes the seasonal variation (winter and summer) of ten drugs of abuse, six metabolites and three benzodiazepines in surface waters from the Jarama and Manzanares Rivers in the Madrid Region, the most densely populated area in Spain. The occurrence of these compounds in tap water in this region is also investigated and a preliminary human health risk characterization performed for those substances found in tap water. Finally, a screening level risk assessment that combines the measured environmental concentrations (MECs) with dose-response data to estimate Hazard Quotients (HQs) for the compounds studied is also presented. The results of this study show the presence of fourteen out of the nineteen compounds analyzed in winter and twelve of them in summer. The most ubiquitous compounds, with a frequency of detection of 100% in both seasons, were the cocaine metabolite benzoylecgonine (BE), the amphetamine-type stimulant (ATS) ephedrine (EPH), the opioid methadone (METH), the METH metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and the three benzodiazepines investigated, namely alprazolam (ALP), diazepam (DIA) and lorazepam (LOR). The highest concentrations observed corresponded to EPH (1020ngL(-1) in winter and 250ngL(-1) in summer). The only compounds not detected in both seasons were heroin (HER) and its metabolite 6-acetylmorphine (6ACM), lysergic acid diethylamide (LSD) and its metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD), and Δ(9)-tetrahydrocannabinol (THC). In terms of overall concentration, all sampling points presented higher concentrations in winter than in summer. Statistical analyses performed to gather evidence concerning occasional seasonal differences in the concentrations of individual substances between summer and winter showed statistically significantly higher concentrations (p<0.05) of BE, EPH and the opioid morphine (MOR) in winter than in summer. Two out of the nineteen compounds studied, namely cocaine (CO) and EPH, were detected in tap water from one sampling point at concentrations of 1.61 and 0.29ngL(-1), respectively. The preliminary human health risk characterization showed that no toxic effects could be expected at the detected concentration level in tap water. The screening level risk assessment showed that MOR, EDDP and the THC metabolite 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH) were present in at least one of the sampling sites in a concentration leading to a Hazard Quotient (HQ) value between 1.0 and 10.0, thus indicating some possible adverse effects. The cumulative HQ or Toxic units (TUs) calculated for each of the groups studied showed that opioids and cannabinoids were present at concentrations high enough to potentially generate some adverse effects on at least one sampling point.

Occurrence of drugs of abuse and benzodiazepines in river waters from the Madrid Region (Central Spain).

This work investigates, for the first time, the occurrence of 10 drugs of abuse, six metabolites, and three benzodiazepines in surface waters from the Jarama and Manzanares Rivers in the Madrid Region, the most densely populated area in Spain and one of the most densely populated in Europe. The results of this study have shown the presence of 14 out of the 19 compounds analyzed at concentrations ranging from 1.45 to 1020 ng L(-1). The most ubiquitous compounds, found in 100% of the samples, were the cocaine metabolite benzoylecgonine (BE), the amphetamine-like compound ephedrine (EPH), the opioids morphine (MOR), methadone (METH), and the METH metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and the three investigated benzodiazepines alprazolam (ALP), diazepam (DIA) and lorazepam (LOR). Meanwhile, the largest concentrations observed corresponded to EPH (up to 1020 ng L(-1)), BE (823 ng L(-1)), EDDP (151 ng L(-1)), and LOR (167 ng L(-1)). The only not detected compounds were heroin (HER) and its metabolite 6-acetylmorphine (6ACM), lysergic acid diethylamide (LSD) and its metabolite 2-oxo-3-hydroxy-LSD (OH-LSD), and Δ(9)-tetrahydrocannabinol (THC). Overall, the levels measured are comparatively higher than those previously reported in Europe. Comparison of the results obtained for samples collected on different days (Thursday and Sunday) did not show meaningful differences between weekdays and weekends. The lack of (eco)toxicological data does not permit to predict or disregard potential adverse effects on wildlife. Risk assessment in humans would require further knowledge, not currently available, on exposure to these compounds through other routes like drinking water and/or food.

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.

Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.

A hereditary defect of the distal tubule accounts for the clinical features of Gitelman syndrome (GS), an autosomal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. Recently, we cloned the cDNA coding for the human Na-Cl thiazide-sensitive cotransporter (TSC; also known as ¿NCCT¿ or ¿SLC12A3¿) as a possible candidate for GS, and Simon et al., independently, described mutations in patients with GS. Now, we show 12 additional mutations consistent with a loss of function of the Na-Cl cotransporter in GS. Two missense replacements, R209W and P349L, are common to both studies and could represent ancient mutations. The other mutations include three deletions, two insertions, and six missense mutations. When all mutations from both studies are considered, missense mutations seem to be more frequently localized within the intracellular domains of the molecule, rather than in transmembrane or extracellular domains. One family, previously reported as a GS form with dominant inheritance, has proved to be recessive, with the affected child being a compound heterozygote. A highly informative intragenic tetranucleotide marker, useful for molecular diagnostic studies, has been identified at the acceptor splice site of exon 9.

Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).

Electrolyte homeostasis is maintained by several ion transport systems. Na-(K)-Cl cotransporters promote the electrically silent movement of chloride across the membrane in absorptive and secretory epithelia. Two kidney-specific Na-(K)-Cl cotransporter isoforms are known, so far, according to their sensitivity to specific inhibitors. We have cloned the human cDNA coding for the renal Na-Cl cotransporter selectively inhibited by the thiazide class of diuretic agents. The predicted protein sequence of 1021 amino acids (112 kDa) shows a structure common to the other members of the Na-(K)-Cl cotransporter family: a central region harboring 12 transmembrane domains and the 2 intracellular hydrophilic amino and carboxyl termini. The expression pattern of the human Na-Cl thiazide-sensitive cotransporter (hTSC, HGMW-approved symbol SLC12A3) confirms the kidney specificity. hTSC has been mapped to human chromosome 16q13 by fluorescence in situ hybridization. The cloning and characterization of hTSC now render it possible to study the involvement of this cotransport system in the pathogenesis of tubulopathies such as Gitelman syndrome.