Occurrence and fate of pharmaceutical products and by-products, from resource to drinking water

International audienceAmong all emerging substances in water, pharmaceutical products (PPs) and residues are a lot of concern. These last two years, the number of studies has increased drastically, however much less for water resources and drinking water than for wastewater. This literature review based on recent works, deals with water resources (surface or groundwater), focusing on characteristics, occurrence and fate of numerous PPs studied, and drinking water including water quality. Through this review, it appears that the pharmaceutical risk must be considered even in drinking water where concentrations are very low. Moreover, there is a lack of research for by-products (metabolites and transformation products) characterization, occurrence and fate in all water types and especially in drinking water

Résidus pharmaceutiques dans les eaux destinées à la consommation humaine (occurrence et devenir pour une évaluation de l exposition et du risque sanitaire)

La présence des substances pharmaceutiques dans les ressources en eaux (souterraines et superficielles) disponibles pour la consommation humaine est une problématique de Santé Publique récente et d'envergure internationale. Les travaux de cette thèse s'inscrivent dans ce contexte et portent sur l'occurrence de ces substances dans les ressources en eau mais également au sein des filières de traitement et des eaux alimentaires. Les travaux menés ont permis de développer une méthodologie d'analyse multirésidus pharmaceutiques à usages humains aux performances satisfaisantes pour l'ensemble des résidus sélectionnés dans cette étude. La mise en œuvre de cette méthodologie lors de campagnes d'échantillonnage et d'analyse a permis ensuite d'apporter de nombreuses données de concentrations des substances pharmaceutiques dans les ressources en eau ainsi que dans l'eau traitée distribuée dans l'Ouest de la France (bassin de la Vilaine et de la Mayenne). L'étude de l'impact des émissions urbaines d'origine anthropique sur les eaux superficielles, de la variation temporelle de la qualité des eaux de surface, et de l'efficacité des filières de traitement de potabilisation pour éliminer les substances pharmaceutiques ont pu être également abordés dans ces travaux. Les travaux de cette thèse participent donc à l'amélioration des connaissances nécessaires pour répondre aux questions de l'exposition chronique et du risque sanitaire liés aux résidus pharmaceutiques à usages humains présents en mélange à l'état de traces dans les eaux alimentaires.The presence of pharmaceutical compounds in drinking-water sources (ground- and surface water) is a recent and a worldwide Public Health issue. Within this framework, this thesis work deals with the occurrence of these substances in water resources, in water utilities, and in drinking-water. This thesis work led to the development of a multi-residue analytical methodology showing satisfactory performances for all pharmaceutical compounds targeted in this study. The implementation of this analytical methodology during sampling and analyses campaigns provided numerous concentrations data about pharmaceutical compounds in dinking-water sources (ground- and surface water) and treated drinking-water in north-west France (The Vilaine and the Mayenne catchment basins). The anthropogenic emission impact on surface water, the temporal variation of surface water quality, and the efficiency of drinking-water treatment process in water utilities to remove pharmaceuticals compounds was also studied and discussed in this work. This thesis work contributes to bring needed knowledge for a further chronic human exposure and health risk assessment related to these compounds occurring in mixture at low-level in drinking-water.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Chapter 3: Exposure based on life cycle

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A 50-year record of quinolone and sulphonamide antimicrobial agents in Seine River sediments

International audiencePurpose: Even though sediments may represent a reservoir for antimicrobial agents, little is known about the persistence of these molecules over time or their accumulation. In this study, six antimicrobial agents, oxolinic acid, flumequine, nalidixic acid, norfloxacin, sulphamethoxazole and trimethoprim, were investigated in a sediment core from the Seine River. This work aimed to (1) measure antimicrobial agent contamination levels in the sediment and identify their origins, (2) obtain information on the persistence of these compounds in sediment over long periods (>4 years) and (3) show the existence of a historical record in sediment of river contamination by antimicrobial agents. Material and methods Sedimentary records were collected in a regularly flooded area at the side of the Seine River downstream of urban Paris. Dating was performed using environmental 137Cs and 210Pb radioisotopes. Antimicrobial agents were extracted and purified using Soxhlet extraction and solid phase extraction. Chromatographic separation of the compounds was achieved with Ultra Performance™ liquid chromatography tandem mass spectrometry. Results and discussion : Antimicrobial agent residues were detected in river sediment deposits to a depth exceeding 80 cm, corresponding to sediment deposits dating from the early 1960s. Five out of six antimicrobial agents were detected: norfloxacin, flumequine, oxolinic acid, nalidixic acid and sulphamethoxazole. Dating of the slices shows evidence of a correspondence between commercialisation of the compounds and their occurrence in the successive sediment deposits. In general, the results from previous studies justify the assumption of relative persistence of these compounds, although no experiments were conducted over periods as long as several decades. Conclusions : Our results show that antimicrobial agents can persist in sediment for up to 30 to 40 years, which raise concerns about the environmental effects of such long-term exposure on aquatic organisms

Assessing antibiotic contamination in metal contaminated soils four years after cessation of long-term waste water irrigation.

International audienceSpreading of urban wastewater on agricultural land may lead to concomitant input of organic and inorganic pollutants. Such multiple pollution sites offer unique opportunities to study the fate of both heavy metals and pharmaceuticals. We examined the occurrence and fate of selected antibiotics in sandy-textured soils, sampled four years after cessation of 100 years irrigation with urban wastewater from the Paris agglomeration. Previous studies on heavy metal contamination of these soils guided our sampling strategy. Six antibiotics were studied, including quinolones, with a strong affinity for organic and mineral soil components, and sulfonamides, a group of more mobile molecules. Bulk samples were collected from surface horizons in different irrigation fields, but also in subsurface horizons in two selected profiles. In surface horizons, three quinolones (oxolinic acid, nalidixic acid, and flumequine) were present in eight samples out of nine. Their contents varied spatially, but were well-correlated one to another. Their distributions showed great similarities regarding spatial distribution of total organic carbon and heavy metal contents, consistent with a common origin by wastewater irrigation. Highest concentrations were observed for sampling sites close to irrigation water outlets, reaching 22 μgkg−1 for nalidixic acid.Within soil profiles, the two antibiotic groups demonstrated an opposite behavior: quinolones, found only in surface horizons; sulfamethoxazole, detected in clay-rich subsurface horizons, concomitant with Zn accumulation. Such distribution patterns are consistent with chemical adsorption properties of the two antibiotic groups: immobilization of quinolones in the surface horizons ascribed to strong affinity for organicmatter (OM),migration of sulfamethoxazole due to a lower affinity for OM and its interception and retention in electronegative charged clay-rich horizons. Our work suggests that antibiotics may represent a durable contamination of soils, and risks for groundwater contamination, depending on the physicochemical characteristics both of the organic molecules and of soil constituents

Fate of Sulfonamides and Tetracyclines in Meat during Pan Cooking: Focus on the Thermodegradation of Sulfamethoxazole

International audienceAlthough antimicrobials are generally found in trace amounts in meat, the human health risk they bear cannot be ignored. With the ultimate aim of making a better assessment of consumer exposure, this study explored the effects of pan cooking on sulfonamides and tetracyclines in meat. Screening of these antimicrobials in cooked meat was first performed by the European Union Reference Laboratory on the basis of HPLC-MS/MS analyses. A proof of concept approach using radiolabeling was then carried out on the most cooking-sensitive antimicrobial—sulfamethoxazole—to assess if a thermal degradation could explain the observed cooking losses. Degradation products were detected thanks to separation by HPLC and monitoring by online radioactivity detection. HPLC-Orbitrap HRMS analyses completed by 1D and 2D NMR experiments allowed the structural characterization of these degradation compounds. This study revealed that cooking could induce significant antimicrobial losses of up to 45% for sulfamethoxazole. Six potential degradation products of 14C-sulfamethoxazole were detected in cooked meat, and a thermal degradation pattern was proposed. This study highlights the importance of considering the cooking step in chemical risk assessment procedures and its impact on the level of chemical contaminants in meat and on the formation of potentially toxic breakdown compounds

Analytical strategy to investigate veterinary medicinal product residues below their regulatory EU-limits in meat

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A non-targeted LC-HRMS approach for detecting exposure to illegal veterinary treatments: The case of cephalosporins in commercial laying Hens

International audienceCephalosporins are of particular importance in human medicine and should be reserved for second-line curative treatment in the veterinary field to avoid any emerging antimicrobial resistance. Due to misuse of ceftiofur in the poultry sector in France, it is now recommended to completely stop using cephalosporins in this sector. Methods currently used for the control of veterinary practices are mostly based on liquid chromatography coupled to mass spectrometry in a targeted mode, including parent compounds and any major metabolites. The aim of the present study was to evaluate the relevance of untargeted metabolomic approaches to highlight a possible exposure of laying hens to cephalosporins using a predictive model including selected treatment biomarkers. An experimentation carried out on living animals involved the administration of cefquinome and ceftiofur. Three biological matrices—droppings, eggs and liver—were investigated. Metabolites were extracted and analysed by liquid chromatography coupled to high resolution mass spectrometry in a full scan mode. Metabolites impacted by the treatment were selected by using univariate and multivariate statistical analyses. Predictive models built from the potential biomarkers selected in the "droppings" matrix were validated and able to classify “treated” and “control” hens. PLS-DA and logistic regression models were compared and both models gave satisfactory results in terms of prediction. Results were of less interest for other matrices in which only biomarkers of exposure to cefquinome were detected

Solid-phase microextraction set-up for the analysis of liver volatolome to detect livestock exposure to micropollutants

International audienceStarting from a critical analysis of a first "proof of concept" study on the utility of the liver volatolome for detecting livestock exposure to environmental micropollutants (Berge et al., 2011), the primary aim of this paper is to improve extraction conditions so as to obtain more representative extracts by using an extraction temperature closer to livestock physiological conditions while minimizing analytical variability and maximizing Volatile Organic Compound (VOC) abundancies. Levers related to extraction conditions and sample preparation were assessed in the light of both abundance and coefficient of variation of 22 candidate VOC markers identified in earlier volatolomic studies. Starting with a CAR/PDMS fiber and a 30min extraction, the reduction of SPME temperature to 40°C resulted in a significant decrease in the area of 14 candidate VOC markers (p<0.05), mainly carbonyls and alcohols but also a reduction in the coefficient of variation for 17 of them. In order to restore VOC abundances and to minimize variability, two approaches dealing with sample preparation were investigated. By increasing sample defrosting time at 4°C from 0 to 24h yielded higher abundances and lower variabilities for 15 and 13 compounds, respectively. Lastly, by using additives favouring the release of VOCs (1.2g of NaCl) the sensitivity of the analysis was improved with a significant increase in VOC abundances of more than 50% for 13 out of the 22 candidate markers. The modified SPME parameters significantly enhanced the abundances while decreasing the analytical variability for most candidate VOC markers. The second step was to validate the ability of the revised SPME protocol to discriminate intentionally contaminated broiler chickens from controls, under case/control animal testing conditions. After verification of the contamination levels of the animals by national reference laboratories, data analysis by a multivariate chemometric method (Common Components and Specific Weights Analysis - ComDim) showed that the liver volatolome could reveal dietary exposure of broilers to a group of environmental pollutants (PCBs), a veterinary treatment (monensin), and a pesticide (deltamethrin), thus confirming the usefulness of this analytical set-up