Lauriane Ledieu
email: lauriane.ledieu@cnrsorleans.fr

Anaëlle Simonneau
email: anaelle.simonneau@univ-orleans.fr

Thomas Thiebault

Laëtitia Fougère

Emilie Destandau

O Cerdan

Fatima Laggoun-Défarge

L Fougere

F Laggoun

Spatial distribution of Pharmaceuticals within the particulate phases of a peri-urban stream

Keywords: Conceptualization, Investigation, Validation, Writing -Original Draft, Visualization. Anaëlle Simonneau: Conceptualization, Supervision, Writing -Review & Editing, Project administration, Funding acquisition

Introduction

Environmental and societal concerns about the occurrence of pharmaceutical products (PPs) within aquatic systems started in the 1970s [START_REF] Hignite | Drugs and drug metabolites as environmental contaminants: chlorophenoxyisobutyrate and salicylic acid in sewage water effluent[END_REF]. These molecules are consumed worldwide [START_REF] Jjemba | Excretion and ecotoxicity of pharmaceutical and personal care products in the environment[END_REF][START_REF] Gracia-Lor | Simultaneous determination of acidic, neutral and basic pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatographytandem mass spectrometry[END_REF] and are continuously released into the environment [START_REF] Loos | EU-wide survey of polar organic persistent pollutants in European river waters[END_REF] as chemical cocktails [START_REF] Petrie | A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring[END_REF][START_REF] Kaushal | Making 'chemical cocktails'-Evolution of urban geochemical processes across the Periodic Table of elements[END_REF]. PPs can be bioaccumulated in aquatic organisms and transferred to the food chain [START_REF] Sumpter | Oestrogenic substances in the aquatic environment and their potential impact on animals, particularly fish[END_REF], with negative effects on animal and human health [START_REF] Gracia-Lor | Simultaneous determination of acidic, neutral and basic pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatographytandem mass spectrometry[END_REF]. Research efforts have therefore increased since the 1990s [START_REF] Hughes | Global synthesis and critical evaluation of pharmaceutical data sets collected from river systems[END_REF] and PPs were qualified as an emerging class of contaminants [START_REF] Boreen | Photodegradation of pharmaceuticals in the aquatic environment: a review[END_REF][START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF]. The long-term ecotoxicological effects of these micropollutants remain unclear [START_REF] Gracia-Lor | Simultaneous determination of acidic, neutral and basic pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatographytandem mass spectrometry[END_REF] and thus represent a major environmental and societal issue. Understanding PP dynamics in hydrosystems is therefore needed in order to manage environmental contamination [START_REF] Dobor | Biofilm controlled sorption of selected acidic drugs on river sediments characterized by different organic carbon content[END_REF][START_REF] Petrie | A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring[END_REF][START_REF] J O U R N A L P R E -P R O O F Thiebault | Raw and modified clays and clay minerals for the removal of pharmaceutical products from aqueous solutions: State of the art and future perspectives[END_REF][START_REF] Boulard | Spatial distribution and temporal trends of pharmaceuticals sorbed to suspended particulate matter of German rivers[END_REF].

In the European Union, about 3,000 PPs are approved for medical treatment [START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF], among which psychotropics [START_REF] Calisto | Psychiatric pharmaceuticals in the environment[END_REF], anti-inflammatory agents, β-blockers [START_REF] Petrie | A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring[END_REF] and analgesics [START_REF] Verlicchi | Hospital effluents as a source of emerging pollutants: an overview of micropollutants and sustainable treatment options[END_REF] are the most frequently prescribed. France has a high drug consumption; for example, in 2018 average spending per inhabitant amounted to 488 € [START_REF] Leem | Bilan économique[END_REF]. High releases are therefore observed in freshwater aquatic environments [START_REF] Fekadu | Pharmaceuticals in freshwater aquatic environments: A comparison of the African and European challenge[END_REF], but only a few studies have been conducted on French rivers [START_REF] Tamtam | Occurrence and fate of antibiotics in the Seine River in various hydrological conditions[END_REF][START_REF] Munoz | Résidus de médicaments dans les milieux aquatiques: besoins et outils pour la surveillance[END_REF][START_REF] Hughes | Global synthesis and critical evaluation of pharmaceutical data sets collected from river systems[END_REF]. These studies evidenced the presence of PPs in both small and large basins comprising urban areas [START_REF] Feitosa-Felizzola | Occurrence and distribution of selected antibiotics in a small Mediterranean stream (Arc River, Southern France)[END_REF][START_REF] Mompelat | Contamination levels of human pharmaceutical compounds in French surface and drinking water[END_REF].

Significant proportions of the consumed PPs can be excreted in an unchanged form [START_REF] Baranowska | The development of SPE procedures and an UHPLC method for the simultaneous determination of ten drugs in water samples[END_REF], and therefore transferred toward wastewater treatment plants (WWTP). The presence of PPs in hydrosystems is then the consequence of the incomplete removal of PPs in domestic and hospital sewage in WWTPs [START_REF] Kümmerer | The presence of pharmaceuticals in the environment due to human usepresent knowledge and future challenges[END_REF]. These micropollutants are subject to J o u r n a l P r e -p r o o f degradation, dilution and sorption processes but can be transported over long distances [START_REF] Tamtam | Occurrence and fate of antibiotics in the Seine River in various hydrological conditions[END_REF][START_REF] Aminot | Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry[END_REF]. PPs are considered to be less persistent than other types of organic contaminants (such as polycyclic aromatic hydrocarbons and polychlorinated biphenyls), as they have fewer interactions with particulate phases because of their lower hydrophobicity [START_REF] Svahn | Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements[END_REF][START_REF] Boulard | Spatial distribution and temporal trends of pharmaceuticals sorbed to suspended particulate matter of German rivers[END_REF] and are thus less likely to be transported through sediment transport [START_REF] Loos | EU-wide survey of polar organic persistent pollutants in European river waters[END_REF]. This pathway is consequently often neglected, but some PPs also display significant affinities with solid organic and mineral matrices [START_REF] Löffler | Environmental fate of pharmaceuticals in water/sediment systems[END_REF][START_REF] Vazquez-Roig | Determination of pharmaceuticals in soils and sediments by pressurized liquid extraction and liquid chromatography tandem mass spectrometry[END_REF][START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF][START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF][START_REF] J O U R N A L P R E -P R O O F Koba | Transport of pharmaceuticals and their metabolites between water and sediments as a further potential exposure for aquatic organisms[END_REF].

In recent decades, analytical procedures that assist in distinguishing and quantifying PPs in solid matrices have been developed especially through pressurized liquid extraction (PLE, Jelić et al., 2009) followed by ultra-high performance liquid chromatography in combination with tandem mass spectrometry (UHPLC-MS², [START_REF] Gracia-Lor | Simultaneous determination of acidic, neutral and basic pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatographytandem mass spectrometry[END_REF]. Studies evaluating PP distribution in sediments provide useful information as they may integrate larger time scales than the dissolved ones [START_REF] Zhou | Sediment-water interactions of pharmaceutical residues in the river environment[END_REF]. Moreover, as the fate of PPs mainly depends on their partitioning between dissolved and particulate phases, an understanding of the sorption processes is required [START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF]. Several studies conducted through batch experiments therefore evaluated the type of interactions involved in PP adsorption [START_REF] Yamamoto | Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments[END_REF], the difference in molecules' mobility [START_REF] Scheytt | Determination of sorption coefficients of pharmaceutically active substances carbamazepine, diclofenac, and ibuprofen, in sandy sediments[END_REF], the role of solid matrix composition and the potential desorption of PPs [START_REF] Stein | Analysis and sorption of psychoactive drugs onto sediment[END_REF]. Predicting the behaviour of PPs is complex because of the variety of processes and parameters involved in their adsorption (Al-Khazrajy & Boxall, 2016) but partitioning is mainly driven by both PP (structure, charge, hydrophobicity, persistence) and particle characteristics (composition, texture;[START_REF] Vazquez-Roig | Risk assessment on the presence of pharmaceuticals in sediments, soils and waters of the Pego-Oliva Marshlands (Valencia, eastern Spain)[END_REF][START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF][START_REF] Thiebault | Competitive adsorption of a pool of pharmaceuticals onto a raw clay mineral[END_REF].

The spatio-temporal evolution of PPs certainly depends on sources, consumption and discharge rates [START_REF] Petrie | A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring[END_REF][START_REF] Wilkinson | Spatial distribution of organic contaminants in three rivers of Southern England bound to suspended particulate material and dissolved in water[END_REF]. In particulate phases, this evolution is also driven by J o u r n a l P r e -p r o o f particle composition and texture as well as by the physico-chemical and hydrological conditions of the hydrosystem [START_REF] Kim | Temporal and spatial trends in the occurrence of human and veterinary antibiotics in aqueous and river sediment matrices[END_REF][START_REF] J O U R N A L P R E -P R O O F De Castro-Català | Ecotoxicity of sediments in rivers: Invertebrate community, toxicity bioassays and the toxic unit approach as complementary assessment tools[END_REF]. Consequently, PPs may show high spatial variabilities between different aquatic environments. Wastewaters from medical institutions display higher emissions than domestic ones [START_REF] Kümmerer | The presence of pharmaceuticals in the environment due to human usepresent knowledge and future challenges[END_REF][START_REF] Verlicchi | Hospital effluents as a source of emerging pollutants: an overview of micropollutants and sustainable treatment options[END_REF][START_REF] Huber | A first screening and risk assessment of pharmaceuticals and additives in personal care products in waste water, sludge, recipient water and sediment from Faroe Islands, Iceland and Greenland[END_REF] and small hydrosystems are more sensitive to these contaminations because of a lower dilution of anthropogenic inputs [START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF]. At a basin scale, different spatial evolutions have already been observed. [START_REF] Schultz | Antidepressant pharmaceuticals in two US effluent-impacted streams: occurrence and fate in water and sediment, and selective uptake in fish neural tissue[END_REF] measured increasing concentrations downstream of the WWTP effluent whereas [START_REF] Aminot | Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry[END_REF] measured the highest accumulation near sewage discharging sites, where sediments presented a high organic carbon content. The same observations were made by Da [START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF] and [START_REF] Zhou | Sediment-water interactions of pharmaceutical residues in the river environment[END_REF], but variabilities according to streamflow conditions were also recorded. At the Loire Bretagne basin scale, Amalric et al. ( 2011) correlated observed contents with urban pressure levels. Because of the complexity of these influencing factors, the spatio-temporal evolution of PPs in solid matrices is rarely investigated [START_REF] Fairbairn | Sediment-water distribution of contaminants of emerging concern in a mixed use watershed[END_REF], especially when it comes to integrating different compartments of the aquatic environment [START_REF] Wilkinson | Spatial distribution of organic contaminants in three rivers of Southern England bound to suspended particulate material and dissolved in water[END_REF].

In this context, the present study attempts to provide new insights into PP occurrences within particulate phases of a small peri-urban stream as these sites are often neglected while represent hotspots of contamination. Their occurrences were also used to study the spatio-temporal accumulation and/or transportation of this kind of contaminants at catchment scale, in both suspended particulate matter and sediments (bed-load and pond sediments). The catchment of the peri-urban Egoutier stream, a tributary of the Loire River, which collects the wastewaters from two medical institutions, was chosen as the study site. These point sources represent a good opportunity to improve our understanding of PPs spatio-temporal distribution as well as the impact of these effluents on stream quality.

J o u r n a l P r e -p r o o f 10 PPs were investigated, based on their consumption in the European Union (e.g. psychotropics, anti-inflammatory agents, β-blockers and analgesics; [START_REF] Calisto | Psychiatric pharmaceuticals in the environment[END_REF][START_REF] Verlicchi | Hospital effluents as a source of emerging pollutants: an overview of micropollutants and sustainable treatment options[END_REF][START_REF] Petrie | A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring[END_REF] as well as their detection frequency in aquatic environments (e.g. anticonvulsants and opioids; [START_REF] Clara | Carbamazepine as a possible anthropogenic marker in the aquatic environment: investigations on the behaviour of carbamazepine in wastewater treatment and during groundwater infiltration[END_REF][START_REF] Campos-Mañas | Opioid occurrence in environmental water samples-a review[END_REF]. The occurrence of these PPs was investigated in the particulate phases at the catchment scale and in the dissolved phase of WWTP effluents. Environmental physico-chemical conditions, composition and textures of solid matrices were also characterized. Lastly, based on the analysis of PPs emissions and properties (persistence, charge state and lipophilicity), different factors driving the accumulation and spatial distribution of the molecules were identified.

II.

Material and Methods

Study site and sampling method

The Egoutier catchment is located east of Orléans, in the Loire River basin (Fig. 1). Characterized by a temperate climate with an average annual rainfall of 650 mm [START_REF] Soucémarianadin | Notice explicative de la carte des sols de Orléans (1/50 000)[END_REF], this small lowland catchment (27 km²) is drained by the Egoutier stream. The mean slope gradient is 0.5% and the geological substrate is composed of Sologne sands and clays, Orleanais sands and Beauce limestone from upstream to downstream [START_REF] Berger | Carte de France (1/50 000[END_REF].

To study the spatial evolution of PPs following a source-to-sink logic, the area investigated in this work was restricted to the upstream part of the catchment, covering 8 km² and including the Beulie pond in its central part (Fig. 1). In this part, the catchment is composed by solely of hydromorphic soils with clay-rich subsoil layers [START_REF] Soucémarianadin | Notice explicative de la carte des sols de Orléans (1/50 000)[END_REF]. The Egoutier stream is thus supplied by stormwater runoff, but also by effluents from two WWTPs and two stormwater point sources from urban areas. The two WWTPs treat effluents from a central army pharmacy (CAP) and a psychiatric hospital (PH, Fig. 1), respectively. CAP effluents are continuously discharged at a flow rate of 7 m 3 /h, whereas PH effluents, with a treatment capacity of 400 beds, are J o u r n a l P r e -p r o o f not continuous and not monitored. Urban storm waters come from runoff processes on both CAP surfaces and urban areas in the eastern part of the catchment. The latter are collected in a network and released into a tributary of the stream (BLS-13b, Fig. 1).

[Figure 1]

Figure 1 : Description of the upstream part of the Egoutier catchment area studied here with land covers [START_REF] Inglada | Theia OSO Land Cover Map[END_REF]. Locations of the two sewage water effluents from the central army pharmacy (CAP) and the psychiatric hospital (PH) and of the samples collected in the dissolved phase (W), in suspended particulate matter (SPM), bed-load (BLS) and Beulie pond sediments (EG).

In order to observe PP transportation by suspended particulate matter (SPM) at the catchment scale, SPM (grey dots, Fig. 1) were sampled at three locations. The first samples were taken downstream the CAP WWTP effluent (SPM-1, and August and October 2019 (Table S1).

In 2018 and 2019, 15 bed-load sediment samples (BLS, brown dots, Fig. 1) were collected all along the watercourse to assess the PPs' spatial distribution and the impact level of WWTP effluents.

BLS were sampled at each storm-and sewage water discharge, and upstream to downstream depending on confluence and accumulation zones, during both winters and summers (April 2018 and 2019; August 2018 and 2019, Table S1), using 50 mL polypropylene Falcon tubes. Because of some dry areas during summer, some replicates were not always sampled in summer (Table S1).

J o u r n a l P r e -p r o o f

Three Beulie pond interface sediments (water/sediment limit) were also collected in April 2018, along a north-south transect using an Ekman Grab (EG, green dots, Fig. 1). All solid samples were then split into two parts; one was stored wet at 5 °C and the other was dried at 50 °C during 48 h.

Finally, two water samples (W, water drops, Fig. 1) were collected at each WWTP discharge to verify the consistency of the PPs detected in solid matrices. The PH effluent (W-PH, Fig. 1) was collected in April 2017 and the CAP effluent (W-CAP, Fig. 1) in August 2018 (Table S1), using 10 L polyethylene bottles that were stored at 5 °C before analysis.

Environmental parameters and sample characteristics

Stream pH conditions were measured during each BLS sampling campaign. This parameter was determined with a portable pH meter MultiLine Multi 3630 IDS.

Particle size distributions for SPM samples were already given by the GEACOS technology [START_REF] Simonneau | GranulomEtric pAssive Capture of dissOlved matter & Sediment[END_REF]. They were quantified by drying each GEACOS sieve from 1 mm to 250, 60, 20 and 5 µm. The grain sizes of all the other sediment samples (moistened fractions sieved under 1.8 mm) were determined using a laser particle sizer Mastersizer 3000 (Malvern) at the GEHCO laboratory. Results obtained are the relative percentages of four grain-size classes: 0 -2 µm for clay grain sizes, 2 -63 µm for silt grain sizes, 63 -250 µm for fine sand grain sizes and 250 -1800 µm for medium to coarse sand grain sizes.

Total organic carbon (TOC) contents were estimated by Rock-Eval pyrolysis [START_REF] Behar | Rock-Eval 6 technology: performances and developments[END_REF]) using a Rock Eval 6 turbo at the ISTO laboratory. Standards provided by Vinci Technologies were used to check the reproducibility of the measures. The mean error and mean correction factor of TOC measurements were 0.14% and 1%, respectively.

Finally, the bulk mineralogy of four samples (three BLS samples from the first campaign in were purchased from Sigma-Aldrich with a purity >98%. The solvents used for PP extraction and separation, methanol (MeOH), acetonitrile (AcN) and formic acid (HCOOH), were purchased from Fisher-Scientific, assuming an analytical grade (purity up to 99.95%).

Extraction procedure

Extraction procedures were carried out at the ISTO laboratory. For water samples solid phase extraction (SPE) using a Chromabond HR-X cartridge (6 mL x 500 mg, Macherey-Nagel) was performed. The cartridge was conditioned with 5 mL of MeOH and 5 mL of ultra-pure water (H 2 O).

The cartridge was then filled with 250 mL of sample before being washed with 5 mL of H 2 O and dried for 30 minutes. The analytes were finally eluted with 3 x 5 mL of MeOH. Complementarily, between 1 and 7 g of bulk sediments, depending on their composition, were extracted by pressurized liquid extraction (PLE) using an ASE-200 (Dionex, 100 °C and 1000 psi) and a mixture of MeOH/ H 2 O (1:1, v/v). For both methods, eluates were then dried under nitrogen flow and reconstituted in 3 mL of H 2 O. Solutions were filtered with a glass-fiber filter (GF/F, Whatman) prior to being stored at 5 °C before analysis. The recovery ratios of the investigated PPs (Table 1) during SPE and ASE were taken as those presented in Thiebault et al. (2017a, b), using the same protocol (Table S2).

J o u r n a l P r e -p r o o f then 100% of B during 3 min, followed by a return to initial conditions (95% of A) during 10 min. The mass spectrometer was a TSQ Endura triple quadrupole equipment fitted with a heated electrospray ionization (H-ESI) interface (Thermo Fisher Scientific). The analytical performances of this method were developed in Thiebault et al. (2017a). For this work, only results with a signal-to-noise ratio higher than the limit of quantification (S/N > 10, Gracia-Lor et al., 2010; LOQ, Table S2) were used for interpretation. The sample analysis was systematically validated by a quality procedure comprising a calibration curve (6 standards), triplicates of 4 samples followed by one standard control and one blank (pure water), and a final calibration curve. For each PP, the identification parameters and quantification accuracy are detailed in Table S2. To ensure reproducibility of the quantification, mean variation coefficients were calculated by analysing triplicates of the standard solutions (Table S2).

III. Results and discussion

1. PPs occurrence and accumulation in the particulate phases Among the 10 PPs investigated in the dissolved phase, 5 were quantified in W-CAP, whereas all the 10 were quantified in W-PH. The PP diversity found in W-PH was therefore greater than in W-CAP, as were the PP concentrations (Fig. S2). In the W-CAP sample, SCA was the most abundant PP, J o u r n a l P r e -p r o o f exhibiting a concentration of 2170 ng.L -1 . TRI and CBZ exhibited medium contents with 290 and 120 ng.L -1 , respectively, and OXA and DIC were the least abundant with concentrations reaching 20 ng.L -1 (Fig. S2). In the W-PH sample, TRA and ACM exhibited the highest concentrations, with 7.97 and 6.33 µg.L -1 , respectively (Fig. S2) and DIC, DIA and TRI were the least concentrated PPs, with 70, 80 and 10 ng.L -1 , respectively (Fig. S2).

The 10 PPs were also quantified at least once in the particulate phases. Quantified in two solid samples, TRA was the least frequently detected but also the most concentrated PP, ranging from 41.9 to 5811.9 ng.g -1 (Fig. 2 and Table S4). Nevertheless, this high concentration appears surprising and should be considered with caution in view of the mean variations in its standard solutions (Table S2). ATE and COD exhibited low occurrences and concentrations in solid matrices, ranging from the limit of detection to 6.6 and 20.3 ng.g -1 , respectively (Fig. 2 and Table S4). DIC and ACM were more frequently detected but their concentrations did not exceed 6.7 and 16.9 ng.g -1 , respectively (Fig. 2 and Table S4). With high abundance and medium to high contents, TRI, DIA and OXA ranged from the limit of detection to 27.5, 39.6 and 141.4 ng.g -1 , respectively (Fig. 2 and Table S4). CBZ and SCA were detected ubiquitously in the particulate phases, ranging from the limit of detection to 130.5 and 176.2 ng.g -1 , respectively (Fig. 2 and Table S4).

The different PPs presented various occurrences and accumulation rates depending on their sensitivity to degradation processes, their solubility and their discharge rates. Consistently with its high degradability (Table 2) and solubility (Table 1), ACM exhibited low concentrations and was seldom detected (Fig. 2 and Table S4). Conversely, the low solubility of DIC and DIA (Table 1) allows their frequent detection in solid matrices (Table S4) in spite of their low concentrations measured in the dissolved phase (Fig. S2). The high detection frequencies and contents of OXA, TRI and CBZ in solid matrices were consistent with their moderate to high emissions (Fig. S2) and persistence (Table 2). Moreover, OXA is the main metabolite of DIA [START_REF] Baker | Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates[END_REF]. The ubiquity of SCA may be explained by its presence in all anthropogenic effluents at high levels, a behaviour already observed J o u r n a l P r e -p r o o f in other hydrosystems [START_REF] Togola | Les substances pharmaceutiques dans les eaux superficielles et souterraines du bassin Loire-Bretagne[END_REF][START_REF] Huber | A first screening and risk assessment of pharmaceuticals and additives in personal care products in waste water, sludge, recipient water and sediment from Faroe Islands, Iceland and Greenland[END_REF]. Nevertheless, despite their moderate to high concentrations in the sewage effluents (Fig. S2) and persistence (Table 2), ATE, COD and TRA were the least frequently detected PPs (Fig. 2 and Table S4), suggesting that other parameters regulate their adsorption. [Table 2]

As PPs are organic molecules, sorption can occur through different types of chemical interactions with both organic and mineral surfaces, depending on the molecular charges [START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF]Svahn & Bjorklund, 2015). This speciation therefore plays a key role in PP adsorption and depends on the molecular structure and functional groups, varying with the pH value [START_REF] Kümmerer | The presence of pharmaceuticals in the environment due to human usepresent knowledge and future challenges[END_REF]. With pH values ranging from 6.9 to 9.5 (mean value of 7.5) in the Egoutier stream, ATE, COD and TRA were cationic, ACM, CBZ, DIA and OXA were neutral, and SCA and DIC were anionic (Table 1). Only the charge state of TRI may be influenced by such a range of pH values (Table 1), but it was generally mostly found as a neutral molecule (i.e. pKa = 7.2). The mineralogical parts of the Egoutier stream solid matrices were composed of quartz, calcite, albite, orthoclase and smectite (Table S3, Fig. S1), consistently with the geology of the catchment [START_REF] Berger | Carte de France (1/50 000[END_REF]. Some exceptions such as the presence of aragonite in BLS collected at the CAP sewage effluent (BLS-2, Fig. S1) and the absence of smectite in BLS collected downstream the pond (BLS-13)

were also observed (Table S3). All solid samples had sandy-loam textures and TOC levels ranging from 0.2 to 18.0% (Table S3). As clay minerals and organic matter are negatively charged, several studies have reported a good affinity of cationic PPs with particles [START_REF] Ramil | Fate of beta blockers in aquaticsediment systems: sorption and biotransformation[END_REF][START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF][START_REF] Svahn | Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements[END_REF][START_REF] Boulard | Spatial distribution and temporal trends of pharmaceuticals sorbed to suspended particulate matter of German rivers[END_REF]. In the present study, cationic, neutral and anionic PPs exhibited a detection frequency of 10, 65 and 66%, respectively (Table S4).

Their concentrations ranged from 3.8 to 20.3 ng.g -1 (mean value of 9.9 ng.g -1 ), 1.2 to 141.4 ng.g -1

J o u r n a l P r e -p r o o f (mean value of 19.6 ng.g -1 ) and 4.4 to 176.2 ng.g -1 (mean value of 33.0 ng.g -1 ), respectively (Fig. 2 and Table S4). The lower occurrences of cationic PPs in this study in comparison with others might be explained by higher TOC levels (e.g. 33% in [START_REF] Svahn | Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements[END_REF]) or by different solid matrix grain-sizes, resulting in variations in the particles' cation exchange capacity (CEC), not characterized in [START_REF] Svahn | Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements[END_REF] and [START_REF] Boulard | Spatial distribution and temporal trends of pharmaceuticals sorbed to suspended particulate matter of German rivers[END_REF]. Consequently, the limited clay contents in Egoutier solid matrices (Table S3) may explain this result. Moreover, as hydrophobic interactions are known to contribute significantly to PP sorption, PP lipophilicity (logD, Table 1) therefore represents another characteristic that plays a key role in their accumulation in particulate phases [START_REF] Yamamoto | Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments[END_REF]. The moderate hydrophobicity (Table 1) of the cationic PPs investigated may also contribute to their lower adsorption.

Distribution of PPs between the different compartments of the aquatic environment

Cocktails observed in the particulate phases collected at sewage discharging sites and downstream were consistent with those quantified in WWTP effluents. All the PPs quantified in the CAP effluent (CBZ, OXA, TRI, DIC and SCA, Fig. S2) were detected at least once in the BLS and SPM sampled downstream (Fig. 2 and Table S4). In the PH effluent, all the PPs investigated were quantified (Fig. S2) and were also detected in SPM and BLS sampled downstream its discharge (Fig. 2 and Table S4).

Therefore, the particulate phases well reflect the sets of PPs released in the dissolved phase.

Surprisingly, CBZ, TRI and SCA were also detected in the first BLS sample collected in the upstream part of the watercourse (BLS-1, Fig. 2 and Table S4), suggesting another source at the locality present in the upstream part of the catchment (Fig. 1). All the neutral and anionic PPs were also detected in the BLS samples collected at stormwater discharge sites (BLS-2 and BLS-13b, Fig. 2 and Table S4). This observation implies leaks in the sewage networks. Except for ACM, only detected in the CAP stormwater effluent, the cocktails of PPs observed in the BLS collected at these discharges were similar (Fig. 2 and Table S4).

J o u r n a l P r e -p r o o f Despite the consistency between the dissolved and particulate phases, the different solid matrices demonstrated various rates of PP accumulation. SPM contents in PPs were less diversified and less concentrated than in BLS samples (Fig. 2 and Table S4). Indeed, the least frequently detected PPs, ACM, ATE, COD, TRA and DIC, were not quantified in SPM and each quantified PP presented a lower concentration in SPM than in BLS samples (Fig. 2 and Table S4). SCA was the most abundant and the most concentrated in both compartments but did not exceed 32.5 ng.g -1 in SPM, whereas it reached 169.4 ng.g -1 in BLS samples (Fig. 2 and Table S4). TRI was also frequently quantified in SPM, ranging from 1.2 to 12.1 ng.g -1 while reaching 27.5 ng.g -1 in BLS samples (Fig. 2 and Table S4). OXA, DIA and CBZ were quantified only once in SPM, in concentrations of 24.3, 24.8 and 28.0 ng.g -1 , respectively, in contrast with BLS samples where they reached 141.4, 39.6 and 130.5 ng.g -1 , respectively (Fig. 2 and Table S4). Total PP concentrations therefore did not exceed 64 ng.g -1 in SPM, but reached 212 ng.g -1 in BLS (without considering the exceptional levels of TRA in one sample, Table S4). This tendency is not in agreement with other studies, in which higher contents were measured in SPM than in BLS in both large and small hydrosystems [START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF][START_REF] Aminot | Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry[END_REF][START_REF] Comtois-Marotte | Analysis of emerging contaminants in water and solid samples using high resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic activity with YESassay[END_REF]. These studies designated SPM as a better sorbent because of its higher levels of TOC and fine particles. However in our case, the sandy-clay soils of the Egoutier catchment [START_REF] Soucémarianadin | Notice explicative de la carte des sols de Orléans (1/50 000)[END_REF] lead to a coarse texture of SPM (Table S3). SPM contents in TOC (ranging from 4.2 to 6.6%, Table S3) and fine particles (2-63 µm, ranging from 0.7 to 7.9%, Table S3) were therefore far lower than those of the BLS samples collected in strong accumulation zones (reaching 11.9% of TOC and 46.4% of 2-63 µm particles, Table S3). This different J o u r n a l P r e -p r o o f composition explains the limited occurrence of less hydrophobic (Table 1) and persistent PPs (ACM, ATE, COD, TRA and DIC, Table 2) which were released in lower quantities (Fig. 2 and Table S4).

[Figure 2]
Moreover, sorption regulates PP sedimentation or transportation at the catchment scale [START_REF] Lahti | Pharmaceuticals in settleable particulate material in urban and nonurban waters[END_REF]. This therefore suggests that lower interactions with SPM limit the transportation of ACM, ATE, COD, TRA and DIC over long distances.

As the Beulie pond sediments are mainly supplied by SPM decantation, these two compartments consequently exhibited similar fingerprints (Fig. 2 and Table S4). Despite the strong accumulation of organic matter (reaching 14.3%) and fine particles (2-63 µm, reaching 72.1%, Table S3), only the PPs transported by SPM were also observed in the pond sediments (Fig. 2 and Table S4).

ACM, ATE, COD, TRA and DIC were absent, suggesting lower transportation distances (Fig. 2 and Table S4) and retention zones within the catchment area. Moreover, lower concentrations in the EG samples than in BLS ones highlight particle accumulation in specific locations upstream of the pond (Fig. 2 and Table S4).

3. Spatial evolution of PPs in the particulate phases at the catchment scale PP contents were highly variable in space and time. In order to have a high-resolution visualization of PPs' spatial evolution in particulate phases, the most persistent (Table 2) neutral and cationic PPs are represented in Figure 3. CBZ, DIA, OXA, ATE and COD were selected because of their concentrations in specific locations compared to ubiquitous PPs such as TRI and SCA. Moreover, they have known specific sources (Fig. S2) and exhibited good affinities with sediments. Total concentrations of these neutral and cationic PPs were therefore compared to TOC and fine particle levels (Fig. 3), as these fractions are the best sorbents [START_REF] Aminot | Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry[END_REF].

Thanks to their properties (hydrophobicity and persistence, Table 1 and2), some of these PPs have already been used as tracers to qualify anthropogenic impacts on the environment [START_REF] Warner | Qualitative and quantitative use of micropollutants as source and process indicators. A review[END_REF]. This is mainly the case for CBZ [START_REF] Clara | Carbamazepine as a possible anthropogenic marker in the aquatic environment: investigations on the behaviour of carbamazepine in wastewater treatment and during groundwater infiltration[END_REF][START_REF] Maskaoui | Colloids as a sink for certain pharmaceuticals in the aquatic environment[END_REF]) and sometimes J o u r n a l P r e -p r o o f

OXA [START_REF] Amalric | Suivi des résidus de substances pharmaceutiques dans les systèmes aquatiques du bassin Loire-Bretagne[END_REF]. These more persistent PPs generally present lower spatio-temporal variabilities [START_REF] Vystavna | Monitoring of trace metals and pharmaceuticals as anthropogenic and socio-economic indicators of urban and industrial impact on surface waters[END_REF][START_REF] Klaminder | Long-term persistence of an anxiolytic drug (oxazepam) in a large freshwater lake[END_REF] but this trend was not observed in the present study (Fig. 3), as the particulate phase contents of every PP were highly variable in space and time (Fig. 2 and3).

[Figure 3] As already observed in other studies [START_REF] Da Silva | Occurrence and distribution of pharmaceuticals in surface water, suspended solids and sediments of the Ebro river basin, Spain[END_REF][START_REF] Zhou | Sediment-water interactions of pharmaceutical residues in the river environment[END_REF][START_REF] Aminot | Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry[END_REF], high concentrations are observed at stormwater and WWTP effluent discharge sites (BLS-2, BLS-3 and BLS-7, Fig. 3). Nevertheless, specific accumulation zones also appeared downstream the PP sources (Fig. 3). In the upstream part of the catchment, between the CAP and PH effluents, PPs were always present but sparsely accumulated (Fig. 3), consistently with the low discharges measured in the CAP sewage waters (Fig. S2). This implies PP transportation, as observed in SPM samples, but only a small deposition of sediments in this part of the watercourse (Fig. 3).

Indeed, low sediment thicknesses not exceeding 3 centimetres were measured during the sampling campaigns. Given the higher discharges of the PH effluent (Fig. S2), a stronger accumulation of PPs was unsurprisingly observed at its discharge (Fig. 3). Large accumulation zones also appeared between this effluent and the Beulie pond (Fig. 3) suggesting specific deposition zones in this part of the watercourse. Indeed, the specific PPs released by the PH (ATE and COD) as well as the most abundant PPs (CBZ, DIA and OXA) exhibited local concentrations downstream the PH (BLS-9 and BLS-11, Fig. 2 and3) where sediment layers up to 67 centimetres thick were measured. These zones stored high proportions of fine particles (more than 46% of silt, Table S3) but PP amounts mainly followed the large variations in organic matter levels (Fig. 3). This was also observed in the Beulie J o u r n a l P r e -p r o o f pond where PP distribution corresponds to that of the TOC (Fig. 3). The main PP-bearing phase also appeared to be organic matter. Besides, sorption processes for PPs such as CBZ were already demonstrated to be dominated by organic carbon-partitioning [START_REF] Fairbairn | Sediment-water distribution of contaminants of emerging concern in a mixed use watershed[END_REF].

Surprisingly, higher concentrations were generally observed in spring (Fig. 2 and3). This can be linked to a lower efficiency of degradation processes, which may be limited by a minimal residence time at higher flow rates [START_REF] Amalric | Suivi des résidus de substances pharmaceutiques dans les systèmes aquatiques du bassin Loire-Bretagne[END_REF] and in colder weather [START_REF] Kim | Temporal and spatial trends in the occurrence of human and veterinary antibiotics in aqueous and river sediment matrices[END_REF]. However, an opposite trend was already observed as higher stormwater supplies in spring can dilute anthropogenic inputs [START_REF] Kolpin | Urban contribution of pharmaceuticals and other organic wastewater contaminants to streams during differing flow conditions[END_REF] and adsorption can be enhanced by longer incubation times during low flow periods [START_REF] Fairbairn | Sediment-water distribution of contaminants of emerging concern in a mixed use watershed[END_REF]. In our case, this tendency seems to be mainly driven by higher supplies in organic matter and fine particles (Fig. 3). It also illustrates seasonal variations of the sedimentary dynamic, as contaminated particles are transported and deposited at greater distances from PP sources in spring (Fig. 2 and3).

In BLS collected downstream of the pond, PP concentrations were under the LOQ (Fig. 3; Table S4). Given the absence of WWTP effluents in the downstream part of the catchment, this evidences the storage capacity of the pond, which is also demonstrated by the decreasing TRI and SCA concentrations towards the outlet in SPM samples (Fig. 2, 3 and Table S4). Nevertheless, CBZ, OXA and COD presented higher concentrations in SPM collected downstream the pond than at the other sampling locations (Fig. 2, 3 and Table S4), illustrating the transport of some contaminated particles beyond the pond. This implies that particles are preferentially transported rather than deposited in this part of the watercourse. Indeed, except for those collected at the stormwater effluent (BLS-13b), BLS also demonstrated lower fine grain-size particles (2 -63 µm) and TOC levels (Table S3 and Fig. 3). The catchment therefore has two distinct sedimentary dynamics with low transportation and strong accumulation zones in the upstream part, in contrast to high transportation and low deposition in the downstream part. At the outlet, SPM therefore represents J o u r n a l P r e -p r o o f the highest risk by spreading PPs over long distances but thanks to the pond and the absence of new sewage water releases, contamination levels remained low.

IV. Conclusions

All the PP investigated were quantified in the particulate phases, but in various abundances and levels. PP discharges and persistence drive their occurrences and the observed concentrations depend on the properties of both the released molecules (charge, persistenice and lipophilicity) and the receiving environment (physico-chemical conditions, composition, and texture), as it drives the processes involved in adsorption. In the Egoutier stream, the low contents in clay grain-sizes, the relatively high persistence and discharges of neutral PPs led to the predominance of hydrophobic interactions with organic matter.

Particulate phases, mostly bed-load sediments, well represent the PP cocktails released into the aquatic environment. The different particulate compartments accumulate PPs in different ways.

Depending on the composition of the suspended particulate matter, the prevalence of neutral PPs and their sorption to organic matter in the Egoutier stream, these solid matrices exhibit low interaction with cationic molecules. The latter are consequently transported over smaller distances and not stored in the pond sediments. In the same way, the most degradable PPs are sparsely accumulated in bed-load sediments, but not in suspended solids and pond sediments.

In accordance with these conclusions, the spatial distribution of PPs in particulate phases at the Egoutier scale mainly reflects the discharge sites. In addition, the most abundantly adsorbed and persistent molecules highlight the sedimentary dynamic of the watercourse, in particular that of organic matter. Sedimentary deposition areas thus strongly stored the molecules because of large deposits of organic matter. These accumulation zones are mainly located upstream of the pond, evidencing the strong storage capacity of the Beulie pond and a preferential transportation over deposition in the downstream part of the catchment. Seasonal variations also appear to be driven by J o u r n a l P r e -p r o o f limited degradation processes and/or higher supplies in organic matter. Moreover, PPs can be transported over longer distances in periods of high flows.

To go further, with such an anthropogenic gradient and point sources of sewage and storm waters, the Egoutier stream could be a favourable place to investigate the spatial distribution of other types of contaminants in the different particulate compartments. Moreover, the sediments of the Beulie pond, which has been in place for centuries, could represent an archive of past contamination levels. [START_REF] Ashton | Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom[END_REF] c [START_REF] Baena-Nogueras | Degradation kinetics of pharmaceuticals and personal care products in surface waters: photolysis vs biodegradation[END_REF] d [START_REF] Bendz | Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Höje River in Sweden[END_REF] e [START_REF] Boreen | Photodegradation of pharmaceuticals in the aquatic environment: a review[END_REF] f [START_REF] Boulard | Spatial distribution and temporal trends of pharmaceuticals sorbed to suspended particulate matter of German rivers[END_REF] g [START_REF] Calisto | Psychiatric pharmaceuticals in the environment[END_REF] h [START_REF] Dobor | Biofilm controlled sorption of selected acidic drugs on river sediments characterized by different organic carbon content[END_REF] i Fekadu et al., 2019 ; j Koba et al. 2018 ; k [START_REF] Koumaki | Degradation of emerging contaminants from water under natural sunlight: The effect of season, pH, humic acids and nitrate and identification of photodegradation by-products[END_REF] l [START_REF] Lam | Aquatic persistence of eight pharmaceuticals in a microcosm study[END_REF] m [START_REF] Lin | Prevalence and sunlight photolysis of controlled and chemotherapeutic drugs in aqueous environments[END_REF] n [START_REF] Liu | Kinetics and degradation products for direct photolysis of βblockers in water[END_REF] o [START_REF] Löffler | Environmental fate of pharmaceuticals in water/sediment systems[END_REF] p [START_REF] Martínez-Hernández | Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment[END_REF] q [START_REF] Müller | Combining in vitro reporter gene bioassays with chemical analysis to assess changes in the water quality along the Ammer River, Southwestern Germany[END_REF] r [START_REF] Nunes | Are there pharmaceutical compounds in sediments or in water? Determination of the distribution coefficient of benzodiazepine drugs in aquatic environment[END_REF] s [START_REF] Ramil | Fate of beta blockers in aquaticsediment systems: sorption and biotransformation[END_REF] t [START_REF] Stein | Analysis and sorption of psychoactive drugs onto sediment[END_REF] u Tang et al., 2019 ; v Yamamoto et al., 2009 ; w Yu et al., 2006 J o u r n a l P r e -p r o o f [START_REF] Inglada | Theia OSO Land Cover Map[END_REF]. Locations of the two sewage water effluents from the central army pharmacy (CAP) and the psychiatric hospital (PH) and of the samples collected in the dissolved phase (W), in suspended particulate matter (SPM), bed-load (BLS) and Beulie pond sediments (EG).

J o u r n a l P r e -p r o o f

Fig. 1 )

 1 to characterize the SPM geochemical fingerprint of this medical institution. The second samples were collected downstream the Beulie pond (SPM-2, Fig.1) to integrate the PH fingerprint and quantify PP transportation despite the strong accumulation zone constituted by the pond. Finally, the third samples were taken at the outlet of the catchment (SPM-3, Fig.1) to measure the total export of PPs. To collect enough material, SPM were collected by using GEACOS (GranulomEtric pAssive Capture of dissolved matter & Sediment,[START_REF] Simonneau | GranulomEtric pAssive Capture of dissOlved matter & Sediment[END_REF] placed in the watercourse during about two months. Four campaigns were realized: between November 2018 and January 2019; March and June 2019; June and August 2019;

  2018 and one EG sample) was analysed by X-Ray Diffraction spectrometry (XRD) at the ISTO J o u r n a l P r e -p r o o f laboratory with an INEL diffractometer adjusted with a Debye-Scherrer configuration. ICDD (International Centre for Diffraction Data) PDF (Powder Diffraction File) characteristic diagrams were used to identify the minerals (Fig. S1). 3. Pharmaceutical contents 3.1. Chemical reagents Standards for acetaminophen (ACM), atenolol (ATE), carbamazepine (CBZ), codeine (COD), diazepam (DIA), diclofenac (DIC), oxazepam (OXA), salicylic acid (SCA), tramadol (TRA) and trimethoprim (TRI)

Figure 2 :

 2 Figure 2: Detection and concentrations of atenolol (ATE), codeine (COD), tramadol (TRA), acetaminophen (ACM), carbamazepine (CBZ), diazepam (DIA), oxazepam (OXA), trimethoprim (TRI), diclofenac (DIC) and salicylic acid (SCA) in bedload sediment samples (BLS 1 to 14, Fig. 1) along the watercourse during the different campaigns. Pharmaceutical mean contents in suspended particulate matter samples (SPM 1 to 3, Fig. 1) and Eckman grabs (EG 1 to 3, Fig. 1) according to sampling period. Dotted lines represent stormwater and sewage water effluents, as well as the Beulie pond location.

Figure 3 :

 3 Figure3: Spatial evolution of persistent neutral (carbamazepine (CBZ), diazepam (DIA) and oxazepam (OXA)) and cationic molecules (atenolol (ATE) and codeine (COD)) total concentrations (∑) compared to the spatial evolution of total organic carbon (TOC) and fine particles (0 -63 µm) percentages in suspended particulate matter (SPM 1 to 3, Fig.1), bed-load (BLS 1 to 14, Fig.1) and Beulie pond sediments (mean contents of EG 1 to 3, Fig.1).

Figure 1 :

 1 Figure 1 : Description of the upstream part of the Egoutier catchment area studied here with land covers[START_REF] Inglada | Theia OSO Land Cover Map[END_REF]. Locations of the two sewage water effluents from the central army pharmacy (CAP) and the psychiatric hospital (PH) and of the samples collected in the dissolved phase (W), in suspended particulate matter (SPM), bed-load (BLS) and Beulie pond sediments (EG).

Figure 2 :Figure 3 :

 23 Figure 2: Detection and concentrations of atenolol (ATE), codeine (COD), tramadol (TRA), acetaminophen (ACM), carbamazepine (CBZ), diazepam (DIA), oxazepam (OXA), trimethoprim (TRI), diclofenac (DIC) and salicylic acid (SCA) in bedload sediment samples (BLS 1 to 14, Fig. 1) along the watercourse during the different campaigns. Pharmaceutical mean contents in suspended particulate matter samples (SPM 1 to 3, Fig. 1) and Eckman grabs (EG 1 to 3, Fig. 1) according to sampling period. Dotted lines represent stormwater and sewage water effluents, as well as the Beulie pond location. J o u r n a l P r e -p r o o f

Table 1 :

 1 For each therapeutic molecule, abbreviation (Abb.),CAS-Number, formula, molecular weight (MW), charge state at pH = 7 (Charge), pKa, solubility and logD are specified.

	[Table 1]
	3.3. Quantification procedure
	Chromatographic separation was performed using an Ultimate 3000 RSLC (Rapid Separation Liquid
	Chromatography, Thermo Fisher Scientific) equipped with a Nucleodur C 18 Gravity Column (150 mm x
	2 mm; 3 µm, Macherey-Nagel) at the ICOA laboratory. Separation was carried out at 30 °C with two
	mobile phases: H 2 O (solvent A) and AcN (solvent B), both acidified with 0.1% of HCOOH. The total
	analysis time was 29 min with the elution gradient as follows: 95% to 5% of solvent A during 16 min,

a : https://pubchem.ncbi.nlm.nih.gov; b : www.drugbank.ca, c : www.chemspider.com.

Table 2 :

 2 Solid-water partition coefficient (Kd), persistence and major degradation processes (BT: biotransformation; PY: photolysis) of the investigated analgesics, antibiotics, anti-inflammatory agents, β-blockers, opioids and psychotropics.

Table 1 :

 1 For each therapeutic molecule, abbreviation (Abb.),CAS-Number, formula, molecular weight (MW), charge state at pH = 7 (Charge), pKa, solubility and logD are specified.

	: https://pubchem.ncbi.nlm.nih.gov;	b : www.drugbank.ca,	c :

a

Table 2 :

 2 Solid-water partition coefficient (Kd), persistence and major degradation processes (BT: biotransformation; PY: photolysis) of the investigated analgesics, antibiotics, anti-inflammatory agents, β-blockers, opioids and psychotropics.

	Therapeutic group	Molecule	Kd (L/kg)			Persistence	Major degradation processes
	Analgesics		ACM	0.5 -7.7	p,v		Low	l,w	BT	l,w
			SCA	3.6 -28.2		a		Low	c	Both	c
	Antibiotics		TRI	18.84-104.6	u	High	d,l	Debated	c,l
	Non-steroidal
	anti-inflammatory	DIC	0.2 -107.1	a,f,h	Low	b	PY	e,k
	agents
	β-blockers		ATE	1.3 -24.6	f,v		Moderate	d,s	BT	n,s,v
	Opioids		COD	2.1 -14.1	t		High	i	PY	m
			TRA	23.7 -63.1	f,j		Moderate	q	PY	q
	Psychotropics	CBZ	0.1 -23.9	j,t,v		High	d,l	PY	l
			DIA	2.3 -12	r			High	o	PY	e,g
			OXA	2 -38.5	f,t		Moderate	o	BT	g
	References:	a Agunbiade and Moodley, 2015 ;

b

J o u r n a l P r e -p r o o f

Acknowledgments

This work and the PhD grant of L. Ledieu were funded by the Région Centre Val de Loire (France) and are part of the Academic Initiative Project MOSAIC led by A. Simonneau. This work was also supported by a grant overseen by the French National Research Agency (ANR) as part of the "Investments d'Avenir" Programme LabEx VOLTAIRE, 10-LABX-0100. This study benefited from collaboration with the GéHCO laboratory and J-P. Bakyonoo is warmly thanked for his help during analysis. We are grateful to P. Penhoud and R. Boscardin for analytical and technical support in XRD analysis and Rock Eval pyrolysis, respectively. L. Baude, H. Alphonse and S. Picault are thanked for the sampling authorization at the G. Daumézon hospital and in the town of Semoy. We acknowledge M.

Hatton and L. Le Forestier during SPM and BLS sampling as well as A. Foucher for support during the Beulie pond interface sediments survey.

V.

Declaration of interests

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: