Biotic nitrosation of diclofenac in a soil aquifer system (Katari watershed, Bolivia)
Graphical abstract
Introduction
Diclofenac (DCF) is one of the most widely prescribed non-steroidal anti-inflammatory drugs (NSAID). DCF has been recently included in the EU Commission watch list of organic pollutants in surface water (SW) (Directive 2013/39/EU) as the consequence of its high frequency of detection rate in SW and its potential ecotoxicological impact. A lot is known about DCF fate, both in the human body and in the environment. The majority of DCF is metabolized in the human body and only 1% of the orally administered dose is excreted as un-metabolized DCF. The main human metabolites of DCF are 4′-OH-DCF and 5-OH-DCF. Both of them are excreted mainly in conjugated form and only < 1% is excreted unchanged. Important metabolites are also 3′-OH-DCF and 4′,5-diOH-DCF (Vieno and Sillanpää, 2014). DCF has been deeply investigated during aerobic biological wastewater treatment. DCF transformation leads to the formation of 4′-OH-DCF and to 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (DCF-lactam) through a dehydration reaction (Bouju et al., 2016). The biodegradation of 4′-OH-DCF was much quicker than that of DCF leading to 4′-OH-DCF-lactam. Formation of dichlorobenzoic acid has also been reported (Pérez and Barcelo, 2008). In a fixed-bed column bioreactor filled with river sediment under aerobic conditions, the p-benzoquinone imine derivative of 5-OH-DCF was identified as the main transformation product (TP) of DCF (Gröning et al., 2007). Extensive transformation of DCF was also evidenced in soil after 112 d of incubation with half-lives in the 1.4–4.3 d range, where 5-OH-DCF was identified as a major intermediate and 2,6-dichlorobenzoic acid as a minor intermediate (Dodgen et al., 2014). Further recent investigations concluded that the improved degradation of DCF was strongly dependent on a high activity of nitrifiers under nitrifying activated sludge (NAS). In these conditions, DCF bio-transformed additionally into its nitrogen-derivatives, N-nitroso-DCF (NO-DCF) and 5-nitro-DCF (NO2-DCF, Osorio et al., 2014). It was anticipated that nitric oxide (NO) was responsible for such reactions to occur (Osorio et al., 2016). NO is a very reactive specie in aqueous media originating as a by-product of nitrification and denitrification processes and quickly evolves in NO-derived reactive species, mainly dinitrogen trioxide (N2O3) and peroxynitrite (ONOO−), both being strong nitrosating species. N2O3 is likely formed in presence of oxygen or under acidic conditions through the decomposition of nitrous acid (HNO2), while ONOO− is likely formed under neutral/basic conditions through the reaction of NO with superoxide (O2−, k = 0.4–1.9 × 109 M− 1 s− 1, Toledo and Augusto, 2012). N2O3 and ONOO− are able to react with phenols (Jewell et al., 2014) and secondary amines (e.g., DCF) to give C-nitroso and N-nitroso derivatives, respectively but are also known to react with primary aromatic amines such as sulfamethoxazole (SMX) to give different TPs including 4-nitro-SMX and desamino-SMX (Nödler et al., 2012). The formation of appreciable NO-DCF and NO2-DCF concentrations was found to be unlikely (in the ng/L range in WWWTP effluents, Osorio et al., 2014) and the presence of oxygen is requested for the reaction of NO with amines to proceed (Itoh et al., 1997). However, DCF degradation has also been reported in the hyporheic zone underlying streams under strictly anoxic conditions (Lewandowski et al., 2011). DCF was also highly removed in manage aquifer recharge under anoxic conditions (Rauch-Williams et al., 2010). Similarly to SMX, DCF degradation was also found to be influenced by denitrifying conditions in a laboratory scale column experiment during the reduction of nitrate (Branzhaf et al., 2012) at near neutral pH. But, up till now, the formation of nitro derivatives was only observed in case of SMX using water/sediment batch experiments (Barbieri et al., 2012). Since, at near neutral pH, the formation of N2O3 can be ruled out due to a pKa (HNO2/NO2−) of 3.3 and ONOO− cannot be produced in absence of oxygen, these results probably call for nitrosation/nitration mechanisms under denitrifying conditions different from those reported under aerobic conditions. One assumption is codenitrification which is a relevant microbial denitrification pathway in soil and that leads to N-nitrosation of secondary amines and desamination reaction for primary amines (Spott et al., 2011). Checking for this assumption will be the main contribution of this work. Specific objectives include: (i) to investigate the relevance of the formation of NO-DCF and NO2-DCF in a soil aquifer system thanks to a monitoring survey of SW and groundwater (GW) samples, (ii) to better understand the correlation between denitrification and the NO-DCF and NO2-DCF formation in batch soil slurry experiments and (iii) to get new insights into the mechanisms of NO2-DCF formation. Diphenylamine (DPA) was also included in this work as an additional secondary aromatic amine due to its high occurrence at our sampling site and due to the availability of N-nitroso-DPA (NO-DPA) and 4-nitro-DPA (NO2-DPA) as analytical standards.
Section snippets
Chemicals
DCF (> 99%), DCF-d4 (> 99%), 4′-OH-DCF (> 99%), 5-OH-DCF (> 99%) and DPA-d10 were purchased from Toronto Research Chemical (Toronto, Canada). NO-DCF and 5-NO2-DCF were a gift from the Water and Soil Quality Research Group of the CSIC, Barcelona (Dr. Sandra Pérez) and were chemically synthesized as previously reported (Osorio et al., 2014). DPA, N-nitroso-DPA (NO-DPA), 4-nitro-DPA (4-NO2-DPA), DPA-d10, cycloheximide (> 94%), potassium nitrite (KNO2), sodium azide (NaN3), K10 montmorillonite were
Field studies
A screening of suspected human metabolites and TPs of DCF and DPA was carried out in WWTP effluents, SW and GW samples by extracting the exact mass of the expected [M + H]+ or [M-H]− ion from the total ion chromatograms (TIC) with a mass window of 5 ppm. All targeted metabolites and TPs except NO2-DPA were detected and confirmed due to the availability of reference standards following 1) a comparison between their retention time (RT) with an allowed tolerance of ± 0.8 min, 2) a comparison between an
Conclusions
To our knowledge, this work revealed for the first time a possible microbial mediated DCF and DPA nitrosation reaction in soil under strictly anoxic conditions. This result was obtained based both on field monitoring and on batch experiments results. Fields studies showed the occurrence of NO2-DCF and NO-DPA at tens of ng/L levels in GW samples, while NO-DCF was encountered to a lesser extent (a few ng/L) and NO2-DPA was never detected. NO2-DCF levels are probably more significant than those
Acknowledgement
This work was supported by the French national program EC2CO “Ecosphère Continentale et Côtière”. We thank Denisse Archundia for having made the Fig. 1.
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