Combining Nontargeted Analysis with Computer-Based Hazard Comparison Approaches to Support Prioritization of Unregulated Organic Contaminants in Biosolids.

Biosolids are a byproduct of wastewater treatment that can be beneficially applied to agricultural land as a fertilizer. While U.S. regulations limit metals and pathogens in biosolids intended for land applications, no organic contaminants are currently regulated. Novel techniques can aid in detection, evaluation, and prioritization of biosolid-associated organic contaminants (BOCs). For example, nontargeted analysis (NTA) can detect a broad range of chemicals, producing data sets representing thousands of measured analytes that can be combined with computational toxicological tools to support human and ecological hazard assessment and prioritization. We combined NTA with a computer-based tool from the U.S. EPA, the Cheminformatics Hazard Comparison Module (HCM), to identify and prioritize BOCs present in U.S. and Canadian biosolids (n = 16). Four-hundred fifty-one features were detected in at least 80% of samples, with identities of 92 compounds confirmed or assigned probable structures. These compounds were primarily categorized as endogenous compounds, pharmaceuticals, industrial chemicals, and fragrances. Examples of top prioritized compounds were p-cresol and chlorophene, based on human health end points, and fludioxonil and triclocarban, based on ecological health end points. Combining NTA results with hazard comparison data allowed us to prioritize compounds to be included in future studies of the environmental fate and transport of BOCs.

(Non)targeted Chemical Analysis and Risk Assessment of Organic Contaminants in Darkibor Kale Grown at Rural and Urban Farms.

This study investigated the presence and human hazards associated with pesticides and other anthropogenic chemicals identified in kale grown in urban and rural environments. Pesticides and related compounds (i.e., surfactants and metabolites) in kale samples were evaluated using a nontargeted data acquisition for targeted analysis method which utilized a pesticide mixture containing >1,000 compounds for suspect screening and quantification. We modeled population-level exposures and assessed noncancer hazards to DEET, piperonyl butoxide, prometon, secbumeton, terbumeton, and spinosyn A using nationally representative estimates of kale consumption across life stages in the US. Our findings indicate even sensitive populations (e.g., pregnant women and children) are not likely to experience hazards from these select compounds were they to consume kale from this study. However, a strictly nontargeted chemical analytical approach identified a total of 1,822 features across all samples, and principal component analysis revealed that the kale chemical composition may have been impacted by agricultural growing practices and environmental factors. Confidence level 2 compounds that were ≥5 times more abundant in the urban samples than in rural samples (p < 0.05) included chemicals categorized as "flavoring and nutrients" and "surfactants" in the EPA's Chemicals and Products Database. Using the US-EPA's Cheminformatics Hazard Module, we identified that many of the nontarget compounds have predicted toxicity scores of "very high" for several end points related to human health. These aspects would have been overlooked using traditional targeted analysis methods, although more information is needed to ascertain whether the compounds identified through nontargeted analysis are of environmental or human health concern. As such, our approach enabled the identification of potentially hazardous compounds that, based on their hazard assessment score, merit follow-up investigations.

Extracting Structural Information from Physicochemical Property Measurements Using Machine Learning─A New Approach for Structure Elucidation in Non-targeted Analysis.

Non-targeted analysis (NTA) has made critical contributions in the fields of environmental chemistry and environmental health. One critical bottleneck is the lack of available analytical standards for most chemicals in the environment. Our study aims to explore a novel approach that integrates measurements of equilibrium partition ratios between organic solvents and water (KSW) to predictions of molecular structures. These properties can be used as a fingerprint, which with the help of a machine learning algorithm can be converted into a series of functional groups (RDKit fragments), which can be used to search chemical databases. We conducted partitioning experiments using a chemical mixture containing 185 chemicals in 10 different organic solvents and water. Both a liquid chromatography quadrupole time-of-flight mass spectrometer (LC-QTOF MS) and a LC-Orbitrap MS were used to assess the feasibility of the experimental method and the accuracy of the algorithm at predicting the correct functional groups. The two methods showed differences in log KSW with the QTOF method showing a mean absolute error (MAE) of 0.22 and the Orbitrap method 0.33. The differences also culminated into errors in the predictions of RDKit fragments with the MAE for the QTOF method being 0.23 and for the Orbitrap method being 0.31. Our approach presents a new angle in structure elucidation for NTA and showed promise in assisting with compound identification.

Chlorination of para-substituted phenols: Formation of α, ß-unsaturated C4-dialdehydes and C4-dicarboxylic acids.

Despite the widespread occurrence of phenols in anthropogenic and natural compounds, their fate in reactions with hypochlorous acid (HOCl), one of the most common water treatment disinfectants, remains incompletely understood. To close this knowledge gap, this study investigated the formation of disinfection by-products (DBPs) in the reaction of free chlorine with seven para-substituted phenols. Based on the chemical structures of the DBPs and the reaction mechanisms leading to their formation, the DBPs were categorized into four groups: chlorophenols, coupling products, substituent reaction products, and ring cleavage products. In contrast to previous studies that investigated the formation of early-stage chlorophenols, the primary focus of this study was on the elucidation of novel ring cleavage products, in particular α, ß-unsaturated C4-dialdehydes, and C4-dicarboxylic acids, which, for the first time, were identified and quantified in this study. The molar yields of 2-butene-1,4-dial (BDA), one of the identified α, ß-unsaturated C4-dialdehydes, varied among the different phenolic compounds, reaching a maximum value of 10.4% for bisphenol S. Molar yields of 2-chloromaleic acid (Cl-MA), one of the identified C4-dicarboxylic acids, reached a maximum value of 30.5% for 4-hydroxy-phenylacetic acid under given conditions. 2,4,6-trichlorophenol (TCP) was shown to be an important intermediate of the parent phenols and the C4-ring cleavage products. Based on the temporal trends of α, ß-unsaturated C4-dialdehydes and C4-dicarboxylic acids, their formation is likely attributable to two separate ring cleavage pathways. Based on the obtained results, an overall transformation pathway for the reaction of para-substituted phenols with free chlorine leading to the formation of novel C4 ring cleavage products was proposed.

Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography-High-Resolution Mass Spectrometry.

The surge in electronic cigarette (e-cig) use in recent years has raised questions on chemical exposures that may result from vaping. Previous studies have focused on measuring known toxicants, particularly those present in traditional cigarettes, while fewer have investigated unknown compounds and transformation products formed during the vaping process in these diverse and constantly evolving products. The primary aim of this work was to apply liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and chemical fingerprinting techniques for the characterization of e-liquids and aerosols from a selection of popular e-cig products. We conducted nontarget and quantitative analyses of tobacco-flavored e-liquids and aerosols generated using four popular e-cig products: one disposable, two pod, and one tank/mod. Aerosols were collected using a condensation device and analyzed in solution alongside e-liquids by LC-HRMS. The number of compounds detected increased from e-liquids to aerosols in three of four commercial products, as did the proportion of condensed-hydrocarbon-like compounds, associated with combustion. Kendrick mass defect analysis suggested that some of the additional compounds detected in aerosols belonged to homologous series resulting from decomposition of high-molecular-weight compounds during vaping. Lipids in inhalable aerosols have been associated with severe respiratory effects, and lipid-like compounds were observed in aerosols as well as e-liquids analyzed. Six potentially hazardous additives and contaminants, including the industrial chemical tributylphosphine oxide and the stimulant caffeine, were identified and quantified in the e-cig liquids and aerosols analyzed. The obtained findings demonstrate the potential of nontarget LC-HRMS to identify previously unknown compounds and compound classes in e-cig liquids and aerosols, which is critical for the assessment of chemical exposures resulting from vaping.

Enhanced Treatment of Municipal Wastewater Effluents by Fe-TAML/H2O2: Efficiency of Micropollutant Abatement.

Combining iron with a tetraamido-macrocyclic ligand (Fe-TAML) as a catalyst and with hydrogen peroxide (H2O2) as the bulk oxidant is a process that has been suggested for the oxidative abatement of micropollutants during water treatment. In this study, the reactivity of the Fe-TAML/H2O2 system was evaluated by investigating the degradation of a group of electron-rich organic model compounds with different functional groups in a secondary wastewater effluent. Phenolic compounds and a polyaromatic ether are quickly and substantially abated by Fe-TAML/H2O2 in a wastewater effluent. For tertiary amines, a moderate rate of abatement was observed. Primary and secondary amines, aromatic ethers, aromatic aldehydes, and olefins are oxidized too slowly in the investigated Fe-TAML/H2O2 systems to be significantly abated in a secondary wastewater effluent. Trichlorophenol is readily oxidized to chloromaleic acid and chlorofumaric acid, which support a one-electron transfer reaction as the initial step of the reaction between Fe-TAML/H2O2 and the target compound. Fe-TAML/H2O2 does not oxidize bromide to hypobromous acid; however, iodide is oxidized to hypoiodous acid, and as a consequence, the H2O2 consumption is accelerated by a catalytic reaction in iodide-containing water. Overall, Fe-TAML/H2O2 is a rather selective oxidant, which makes it an interesting system for the abatement of electron-rich phenolic-type pollutants.

Unexpected transformation of dissolved phenols to toxic dicarbonyls by hydroxyl radicals and UV light.

Water treatment systems frequently use strong oxidants or UV light to degrade chemicals that pose human health risks. Unfortunately, these treatments can result in the unintended transformation of organic contaminants into toxic products. We report an unexpected reaction through which exposure of phenolic compounds to hydroxyl radicals (•OH) or UV light results in the formation of toxic α,ß-unsaturated enedials and oxoenals. We show that these transformation products damage proteins by reacting with lysine and cysteine moieties. We demonstrate that phenolic compounds react with •OH produced by the increasingly popular UV/hydrogen peroxide (H2O2) water treatment process or UV light to form toxic enedials and oxoenals. In addition to raising concerns about potential health risks of oxidative water treatment, our findings suggest the potential for formation of these toxic compounds in sunlit surface waters, atmospheric water, and living cells. For the latter, our findings may be particularly relevant to efforts to understand cellular damage caused by in vivo production of reactive oxygen species. In particular, we demonstrate that exposure of the amino acid tyrosine to •OH yields an electrophilic enedial product that undergoes cross-linking reaction with both lysine and cysteine residues.

Formation and Fate of Carbonyls in Potable Water Reuse Systems.

Low molecular weight, uncharged compounds have been the subject of considerable study at advanced treatment plants employed for potable water reuse. However, previously identified compounds only account for a small fraction of the total dissolved organic carbon remaining after reverse osmosis treatment. Uncharged carbonyl compounds (e.g., aldehydes and ketones) formed during oxidation have rarely been monitored in potable water reuse systems. To determine the relative importance of these compounds to final product water quality, samples were collected from six potable water reuse facilities and one conventional drinking water treatment plant. Saturated carbonyl compounds (e.g., formaldehyde, acetone) and α,ß-unsaturated aldehydes (e.g., acrolein, crotonaldehyde) were quantified with a sensitive new analytical method. Relatively high concentrations of carbonyls (i.e., above 7 µM) were observed after ozonation of wastewater effluent. Biological filtration reduced concentrations of carbonyls by over 90%. Rejection of the carbonyls during reverse osmosis was correlated with molecular weight, with concentrations decreasing by 33% to 58%. Transformation of carbonyls resulted in decreases in concentration of 10% to 90% during advanced oxidation, with observed decreases consistent with rate constants for reactions of the compounds with hydroxyl radicals. Overall, carbonyl compounds accounted for 19% to 38% of the dissolved organic carbon in reverse osmosis-treated water.

Chlorination of Phenols Revisited: Unexpected Formation of α,ß-Unsaturated C4-Dicarbonyl Ring Cleavage Products.

Despite decades of research on the fate of phenolic compounds when water is disinfected with hypochlorous acid (HOCl), there is still considerable uncertainty regarding the formation mechanisms and identity of ring cleavage products, especially at higher chlorine doses. This study focuses on the formation of electrophilic ring cleavage products-a class of compounds that poses potential health risks at relatively low concentrations-from the reactions of phenols with chlorine. By monitoring the formation of products of reactions between ring cleavage products and the model nucleophile N-α-acetyl-lysine, we identified the α,ß-unsaturated dialdehyde 2-butene-1,4-dial (BDA) and its chlorinated analogue, chloro-2-butene-1,4-dial (Cl-BDA), after the chlorination of phenol, para- and ortho-substituted chlorophenols (2-Cl, 4-Cl, 2,4-diCl-, 2,6-diCl, and 2,4,6-triCl-phenol), and 3,5-di-Cl-catechol. Maximum yields of BDA were observed when chlorine was present in large excess (HOCl/phenol ratios of 30:1 to 50:1), with yields ranging from 18% for phenol to 46% for 3,5-diCl-catechol. BDA and Cl-BDA formation was also observed during the chlorination of brominated phenols. For methyl-substituted phenols, the presence of methyl substituents in both positions ortho to the hydroxy group inhibited BDA and Cl-BDA formation, but the chlorination of cresols and 2,3-dimethylphenol yielded methyl- and dimethyl-BDA species. This study provides new insights into the formation of reactive and toxic electrophiles during chlorine disinfection. It also provides evidence for the importance of phenoxy radicals produced by one-electron transfer reactions initiated by chlorine in the production of dicarbonyl ring cleavage products.

Ring-Cleavage Products Produced during the Initial Phase of Oxidative Treatment of Alkyl-Substituted Aromatic Compounds.

Chemical oxidation with hydroxyl radical (HO•) and sulfate radical (SO4•-) is often used to treat water contaminated with aromatic compounds. Although oxidation of aromatics by these radicals has been studied for decades, the commonly accepted transformation pathway-sequential hydroxylation of the ring followed by ring cleavage and mineralization of the resulting products-does not account for the loss of the parent compound observed during the initial phase of the process. To assess the importance of pathways for aromatic compound oxidation that do not result in ring hydroxylation, we identified products formed after the initial reaction between HO• or SO4•- and benzene, toluene, ethylbenzene, and (BTEX) xylene isomers. We quantified products of ring hydroxylation and oxidation of alkyl substituents as well as a suite of ring-cleavage products, including acetaldehyde, formic acid, 6-, 7-, or 8-carbon oxoenals and oxodials. Other ring-cleavage products, which were most likely aldehydes and organic acids, were observed but not quantified. When SO4•- was used as the oxidant, aromatic organosulfates also were formed. Our results indicated that the initial phase of the oxidation process involves radical addition, hydrogen abstraction, or one-electron transfer to the ring followed by reaction with O2. The hydroxycyclohexadienylperoxy radical produced in this reaction can eliminate hydroperoxyl radical (HO2•) to produce a phenolic compound or it can rearrange to form a bicyclic peroxy intermediate that subsequently undergoes ring cleavage. Hydroxylation of the ring and oxidation of the alkyl substituent accounted for approximately 15-40% of the reacted mass of the parent compound. Ring-cleavage products for which quantification was possible accounted for approximately 2 to 10% of the reacted mass. Our results raise concerns about the formation of toxic ring-cleavage products during the initial stage of oxidation whenever HO• or SO4•- is used for the treatment of water containing benzene or alkylbenzenes.

Effect of Histone Lysine Methylation on DNA Lesion Reactivity in Nucleosome Core Particles.

Lysine methylation is a common post-translational histone modification that regulates transcription and gene expression. The lysine residues in the histone tail also react with damaged nucleotides in chromatin, including abasic sites and N7-methyl-2'-deoxyguanosine, the major product of DNA methylating agents. Lysine monomethylation transforms the ε-amine into a secondary amine, which could be more nucleophilic and/or basic than the ε-amine in lysine, and therefore more reactive with damaged DNA. The effect of lysine methylation on the reactivity with abasic sites and N7-methyl-2'-deoxyguanosine was examined in nucleosome core particles using a methylated lysine analogue derived from cysteine. ε-Amine methylation increases the rate constant for abasic site reaction within nucleosome core particles. Reactivity at the two positions examined increased less than twofold. Mechanistic experiments indicate that faster ß-elimination from an intermediate iminium ion accounts for accelerated abasic reactivity. The rate constants for nucleophilic attack (Schiff base/iminium ion formation) by the lysine and methylated lysine analogues are indistinguishable. Similarly, the rate constants describing nucleophilic attack by the lysine and methylated lysine analogues on ß-2'-fluoro-N7-methyl-2'-deoxyguanosine to form DNA-protein cross-links are also within experimental error of one another. These data indicate that abasic site containing DNA will be destabilized by lysine methylation. However, these experiments do not indicate that DNA-protein cross-link formation, a recently discovered form of damage resulting from N7-guanine methylation, will be affected by this post-translational modification.

The Role of Reactive Nitrogen Species in Sensitized Photolysis of Wastewater-Derived Trace Organic Contaminants.

Under conditions typically encountered in the aquatic environment, the absorption of sunlight by nitrite and nitrate leads to the transformation of trace organic contaminants. In addition to the well understood mechanism through which hydroxyl radical (·OH) produced by nitrate and nitrite photolysis oxidizes contaminants, absorption of light also results in the formation of reactive nitrogen species that transform organic contaminants. To assess the importance of this process on the fate of trace organic contaminants, radical quenchers and transformation product analysis were used to discriminate among potential reaction pathways. For sulfamethoxazole, an antibiotic that is frequently detected in municipal wastewater effluent, nitrate and nitrite-sensitized photolysis pathways resulted in production of transformation products that were not detected during direct photolysis or reaction with ·OH. The reactivity of sulfamethoxazole with the reactive species produced when nitrite absorbed sunlight was affected by the presence of hydroxyl radical scavengers, indicating the likely involvement of nitrogen dioxide, which forms when nitrite reacts with hydroxyl radical. Reactive nitrogen species also reacted with emtricitabine, propranolol, and other trace organic contaminants commonly detected in wastewater effluent, indicating the potential importance of this process to the fate of other trace organic contaminants. A kinetic model indicated that reactive nitrogen species could be important to the phototransformation of trace organic contaminants when relatively high concentrations of nitrite are present (e.g., in surface waters receiving reverse osmosis concentrate from potable water reuse projects or in agricultural runoff).

Trace Element Removal in Distributed Drinking Water Treatment Systems by Cathodic H2O2 Production and UV Photolysis.

As water scarcity intensifies, point-of-use and point-of-entry treatment may provide a means of exploiting locally available water resources that are currently considered to be unsafe for human consumption. Among the different classes of drinking water contaminants, toxic trace elements (e.g., arsenic and lead) pose substantial operational challenges for distributed drinking water treatment systems. Removal of toxic trace elements via adsorption onto iron oxides is an inexpensive and robust treatment method; however, the presence of metal-complexing ligands associated with natural organic matter (NOM) often prevents the formation of iron precipitates at the relatively low concentrations of dissolved iron typically present in natural water sources, thereby requiring the addition of iron which complicates the treatment process and results in a need to dispose of relatively large amounts of accumulated solids. A point-of-use treatment device consisting of a cathodic cell that produced hydrogen peroxide (H2O2) followed by an ultraviolet (UV) irradiation chamber was used to decrease colloid stabilization and metal-complexing capacity of NOM present in groundwater. Exposure to UV light altered NOM, converting ∼6 µM of iron oxides into settable forms that removed between 0.5 and 1 µM of arsenic (As), lead (Pb), and copper (Cu) from solution via adsorption. After treatment, changes in NOM consistent with the loss of iron-complexing carboxylate ligands were observed, including decreases in UV absorbance and shifts in the molecular composition of NOM to higher H/C and lower O/C ratios. Chronoamperometric experiments conducted in synthetic groundwater revealed that the presence of Ca2+ and Mg2+ inhibited intramolecular charge-transfer within photoexcited NOM, leading to substantially increased removal of iron and trace elements.

Integrated Evaluation Concept to Assess the Efficacy of Advanced Wastewater Treatment Processes for the Elimination of Micropollutants and Pathogens.

A multidisciplinary concept has been developed to compare advanced wastewater treatment processes for their efficacy of eliminating micropollutants and pathogens. The concept is based on (i) the removal/formation of selected indicator substances and their transformation products (TPs), (ii) the assessment of ecotoxicity via in vitro tests, and (iii) the removal of pathogens and antibiotic resistant bacteria. It includes substances passing biological wastewater treatment plants regulated or proposed to be regulated in the European Water Framework Directive, TPs formed in biological processes or during ozonation, agonistic/antagonistic endocrine activities, mutagenic/genotoxic activities, cytotoxic activities, further activities like neurotoxicity as well as antibiotics resistance genes, and taxonomic gene markers for pathogens. At a pilot plant, ozonation of conventionally treated wastewater resulted in the removal of micropollutants and pathogens and the reduction of estrogenic effects, whereas the in vitro mutagenicity increased. Subsequent post-treatment of the ozonated water by granular activated carbon (GAC) significantly reduced the mutagenic effects as well as the concentrations of remaining micropollutants, whereas this was not the case for biofiltration. The results demonstrate the suitability of the evaluation concept to assess processes of advanced wastewater treatment including ozonation and GAC by considering chemical, ecotoxicological, and microbiological parameters.

Electrochemical Transformation of Trace Organic Contaminants in the Presence of Halide and Carbonate Ions.

Electrochemical treatment on anodes shows promise for the oxidation of organic contaminants in industrial wastewater and reverse osmosis concentrate from municipal wastewater recycling due to the high conductivity of the matrix and the concomitant low energy demand. The effect of background electrolyte composition (Cl(-), HCO3(-), and NH4(+)) on the formation and fate of electrochemically produced heterogeneous (HO(•)ads and Cl(•)ads) and homogeneous (HOCl and HOBr) oxidants was evaluated on Ti-IrO2 and boron-doped diamond (BDD) electrodes using a suite of trace organic contaminants that exhibited varying reactivity with HO(•), CO3(•-), HOCl, and HOBr. The contributions of adsorbed and bulk oxidants to contaminant degradation were investigated. Results show that transformation rates for most contaminants increased in the presence of chloride and trace amounts of bromide; however, elevated concentrations of HCO3(-) often altered transformation rates due to formation of selective oxidants, with decreases in reactivity observed for electron-poor contaminants and increases in reactivity observed for compounds with amine and phenolic moieties. Using this information, rates of reactions on anode surfaces and measured production and loss rates for reactive homogeneous species were used to predict contaminant removal in municipal wastewater effluent. Despite some uncertainty in the reaction mechanisms, the model accurately predicted rates of removal of electron-rich contaminants but underestimated the transformation rates of compounds that exhibited low reactivity with HOCl and HOBr, possibly due to the formation of halogen radicals. The approach employed in this study provides a means of identifying key reactions for different classes of contaminants and for predicting the conditions under which anodic treatment of wastewater will be practical.

Oxidation of Benzene by Persulfate in the Presence of Fe(III)- and Mn(IV)-Containing Oxides: Stoichiometric Efficiency and Transformation Products.

Sulfate radical (SO4(•-)) is a strong, short-lived oxidant that is produced when persulfate (S2O8(2-)) reacts with transition metal oxides during in situ chemical oxidation (ISCO) of contaminated groundwater. Although engineers are aware of the ability of transition metal oxides to activate persulfate, the operation of ISCO remediation systems is hampered by an inadequate understanding of the factors that control SO4(•-) production and the overall efficiency of the process. To address these shortcomings, we assessed the stoichiometric efficiency and products of transition metal-catalyzed persulfate oxidation of benzene with pure iron- and manganese-containing minerals, clays, and aquifer solids. For most metal-containing solids, the stoichiometric efficiency, as determined by the loss of benzene relative to the loss of persulfate, approached the theoretical maximum. Rates of production of SO4(•-) or hydroxyl radical (HO(•)) generated from radical chain reactions were affected by the concentration of benzene, with rates of S2O8(2-) decomposition increasing as the benzene concentration increased. Under conditions selected to minimize the loss of initial transformation products through reaction with radicals, the production of phenol only accounted for 30%-60% of the benzene lost in the presence of O2. The remaining products included a ring-cleavage product that appeared to contain an α,ß-unsaturated aldehyde functional group. In the absence of O2, the concentration of the ring-cleavage product increased relative to phenol. The formation of the ring-cleavage product warrants further studies of its toxicity and persistence in the subsurface.

Exploring Trends of C and N Isotope Fractionation to Trace Transformation Reactions of Diclofenac in Natural and Engineered Systems.

Although diclofenac ranks among the most frequently detected pharmaceuticals in the urban water cycle, its environmental transformation reactions remain imperfectly understood. Biodegradation-induced changes in 15N/14N ratios (εN = -7.1‰ ± 0.4‰) have indicated that compound-specific isotope analysis (CSIA) may detect diclofenac degradation. This singular observation warrants exploration for further transformation reactions. The present study surveys carbon and nitrogen isotope fractionation in other environmental and engineered transformation reactions of diclofenac. While carbon isotope fractionation was generally small, observed nitrogen isotope fractionation in degradation by MnO2 (εN = -7.3‰ ± 0.3‰), photolysis (εN = +1.9‰ ± 0.1‰), and ozonation (εN = +1.5‰ ± 0.2‰) revealed distinct trends for different oxidative transformation reactions. The small, secondary isotope effect associated with ozonation suggests an attack of O3 in a molecular position distant from the N atom. Model reactants for outer-sphere single electron transfer generated large inverse nitrogen isotope fractionation (εN = +5.7‰ ± 0.3‰), ruling out this mechanism for biodegradation and transformation by MnO2. In a river model, isotope fractionation-derived degradation estimates agreed well with concentration mass balances, providing a proof-of-principle validation for assessing micropollutant degradation in river sediment. Our study highlights the prospect of combining CSIA with transformation product analysis for a better assessment of transformation reactions within the environmental life of diclofenac.

Why Small Differences Matter: Elucidation of the Mechanisms Underlying the Transformation of 2OH- and 3OH-Carbamazepine in Contact with Sand Filter Material.

Carbamazepine (CBZ) is a worldwide used antiepileptic drug, which is metabolized to a large extent in the human body to several metabolites, including 10,11-dihydroxy-10,11-dihydrocarbamazepine (DiOHCBZ), 2-hydroxycarbamazepine (2OHCBZ), and 3-hydroxycarbamazepine (3OHCBZ). 2OHCBZ and 3OHCBZ were previously detected in raw and treated wastewater revealing their widespread emission into the aquatic environment, eventually leading to the contamination of drinking water resources. Sand filtration is frequently applied in drinking water treatment for the removal of inorganic species and suspended particles but has been shown to be capable of removing trace organic contaminants. This study focuses on the elucidation of the (bio)transformation mechanisms of 2OHCBZ and 3OHCBZ in contact with material taken from a rapid sand filter of a German waterworks. Despite their similar structure, which differs only in the position of the phenolic OH moiety, both compounds underwent distinct transformation reactions leading to the formation of a variety of transformation products (TPs). The main biochemical reactions thereby included enzymatic transformation of 2OHCBZ resulting in the formation of a reactive iminoquinone intermediate (2OHCBZ) and nitration via peroxynitrite (2OHCBZ and 3OHCBZ) as well as formation of radicals leading to dimerization (3OHCBZ). Further transformation reactions included hydroxylation, ring cleavage, loss of carbamoyl group, and decarboxylation, as well as O-methylation.