Assessing Transformation Products of Chemicals by Non-Target and

Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening Strategies and Workflows Volume 1 Downloaded from pubs.acs.org by 80.82.77.83 on 04/01/17. For personal use only.

Chapter 1

Chemicals of Emerging Concern and Their Transformation Products in the Aqueous Environment Jörg E. Drewes* and Thomas Letzel Chair of Urban Water Systems Engineering, Technical University of Munich, 85748 Garching, Germany *E-mail: [email protected].

The interest in understanding the environmental relevance of transformation products (TPs) which are generated from chemicals of emerging concern (CECs) via abiotic and biotic processes has increased significantly in the recent past. Studies published so far have elucidated numerous aspects of TPs from CECs including the development of appropriate analytical methods for their identification and quantification, their formation pathways during various processes including biodegradation, chemical oxidation and photolysis, strategies to predict transformation pathways, and assessments regarding their toxicological relevance. In order to assess the relevance of TPs in the aquatic environment, appropriate and standardized analytical approaches and assessment protocols are needed to address the selection, identification and quantification of TPs, their role in natural water systems and engineered treatment processes, and their toxicological relevance.

Introduction The presence of trace organic chemicals in the aqueous environment has been reported for several decades, but for the last 20 years attention has shifted from legacy contaminants including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, solvents and pesticides to chemicals that are released into the environment via discharges of municipal wastewater effluents, urban stormwater, and agricultural runoff (1, 2). These “chemicals of emerging concern (CECs)” © 2016 American Chemical Society


are comprised of pharmaceutical residues and their metabolites, household chemicals, personal care products, endocrine disrupting compounds, and emerging disinfection by-products and pesticides. A vast number of studies on CECs has been published both on the fate and transport in the natural environment and engineered systems and their toxicological relevance to aquatic and human health. These studies focused primarily on the parent compounds (PC). Both, in the natural water environment and during engineered water treatment processes, CECs are not completely mineralized but may undergo transformation by both abiotic and biotic processes resulting in intermediates which are usually more polar. Transformation products (TPs) are mainly formed through hydrolysis, oxidation, hydroxylation, conjugation, cleavage, dealkylation, methylation, and demethylation (3). While most TPs are less persistent in the aquatic environment (i.e., half lifes of less than two months), more polar and thereby less bioaccumulative, and less toxic than the parent compounds (4), there are a number of prominent exceptions. Indeed, some TPs can be more persistent in engineered or natural systems and some might exhibit higher sublethal, behavioral or developmental effects in aquatic organisms or potential adverse effects to human health as compared to the parent compounds (5, 6). Thus, this topic deserves further research and, where action is warranted, appropriate mitigation strategies. In the early 1970s, TPs were first documented for halogenated and later nitrogeneous disinfection by-products, generated during the disinfection of water and wastewater, although the specific parent compounds weren’t always known (7, 8). In the 1980s and 1990s, research on the formation of TPs was expanded to degradation pathways of pesticides (9). Since then, interest also grew to evaluate transformation products from parent compounds of CECs (10, 11), which is also illustrated by the increasing number of studies published recently in the peer-reviewed literature on this subject. Figure 1 illustrates the steady increase regarding the number of published items and citations per year for the last ten years on the topic of ‘transformation products in the aqueous environment’ based on a Web of Science™ query (www.webofknowledge.com). The studies published during this period have elucidated numerous aspects of TPs from CECs including the development of appropriate analytical methods for their identification and quantification, their formation pathways during various processes including biodegradation, chemical oxidation and photolysis, strategies to predict transformation pathways, and assessments regarding their toxiciological relevance. Considering the number of chemicals in commerce and estimates of a total of 80,000 to 100,000 individual chemicals in municipal wastewater [12], the identification of transformation products is a daunting task given the vast number of possible structures, the complexity of matrices, and their (often) low concentrations. Considering international legislation regulating chemicals today, there is very little recognition given to parent compounds as well as transformation products of CECs. Thus, to focus efforts directed to assess the relevance of TPs in the aquatic environment, appropriate and standardized analytical approaches and assessment protocols are needed to address the selection, identification and quantification of TPs, their role in natural water systems and engineered treatment processes, and their toxicological relevance. 4


Figure 1. Number of published items (total 294) and citations (sum of times cited 3,182) according to Web of Science™ on the topic of “transformation products in the aqueous environment” for the time period 2005-2015.

Analytical Challenges The analytical approaches, which are currently employed for the quantification and identification of PCs and TPs require effective molecule separation and accurate triple quadrupole or high resolution mass spectrometers (HRMS). Advances in the development of these instruments have enabled reliable selective target analysis as well as screening for expected and unknown compounds. The initial method of choice for the analysis of known TPs in aqueous samples has been target analysis (Figure 2). However, this approach requires prior knowledge of the target chemical and for their quantification the availability of reference standards. Frequently, these reference standards for specific TPs are not readily available commercially and synthesis is cost prohibitive for many laboratories. With the advent of reversed phase liquid chromatography coupled with high resolution mass spectrometry (RPLC-HRMS), in particular time-of-flight (ToF) and Orbitrap MS instruments, very powerful tools are now available to detect PCs and their TPs at very low concentrations in various environmental matrices. Since these instruments are capable of screening and detecting a very high number of compounds as long as they ionize under the experimental conditions, databases can be built that record retention time (RT), fragmentation, exact masses, and isotopic pattern. Examples of these databases are MassBank, StoffIdent, ChemSpider, Chemicalize, or DAIOS (3, 13). These databases can be used in combination with computational (in silico) prediction tools (e.g., MetFrag, 5


Eawag-PPS, CATABOL, PathPred, Meteor) for the tentative identification of the molecule instead of reference standards in an analytical strategy called ‘suspect screening’ (14). Confirmation of structure applying MS/MS analysis might strengthen the analytical strategy and increases the confidence levels of identification (15).

Figure 2. Analytical strategies for the identification and quantification of parent compounds and transformation products. Adapted with permission from Reference (13). Copyright 2016 Elsevier.

The third option is described as ‘non-target screening’ and implies the tentative identification of novel TPs without any previous knowledge. For non-target screening, high-resolution MS is required in order to have high mass accuracy for confirmation of proposed molecular formula and reliable interpretation of the MS/MS spectra (14). An example where non-target workflows have been successfully applied is the identification of TPs of three benzotriazoles (16). Given the generation of massive quantities of data, post-acquisition data-processing tools are necessary (e.g., MZmine; EnviMass). However, the procedures applied in these software tools and workflows can differ widely and more specific and harmonized workflows are needed for suspect and non-target analysis. Subsequent chapters of this book will report on new methods for a comprehensive assessment of TPs and illustrate approaches to harmonize workflows for suspect and non-target screening. These discussions include commercial strategies offered by HR-MS vendors for non-target and suspected screening of water samples. 6


Toxicological Relevance of TPs In order to prioritize the most relevant TPs, the identification should be coupled with an assessment of their toxicological relevance since conservation of structure in TPs might also imply conservation or even creation of bioactivity across multiple biological endpoints (6). Such an assessment can occur by employing either effect-directed analysis (EDA) or by using bioanalytical tools for specified endpoints. Bioanalytical tools are defined as in vitro cell-based and in vivo bioassays indicative of modes of toxic action that are relevant for human and/or ecosystem health (17). EDA is a common approach to identify non-target chemicals based on their toxicological effects for select endpoints and is being used in regulatory settings to toxicity identification and evaluation (18). How toxicity of TPs occurring in natural and engineered systems can be assessed is reported in this book in two chapters.

Role of TPs in Water Treatment Processes TPs occurring in the aquatic environment can be classified into two main categories including products formed during abiotic and biotic processes in natural and engineered water systems (14). Abiotic TPs are generated by processes involving hydrolysis, photolysis, and photocatalytic degradation pathways in natural water systems as well as engineered water treatment processes (e.g., chlorination, ozonation, advanced oxidation processes). Biotic pathways can result in TPs involving microbial activities in streams, groundwater aquifers but also engineered biological treatment processes (e.g., activated sludge treatment, biofiltration, wetlands). However, numerous different TPs may be formed within only one type of treatment, applied under sometimes even very similar operating conditions (19). While processes employed in water and wastewater treatment ususally reduce the total concentration of parent compounds as well as TPs (20, 21), mass balances for select chemicals revealed that the efficiency of treatment processes based on the removal of the PC is actually negligible if the fate of all TPs is being considered. For example, Schulz et al. proposed degradation pathways of five major TPs of the triiodinated X-ray contrast medium iopromide under oxic redox conditions (22). When investigating conventional activated sludge processes, iopromide was rapidly transformed but the accumulated molar concentration of iopromide and its TPs after secondary treatment remained the same. The fate and transport of PCs and TPs in both natural and engineered systems is reported in several chapters of this book suggesting strategies but also pointing to limitations for the development of a more comprehensive assessment of CECs in the aquatic environment.

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Assessing Transformation Products of Chemicals by Non-Target and

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