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Effect-Directed Analysis (EDA): A Promising Tool for Nontarget
Identification of Unknown Disinfection Byproducts in Drinking
Water
Huiyu Dong, Amy A. Cuthbertson, and Susan D. Richardson*
Cite This: Environ. Sci. Technol. 2020, 54, 1290−1292 Read Online
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■ DRINKING WATER DISINFECTION BYPRODUCTS
Drinking water disinfection is a major public health achieve-
ment of the 20th Century and has significantly increased life
expectancy. However, an unintended consequence is the
formation of disinfection byproducts (DBPs), which can be
cytotoxic, genotoxic, mutagenic, and developmentally toxic.
Although >700 DBPs have been identified in drinking water,
> 50% of the total organic halogen resulting from water
chlorination and chloramination remains unknown.1 More-
over, only approximately 100 DBPs have undergone system-
atic, quantitative, and comparative toxicological analyses.2
Thus, unveiling the unknown DBPs, especially toxicity-drivers,
in drinking water, is important for drinking water safety and is
currently a hot topic in the research community.
■ NON-TARGET IDENTIFICATION OF UNKNOWN
DBPS
The development and use of high resolution mass spectrom-
etry (HRMS), as well as new liquid chromatography (LC)-
tandem MS methods, are the driving force in unknown DBP
identification and suspect screening. Nontarget analysis
typically involves background subtraction, library searching
with standard or user-defined libraries, manual interpretation
of mass spectra, exact mass and molecular formula
determination, and confirmation of tentative identifications
with chemical standards. Because DBPs are formed through
many possible reactions with natural organic matter, whose
structures are heterogeneous and largely unknown, it is
challenging to profile unknown DBPs in drinking water.
Manual data inspection is necessary for unknown identification
because automatic workflows are not available, and most
unknown DBPs are not present in MS libraries. This inevitably
slows down nontarget analysis.
Another challenge is determining the toxicity contribution. A
popular new approach for toxicity assessment of DBPs in
drinking waterTIC-Toxis based on quantitative or
semiquantitative analysis of known DBPs and toxicity
modeling using DBP-specific toxicity data collected for >100
DBPs.3 Using this approach, iodo-DBPs, bromo-DBPs, and
nitrogen-containing DBPs (“N-DBPs”), such as haloacetoni-
triles, haloacetamides, and halonitromethanes, are currently
believed to be the toxicity-drivers. However, it is difficult to
assess concentrations and toxicity contributions for unknown
DBPs, due to the absence of structural information and toxicity
data (especially for molecular weights >500 Da).
Further, while >1000 DBP molecular formulas can be
observed in a single drinking water sample, determining which
compound or group of compounds contributes the most to
toxicity among numerous unknown DBPs is almost impossible.
Based on these considerations, prioritization of the most toxic
fractions before nontarget identification is important.
■ EFFECT DIRECTED ANALYSIS
Effect-directed analysis (EDA), a promising but under-utilized
approach, could be applied to reduce the complexity and to
identify toxicity-driving unknown DBPs.4 A typical EDA
process includes fractionation, effect assay, and chemical
analysis (Figure 1). As early as the 1980s, the U.S.
Environmental Protection Agency proposed EDA for toxicity
Received: January 1, 2020
Published: January 17, 2020
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evaluation of water. EDA can reduce mixtures of thousands of
compounds to small fractions through sophisticated fractiona-
tion procedures with respect to toxicological end points. Thus,
EDA not only accelerates the discovery of toxicologically
important DBPs, but also provides toxicity forcing-factor
information. Many years ago, an EDA approach enabled the
identification of a DBP called MX (3-chloro-4-(dichlorometh-
yl)-5-hydroxy-2(5H)-furanone). MX was originally isolated
from chlorinated pulp mill effluent using a fractionation
approach with thin layer chromatography, silica gel chroma-
tography, and preparative LC. This single compound was
responsible for most of the Ames mutagenicity in the effluent
and was subsequently found in many chlorinated tap waters.5
EDA was key to its discovery, but interestingly, EDA has not
been widely used since for drinking water applications.
Given that natural organic matter in drinking water is a
complicated matrix and DBPs are expected at low concen-
tration (ng L−1−μg L−1), sample extraction and preconcentra-
tion are necessary. Water extraction, preconcentration, and
fractionation procedures should be carefully designed to
capture a wide range of potential DBPs, taking full advantage
of analytical instrumentation and eliminating interfering matrix
components. As shown in Figure 1, fractionation based on
physicochemical properties, including molecular weight, polar-
ity, hydrophobicity, and volatility, is a prerequisite to
determine toxicity-driving DBP fractions in drinking water.
For example, a sequential elution with solvents of increasing
hydrophobicity or sequential solid-phase extraction with
respect to the increasing focus on hydrophilic compounds
can be used to fractionate unknown DBPs with different
polarity.
Epidemiologic research has demonstrated low but significant
associations between disinfected drinking water and adverse
health effects (e.g., bladder and colorectal cancer). A large
number of DBPs have been shown to be cytotoxic, genotoxic,
mutagenic, and developmentally toxic. After fractionation,
extraction, and preconcentration procedures, the toxicity assay
will determine which fraction(s) are driving the majority of the
observed toxicity of the mixture, and will facilitate the
identification of the most important chemical drivers. Due to
numerous DBPs present in drinking water, many of which are
already known to be toxic, a fraction of DBPs, rather than a
single DBP, likely drives the toxicity in drinking water.
After identification of a toxicity-driven fraction, the chemical
nontarget analysis becomes more specific. For nontarget
analysis of unknown DBPs, it is important to obtain a clean
mass spectrum that can be further interpreted; this requires a
sensitive chromatographic separation of analytes and software
that can deconvolute overlapping mass spectra of coeluting
compounds. GC-HRMS using a high resolution time-of-flight
(TOF), Orbitrap, or magnetic sector mass spectrometer can be
used for analyzing volatile and semivolatile unknown DBPs,
while LC-HR-tandem MS with a quadrupole (Q)-TOF,
Orbitrap,or Fourier transform (FT)-ion cyclotron resonance
(ICR) mass spectrometer can be used for analysis of highly
polar, nonvolatile hydrophilic fractions and higher molecular
weight compounds. These instruments provide highly resolved,
accurate, and sophisticated software for identification of
unknown DBPs.
■ A WAY FORWARD FOR IDENTIFYING TOXICITY
DRIVERS
EDA is a promising tool to identify the forcing agents of
toxicity in disinfected water. While the traditional compound-
by-compound approach has provided some information on
toxicity drivers, it is a slow and tedious process, where time is
also spent on the analysis of nontoxic or minimally toxic DBPs.
With >50% of the halogenated DBPs still unknown, we believe
the time has come to take a more effective, streamlined
approach with EDA to resolve forcing agents for the toxicity of
disinfected drinking water.
■ AUTHOR INFORMATION
Corresponding Author
Susan D. Richardson − University of South Carolina,
Columbia, South Carolina; orcid.org/0000-0001-
6207-4513; Phone: +1-803-777-6932;
Email: richardson.susan@sc.edu
Other Authors
Huiyu Dong − University of South Carolina, Columbia,
South Carolina, and Research Center for Eco-
Environmental Sciences, Chinese Academy of Sciences,
Beijing, China; orcid.org/0000-0002-5955-6228
Amy A. Cuthbertson − University of South Carolina,
Columbia, South Carolina, and University of California,
Berkeley, California; orcid.org/0000-0002-7634-
3734
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.est.0c00014
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
Dr. Huiyu Dong was financially supported by the National
Natural Science Foundation of China (51525806, 51878648),
Chinese Academy of Sciences (QYZDY-SSW-DQC004), and
Chinese Scholarship Council (201804910238).
Figure 1. Process for EDA of unknown DBPs in drinking water.
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■ REFERENCES
(1) Richardson, S. D. Disinfection by-products: Formation and
occurrence of drinking water, In: The Encyclopedia of Environmental
Health, Vol. 2, Nriagu, J. O., Ed.; Elsevier: Burlington. 2011; pp 110−
136.
(2) Wagner, E. D.; Plewa, M. J. CHO cell cytotoxicity and
genotoxicity analyses of disinfection by-products: An updated review.
J. Environ. Sci. 2017, 58, 64−76.
(3) Plewa, M. J.; Wagner, E. D.; Richardson, S. D. TIC-Tox: A
preliminary discussion on identifying the forcing agents of DBP
mediated toxicity of disinfected water. J. Environ. Sci. 2017, 58, 208−
216.
(4) Escher, B. I.; van Daele, C.; Dutt, M.; Tang, J. Y. M.;
Altenburger, R. Most oxidative stress response in water samples
comes from unknown chemicals: the need for effect-based water
quality trigger values. Environ. Sci. Technol. 2013, 47, 7002−7011.
(5) Kronberg, L.; Vartiainen, T. Ames mutagenicity and concen-
tration of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-
2(5H)-furanone and of its geometric isomer E-2-chloro-3-(dichlor-
omethyl)-4-oxo-butenoic acid in chlorine-treated tap waters. Mutat.
Res., Genet. Toxicol. Test. 1988, 206, 177−182.
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https://dx.doi.org/10.1016/j.jes.2017.04.021
https://dx.doi.org/10.1016/j.jes.2017.04.021
https://dx.doi.org/10.1016/j.jes.2017.04.014
https://dx.doi.org/10.1016/j.jes.2017.04.014
https://dx.doi.org/10.1016/j.jes.2017.04.014
https://dx.doi.org/10.1021/es304793h
https://dx.doi.org/10.1021/es304793h
https://dx.doi.org/10.1021/es304793h
https://dx.doi.org/10.1016/0165-1218(88)90158-9
https://dx.doi.org/10.1016/0165-1218(88)90158-9
https://dx.doi.org/10.1016/0165-1218(88)90158-9
https://dx.doi.org/10.1016/0165-1218(88)90158-9
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