Review

Cite This: Anal. Chem. XXXX, XXX, XXX−XXX pubs.acs.org/ac

Water Analysis: Emerging Contaminants and Current Issues

Susan D. Richardson*,† and Susana Y. Kimura‡
†
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29205, United States
‡

■
Department of Chemistry, University of Calgary, Calgary, Alberta T2N 1N4, Canada
CONTENTS New Methods and Assays Q
Adsorbents Q
Background A Metal Organic Frameworks (MOFs) R
Major Analysis Trends C Bioanalytical Methods R
Sample Processing and Extraction Trends C Drinking Water and Swimming Pool Disinfection
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Chromatography Trends D Byproducts R

Emerging Contaminant Trends D
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Drinking Water DBPs R

New Emerging Contaminant Group D Reviews R
General Reviews, New Approaches, Large Occur- New Methods S
rence Studies, and Important Toxicology Develop- Brominated and Iodinated DBPs T
ments D Fate and Formation Mechanisms U
Emerging Contaminant Reviews D NDMA and Nitrosamine Methods, Formation,
New Approaches and Large Occurrence Studies and Fate V
of ECs E Pollutant DBPs V
Important Toxicology Developments E Swimming Pool DBPs V
New Regulations/Regulatory Methods E Sunscreens/UV Filters W
Perchlorate F Brominated and Emerging Flame Retardants X
New Regulatory Methods for Drinking Water F Reviews X
EPA Method 537.1: Selected Per- and Polyfluori- Occurrence and Fate X
nated Alkyl Substances (PFASs) in Drinking New Methods X
Water F Dioxane Y
Antibiotic Resistance Genes (ARGs) F Algal Toxins Y
Reviews F Reviews Y
Database of PCR Primers G New Methods Z
Occurrence G Occurrence Z
Fate in Water Treatment G Microplastics Z
Sucralose and Other Artificial Sweeteners H New Methods AA
Nanomaterials H Occurrence and Fate AA
Methods H Author Information AB
Occurrence Studies I Corresponding Author AB
Fate Studies I ORCID AB
Per- and Polyfluoroalkyl Substances J Notes AB
Reviews J Biographies AB
Discovery of New PFASs K Acknowledgments AB
Occurrence K References AB
Fate L

■
New Methods L
Pharmaceuticals and Hormones M BACKGROUND
Environmental Occurrence and Transportation
Pathways M This biennial review covers developments in water analysis for
Biological Treatment and Transformation Prod- emerging environmental contaminants over the period of
ucts N October 2017−October 2019. Analytical Chemistry’s policy is
Abiotic Transformations O to limit reviews to a maximum of ∼250 significant references
Elimination/Reaction During Oxidative Water and to mainly focus on new trends. Therefore, only a small
Treatment O fraction of the quality research publications is discussed. The
Hormones P previous Water Analysis review (with Thomas Ternes) was
Antibiotics P published in 2018.1 This year, Susana Kimura joined me to
Suspect Screening P
Psychoactive Pharmaceuticals and Illicit Drugs P Special Issue: Fundamental and Applied Reviews in Analytical
Opioids P Chemistry 2020
Multiresidue Methods P

© XXXX American Chemical Society A DOI: 10.1021/acs.analchem.9b05269

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Table 1. List of Acronyms

ADONA 4,8-dioxa-3H-perfluorononanoic acid MC-LR microcystin LR
AFFFs aqueous film forming foams MCL maximum contaminant level
AgNPs silver nanoparticles MDL method detection limit
AOF adsorbable organic fluorine MOFs metal organic frameworks
AOPs advanced oxidation processes MPs microplastics
ARB antibiotic resistant bacteria MS mass spectrometry
ARGs antibiotic resistance genes N-DBPs nitrogen-containing DBPs
CCL Contaminant Candidate List NDMA N-nitrosodimethylamine
DBPs disinfection byproducts NMR nuclear magnetic resonance
DEET N,N-diethyl-meta-toluamide NMs nanomaterials
DOC dissolved organic carbon NOM natural organic matter
DWTP drinking water treatment plant NPs nanoparticles
E2 17β-estradiol PBDEs polybrominated diphenyl ethers
ECs emerging contaminants PCR polymerase chain reaction
EDA effect-directed analysis PFASs per- and polyfluoroalkyl substances
EE2 17α-ethinylestradiol PFBA perfluorobutanoic acid
ELISA enzyme-linked immunosorbent assay PFCAs perfluorocarboxylic acids
EPA Environmental Protection Agency PFHxA perfluorohexanoic acid
ESI electrospray ionization PFNA perfluorononanoic acid
EU European Union PFOA perfluorooctanoic acid
FT Fourier-transform PFOS perfluorooctanesulfonate
GAC granular activated carbon PFSAs perfluorosulfonic acids
GC gas chromatography POCIS polar organic chemical integrative samplers
GenX hexafluoropropylene oxide dimer acid (HFPO−DA) POPS persistent organic pollutants
HAAs haloacetic acids qPCR quantitative polymerase chain reaction
HANs haloacetonitriles QTOF quadrupole-time-of-flight
HILIC hydrophilic interaction liquid chromatography REACH Registration, Evaluation, and Authorization of Chemicals
HR high resolution SPE solid phase extraction
HRMS high resolution mass spectrometry SPME solid phase microextraction
IC ion chromatography THMs trihalomethanes
ICP inductively coupled plasma TOF time-of-flight
IR infrared TOX total organic halogen
LC liquid chromatography TPs transformation products
LLE liquid−liquid extraction UCMR Unregulated Contaminant Monitoring Rule
LOD limits of detection UPLC ultraperformance liquid chromatography
LOQ limit of quantification WWTP wastewater treatment plant

Table 2. Useful Websites

Web site comments
www.epa.gov U.S. EPA’s Web site
http://www2.epa.gov/dwanalyticalmethods U.S. EPA approved methods for drinking water compliance monitoring
http://www2.epa.gov/water-research/epa-drinking-water-research-methods drinking water methods developed by U.S. EPA’s Office of Water
www.comptox.epa.gov/dashboard EPA’s CompTox Chemistry Dashboard
www.standardmethods.org link to Standard Methods Online
http://ec.europa.eu/environment/chemicals/reach/reach_en.htm REACH Web site
http://chm.pops.int/TheConvention/ThePOPs/ListingofPOPs/tabid/2509 Stockholm Convention persistent organic pollutants (POPs)
https://metlin.scripps.edu METLIN database
http://cfmid.wishartlab.com CFM-ID database and tool
http://www.hmdb.ca Human Metabolome Database (HMDB)
https://omictools.com/metfrag-tool Metfrag
www.mzcloud.org mzCloud
https://comptox.epa.gov/dashboard/chemical_lists/STOFFIDENT Stoff-Ident database
http://www.massbank.jp MassBank
http://mona.fiehnlab.ucdavis.edu MassBank of North America
https://massbank.eu/MassBank European MassBank
http://gnps.ucsd.edu/ProteoSAFe/libraries.jsp Global Natural Products Social Molecular Networking (GNPS)

cover the section on Pharmaceuticals and Hormones. We Numerous abstracts were consulted before choosing the best
welcome any comments you have on this Review. representative ones to present here. Abstract searches were
B DOI: 10.1021/acs.analchem.9b05269
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carried out using Web of Science, and in many cases, full
articles were obtained. A table of acronyms is provided (Table
1) as a quick reference to the acronyms of analytical techniques
and other terms discussed in this Review. Table 2 provides
some useful Web sites.
Major Analysis Trends. Nontarget, unknown analysis
continues as a hot trend, and development of workflows
continues to be popular, as it is labor-intensive and time-
consuming to manually interpret thousands of unknown
compounds and spectral features. High-resolution (HR) mass
spectrometry (MS) remains the foundation of unknown
identification; more studies are going beyond just determining
molecular formulas with HRMS and are increasingly obtaining
accurate mass data for fragment ions and proposing tentative
structures for these unknowns (whether newly identified
compounds or transformation products). Negative mass
defects, determined in concert with HRMS, have also become
a popular trend for identifying new halogenated unknowns,
including PFASs and brominated/iodinated disinfection by-
products (DBPs). Library database creation, in silico methods,
and user-created software are also increasing in popularity,
with many researchers writing their own software and
workflows using R. Several research groups are posting these
databases and tools free online (Table 2). Databases include
Metlin, mzCloud, MassBank, European MassBank, MassBank
of North America, the Global Natural Products Social
Molecular Networking (GNPS), the Human Metabolome
Database (HMDB), Stoff-Ident, and ChemSpider. Workflow
tools include Metfrag (a metabolomics MS/MS fragmentation
predictor), Competitive Fragmentation Modeling for Metab-
olite Identification (CFM-ID), which predicts MS/MS spectra,
and CFM-EI, which predicts electron ionization (EI) mass
spectra.
Another valuable resource is the U.S. EPA’s CompTox
Chemicals Dashboard, which now contains approximately
875 000 chemicals (www.comptox.epa.gov/dashboard). This
curated and freely available resource is a Web-based
application providing access to a number of databases
developed by the U.S. EPA’s Center for Computational
Chemistry and Exposure. The underpinning substance data-
base notably includes a number of PFAS lists (https://
comptox.epa.gov/dashboard/chemical_lists/?search=pfas)
with the Master List containing over 6300 PFAS chemicals
(https://comptox.epa.gov/dashboard/chemical_lists/
PFASMASTER) and incorporating experimental and predicted
physicochemical and fate and transport data and, where
available, toxicological information. The Dashboard was also
recently demonstrated to outperform ChemSpider in identify-
ing unknown contaminants using monoisotopic mass and
molecular formula and metadata candidate ranking (https://
link.springer.com/article/10.1007%2Fs00216-016-0139-z).
Further, a new paper by McEachran et al. reports the
prediction of MS/MS spectra for the entire DSSTox database
using competitive fragmentation modeling and CFM-ID.2 This
has been added to the Dashboard and provides mapping
between predicted spectra, structures, associated compounds,
and chemical metadata (including CAS number, molecular
formula, MS-ready monoisotopic mass, SMILES structure, and
data sources).
NIST and Wiley MS/MS libraries are also now available; the
NIST 2017 database contains >15 000 compounds and
>652 475 spectra, and Wiley’s MS for ID database contains
>1200 compounds and >10 000 spectra. NIST is expected to
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release an updated MS/MS library in 2020, which will almost
double the number of compounds and spectra.
A significant new paper was published in 2019 by
researchers at NIST, who developed a new “Hybrid Search”,
which allows metabolites absent in tandem-MS libraries to be
identified using a combination of direct peak matching with
neutral-loss matching.3 This new searching method was
successful in finding structurally similar compounds in the
library by elevating the scores of similar compounds by
matching shifted peaks. In particular, this new hybrid searching
was demonstrated to greatly increase the number of
metabolites found in biological samples, and it worked for
many different compound classes.
With new replacement per- and polyfluoroalkyl substance
(PFAS) chemicals recently found in the environment and
more than 6000 now used globally, a trend in PFAS research is
the use of surrogate methods to measure total fluorine or total
organic fluorine. These methods include extractable organic
fluorine (EOF) and adsorbable organic fluorine (AOF), which
are combustion-ion chromatography (IC) methods, particle-
induced gamma ray emission (PIGE) spectroscopy, which
quantifies elemental fluorine on surfaces, 19F NMR spectros-
copy, and the total oxidizable precursor (TOP) assay, which
oxidizes and converts perfluoroalkylacid (PFAA) precursors
into PFAAs, which are measured using LC−MS/MS. Studies
using these surrogate techniques are increasing so that
researchers can get a handle on the total fluorine/organic
fluorine, rather than being limited only to measurement of
specific PFAS compounds. Surrogate measurements are also
popular in DBP research, with total organic chlorine (TOCl),
bromine (TOBr), and iodine (TOI) being used to capture the
speciated total organic halogen and the TONO assay to
capture total nitrosamine exposure.
One new analytical technique stands out this year:
differential ion mobility (DIMS)-MS. While DIMS-MS has
been widely used for pharmaceuticals, peptides, and proteins
the past few years, it is now being used for environmental
analyses. Like ion mobility (IM)-MS, which was reported in
the 2018 Analytical Chemistry review on Water Analysis,1
DIMS-MS provides an added dimension in separation (based
on the cross-section of molecules). IMS and DIMS both work
by separating molecules (ions) in the gas phase based on their
mobility in a carrier buffer gas, with separations occurring in
milliseconds. Because IMS separates in time, it is best suited
for TOF mass analyzers. However, because DIMS is based on
other factors in addition to cross-section and because the
separation is in space, it is compatible with any mass analyzer.
An example included in this review involves the application of
DIMS-MS to separate PFAS isomers (linear, secondary-
branched, and tertiary-branched) without the use of traditional
chromatography (e.g., LC) (see the Per- and Polyfluoroalkyl
Substances section). This technique is likely to be used more
and more as the environmental community discovers it.
Sample Processing and Extraction Trends. Stable
isotopic labeling (SIL)-SPE-LC−MS/MS was reported in a
new method, which allows improved extraction and trace
analysis (ng/L) of amino compounds in water. This technique
uses two labeling reagents, formaldehyde and deuterated
formaldehyde (CD2O) to react with amino compounds
directly in water. Two types of isotopically methylated
products are produced, which allows improved extraction
efficiencies with SPE and high sensitivity for LC−HRMS/MS.
With the characteristic isotopic patterns, a data prioritization
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process can be created to identify amino compounds among
thousands of m/z ions. An example in this review involves the
identification of 77 amino acids and peptides in source waters,
which allows the study of amino precursors for nitrogenous
DBP formation (see Drinking Water and Swimming Pool
Disinfection Byproducts section).
As before, SPE, online SPE, and solid phase microextraction
(SPME) continue to be popular extraction techniques,
including new variations of SPME, such as coated blade
spray (see Pharmaceuticals and Hormones section). Liquid−
liquid extraction (LLE) is also sometimes used because it can
provide better recoveries for volatile and semivolatile
compounds (like DBPs) and often uses less solvent than
SPE. Multilayer SPE (with different polarity sorbents)
continues to be a hot trend to allow improved recovery of
compounds of varied polarity. An example in this current
review includes the use of graphitized carbon black, WCX, and
WAX phases stacked into a single SPE cartridge to extract
halomethanesulfonic acids in drinking water (see Drinking
Water and Swimming Pool Disinfection Byproducts section).
Also, ionic liquids (ILs) continue to be used for extraction of
emerging contaminants (ECs). An example in this Review
includes the use of polymeric ionic liquids with headspace-
SPME to measure UV filters in water.
In addition, metal organic frameworks (MOFs) are
increasingly being synthesized and are now being used in
environmental applications, including analytical methods for
extracting pharmaceuticals from water. MOFs are hybrid
porous materials that incorporate metal-containing nodes and
organic linkers to form crystalline structures with large surface
areas. A new method cited in the Pharmaceuticals and
Hormones section includes detection of drugs in environ-
mental waters via the deactivation of luminescence using
MOFs.
Chromatography Trends. A stand-out this year for
something a little different in the chromatography world for
ECs is ultraperformance convergence chromatography
(UPC2). UPC2 is mostly just a new name for supercritical
fluid chromatography (SFC), except that it also employs the
use of organic cosolvents in addition to supercritical CO2,
which allows gradient elution, higher flow rates, faster run
times, and more polar solvent systems that can better separate
chemicals not normally retained on an LC column. UPC2
encompasses both super- and subcritical regions, which
expands past the density modulation of CO2-only SFC.
While SFC was somewhat popular several years ago, it
declined in use and was never widely applied to ECs. This
year, UPC2 found a use with ESI-MS/MS for improved
separations of ultrashort-chain PFASs (2−3 carbons), which
are typically not retained on an LC column. It also allowed the
separation of longer-chain PFASs (4−14 carbons) at the same
time. An example in the PFAS section illustrates how UPC2-
ESI-MS/MS can provide separations for 29 ultrashort- and
longer-chain PFAS molecules in a short run time, with low
detection limits (sub-pg). As in previous years, LC, UPLC, gas
chromatography (GC), and GC × GC continue to be popular
chromatography options for separating ECs, usually coupled
with MS or MS/MS. Hydrophilic interaction LC (HILIC)
columns also continue to gain in popularity for retaining and
improving separations for highly polar compounds that are not
well retained by common C18 LC columns.
Emerging Contaminant Trends. The number of
chemicals continues to expand for the per- and polyfluoroalkyl
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substance (PFAS) area, particularly for new replacement
compounds for perfluorooctanesulfonate (PFOS) and per-
fluorooctanoic acid (PFOA), including shorter chain com-
pounds and ethers. Replacement flame retardants also continue
to be popular in research, where “what is old has become new
again”, with manufacturers shifting away from brominated
flame retardants back to chloroalkyl phosphates. Exploring
mechanisms of formation for DBPs is also a hot topic, as is the
study of more iodinated DBPs and nitrogenous DBPs (N-
DBPs), which are among the most toxic.
New Emerging Contaminant Group. This year, anti-
biotic resistance genes (ARGs) are added as a new emerging
contaminant class. The global spread of antibiotic resistant
bacteria and ARGs has become a major issue, resulting in
illness and even death, due to the inability of many antibiotics
to treat resistant pathogens. Many studies, especially in Europe,
the U.S., and China, are now investigating sources, occurrence,
fate, and treatment to remove them (see section Antibiotic
Resistance Genes (ARGs)).
■ GENERAL REVIEWS, NEW APPROACHES, LARGE
OCCURRENCE STUDIES, AND IMPORTANT
TOXICOLOGY DEVELOPMENTS
This section includes general reviews, new approaches, large
occurrence studies, and important toxicology developments for
ECs. Reviews that relate to specific areas (e.g., PFASs,
pharmaceuticals, DBPs) can be found in those specific
sections. Several reviews and special issues of journals have
focused on water analysis, and several specifically on ECs. Due
to reference number limitations, only a few are cited here. Two
notable special issues include Accounts of Chemical Research
(2019, volume 52, issue 4), entitled “Water for Two Worlds:
Urban and Rural Communities” and Current Opinion in
Environmental Science & Health (2019, volume 7), entitled
“Drinking Water Contaminants and Health Effects”. In the first
special issue, 19 articles review the latest in treatment
technologies for protection of water supplies. In the second,
17 articles review emerging and some classical contaminants of
concern as well as toxicity assays relevant to drinking water.
Hot topics, such as potable reuse, are also included. One
notable paper by Khan et al. outlines which chemicals to be
concerned about for potable reuse.4 These special issues are
chocked full of excellent, provocative reviews and are must-
reads.
When considering potable reuse (reusing wastewater for
drinking water), advanced oxidation processes (AOPs) are
usually implemented to more effectively remove wastewater
contaminants. To that end, Miklos et al. published a review on
AOPs for water and wastewater treatment and included
discussions of ozone-based AOPs, UV-based AOPs, electro-
chemical AOPs, catalytic AOPs, and physical AOPs as well as
oxidation byproducts that can be formed in these processes.5
Emerging Contaminant Reviews. Environmental mon-
itoring of organic water pollutants identified by European
Union guidelines was the subject of a review by Sousa et al.,
who discussed European legislation, occurrence of ECs and
priority substances in surface and ground waters, and future
challenges.6 In another review, Lorenzo et al. outlined
analytical challenges for determining emerging persistent
organic pollutants in aquatic ecosystems.7 This review focused
on the most recent literature (2011−2017) for determining
classical polybrominated diphenyl ethers (PBDEs) and PFASs
as well as newer ones. Recent developments in extraction,
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preconcentration, and instrumental detection are summarized.
Seven major class of contaminants, analgesics, antibiotics,
antineoplastics, beta-blockers, perfluorinated compounds,
personal care products, and plasticizers, was the subject of a
comprehensive review by Wilkinson et al., who discussed their
occurrence, fate, and transformation.8 Key aspects include the
fact that some replacement chemicals (for those banned or
phased-out) are similarly persistent in the environment and
that many ECs can sorb to micro- and nanoplastics, which will
likely remain a problem in the environment due to slow
decomposition.
Hernandez et al. reviewed the role of analytical chemistry in
exposure science, with a focus on the aquatic environment.9 In
this review, analytical strategies and tools are discussed (with
an emphasis on HRMS), along with the role of effect-directed
analysis (EDA), the relevance of transformation products, and
real-time, early warning systems. Trends and perspectives are
also discussed. Emerging contaminants and potential engineer-
ing solutions was the topic of another review by Richardson
and Kimura, who outlined occurrence, sources, fate, and
treatment options for successfully removing many of these
ECs.10 The impact of climate change was also discussed. Tran
et al. reviewed the occurrence and fate of 60 ECs in wastewater
treatment plants (WWTPs) from different geographic
regions.11 Occurrence patterns of contaminants from Asia,
Europe, and North America were compared, and the efficacy of
different WWTP removal strategies (sorption, biodegradation)
was discussed, along with factors, such as redox conditions,
microbial populations, the presence of primary substrates, and
the effect of temperature and pH on their removal.
New Approaches and Large Occurrence Studies of
ECs. Gago-Ferrero et al. published a poignant paper
demonstrating that regulatory databases can be effectively
combined with HRMS to prioritize, and even identify for the
first time, new potentially hazardous chemicals in the
environment.12 In this study, 160 of the 23 000 chemicals
registered in the National Swedish Product Register were
prioritized according to quantitative knowledge/market
availability, quantity used, extent of use on the market, and
predicted compartment-specific environmental exposure
through usage. A LC−HRMS suspect screening strategy was
then used to probe for these compounds in treated wastewater.
In total, 36 tentative identifications were made, and 23 were
confirmed with standards, including compounds not previously
considered in environmental studies.
Bradley et al. conducted a large occurrence study of 482
organic compounds and 19 inorganic compounds in tap water
from 11 states in the U.S.13 Samples were collected from
homes with public drinking water or private wells and also
from drinking water treatment plants. Seventy-five organics
were detected at least once, and DBPs dominated the
detections, with 6/10 most frequently detected. In addition,
chemicals designed to be bioactive (e.g., pesticides and
pharmaceuticals) comprised 48% of the organic chemicals
detected. Of these compounds, only uranium (in one private
well) exceeded the regulatory limit.
Important Toxicology Developments. Two toxicology
papers published the last 2 years are worthy of mention in this
opening section, due to their broad applicability to emerging
contaminants and whole water samples. First, Dong et al.
developed a new high-throughput thiol reactivity assay that can
effectively predict mammalian cell cytotoxicity of water
samples.14 This new colorimetric assay is entirely chemically
E DOI: 10.1021/acs.analchem.9b05269
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based, such that no biological safety hoods or cell cultures are
needed. The approach is based on reactivity with N-
acetylcysteine and came from the idea that the cysteine thiol
in glutathione is the major reductant against reactive toxicants
in the body that can induce adverse biological responses if the
thiol pool is overwhelmed and depleted. This rapid method
had been previously tested against α-halo-carbonyl com-
pounds, and in this current study, it also predicted the
cytotoxicity of a wide range of impacted water and wastewater
samples. Therefore, it can be used to rank order mammalian
cell cytotoxicity of water samples and can be used for rapid,
preliminary screening before conducting more intensive
analytical biological assays.
In the other paper, Neale and Escher outline how in vitro
bioassays can be used to assess drinking water (and other
water) quality.15 Two similar and currently popular ap-
proaches, “iceberg modeling” and “TIC-Tox”, were described
and compared. For iceberg modeling, the bioanalytical
equivalent concentration (BEQbio) is compared to the BEQ
from a chemical analysis (BEQchem) and can reveal which
chemical or group of chemicals explains the majority of the
effect from the extracted water sample. This approach revealed
that volatile DBPs only had a minor contribution to the
observed oxidative stress response in drinking water samples
collected in France. For TIC-Tox, the total ion current (TIC)
of the chromatographic peak area (from GC−MS or LC−MS)
of a measured analyte or its actual measured concentration is
multiplied by the compound’s known toxicity index. This has
been used to identify the forcing agents in disinfected drinking
water, with haloacetonitriles and haloacetamides determined to
be the main drivers of toxicity in drinking water extracts from
Europe.
■
NEW REGULATIONS/REGULATORY METHODS
Recent U.S. Rules and Regulations include the U.S. Environ-
mental Protection Agency’s (EPA’s) Fourth Unregulated
Contaminant Monitoring Rule (UCMR-4) and the Fourth
Contaminant Candidate List-4 (CCL-4). The UCMR-4
requires drinking water utilities to monitor for 30 contami-
nants from 2018 to 2020; it is currently providing national
occurrence data for priority unregulated contaminants for
future regulatory consideration (www.epa.gov/dwucmr/
fourth-unregulated-contaminant-monitoring-rule). This Rule
supports the Safe Drinking Water Act and Amendments,
which requires every 5 years, a list of no more than 30
unregulated contaminants to be monitored nationally. The
CCL-4 was finalized in November 2016 and is the drinking
water priority contaminant list for regulatory decision making
and information collection. The CCL-4 contains 97 chemicals
or chemical groups and 12 microbial contaminants (www.epa.
gov/ccl/contaminant-candidate-list-4-ccl-4-0). The UCMR-4
and CCL-4 were previously described in detail in the last
Analytical Chemistry review.1 EPA is currently evaluating
nominations and other contaminant data and information
and plans to publish a draft CCL-5 for public review and
comment soon. EPA is also currently working on the UCMR-5
and plans to publish the final rule by December 2021. In the
EPA’s PFAS Action Plan, published in February 2019, EPA
stated its intention to propose monitoring for PFASs in UCMR
5, utilizing newer methods at lower minimum reporting levels
than previously possible (https://www.govinfo.gov/content/
pkg/FR-2019-05-30/pdf/2019-11168.pdf).
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Perchlorate. A new development this year is a notice of
proposed rule-making for perchlorate. Perchlorate was
originally on the CCL-1, 2, and 3 lists as well as the first
UCMR, and EPA had announced in 2011 that it had decided
to regulate it. However, no maximum contaminant level
(MCL) has been set, and perchlorate is still not yet regulated.
On May 23, 2019, the U.S. EPA announced that it is seeking
public input on a MCL and a health-based maximum
contaminant level goal (MCLG) for perchlorate (https://
www.epa.gov/newsreleases/epa-seeks-comment-proposed-
options-regulating-perchlorate-drinking-water). Specifically,
EPA is seeking comment on a proposed National Primary
Drinking Water Regulation (NPDWR) for perchlorate to
establish a MCL and a health-based MCLG at 56 μg/L. It is
also seeking comment on three alternative regulatory options:
(1) An MCL and MCLG for perchlorate set at 18 μg/L; (2)
An MCL and MCLG for perchlorate set at 90 μg/L; or (3)
Withdrawal of the agency’s 2011 determination to regulate
perchlorate in drinking water.
New Regulatory Methods for Drinking Water. Since
the last Analytical Chemistry review, one new regulatory
method, EPA Method 537.1, has been published for measuring
additional PFASs in drinking water. Three other EPA Methods
are close to being released: (1) EPA Method 559, which will
measure nonylphenol and octylphenol in drinking water; (2)
EPA Method 533, which will measure additional PFASs,
including shorter chain molecules in drinking water; and (3)
EPA Method 558, which will measure N-methyl-2-pyrrolidone
and urethane in drinking water.
EPA Method 537.1: Selected Per- and Polyfluorinated
Alkyl Substances (PFASs) in Drinking Water. In
November 2019, an updated EPA method was created for
measuring additional PFASs in drinking water: EPA Method
537.1, “Determination of Selected Per- and Polyfluorinated
Alkyl Substances in Drinking Water by Solid Phase Extraction
and Liquid Chromatography/Tandem Mass Spectrometry”
(www.epa.gov/water-research/epa-drinking-water-research-
methods). This method uses SPE with LC−MS/MS and is an
update of the previous EPA Method 537. It was developed in
support of a future UCMR. Since the development of EPA
Method 537, more PFASs have been identified or introduced
as PFOA/PFOS alternatives in manufacturing that have the
potential to contaminate drinking water. This new updated
method increases the number of PFAS molecules from 14 to
18 and includes hexafluoropropylene oxide dimer acid (HFPO-
DA, also known as GenX), along with three additional PFASs:
11-chloroeicosafluoro-3-oxaundecane-1-sulfonic acid (11Cl-
PF3OUdS), 9-chlorohexadecafluoro-3-oxanone-1-sulfonic
acid (9Cl-PF3ONS), and 4,8-dioxa-3H-perfluorononanoic
acid (ADONA). GenX and ADONA are PFOA replacement
compounds; 11Cl-PF3OUdS and 9ClPF3ONS are found in
F53B, which has been used in China since the 1970s as wetting
agents and mist-suppressing agents in the metal plating
industry (e.g., chrome plating).
■
ANTIBIOTIC RESISTANCE GENES (ARGs)
While antibiotics are a cornerstone of modern health care, their
intensive use and misuse has resulted in antibiotic resistant
bacteria (ARB) and antibiotic resistance genes (ARGs) that
have made their way into the environment. Not only are
antibiotics heavily used by humans, but they are also heavily
used in livestock, poultry, and other animals to prevent disease
and promote growth. Urban wastewater is regarded as a
F DOI: 10.1021/acs.analchem.9b05269
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predominant source of ARB and ARGs to the environment,
but there are many other sources, including sludge and animal
waste applied to land and even drinking water treatment.
Antibiotic resistance can spread by horizontal gene transfer
processes, as well as by vertical processes, through transfer of
genetic material to offspring.16 Many studies have now
documented the widespread presence of ARB and ARGs
worldwide, and due to antibacterial resistance, many people die
each year from resistant pathogenic bacteria. The death toll in
Europe from ARB is estimated at 25 000 per year, and ARB-
related illnesses in the U.S. are estimated at 2 million per
year.17
The World Health Organization (WHO) established a
global action plan in 2015 with a “One Health” approach to
counter antibiotic resistance at diverse levels.16 The European
Union (EU) has also established a Joint Programming
Initiative on antibiotic resistance (www.jpiamr.eu), and many
large research efforts have recently launched to tackle this
important worldwide problem. Due to the increasing
importance of ARGs and their emergence as important
environmental contaminants, they are included in this review
for the first time.
Reviews. There have been numerous review articles
published in the last 2 years on ARB and ARGs. Michael-
Kordatou et al. wrote an excellent review on the use of AOPs
for inactivating ARB and ARGs, discussing the role of
operating parameters and oxidative damage mechanisms.16
AOPs included the combination of UV or solar light with
hydrogen peroxide, ozone, and TiO2 as well as Fenton
photocatalysis. While ozone can be effective for inactivating
ARB and removing ARGs, a prolonged time is required for
complete elimination using the photocatalytic processes to
avoid post-treatment repair and bacterial recovery. The authors
note that in some cases, AOPs can select for resistance during a
single course of treatment and also that the majority of cellular
damage by advanced chemical oxidation may be on the cell
wall and membrane structures of the bacteria, leaving internal
cellular components intact and able to repair the damage. The
authors listed several other challenges, including identifying
and understanding how chemical, biological, and micro-
biological components of wastewater effluents affect the
efficiency of AOPs to inactivate ARB and remove ARGs.
Li and Gu wrote an intriguing review on the threat of
disinfection of drinking water and DBPs on antimicrobial
resistance.18 Both disinfectants and DBPs at minimum
inhibitory concentrations (MICs) and sub-MICs have been
shown to cause antimicrobial resistance via genetic mutations
and/or horizontal ARG transfer. DBPs implicated to-date
include dibromo-, trichloro-, and iodoacetic acid, dichloroace-
tonitrile, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-fura-
none (MX), bromate, and chlorite. DBP-specific mutations
have been identified in new genes and in previously recognized
ARGs.
Implications of reclaimed wastewater reuse for irrigation in
agriculture was the focus of another review by Christou et al.,
who discussed the knowns and unknowns of the fate of
antibiotics, ABR, and ARGs.19 Sorption, transport, and
transformation in soil, detection and quantification in soils
and crops, effects of antibiotics on soil biota, and uptake of
antibiotics in crop plants were critically reviewed. Finally,
antibiotic resistance in China was the focus of another review
by Qiao et al., who discussed the occurrence of antibiotics and
ABRs in surface water, wastewater effluent, soils, and animal
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
waste. Issues of enrichment and dissemination of ARGs in the
environment were also highlighted.20
Database of PCR Primers. Polymerase chain reaction
(PCR) is the primary method for identifying and detecting
ABRs in the environment, and Gorecki published a new
literature-based database of PCR primers to help facilitate their
detection in environmental and clinical samples.21 This
database includes 607 PCR primer pairs designed to amplify
various genes conferring resistance to antibiotics in 10 classes
of antimicrobial agents. The specificity, efficacy, and taxonomic
efficacy were evaluated, and the primer pairs were validated in
bioinformatic and experimental PCR surveys.
Occurrence. Several studies have investigated the occur-
rence of ARGs in environmental waters. For example, Cacace
et al. conducted a large European study of ARGs in wastewater
and receiving water bodies in urban settings.22 Quantitative
PCR (qPCR) was used to measure the abundance of nine
ARGs and a class 1 integron in 16 WWTPs from 10 different
countries. Six ARGs were found in all effluent and river water
samples, with intl1 and sul1 the most abundant. Also, blaOXA‑58
was consistently above the limit of quantification and was
recommended for inclusion in future studies. This ARG is
typically associated with Acinetobacter baumannii but has also
been recently linked to several other bacteria, suggesting it is
more prevalent than previously thought.
Hurricane Harvey was the focus of another study by Yu et
al., who found elevated levels of pathogenic indicator bacteria
and ARGs following the flooding in Houston, TX.23
Interestingly, qPCR revealed that ARGs were more abundant
in indoor floodwater than in street floodwater or bayou water.
In addition, sediments that were mobilized by the floodwaters
showed higher levels of pathogens postflood in residential
areas and public parks. Reclaimed water distribution systems
were the focus of another study by Garner et al., who carried
out a shotgun metagenomics sequencing approach to
comprehensively measure ARGs before and after treatment
and at five points of use from four full-scale treatment plants.24
Four ARGs were also quantified using qPCR: qnrA, blaTEM,
vanA, and sul1. Some ARGs were elevated in all or some of the
reclaimed point-of-use samples compared to the corresponding
potable samples, demonstrating that reclaimed water can
convey higher abundances of certain ARGs than conventional
drinking water.
Aging landfills were the focus of a study by Wu et al., who
measured ARGs, antibiotics, and heavy metals in refuse and
leachates from landfills aging from <3 to >20 years.17 While
antibiotic levels were lower in refuse and leachates from older
landfills, ARGs were significantly higher. Interestingly, heavy
metal concentrations were significantly correlated with
elevated levels of ARGs. In another study, Auguet et al.
identified sewers as potential reservoirs of antibiotic resist-
ance.25 Wastewater and biofilms were analyzed for ARGs at the
inlet and outlet of a pressurized sewer pipe, where sul1 and sul2
were found to be the most abundant ARGs. This study
revealed that sewer biofilms can be a source and a sink of ARB
and ARGs, and that community composition, rather than
antibiotic concentration, is the main factor driving the diversity
of the sewage resistome.
Hospital wastewaters were the focus of many studies of
ARGs the last 2 years. For example, Proia et al. measured the
occurrence and persistence of carbapenemases genes in
hospital, WWTP influents/effluents, and receiving river
waters.26 The genes blacKPC, blaNDM, and blaOXA‑48 were
G DOI: 10.1021/acs.analchem.9b05269
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quantified in particle-attached and free-living bacteria in
samples collected over a 1-year period in Belgium. While
absolute abundance of ARGs was lower in WWTP effluents,
the relative abundance (normalized per 16S rRNA) was never
lowered through wastewater treatment. In addition, particle-
attached ARG levels were significantly higher in the effluents,
and ARG levels were much higher in river water downstream
of the WWTPs.
Antibiotic manufacturing sites were the focus of another
study by Gonzalez-Plaza, who analyzed ARGs effluents from
azithromycin synthesis and veterinary drug formulation
facilities.27 Sediments in receiving waters (river and creek)
were also analyzed. Both industries showed a high and similar
abundance of sul1, sul2, qacE/qacEΔ1, tet(A), class 1 integrons
(intI1), and lncP-1 plasmids (korB), which increased in
receiving sediments. Effects were more pronounced in the
river sediments, due to lower background levels.
Fate in Water Treatment. The impact of blending direct
potable reuse (DPR) water with traditional drinking water on
ABR and ARGs was investigated in a study by Garner et al.,
which focused on premise plumbing.28 Water from four
utilities was treated in bench- and pilot-scale treatment to
simulate DPR with blending and was incubated in simulated
premise plumbing with PVC pipe and brass coupons. While
regrowth of total bacteria occurred, they were not more
abundant in water or biofilm of any DPR scenario than the
corresponding conventional drinking water. The opportunistic
pathogen marker genes (anrA, vanA, and intI1) were also not
significantly greater. In another study, Kappell et al.
investigated the effects of zinc orthophosphate, which is
commonly used as a corrosion inhibitor in drinking water
distribution systems, on ARB and ARGs in drinking water.29
Zinc orthophosphate was added to 1 L of microcosms
inoculated with real source water and was mixed for 14 days.
After plating with nine antibiotics, significant differences were
found in the abundance of ARB, and qPCR showed a
significant difference in the absolute and relative abundance of
intI1, sul2, and qacH genes, which depended on the
concentration of zinc orthophosphate. Finally, results revealed
that the zinc component was the selective pressure of antibiotic
resistance.
A source-to-tap water was the focus of another study by Su
et al., who measured 27 target ARGs in the Pearl River Delta
region in China.30 Levels of ARGs were much lower in tap
water than source water, due to sand filtration and
sedimentation removal. On the other hand, granular activated
carbon (GAC) increased the abundance of ARGs, and
Pseudomonas is thought to be involved in the proliferation
and distribution of ARGs in the drinking water treatment
system. While ARGs and bacteria were significantly reduced in
the finished drinking water, they were still present.
In a full-scale WWTP study, Liu et al. demonstrated that
chlorine disinfection can increase the abundances of intra-
cellular and extracellular ARGs.31 Chlorine increased the
abundances of extracellular ARGs ermB, tetA, tetB, tetC, sul1,
sul2, sul3, ampC, aph(2′)-Id, ratG, and vanA up to 3.8-fold and
intracellular ARGs by 7.8-fold. E. coli levels before chlorination
showed strong correlations with the extracellular ARGs in the
final effluents, and lower temperature/higher ammonia
appeared to correlate with intracellular ARGs. The impact of
chlorine, chloramine, chlorine dioxide, ozone, UV, and
hydroxyl radicals on ARGs was addressed in a new study by
He et al.32 qPCR was used to measure degradation, and
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
culture-based natural transformation was used to measure
biological deactivation. Under practical disinfectant exposures,
extracellular and intracellular ARGs were degraded by ≥90%
with chlorine, ozone, and UV; chloramine and chlorine dioxide
were not effective. Intracellular ARG degradation and
deactivation always lagged cellular inactivation.
Continuous ozonation of urban wastewater was evaluated
for the removal of antibiotics, antibiotic-resistant E. coli, ARGs,
and phytotoxicity in a study by Iakovides et al.33 As expected,
the efficiency was highly ozone dose and contact time
dependent, with removal of the eight antibiotics achieved in
40 min at an ozone dose of 0.125 g of O3/g of dissolved
organic carbon (DOC). The inactivation of E. coli was
achieved with a hydraulic retention time of 40 min and 0.25
g of O3/g of DOC. The abundance of ARGs (intI1, aadA1,
dfrA1, qacEΔ1, and sul1) also decreased with increasing
hydraulic retention time and ozone dose. However, higher
ozone doses were required to confer permanent damage and/
or death to prevent post-treatment regrowth of total bacteria
and ARB.
■ SUCRALOSE AND OTHER ARTIFICIAL
SWEETENERS
Artificial sweeteners are common ingredients in foods and soft
drinks, and due to their widespread presence and stability in
the environment, they have become common tracers for
anthropogenic inputs and have mostly replaced caffeine for this
purpose. Many studies are now using their concentrations to
estimate the percent wastewater contamination in ground-
water. Sucralose and acesulfame have become common tracers
because they are among the most persistent in the environ-
ment and in wastewater treatment and also have good
detection using LC−MS. However, other artificial sweeteners
are also used, including saccharin, cyclamate, aspartame,
neotame, stevioside, glycyrrhizic acid, and neohesperidine
dihydrochalcone. In addition, many studies have investigated
artificial sweeteners as environmental contaminants, with some
effects observed in aquatic organisms and toxicity assays,
especially for photodegradation products.
Several review articles have been written on the use of
artificial sweeteners as a wastewater indicator. For example,
Jmaiff Blackstock et al. reviewed recent applications and
provided a critical evaluation of using artificial sweeteners to
assess wastewater impact.34 The specificity of artificial
sweeteners to wastewater, their removal in wastewater
treatment, occurrence in wastewater and environmental waters,
attenuation in the environment, and methods for their
determination were also discussed. McCance et al. explored
the applicability of various emerging contaminants as novel
groundwater tracers for wastewater impacts.35 The suitability
of the artificial sweeteners acesulfame, sucralose, saccharin, and
cyclamate were discussed, as well as DBPs, pharmaceuticals,
industrial compounds, and pesticides. Acesulfame was
suggested to be the most promising marker, due to its
ubiquitous occurrence at relatively high concentrations (20−
2500 μg/L); however, recent studies show that it can undergo
photodegradaton and biodegradation. Sucralose is also very
prevalent in the environment, but its sensitivity by mass
spectrometry is not as good as acesulfame. Saccharin and
cyclamate are other possibilities, but they are greatly reduced
during wastewater treatment. Finally, Luo et al. reviewed
analytical methods for artificial sweeteners along with their
occurrence in the environment.36 Concentrations generally
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follow this order: WWTP influent > WWTP effluent > surface
water > groundwater > drinking water, with significant
differences among different countries that are correlated with
consumption patterns and WWTP removal efficiencies.
New studies on artificial sweeteners include one by Bechner
et al., who investigated oxidation products formed by the
reaction of acesulfame with ozone along with a toxicological
assessment of the byproducts.37 The ozonated reaction mixture
was genotoxic, and two major oxidation products were
tentatively identified. Purification of only one of these products
was possible (but it was found not toxic), as the second
(aldehyde) product was not stable and was lost during the
purification process.
Currens et al. used the relative concentrations of a
degradable, human-specific pharmaceutical, acetaminophen,
and a persistent artificial sweetener, sucralose, to differentiate
sources of human extreta in surface waters.38 The presence of
acetaminophen was related primarily to untreated human
excreta, with concentrations rapidly decreasing during waste-
water treatment. Sucralose in surface water was related to
inputs of both raw sewage and WWTP effluents. This
coanalyte indicator approach revealed the presence of domestic
sewage that was not fully treated. Kahl investigated the
biodegradation of acesulfame in biological wastewater treat-
ment and found that it could degrade substantially, with
sulfamic acid formed as a degradation product in quantitative
amounts.39 Several microbial species, including Phyllobacter-
iaceae, Methylophilaceae, Bradyrhizobiaceae, and Pseudomonas,
were suggested responsible. Finally, Yang et al. measured the
occurrence and distribution of 93 pharmaceuticals and
personal care products (PPCPs) and 5 artificial sweeteners in
surface water and groundwater from south China. Results
suggest that acesulfame, sucralose, and cyclamate could be
good indicators of wastewater contamination.40 Sucralose was
found to be the most suitable marker to reflect domestic
wastewater contamination to surface waters and groundwater.
■
NANOMATERIALS
Nanomaterials (NMs) continue to be a hot topic, with
measurements of their environmental occurrence, fate, and
toxicity, and new NMs continually being developed. Nano-
silver (nAg) remains the most popular, with medical bandages,
gym socks, t-shirts, food containers, baby blankets, towels, and
children’s toys incorporating them. Studies also continue on
graphene, fullerenes, single-walled carbon nanotubes, nTiO2,
nZnO, and nCeO2. There is a developing consensus that NMs
may pose a relative low environmental risk, but there is a lack
of data in many areas.41 Nanospecific effects are also well
documented, which are different from the effects of both ions
and larger particles, but these effects are not consistent for all
NM species.41 These points, along with many others, are
included in an excellent review by Lead et al. on the behavior,
fate, bioavailability, and effects of NMs in the environment.41
This review is an update to an earlier one by these authors
published in 2008, and it also discusses key knowledge gaps for
NMs.
Methods. Several new methods have been published the
past few years. For example, Sikder et al. report a simple, rapid
UV−vis method for measuring Ag nanoparticle (AgNP)
concentrations and dissolution in seawater.42 The equations
developed from the dependence of λmax and the extinction
coefficient on NP size are used to calculate the size and
concentration of polyvinylpyrrolidone (PVP)-stabilized AgNPs
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
in seawater. Concentrations are determined as the difference
between the total and dissolved Ag, measured by inductively
coupled plasma (ICP) MS. In another method paper, Gigault
designed a specific microfluidic device (“estuary on a chip”) to
evaluate the influence of salinity gradients encountered in
estuaries on the aggregation behavior of nC60 NPs.43 Using this
device, the authors discovered that a very short exposure time
(2 s) to the salinity gradient significantly affected the
aggregation properties. Results indicate that the salinity
gradient can enhance the stability of these nC60 NPs, especially
at high ionic strength. Zhao et al. used a simple approach to
simultaneously determine the type, concentration, and size of
TiO2 NPs.44 For this method, Raman spectroscopy and
surface-enhanced Raman spectroscopy (SERS) were used to
identify and discriminate rutile and anatase forms of TiO2 NPs
from their Raman signatures. Concentrations could be
determined from Raman peak intensity. Particle sizes were
determined by using the ratio of the Raman intensity of TiO2
to the SERS intensity of the myricetin bound to the NPs.
TiO2 NPs in commercial sunscreens were the topic of
another new method by Philippe, who developed new
extraction and characterization methods using ultrafiltration
and ultracentrifugation with a surfactant.45 These methods
were used to evaluate 11 commercial sunscreens with different
compositions. Ultracentrifugation allows 250 mg to be
extracted from 5 g of sunscreen in 1 day. Recoveries for
ultrafiltration and ultracentrifugation were 52−96% and 78−
98%, respectively. Isotopically labeled NPs were used in a new
method by Supiandi et al., who synthesized isotopically labeled
111
Cd77Se/68ZnS quantum dots, which allowed their study in
river, estuarine, and sea waters at low, environmentally relevant
concentrations.46 Limits of quantification (LOQs) for Zn, Cd,
and Se in purified water were at 10, 0.3, and 6 ng/L,
respectively, but were higher in real environmental waters (3.4
ng/L to 3.5 μg/L). Peters et al. developed a new single-particle
ICPMS method to measure Ag, CeO2, and TIO2 NPs in
surface water.47 Detection limits were 0.1, 0.05, and 10 ng/L,
respectively; size detection limits were 14, 10, and 100 nm,
respectively. This method was used to measure these NPs in
two rivers in The Netherlands, where nAg and nCeO2 were
found, along with microsized TiO2. nAg, nCeO2, and μTiO2, in
all river samples at concentrations ranging from 0.3 to 2.5 ng/
L, 0.4−5.2 ng/L, and 0.2−8.2 μg/L, respectively. Average
particle sizes were 15, 19, and 300 nm, respectively.
Occurrence Studies. Several interesting occurrence
studies have been conducted the last 2 years for NMs. For
example, Sanchis et al. investigated the occurrence of 10
fullerenes in the Sava River, which flows through four
countries: Slovenia, Croatia, Bosnia-Herzegovina, and Serbia.48
Fullerenes included C60 fullerene, C70 fullerene, C76 fullerene,
C78 fullerene, C84 fullerene, C60 pyrrolidine tris-acid ethyl ester,
6,6-thienyl C61 butyric acid methyl ester, 6,6-phenyl C61
butyric acid methyl ester, 6,6-phenyl C71 butyric acid methyl
ester, and N-methyl fulleropyrrolidine. Two sampling
campaigns involved the collection of 27 river samples and 12
sediment samples from 12 sampling points along the river.
Results showed that C60 was the most prevalent fullerene, with
concentrations of 8 pg/L−59 ng/L and 108−895 pg/g (dry
weight) in water and sediments, respectively; C70 fullerene, 6,6-
phenyl-C61 butyric acid methyl ester, and N-methyl full-
eropyrrolidine were also found. Higher levels were observed
during a time of drought in 2015 compared to 2014, which
experienced severe flooding.
I DOI: 10.1021/acs.analchem.9b05269
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Sewage spills were the focus of another study by Loosli et al.,
who used multielement single particle (SP)-ICPMS and
transmission electron microscopy (TEM) to measure TiO2
engineered NPs and other metals released from these spills.49
These types of sanitary sewer overflows are a common
problem in the U.S. and tend to occur during high rain events,
when the sewer system cannot keep up with the high flow of
water. High levels, up to 100 μg/L, of TiO2 NPs were found in
the sewage-impacted surface waters, and TEM analysis
indicated that they were regular-shaped. Results also showed
that natural TiO2 particles were often associated with at least
one of the following elements: Al, Fe, Ce, Si, La, Zr, Nb, Pb,
Ba, Th, Ta, W, or U.
Wang et al. conducted an interesting long-term study
investigating the transfer of silver from soil to the food chain
after 20 years of field applications of sewage sludge.50 This field
experiment began in 1942 in the U.K. and was originally
designed to investigate the effects of manure (including sewage
sludge) on soil organic matter and crop yield. ICPMS was used
to measure silver in samples archived from 1942 to 1961.
Results showed that repeated application of these sludges to
crop soils resulted in increases from 1.9 mg/kg (control) to 51
mg/kg. However, the majority of the silver was present as
insoluble Ag2S, which markedly reduces the bioavailability of
Ag. In addition, Ag in the archived crop samples (barley, beans,
cabbage, carrots, peas, potatoes, red beets, and sugar beets)
were <0.70 mg/kg in the edible tissues, which is much lower
levels that what would cause effects in animals or humans
(>100 mg/kg).
Fate Studies. The persistence of engineered NPs in
complex wetland mesocosms was the topic of another study by
Espinasse et al., who found that nAg, nTiO2, nCeO2, and
single-wall carbon nanotubes (SWCNTs) introduced as a
single pulse persisted in the water column for longer periods of
time, ranging from 36 h to 10 days.51 Residence times followed
the order: nAg > nTiO2 > SWCNT > nCeO2. In another
study, Liu et al. investigated the impact of surface coatings for
Ag NP dissolution rates.52 Bovine serum albumin (BSA) and
two thiolated polyethylene glycols (PEGs) of different
molecular weights (1000 and 5000 Da) were tested as model
capping agents. Tapping-mode atomic force microscopy
(AFM) was used to measure changes in the Ag NP height
over time. The surface coatings resulted in much lower
dissolution rates of 0.39, 0.20, and 0.14 nm/d for BSA,
PEG1000, and PEG5000-coated Ag NPs, respectively,
compared to the dissolution rate of 1.69 nm/d for
unfunctionalized Ag NPs. This was explained by the steric
barrier that these coatings present for mass transfer of reactants
to sites on the Ag NP surface, which diminish the dissolution
rate. However, the BSA-coated NP behavior was different, with
initial enhanced dissolution, which slowed over time.
Phototransformation of graphene oxide was the focus of
another fate study by Han et al., who used modeling to
simulate time-dependent environmental exposure concentra-
tions of graphene oxide and its major phototransformation
product in river water.53 The degree of phototransformation
was closely associated with river flow conditions, with up to
40% phototransformed under low flow conditions and only
2.5% at mean flow conditions. In addition, most of the
photoreduced graphene oxide is expected to settle in the
sediment layers. Qin et al. investigated the fate of Ag NPs
under three different water treatment preoxidants: NaClO,
H2O2, and KMnO4.54 The morphology of the Ag NPs, as
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
measured by TEM, was changed after reacting with these three
oxidants, with the PVP coating broken after reacting with
NaClO, a larger size and hexagonal (v. spherical) shape after
reacting with H2O2, and a change in shape after reacting with
KMnO4. A higher dose of oxidant, presence of Ca2+ ions, and
smaller size of Ag NPs promoted their decay. The presence of
humic acid and sulfide ions inhibited the decay, and pH also
played an important role.
■ PER- AND POLYFLUOROALKYL SUBSTANCES
Perfluorinated compounds were recently renamed per- and
polyfluoroalkyl substances (PFASs) to distinguish them from
other simpler perfluorinated compounds with only carbon and
fluorine atoms. More than 6300 PFASs are now documented,
with perfluoroalkyl carboxylic acids (PFCAs) and perfluoro-
alkanesulfonic acids (PFSAs) the most studied. PFOA and
PFOS were among the first identified in the environment and
are still widely measured, but there are many other PFASs,
including 4-carbon PFASs (e.g., perfluorobutanoic acid
[PFBA] and perfluorobutanesulfonate [PFBS]), GenX (hexa-
fluoropropylene oxide dimer acid), ADONA, and F53B, that
are replacements for PFOS and PFOA. PFASs repel both water
and grease, and their structures contain one of the strongest
chemical bonds (C−F) known in chemistry. PFASs are used in
many products, including food packaging (e.g., microwave
popcorn bags), fabrics, carpets, nonstick cooking pans, paints,
adhesives, electronics, personal care products, and firefighting
foams.
PFASs are environmentally persistent and accumulate in red
blood cells. PFASs are commonly found in blood from people
around the world, as well as in wildlife, including animals in the
Arctic that live far from PFAS sources, highlighting their
atmospheric transport. Health concerns for PFASs include
cancer, reproductive and developmental effects, endometriosis,
bioaccumulation, immunotoxicity, ulcerative colitis, and
thyroid disease. A new animal toxicology study conducted by
the U.S. EPA and the National Toxicology Program shows that
GenX exposure produces multiple effects that are similar to
prior toxicity evaluations of PFOA and PFOS, with adverse
maternal, fetal, and postnatal effects in Sprague−Dawley rats.56
PFASs can occur in the environment from their direct use
and also due to biotransformation of PFAS precursors, such as
dipolyfluoroalkyl phosphates, fluorotelomer alcohols,
perfluoroctyl sulfonamides, and sulfonamidoethanols. PFAS
contamination of biosolids can result, along with accumulation
in plants and crops when these biosolids are applied as
fertilizers. In addition, PFASs are mobile in groundwater, and
they have been measured in drinking water throughout the
world. PFOS was phased out in North America in 2002, and
PFOA was phased out in the U.S. in 2015. A new drinking
water health advisory was also recently established in the U.S.
for PFOA and PFOS: 70 ng/L for the sum of PFOA and PFOS
(www.epa.gov/ground-water-and-drinking-water/drinking-
water-health-advisories-pfoa-and-pfos). From 2013 to 2015,
PFAS concentrations exceeded this health advisory level in
drinking water systems serving ∼6 million people.55 On top of
the U.S. national guideline, seven states, Alaska, Maine,
Minnesota, New Jersey, North Carolina, Texas, and Vermont,
have their own water quality guideline levels for PFOA and/or
PFOS, ranging from 13 to 1000 ng/L. In 2019, North Carolina
set the first drinking water health goal for the new PFAS
replacement GenX, at 140 ng/L. PFOA and PFOS are
currently on the CCL-4 (www.epa.gov/ccl/contaminant-
J DOI: 10.1021/acs.analchem.9b05269
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candidate-list-4-ccl-4-0), and six PFASs were on the UCMR-
3, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluor-
ohexanesulfonic acid (PFHxA), perfluoroheptanoic acid
(PFHpA), and perfluorobutanesulfonic acid (PFBS) (http://
water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/ucmr3), such
that there are national occurrence data in U.S. drinking
water. Europe restricts the use of PFOS as part of the
European Union’s REACH program (http://ec.europa.eu/
environment/chemicals/reach/reach_en.htm), and the Stock-
holm Convention lists PFOS as a persistent organic pollutant
(POP) (http://chm.pops.int/TheConvention/ThePOPs/
ListingofPOPs/tabid/2509/Default.aspx), as well as PFOA,
and now prohibits the manufacture and use of PFOA, with a
few exceptions for use (https://www.meti.go.jp/english/press/
2019/0514_001.html). Several European countries also have
their own guidelines, including Germany, Denmark, and
Sweden.55 Moreover, many drinking water sources have been
closed down or have had advanced treatments implemented to
lower PFAS concentrations in tap water, due to exceedances of
guidelines or to application of the precautionary principle.55
On September 3, 2019, Denmark made a bold move in
announcing a ban of PFAS in paper and cardboard used in
food contact materials, effective July 2020 (www.cnn.com/
2019/09/04/health/denmark-pfas-food-packaging-ban-intl/
index.html). The European Food Safety Authority plans to
revise the tolerable intake of PFAS (www.efsa.europa.eu/en/
press/news/181213).
The relative source contribution (RSC) of U.S. drinking
water to overall PFAS exposure was estimated in a new study
by Hu et al.57 For this, 15 PFASs were measured in home tap
water samples from 225 participants in a national prospective
cohort of U.S. women in the Nurses’ Health Study. Plasma
concentrations were estimated from tap water intake and were
compared to measured plasma PFAS concentrations for a
subset of 111 participants. Tap water PFOA and PFNA were
statistically significant predictors of plasma concentrations for
women who consumed ≥8 glass of tap water per day. RSCs for
tap water contributions were 12% for PFOA, 13% for PFNA,
2.2% for PFOS, 3.0% for branched PFOS, and 34% for PFHxA.
Increased PFAS concentrations were apparent from 1989 to
2016. Overall results compared favorably with the RSC of 20
used in risk assessments for legacy PFASs by several
government agencies.
Reviews. Dauchy wrote an excellent review on the current
state of the science of PFASs in drinking water, discussing
sources and occurrence in source waters, removal efficiency in
drinking water treatment, concentrations found in tap water,
and effects of exposure to contaminated tap water, along with
current regulations and guidance values.55
McDonough et al. published an excellent overview of total
PFAS methods for water.58 Advantages and disadvantages of
each approach was discussed, along with trade-offs between
selectivity and inclusivity. Methods include combustion ion
chromatography (CIC) methods (extractable organic fluorine
[EOF] and adsorbable organic fluorine [AOF]), particle-
induced gamma ran emission (PIGE) spectroscopy, 19F NMR
spectroscopy, and the total oxidizable precursor (TOP) assay.
Some methods that are too inclusive (e.g., PIGE) do not allow
organic and inorganic fluorine to be differentiated. The TOP
assay is the most sensitive (because it is based on LC−MS/MS
for target precursors), but it is limited to compounds that
oxidize to form LC-amenable hydroxyl-radical resistant PFASs.
Thus, other nontargeted PFASs are missed. 19F NMR requires
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
extensive preconcentration to achieve sufficient sensitivity to
be practical. EOF and AOF are regarded as the best suited to
capture most PFASs (known and unknown) at sufficient
sensitivity to measure total PFAS in environmental waters.
Ateia et al. published a nice review on the overlooked short-
and ultrashort-chain PFASs, providing a summary of methods,
occurrence, removal techniques from water (and challenges),
and future research directions.59 Finally, Munoz et al. reviewed
the newer ether PFAS replacements that have been recently
discovered in the environment: GenX, F53B, ADONA, and
other emerging fluoroalkylether compounds.60 An inventory of
these novel compounds is provided, along with a review of
their occurrence, fate, effects, and analytical methods.
Discovery of New PFASs. Following up on their initial
discovery of GenX and GenX analogues, McCord and Strynar
continued to apply nontargeted screening using LC−HRMS/
MS to the Cape Fear River (North Carolina), which is heavily
impacted by fluorochemicals.61 The continued presence of
perfluorinated ether acids was confirmed, with a total of 37
chemicals and 58 isomers detected. Novel structures included
perfluorinated ether acid compounds with two acidic sites,
polyfluorinated ether acids with a single hydrogenation, and
previously unreported perfluorinated ether acids. These
compounds were monitored during a time of emission source
control. Negative mass defects that are indicative of
halogenated compounds (including fluorinated compounds)
was a key feature in the high-resolution MS data that allowed
these compounds to be spotted.
Occurrence. Source water and drinking water was the focus
of a large U.S. occurrence study by Boone et al., who measured
17 PFASs in water from 25 drinking water treatment plants
from 24 states.62 Summed PFAS levels ranged from <1 to 1102
ng/L. Median total PFAS was 21.4 ng/L in source water and
19.5 ng/L in finished drinking water. Only one drinking water
treatment plant (DWTP) exceeded EPA’s health guideline
value of 70 ng/L (sum of PFOA and PFOS). Interestingly,
DWTPs located on different large rivers showed distinct
profiles, with three DWTPs from one river dominated by
PFOA and three on the second river dominated by PFBA.
Guelfo and Adamson evaluated a national data set (the
UCMR-3) to gain insights into sources, composition, and
concentration of PFASs in U.S. drinking water.63 This data set
included 36 139 samples from >5000 public water systems,
with data on 6 PFASs (PFOA, PFOS, PFBS, PFHxS PFHpA,
PFNA). Approximately 50% of the samples with PFAS
detections contained at least 2 PFAS compounds, and 72%
of detections were in groundwater. While large drinking water
systems had the most PFAS detections, smaller systems had
higher levels (median levels of 0.12 μg/L for small systems and
0.053 μg/L for large systems). Statistical bivariate and
multivaritate analyses suggested PFAS impacts due to fire-
fighting foams and WWTP effluents. Analyses also indicated
increasing levels over time.
Drinking water in China was the focus of another study by
Li et al., who measured 17 PFASs in drinking water from 79
cities. These PFASs were ubiquitous, ranging from 4.5 to 174.9
ng/L for the sum of the 17 measured and a mean of 35.1 ng/
L.64 PFBA was the most abundant, with a median of 17.9 ng/L,
followed by PFOA, PFNA, and PFOS. Industrial sources
contributed to higher drinking water levels; population density
and gross domestic product (GDP) were also factors. Except
for PFASs in Yunnan, Jiangsu, and Jiangxi, concentrations in
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drinking water from 28 provinces were less than suggested
drinking water advisories.
Swedish groundwater and surface water was the subject of a
large PFAS occurrence study, in which 493 samples were
collected and analyzed for 26 PFAS compounds.65 Samples
were collected from surface water, groundwater, landfill
leachate, WWTP effluents, and lakes, focusing on hot spots
and drinking water sources. Highest total PFAS levels were
found in surface water (13 000 ng/L) and groundwater (6400
ng/L). PFCAs were the dominant group (64%), with high
contributions from C4−C8 (94%), indicating high mobility of
shorter chain PFCAs. The EU Water Framework Directive
concentration of 0.65 ng/L for the sum of PFOS isomers
(linear and branched) was exceeded in 46% of the samples,
and the drinking water guideline of 90 ng/L for the sum of 11
PFASs was exceeded in 3% of the samples from drinking water
sources. Branched isomers were also prevalent, including
branched perfluorooctane sulfonamide, PFHxS, and PFOS.
Groundwater near Melbourne, Australia was the focus of
another occurrence study by Szabo et al., who investigated the
impact of recycled wastewater used for crop irrigation.66 SPE
and LC−MS/MS was used to measure 20 PFASs (11 PFCAs,
8 PFSAs, and 1 fluorotelomer sulfonate). PFASs were detected
in all groundwater samples, with total levels ranging from
<0.03 to 74 ng/L. Highest levels were found at the center of
the irrigation district, with PFOS the most detected, followed
by PFBS, PFOA, and PFBA. These levels were greater than
normal background groundwater levels and were typical of
WWTP effluents, indicating that recycled wastewater can be a
source of PFAS contamination in groundwater.
A firefighter training area was the focus of a new study by
Dauchy et al., who investigated PFAS in runoff water and
wastewater.67 More than 50 PFASs were measured in 43 water
samples using target and suspect screening with LC−MS/MS.
Results showed an overwhelming contribution of fluoro-
telomers, indicating that PFAS emissions from the use of
firefighting foams cannot be monitored by only measuring
PFCAs. Total mass discharge to the river and lagoon was 387
and 56 kg per year, respectively. In a related study, Dauchy et
al. investigated the seepage of PFAS compounds through soil
into groundwater at a firefighter training site that had been
used for more than 3 decades.68 A total of 44 soil cores and 17
groundwater samples were collected, and PFOS, 6:2
fluorotelomer sulfonic acid (6:2 FTSA), and 6:2 fluorotelomer
sulfonamide alkylbetaine (6:2 FTAB) were the most
predominant PFASs in the surface soil. Deep seepage (15
m) into the groundwater was found for many PFASs, with
distinctive PFAS compounds that are present in the firefighting
foams. Levels ranged from 300 to 8300 ng/L, despite the
presence of clay layers below the soil surface.
Snow was analyzed in a study by Wang et al. to investigate
its use as an atmospheric tracer for tracking interactions of air
circulation patterns in western China.69 Large spatial differ-
ences were observed, with long-chain PFASs (>10 carbons) in
the north and west, and short-chain PFASs (<6 carbons) in the
south and east. Results demonstrated that snow could be used
to track the interactions between the westerly winds and the
Indian Monsoon.
Two interesting studies investigated PFASs in water and
home vegetable gardens. In the first, Bao et al. measured 10
PFASs in groundwater and homegrown vegetables and eggs in
local residences near a fluorochemical industrial park in
China.70 PFBS and PFOA were predominant in the ground-
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
water, with maximum concentrations of 21.2 and 2.51 μg/L,
respectively. Short-chain PFASs (including PFBS and PFBA)
were found as major contaminants in the vegetables and eggs
from the residential gardens. Statistically significant relation-
ships were found between PFAS levels in groundwater and in
the vegetables. In the other study from the U.S., PFBA was the
primary contaminant found in outdoor tap water sampled,
followed by perfluoropentanoic acid (PFPeA). While PFBA,
PFOA, and PFOS were present at higher levels in soil samples,
only PFBA was readily translocated into plants.71 Results
demonstrate that short-chain PFAS have the highest potential
to translocate to and bioaccumulate in edible plants.
Fate. Interesting fate studies continue to be published for
PFAS. For example, Yi et al. examined the biotransformation of
aqueous film forming foam (AFFF) component 6:2
fluorotelomer thioether amido sulfonate (6:2 FtTAoS) under
sulfate-reducing conditions in microcosms.72 Suspect screening
and nontarget analysis were used with LC−HRMS/MS to
identify the transformation products. Results showed that 6:2
FtTAoS transformed primarily to 6:2 fluorotelomer thioether
propionate (6:2 FtTP), which was stable, indicating that the
thioether group is stable under sulfate-reducing conditions.
However, the TOP assay indicated that only 67% of the initial
PFAS mass was recovered in the microcosms, suggesting
additional formation of volatile transformation products or
products not detected with the TOP assay.
The distribution of PFASs between bulk water and
suspended particles, and pore water and benthic sediments
from a tropical urban water body were the focus of another fate
study by Chen et al.73 A total of 21 PFASs were measured,
including PFCAs, PFSAs, perfluorooctane sulfonamides, N-
alkyl perfluoroalkane sulfonamide-ethanols, bis-
(perfluorooctyl)phosphinic acid, and 5:3 fluorotelomer
carboxylic acid. Distribution of PFASs between the sorbed
and dissolved phase was largely dependent on perfluooralkyl
chain length, with shorter chain PFASs (≤7 carbons) mostly in
the dissolved phase, and longer chain compounds mostly in
suspended particles and sediment. Suspended particles had
much higher concentrations of PFASs (by a factor of >100)
compared to benthic sediments. Pore water had 1−2 times
higher concentrations than that of overlying bulk water. Results
indicate that the distribution of PFASs in the field, especially
for suspended particles and bulk water, cannot be represented
by lab results and that using water samples from the bottom
layer to estimate pore water concentrations could lead to
biased results.
New Methods. Many new methods have been developed
for PFASs the last 2 years, with an emphasis on short-chain
analogues. For example, Yeung et al. developed an ultra-
performance convergence chromatography (UPC2)-ESI-MS/
MS method for the simultaneous analysis of ultrashort-chain
PFASs (two- and three-carbon) and longer chain PFASs
(PFCAs, PFSAs, perfluorophosphonates (PFPAs), perfluoro-
phosphinates (PFPiAs), and polyfluoroalkyl phosphate diesters
(diPAPs)) in river water and rain samples.74 As mentioned
earlier in the Chromatography Trends section, “convergence
chromatography” is mostly just a new name for supercritical
fluid chromatography (SFC), except that it also allows the use
of organic cosolvents in addition to supercritical CO2.. UPC2
enabled the separation of the ultrashort-chain PFASs that
would normally not be retained on an LC column, and it also
allowed the separation of longer chain PFASs (4−14
carbons).74 Several columns were investigated, and the Torus
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DIOL column, along with a gradient elution with supercritical
CO2 and 0.1% NH4OH in methanol, offered the best
separations for the 29 PFAS analytes. Low detection limits
(e.g., 0.4 pg of trifluoroacetate [TFA] on-column), narrow
peak widths (3−6 s), and a short run time (8 min) were
achieved, along with good linearity and repeatability. Results
showed that ultrashort-chain PFCAs (2−3 carbons) accounted
for more than 40% of detectable PFASs in rain. The sources of
TFA and other short-chain PFASs are not clear.
Janda et al. created a simple and robust method that can
measure seven short-to-medium chain PFCAs (C2−C8).75
Oasis WAX SPE with a sample pH of 3.9 was optimal for
extraction, and a core−shell C18 LC column with an acidified
eluent was optimal for LC separation. LOQs of 0.6−26 ng/L
were achieved, along with mean recoveries of 83−107%. TFA
and PFOA were the dominant analytes, with TFA even more
ubiquitous, with levels up to 17 μg/L in drinking water,
groundwater, and surface waters not known to be impacted by
PFASs.
McCord and Strynar from the U.S. EPA published a
combined target-nontarget screening HRMS method and
described their workflow with a step-by-step Standard
Operating Procedure (SOP), along with a 9 min video that
shows all of the steps, including sampling, sample preservation,
solid phase extraction, creation of calibration curves, and
analysis using HRMS (quantitative and qualitative nontarget
identification), including software steps.76 This is a must-watch
for anyone wanting to learn these PFAS methods.
A total of 53 legacy and emerging PFASs from 14 compound
classes was the focus of another method by Coggan et al.77
SPE with a weak anion exchange cartridge and LC−MS/MS
was used for analysis. Method quantification limits ranged from
0.35 to 26 ng/L, method detection limits ranged from 0.28 to
18 ng/L, and a short 14 min analysis was achieved. This
method enabled the detection of FTCAs, perfluorooctane
sulfonamides (FOSAs), PFPAs, and diPAPs for the first time in
Australian WWTPs, where levels up to 193 ng/L were found.
Differential ion mobility (DIMS)-MS was used in a new
method by Ahmed et al. to separate PFAS isomers without the
use of traditional chromatography (e.g., LC).78 This separation
occurs in milliseconds and allowed the separation of linear,
secondary-branched, and tertiary-branched isomers of PFOA
and PFOS, including ones that differ by the position of a single
perfluoromethyl group. A DIMS carrier gas composed of 50:50
He/N2 was important for their separation.
A molecularly imprinted polymer (MIP) electrochemical
sensor was the focus of a new method for PFOS.79 The sensor
is based on a gold electrode modified with a thin coating of
MIP, prepared by anodic electropolymerization of o-phenyl-
enediamine in the presence of PFOS as the template.
Detection limits of 0.04 nM were achieved, along with good
selectivity and reproducibility.
Fluorine-specific detection with LC−ICPMS/MS was used
in a new nontarget method for PFASs.80 Postcolumn addition
of a barium solution allowed the conversion of F− into a
detectable BaF+ species in the argon plasma of the ICPMS.
Element-specific detection limits of 0.49 mg of F/L were
achieved. The analysis of spiked river water at sub-μg/L levels
gave acceptable recoveries using SPE for preconcentration.
A new adsorbable organic fluorine (AOF) method using
combustion ion chromatography (CIC) was developed by
Abercron et al.81 Activated carbon AOXpack Premium was
used as the adsorbent, and recoveries of 16−121% were
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
achieved for 25 PFAS reference standards. The method was
demonstrated on surface waters, municipal and industrial
wastewaters, and groundwaters. Levels up to 24.5, 8.5, and 555
μg/L were found for surface water, municipal wastewater, and
industrial wastewater, respectively.
A novel passive sampling device was used in a new method
by Kaserzon et al. for time-integrative monitoring of PFASs in
contaminated groundwater.82 The passive sampler was made of
microporous polyethylene and was deployed for 83 days and
calibrated at five AFFF impacted groundwater locations. Using
this passive sampler, 17 PFASs were detected in the
groundwater, compared to only 15 from grab samples. At the
same time, the time-weighted average water concentrations
were strongly correlated with grab samples. In addition to
allowing an integrative sampling over time, the passive sampler
also showed higher sensitivity for 4:2 FTS and FOSA.
Finally, Lath et al. investigated sorption of PFOA on
labware, including filter membranes, polypropylene, poly-
styrene, polycarbonate, and glass tubes.83 This is important
because significant losses due to sorption have been observed
previously but has not been investigated in detail systemati-
cally. Sorption onto the different filter membrane types ranged
from 21 to 79%, and sorption on different sample tubes ranged
from 14 to 45%. Greater PFOA sorption was found for
polypropylene tubes; sorption losses decreased when concen-
trations of PFOA increased, indicating that binding sites on the
tube walls could reach saturation.
■
PHARMACEUTICALS AND HORMONES
Increasing population and economic activities are leading to an
increase of anthropogenic contaminants including pharma-
ceuticals and hormones into the environment that could
potentially produce adverse human and ecological health
effects. For example, observed effects include behavioral
changes, morphological anomalies, and survival of fish as a
result of environmental exposure to antidepressants84 and
increasing antibiotic resistance bacteria caused by antibiotics in
the environment.17 There are more than 3000 active
pharmaceutical ingredients in the market. Pharmaceuticals
are released to the environment by various routes including
municipal wastewater effluents, industrial discharge, urban
runoff, precipitation, and landfill leaching, as discussed by
Wilkinson et al.85 Environmental pollutants can undergo
chemical and biological transformations to produce trans-
formation products (TPs), bioaccumulate in organisms, adsorb
to natural (i.e., sediments) or anthropogenic materials (i.e.,
microplastics), and volatilize to the atmosphere. In this
complex scenario, the authors identified four major challenges
that include the identification of new contaminants and their
transformation products, careful fate and toxicity studies of
compounds used to replace other contaminants (i.e., PFASs),
the role of antibiotics in antimicrobial resistance, and studies
on the fragmentation and fate of plastics.
There is also a growing concern on the possible human
health effects from long-term exposure to low-level concen-
trations of pharmaceuticals in the environment. To address this
concern, the European Commission published in early 2019
the European Union Strategic Approach to Pharmaceuticals in the
Environment that proposes to (1) promote prudent use of
pharmaceuticals, (2) support the development of pharmaceut-
icals that are less harmful for the environment, (3) improve
environmental assessment, (4) improve the management of
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waste, (5) expand environmental monitoring, and (6) identify
knowledge gaps.86
Chromatographic methods coupled to mass spectrometry
are the primary analytical techniques used to identify and
quantify pharmaceuticals, hormones, and their metabolites and
TPs. Liquid chromatography followed by tandem mass
spectrometry is still the preferred method to study environ-
mental pollutants in liquid and solid matrixes, as reported by
Carmona and Picó.87 Their literature review revealed that 92%
of studies use liquid chromatography to separate analytes
where most studies use tandem mass spectrometry (MS/MS)
technology (50%), followed by high-resolution quadrupole
time-of-flight (QTOF) technology (24%) and less frequently
Orbitrap mass spectrometers, linear ion traps, and single
quadrupoles.
Environmental Occurrence and Transportation Path-
ways. Stormwater may represent a major urban contribution
and transportation pathway for environmental pollutants.
Fairbairn et al. investigated the occurrence and removal of
384 contaminants in three large stormwater pipes and three
pairs of iron-enhanced sand filters in the major metropolitan
area of Minneapolis-St. Paul, Minnesota.88 A total of 31
contaminants were detected in ≥50% of the samples, including
pharmaceuticals, personal care compounds, pesticides, flame
retardants, plasticizers, and polyaromatic hydrocarbons
(PAHs), among others. The study found a high seasonal and
site-type dependence for several contaminant concentrations,
for instance a warm-weather runoff-based profile included
herbicides. Samples from winter or late summer contained
hydrophobic compounds (PAHs) that suggested less runoff-
dependent sources such as sediments. A third profile indicated
a mixed-source (runoff, nonrunoff, or atmospheric) that
included pharmaceuticals and personal and consumer prod-
ucts. Stormwater concentrations of acetaminophen, caffeine,
metformin, and N,N-diethyl-meta-toluamide (DEET) were
similar to those found in wastewater effluents. These results
indicate that stormwater loading into rivers might be higher
than that of wastewater effluents. The authors highlight that
more studies that investigate pharmaceutical occurrence and
removal in stormwater are needed to understand the effects of
stormwater discharges to surface waters. Finally, the study
found that, iron-embedded sand filters significantly removed
14 of the 48 most detected contaminants with median removal
efficiencies of 28−100%.
Pharmaceuticals may also spread to the environment
through atmospheric particulates and precipitation according
to Ferrey et al.89 LC−MS/MS and GC−MS were used to
analyze 126 chemicals in air and precipitation samples in the
metropolitan area of Minneapolis-St. Paul, Minnesota. Four
antibiotics (ofloxacin, ciprofloxacin, enrofloxacin, and sulfame-
thoxazole) were found in precipitation with a maximum
concentration of 10 ng/L and only ofloxacin was detected in
air. Iopamidol (X-ray contrast media) and naproxen (anti-
inflammatory drug) were quantified in snow with maximum
concentrations of 228 and 3.74 ng/L, respectively. Bisphenol
A, DEET, and cocaine were the most frequently detected in
both air and rain samples. Although sources of these chemicals
are not well understood, it was suggested that land application
of biosolids produced from wastewater treatment plants may
generate particulates that can be transported through air.
Reclaimed wastewater is increasingly being used for
agricultural irrigation in regions where water scarcity is a
problem. Carter et al. used a source-pathway-receptor analysis
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
to develop a framework to evaluate the impacts of
pharmaceuticals in reclaimed wastewater on environmental
and human health.90 Although there is a good understanding
of pharmaceuticals in wastewater, the authors identified
knowledge gaps on how pharmaceuticals are taken up by
receptors (humans, wildlife, livestock, plants, aquatic species,
and soil microorganisms) and the effect of metabolites on the
various receptors. Furthermore, countries with limited infra-
structure for wastewater treatment are increasingly using raw
sewage or partially treated wastewater on agricultural fields.
Lesser et al. investigated the occurrence of 218 contaminants
in Mezquital Valley, Mexico, where untreated wastewater is
directly applied to 80 000 ha of agricultural fields.91 The study
analyzed wastewater, spring water, and groundwater from 30
different sites. Of the 65 pharmaceuticals and 3 hormones
detected in wastewater, metformin (1.3−107 μg/L), caffeine
(0.15−42.8 μg/L), and acetaminophen (<14.8 ng/L−67.2 μg/
L) were the highest detected. However, in groundwater and
spring water, the most frequently detected compounds
included carbamazepine (<1.8−99.7 ng/L), sulfamethoxazole
(<1.3−46.6 ng/L), DEET (<0.4−5280 ng/L), and benzoyl-
ecgonine (<0.3−0.99 ng/L), due to their low adsorption to
soils.
An increasing number of studies in regions with insufficient
wastewater treatment have reported high concentrations of
pharmaceuticals and hormones in surface waters92−95 and
drinking water.95 Yao et al. conducted a nationwide occurrence
study of pharmaceuticals in Chinese rivers across 31
provinces.92 The authors found that 54% of drugs detected
in rivers originated from untreated raw sewage, which was
estimated to be more than 50% of the total wastewater
discharge to rivers. In the city of Cuernavaca, Mexico, Rivera-
Jaimes et al. found high levels of analgesic and anti-
inflammatory drugs naproxen (732−4880 ng/L), acetamino-
phen (354−4460 ng/L), diclofenac (258−1398 ng/L), and
lipid regulator bezafibrate (826−2100 ng/L) in surface waters
before and after a wastewater treatment plant (WWTP).94
Although wastewater treatment was able to remove pharma-
ceuticals (>98%), high concentrations were still persistent in
surface waters after the WWTP, which indicated additional
sources of raw sewage flowing into the river. Furthermore,
wastewater-impacted surface waters may be used as drinking
water sources. Reis et al. investigated the occurrence of 28
drugs in six drinking water treatment plants in the state of
Minas Gerais, Brazil.95 The authors found unusually high
concentrations (up to 11.9 μg/L) of pharmaceuticals in source
waters used for drinking water, and these compounds had
varying removal efficiencies (32−100%) in drinking water
treatment plants. Steroids betamethasone and prednisone,
antifungal fluconazole, and lipid-regulator atorvastatin were
among the most persistent in drinking waters, with
concentrations ranging from <5 ng/L to 6.3 μg/L. In a recent
review by Peña-Guzman, hormones estrone and 17β-estradiol
and endocrine disruptor bisphenol A were the most commonly
detected in Latin America.96
Biological Treatment and Transformation Products.
Pharmaceuticals are removed from wastewater primarily by
two processes: biodegradation and bioabsorption.97,98 Costa et
al. provided an overview of current biological processes for the
removal of pharmaceutical compounds with a special focus on
these two processes.97 Oberoi et al. reviewed the behavior and
removal of different antibiotics in biological treatment systems
with an emphasis on the biodegradation and adsorption
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mechanisms.98 Both reviews suggested that a higher biomass
content in bioreactors may increase pharmaceutical removal.
Increased biomass can be achieved by the addition of free-
floating plastic media (fixed-film systems) where micro-
organisms can attach and grow.99 Shreve et al. evaluated the
removal of 98 environmental pollutants in 6 full-scale WWTPs
with fixed-film systems and found a higher removal for 17
compounds, including atenolol, diclofenac, gemfibrozil, DEET,
4-nonyphenol, and 4-tert-octylphenol, as well as chlorinated
flame retardants, compared to a conventional wastewater
treatment bioreactor. However, biological treatment utilizes a
wide range of unspecified microorganisms to biodegrade a
wide variety of contaminants. As an alternative, isolated
enzymes that target specific chemicals might provide a more
systematic approach. Stadlmair et al. reviewed the current
research on enzyme biodegradation and target enzyme
screening options with a special focus on MS-based and
high-throughput technologies.100
The assessment of TPs of target pharmaceuticals produced
by new biological treatments is a challenging task because TPs
are often unknown compounds. A novel automated suspect
screening method was developed by Jaén-Gil et al. that
comprehensively evaluated the TPs for nine antibiotics
generated in microalgae wastewater treatment.101 The analysis
was carried out with a direct injection into an online turbulent
flow LC−HRMS followed by automatic data processing for
analyte identification. The software simulation program
predicted TPs by applying 17 potential chemical trans-
formations including methylation, oxidation, and reduction
hydroxylation. This new methodology was able to tentatively
identify 40 TPs from experimental batch reactors treated with
microalgae (with light) and without microalgae (light and dark
conditions). Results suggested that microalgae were able to
biodegrade macrolides but were not able to biotransform
fluoroquinolones.
Selective biodegradation of enantiomeric pharmaceuticals
can occur in biological wastewater treatment, as investigated by
Andrés-Costa et al.102 Racemic mixtures of enantiomers (R)-
fluoxetine and (S)-fluoxetine were exposed to river and
activated sludge microsomes. River microsomes were not
very selective in their biotransformation. However, activated
sludge microorganisms preferentially biodegraded the (S)-
fluoxetine to metabolite (S)-norfluoxetine, thereby selectively
enriching (R)-fluoxetine and metabolite (S)-norfluoxetine in
treated waters. Ecotoxicological tests showed a distinct and
higher enantiomer-specific toxicity for (R)-fluoxetine and (S)-
norfluoxetine in Tetrahymena thermophila, a protozoan
prevalent in activated sludge. No enantiomer-specific toxicity
was observed for Daphnia magna, a water flea species
commonly used for toxicological testing. These results suggest
that although the general removal of fluoxetine might indicate
a lower biological impact overall, the enrichment of the
enantiomer with a higher toxicity may in fact produce higher
toxicological effects for specific organisms.
Pharmaceuticals and personal care products are biotrans-
formed in WWTPs from parent compounds to metabolites.
For example, triclosan can undergo an alkylation reaction to
form methyl triclosan. However, Fu et al. observed for the first
time that plant cells and whole plants can uptake methyl
triclosan and convert it back to the original parent compound,
triclosan.103 Arabidopsis thaliana cells were exposed to methyl
triclosan and a steady decline was observed in the growth
media (within 12 h), with a concurrent uptake of methyl
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
triclosan in cells. The triclosan concentration in the cells
increased over time, reaching a maximum of 15% molar
conversion of methyl triclosan to triclosan after 144 h of
incubation time. Lettuce and carrots were also exposed to
methyl triclosan under hydroponic conditions. Triclosan was
found in leaves and roots, with slightly higher concentrations
in lettuce compared to carrots, confirming that whole plants
can also convert methyl triclosan to triclosan.
Abiotic Transformations. The natural attenuation of
antibiotics in the environment can occur by biotic or abiotic
processes, as investigated by Li et al.104 The authors conducted
a series of experiments to investigate the degradation of
sulfamethoxazole and formation of TPs by direct and indirect
photodegradation, hydrolysis, and microbial and bacterial
degradation. Results were analyzed and modeled by path
coefficient analysis that quantified the cause and effect between
the contributions of different degradation processes in the
attenuation of sulfamethoxazole. The model suggested that
direct and indirect photodegradation were the major pathways
of sulfamethoxazole degradation. Additionally, toxicity pre-
dictions suggested that TPs emerging from photodegradation
were more toxic than those from biodegradation.
Willach et al. investigated the phototransformation of
sulfamethoxazole by natural light and several UV light sources
commonly used in drinking water treatment.105 Compound-
specific stable isotope and HRMS were used to identify the
TPs and determine the isotopic fractionation produced by each
light source. Isotopic fractionation occurs when lighter
isotopes react faster than heavier isotopes (normal effect) in
a chemical reaction or vice versa (inverse effect). Results
showed that isotopic fractionation occurred when UV-B and
UV-A wavelengths were included in the light source. Isotopic
fractionation was not observed for UV-C and was not affected
by pH-dependent speciation. However, it was found that the
neutral form of sulfamethoxazole degraded faster than its
anionic species.
Two studies investigated the role of reactive oxygen species
and reactive nitrogen species on the photodegradation of
sulfonamides. Ge et al. found that the hydroxyl radical (•OH)
was highly reactive toward the neutral and anionic species of
sulfonamides, while singlet oxygen (1O2) reacted faster with
the anionic form of most sulfonamides.106 Identification of TPs
show that the 1O2 oxidation reaction occurs at the amino
moiety of the molecule, whereas •OH will undergo multiple
hydroxylation. Results also suggested that 1O2 has a higher
contribution than •OH to the overall phototransformation of
sulfonamides under sunlit waters. Scholes et al. found that
nitrate and nitrite-sensitized photolysis of sulfamethoxazole
produced TPs that were not identified during direct photolysis
or reaction with •OH.107 The new TPs incorporated a nitroso
group into their molecule. The authors indicated that nitrogen
dioxide (•NO2), produced from the reaction of nitrite and
•
OH, is a possible key intermediate that leads to previously
unidentified TPs.
Arsand et al. investigated the degradation and TPs of
antibiotics amoxicillin and ampicillin by photolysis.108 The
authors tentatively identified more than 65 TPs using an
Orbitrap high-resolution mass spectrometer. The TP database
was used to analyze the composition of industrial wastewater
from a pharmaceutical company that produced these anti-
biotics. This study tentatively identified 15 TPs in wastewater
influents. After wastewater treatment (pH adjustment,
coagulation, decantation, aeration, and UV photolysis), six
O DOI: 10.1021/acs.analchem.9b05269
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amoxicillin TPs were still detected and all ampicillin’s TPs
were completely degraded. These results suggest that the
treatment of pharmaceutical wastewater was efficient in the
degradation of TPs of amoxicillin and ampicillin.
Cephalosporins are beta-lactam antibiotics widely used to
treat human and veterinary infections. Although cephalosporin
antibiotics have been considered not to significantly affect the
aquatic environment, knowledge on their degradation, TPs,
and ecological impact is limited and should not be dismissed as
unimportant.109 Ribeiro et al. investigated the degradation of
two cephalosporin antibiotics, ceftiofur and cefapirin, by
hydrolysis and photolysis.110 The authors found that both
compounds showed base-catalyzed hydrolysis and degraded in
a few minutes at pH > 11. At neutral conditions, the half-life of
ceftiofur was 1.4 and 14.7 days in buffered and natural waters,
respectively. Results suggested that ceftiofur has strong matrix
stability. In contrast, cefapirin showed similar half-lives (3 and
4.2 days) in these same matrixes. High photodegradation rates
were observed for both antibiotics.
Elimination/Reaction During Oxidative Water Treat-
ment. Ozonation is often followed by biological treatment to
eliminate products formed during ozonation. Zucker et al.
investigated the degradation of the antidepressant venlafaxine
and formation of N-oxide TP norvenlafaxine, throughout
ozonation and biological post-treatment.111 The authors found
that norvenlafaxine forms and subsequently degrades during
ozonation of the secondary effluent. The biological stability of
norvenlafaxine was higher than venlafaxine, its parent
compound, which indicates that the TP is poorly removed in
biological systems. Pilot well studies confirmed that
norvenlafaxine transforms back to its parent compound and
remains persistent for a longer time.
The degradation of 30 different pharmaceuticals by a
combined ozonation and electrolysis treatment (E-peroxone)
was investigated by Li et al.112 E-peroxone produces hydrogen
peroxide in situ which leads to the generation of •OH radicals
that enhance the removal of target pharmaceuticals. A
synergistic effect was observed for pharmaceuticals with
carboxylic (i.e., clofibric acid, gemfibrozil) and amide groups
(i.e., chloramphenicol, bezafibrate), which had poor removals
with only ozonation or electrolysis alone.
Monochloramine (NH2Cl) is formed when chlorine is
added to ammonia-containing waters in wastewater reuse
applications. There has been an increasing interest in
combining UV/NH2Cl for the elimination of pharmaceut-
icals.90 Sun et al. investigated the removal of triclosan,
carbamazepine, sulfamethoxazole, 17β-estradiol (E2), and
ethinyl estradiol (EE2) by UV/NH2Cl.113 The authors found
that overall removal was mainly attributed to •OH, •Cl, and
direct photolysis. However, reactive nitrogen species were
highly reactive toward the phenolic groups of hormones E2
and EE2, leading to significant degradation compared to UV or
NH2Cl alone.
Luo et al. reported the degradation of pharmaceuticals in
urine by ferrate (VI).114 Urine can be collected through urine-
diverting flush toilets that could potentially be used for
pharmaceutical removal and nutrient recovery processes. High
concentrations of ammonium (0.5 M) had a strong scavenging
effect, but at lower concentrations (<0.25 M), ammonium
enhanced the degradation of pharmaceuticals. Bicarbonate was
found for the first time to significantly promote the oxidation
of aniline-containing sulfonamide antibiotics by forming a
stable Fe(V) intermediate in situ.
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
Hormones. Yagishita et al. developed a molecular
imprinted polymer (MIP) that mimics an estrogen receptor
to selectively adsorb environmental estrogens including E2 and
estriol (E3) from sewage samples.115 The extract obtained by
MIP exhibited estrogenic activity tested with the in vitro yeast
two-hybrid (Y2H) bioassay. In contrast, the fraction that was
not adsorbed by MIP showed no estrogenic activity. LC-
QTOF-MS analysis of MIP and styrene-divinylbenzene (SDB)
resin extracts showed 75% less peaks for MIP extracts
compared to SDB extracts that led to the tentative
identification of two nontarget estrogens, equol and 6,8-
dichlorogenistein. These two compounds were not observed in
SDB extracts, possibly due to ion suppression.
Shen et al. developed an analytical method using LC−MS/
MS to quantify 61 natural and synthetic progestins and their
derivatives in river water and wastewater effluents.116
Detection limits were 0.06−0.6 ng/L and 0.03−0.40 ng/L
for wastewater effluents and river waters, respectively. River
waters from Beijing, China, were evaluated, and natural
progestin metabolites were found at levels 63 times higher
than the parent compound. In this study, synthetic
progesterone derivatives were detected for the first time.
Antibiotics. Kim et al. reviewed analytical methods used
for the detection of veterinary antibiotics and highlighted the
importance of standardized analytical procedures for environ-
mental monitoring.117 The same group developed an online
solid phase extraction (SPE)-HRMS method for the
quantification of 18 veterinary antibiotics from eight different
chemical classes.118 Method detection limits ranged from 0.2
to 11.9 ng/L. Trimethoprim was quantified in groundwater
near KyungGi-Do, South Korea, at 4 ng/L. Clopidol,
flumequine, and sulfadiazine were detected in river water
with concentrations ranging from 8.23 to 67.8 ng/L.
Wastewater effluents also contained four antibiotics (amox-
icillin, fenbendazole, lincomycin, and trimethoprim) at
concentrations from 1.26 to 128 ng/L.
Suspect Screening. Alygizakis et al. conducted a
retrospective analysis of HRMS data for water samples from
14 countries analyzed in 8 reference laboratories. 119
Advantageously, retrospective analysis of archived data allows
for the possibility of establishing temporal and spatial
occurrences of new contaminants through suspect screening.
For example, several surfactants such as polyethylene glycols
were the most frequently detected compounds, suggesting
widespread occurrence. Two subsequent studies focused on
standardizing HRMS data and LC analyses to support
retrospective suspect screening more efficiently. The Norman
platform was developed for archiving raw MS data and
chromatographic information in a standard format. 120
Retention time prediction models were developed based on
the chromatographic separation of 2793 analytes with
hydrophilic interaction and reversed phase liquid chromatog-
raphy in positive and negative ESI modes. Retention time
prediction models can help facilitate identification of new
contaminants by nontarget analysis of water samples.121
Psychoactive Pharmaceuticals and Illicit Drugs. Pavla
et al. published a review on the effects of antidepressants on
aquatic animals, including invertebrates, fish, and amphib-
ians.122 The authors report that based on current studies,
antidepressants in surface waters are able to affect the behavior,
reproduction, development, and survival of aquatic inverte-
brates and vertebrates. For example, venlafaxine affected the
behavior of fish and has the potential to reduce their survival.
P DOI: 10.1021/acs.analchem.9b05269
Review
Tricyclic antidepressants resulted in a significant increase in
fish mortality, development retardation, morphological anoma-
lies, and pathological changes in various organs. In a recent
environmental occurrence and risk assessment study of
psychoactive drugs in coastal waters, it was found that
antidepressants venlafaxine, citalopram, sertraline, and a
methadone metabolite were present in concentrations that
could potentially cause chronic effects to exposed organisms.99
Tisler et al. investigated the TPs of fluoxetine by
photodegradation and biodegradation in zebrafish embryos.123
TPs were identified using LC−HRMS in positive and negative
ESI modes. Under direct and indirect photolysis, fluoxetine
undergoes O-dealkylation, hydroxylation, substitution, and N-
acylation to form 26 TPs. Photodegradation was enhanced at
higher pH, where the neutral species of fluoxetine and neutral/
anionic primary TPs are predominant. Furthermore, 10
metabolites were detected in zebrafish embryos, and 7 of
these were also identified as TPs from photodegradation.
Illicit drugs in drinking water were first reported 10 years
ago, according to a recent review by Davoli et al.124 Although
drugs of abuse have been reported at trace levels in drinking
water, the authors highlight that the environmental and health
risks still remain largely unknown. Like most anthropogenic
substances, illicit drugs enter the water cycle through
wastewater effluents discharged to the environment. Kriz-
man-Matasic et al. conducted an 8-year study that monitored
the temporal variability of illicit drugs in wastewater in the city
of Zagreb, Croatia.125 Wastewater analysis showed that the
most consumed substance was cannabis, followed by heroin,
cocaine, and amphetamine. Throughout the 8-year study
period, the consumption for most illicit drugs increased, except
for heroin, which was found to decrease with an associated
increase of methadone, a therapy drug used to treat heroin
addiction.
Opioids. In recent years, prescribed opioids have attracted
public attention due to their strong addiction tendencies that
have led to a sharp increase in deaths caused by opioid
overdoses. Krizman-Matasic et al. developed an analytical
method for the quantification of 27 opioids and their
metabolites using LC−MS/MS.126 Method quantification
limits were between 0.1 and 3.5 ng/L in river water and
wastewater (raw and treated). Tramadol, codeine, morphine,
methadone, and their metabolites were the most prevalent,
with a wide range of concentrations up to 859 ng/L. In another
study, Campos-Mañas et al. conducted a retrospective analysis
of a HRMS database for surface water and wastewater samples
from the state of Minnesota in 2009.127 The database was
analyzed for more than 200 opioids and their metabolites.
Sample extracts were reanalyzed with LC−MS/MS, and 10
analytes were confirmed with pure standards, including
codeine, dextromethorphan, methadone, hydrocodone, dihy-
drocodeine, oxycodone, tramadol, and three metabolites.
Dextromethorphan and its metabolite dextrorphan, as well as
tramadol, were frequently detected in wastewater and receiving
rivers downstream.
Multiresidue Methods. Hermes et al. developed a direct
injection analytical method for 154 compounds comprised of
84 micropollutants and 70 TPs/metabolites.128 The method
was developed using LC−MS/MS with scheduled multiple
reaction monitoring. LOQs were in the lower to mid ng/L
range for most analytes, with recoveries of 75−125% from
surface waters and wastewater. Simultaneous monitoring of
contaminants and their metabolites showed that the metabolite
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
clopidogrel acid was found at higher concentrations than its
parent compound clopidogrel. Also, biological TP valsartan
acid was detected at high concentrations in surface waters and
wastewater treated effluents.
A multiresidue method developed by Casado et al. analyzed
275 pesticides and 101 veterinary drugs in 29 samples from
small waterways across 10 countries in the European Union
(EU).129,130 Samples were extracted and then analyzed with
LC coupled to Orbitrap HRMS/MS. Results showed 103
pesticides, 24 of which are banned in the EU, where herbicides
were the main contributor to the total amount of pesticides
detected in samples. Also, a total of 21 veterinary drugs were
detected, with dicloxacillin (β-lactam antibiotic) present in
two-thirds of the samples.
Mijangos et al. developed an analytical method to analyze 41
environmental pollutants using poly(ether sulfone) micro-
extraction followed by LC−MS/MS.131 A dual microextraction
was performed at two pH conditions for acidic, neutral, and
basic analytes. A direct comparison with SPE showed lower
matrix effects and a lower analysis cost. Method detection
limits were between 0.4 and 26 ng/L with good recoveries
(80−119%). Antihypertensive pharmaceuticals, irbesartan and
valsartan, were detected at high concentrations in effluents of a
WWTP and the downstream estuary in the Basque Country in
Spain. A larger temporal and spatial analysis of the region (3
WWTPs and 3 estuaries) found that antihypertensive
pharmaceuticals (irbesartan and valsartan), anti-inflammatory
drugs (diclofenac and acetaminophen), caffeine, an artificial
sweetener (acesulfame), and a corrosion inhibitor (2-
hydroxybenzothiazole) were the most prevalent com-
pounds.132 Results suggested that the studied estuaries had
two inputs from wastewater treated effluents and harbor
activities.
Zhong et al. developed an online SPE LC−MS/MS method
for the simultaneous determination of 87 environmental
pollutants, including pharmaceuticals, PFASs, personal care
products, and flame retardants with one single run lasting 30
min.133 Multiple parameters were optimized that included a
sample pH of 10 and acidic loading solvent (pH 2.7).
Detection limits ranged from 0.16 to 5.13 ng/L, with 70−
130% recoveries.
́
A study by Martinez-Piernas et al. developed a multiresidue
method to analyze 74 micropollutants in lettuce, strawberries,
and radishes that have been irrigated with wastewater-treated
effluents.134 The method was based on the QuEChERs
(Quick, Easy, Cheap, Effective and Rugged) extraction method
followed by LC−MS/MS. Method detection limits were 0.01−
2 ng/g, with 70−120% recoveries for most compounds.
Twelve compounds were detected in lettuce and radish crops,
with N-formyl-4-aminoantipyrine (analgesic metabolite) as the
most bioaccumulated compound and one which had not been
previously reported in plants. N-Acetyl-4-aminoantipyrine
(analgesic metabolite), hydrochlorothiazide (antihypertensive
drug), mepivacaine (anesthetic), and venlafaxine (antidepres-
sant) were also reported for the first time in plant crops.
New Methods and Assays. Scala-Benuzzi et al. developed
a new electrochemical paper-based immunocapture assay
(EPIA) that can detect the synthetic hormone EE2 with a
detection limit of 0.1 ng/L and a linear range of 0.5−120 ng/
L.135 This innovative assay is based on a novel capture and
preconcentration step using anti-EE2 antibodies and paper
microzones modified with silica nanoparticles. The bound EE2
is desorbed with sulfuric acid and electrochemically detected
Q DOI: 10.1021/acs.analchem.9b05269
Review
by Osteryoung square wave voltammetry (OSWV). Matrix
interferences were not significant at humic acid concentrations
up to 10 mg/L. This paper-based analytical device has the
required sensitivity to detect EE2 at environmentally relevant
concentrations and is low cost and easy to use.
Justen et al. reported the use of coated blade spray (CBS), a
SPME-based technique, for fast pharmaceutical analysis. CBS
enables the direct use of mass spectrometry using a limited
amount of solvent for analyte desorption.136 The total analysis
time was less than 11 min, with LODs lower than 50 ng/L for
nine pharmaceuticals.
Boulard et al. developed a method that separates extremely
polar contaminants, including 11 pharmaceuticals, 15
pharmaceutical metabolites and TPs, and the artificial
sweetener acesulfame.137 A large injection volume was
introduced to a hydrophilic interaction liquid chromatography
(HILIC) column followed by ESI-MS/MS. LODs for 27
analytes in treated wastewater, surface water, and groundwater
were in the low ng/L range. Extreme matrix effects were
observed for antivirals emtricitabine and acyclovir due to
coelution with nitrate and chloride. Matrix effects were
corrected with deuterated internal standards.
A rapid polarity switching method for the determination of
30 pharmaceuticals and personal care products was recently
developed by Abdallah et al. using an LC−Orbitrap-HRMS.138
The method quantified 30 acidic and basic analytes by
extracting samples with SPE followed by an LC−HRMS single
run, which rapidly switched the polarity of the ESI source.
Method quantification limits ranged between 2.7 and 83.8 ng/
L. Wastewater and surface waters from Egypt were analyzed
with the optimized method and found to contain high levels of
the analgesics acetaminophen and ibuprofen, and the
antidiabetic glyburide.
Adsorbents. Tomai et al. reported the use of oxidized
buckypaper as a sorbent membrane for a stir-disc SPE module
for the first time.139 The device consisted of a polypropylene
mesh pouch that contained the buckypaper disc. A total of 76
pharmaceuticals and pesticides were evaluated to optimize
adsorption and desorption time, stirring speed, type and
volume of solvent, and sample volume. Results showed that
pKa and log P were the main parameters that affected the
performance of the device. For instance, hydrophilic
compounds with log P < 1 were poorly adsorbed, and
hydrophobic compounds with log P > 1 exhibited higher
recoveries of 50−100%. The regenerative potential of this
device still needs to be investigated.
The use of passive samplers has been increasing over the
past 2 decades. Polar organic chemical integrative samplers
(POCIS) are used to extract hydrophilic organic contaminants
from environmental waters as described by Godlewska et al.140
The authors reviewed the different sorbents used in POCIS, as
well as exposure duration and sampling media. POCIS
provides many advantages including the ability to detect
ultratrace pollutants, ease of long-term sampling, easy
determination of time-weighted average analyte concentra-
tions, and simplicity of use. However, the authors stressed a
few drawbacks especially the need to calibrate passive probes
to determine the analyte uptake behavior or sampling rate
(before applying them in field conditions), what type of
calibration to use, and interferences from water quality
conditions (i.e., dissolved organic matter, salinity, pH, and
temperature) on analyte uptake. Li et al. proposed perform-
ance reference compound (PRC) antipyrine-d3 to correct for
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
sampling rates.141 Before exposure, passive samplers are loaded
with PRCs, and their desorption rates during analyte exposure
are correlated with analyte uptake which can be used to correct
for sampling rates.
Grandy et al. designed and tested a robust field extraction
device that aimed to minimize analyte degradation and loss
during subsequent extract transportation.142 The device
contained stainless steel bolts coated with a layer of HLB/
PAN particles that served as the extraction sorbent. Similar to
SPME, the device had a mechanism that allowed for the
exposure and retraction of the coated bolts. After exposure to
the water sample, the device enclosed the adsorbent material to
avoid analyte loss during transportation. Extracted chemicals
were stable for 12 days of storage at room temperature. The
device was tested in river waters in five different locations.
More than 80 contaminants were tentatively identified that had
a wide range of log P values.
Metal Organic Frameworks (MOFs). MOFs are hybrid
porous materials that incorporate metal-containing nodes and
organic linkers to form crystalline structures with large surface
areas. MOFs are increasingly being synthesized and tested as
adsorbents for many environmental applications including
micropollutant removal from water as described in a review by
Joseph et al.143 Although MOFs have been shown to be
effective at removing micropollutants from water, they are
significantly affected by pH due to interactions between
micropollutant speciation and the MOF functional groups.
Furthermore, more work is needed to investigate MOF
adsorption mechanisms, their capacity for regeneration, and
improved synthesis methods.
Additionally, analytical methods have been developed for the
detection of pharmaceuticals with MOF-based adsorbents.
Wang et al. developed a composite MOF/poly(vinyl alcohol)
cryogel, an elastic and chemically stable material used to
extract and analyze nonsteroidal anti-inflammatory drugs
(NSAIDs).144 Limits of detection were between 7 and 37
ng/L for four NSAIDs tested with good recoveries. This
method required less sample volume compared to other
adsorbent materials. Hou et al. proposed an indium organic
framework as a luminescent probe for the detection of
antibiotic nitrofurazone.145 The authors found that by
changing organic solvents, one of the prepared MOF materials
selectively reduced its luminescence in nitrofurazone-contain-
ing solutions. This proof-of-concept study showed that the
deactivation of luminescence from MOF materials can
potentially be used to detect drugs in environmental waters.
However, additional research is needed to detect drugs under
realistic environmental conditions.
Bioanalytical Methods. Micropollutants in water are
extensively monitored, and most methods assess the
concentrations of individual compounds. However, targeted
analyses do not account for the unknown chemical
composition of the waters. Bioanalytical tools may be used
to evaluate overall water quality by assessing the effects that
micropollutants, known and unknown, produce as described in
a recent article by Dingemans et al.146 Effect-based monitoring
was proposed as an alternative approach that can shed light on
environmental and human risks from unknown, complex, and
mixtures of micropollutants. However, careful bioanalytical
method selection (e.g., behavioral, physiological or biochem-
ical changes, mortality), improvements for high-throughput
analysis, and systematic methodologies for interpretation of
results need to be further developed.
R DOI: 10.1021/acs.analchem.9b05269
Review
Two studies have integrated chemical and bioanalytical
methods to assess water samples and provide important
insights on the biological effects that micropollutants produce.
Tousova et al. quantified 168 target compounds and used in
vitro bioassays to test for (anti)androgenic, estrogenic, and
dioxin-like effects in waters from the Bosna River in Bosnia and
Herzegovina.147 Observed estrogenicity correlated with target
natural estrogens detected in waters, however, the chemical
drivers for the other observed effects remained inconclusive.
Zhang et al. evaluated treated wastewater effluents from the
UK and Japan with an in vitro bioassay that measured the
biological activities of pharmaceuticals targeting G protein-
coupled receptors (which represents 40% of all marketed
drugs). These biological activities were then compared to
concentrations of a psychoactive (sulpiride), a gastric
(pirenzepine), and three beta-blocker drugs.148 Results
indicated that sampled wastewater effluents contained micro-
pollutants with antagonistic activities against five receptors.
The bioassay detected the presence of other unknown
compounds that target dopamine and acetylcholine receptors
other than sulpiride and pirenzepine. Also, a mixture effect was
observed against adrenergic (β1) receptors.
Sanchis et al. developed five enzyme-linked immunosorbent
assays (ELISA) for the detection of a biocide (Irgarol 1051),
two antibiotics (sulfapyridine and chloramphenicol), a
hormone (17 β-estradiol), and an algal toxin (domoic
acid).149 The ELISA bioassays were correlated against
chemical analysis by LC−HRMS with detection limits between
0.12 and 1.39 ng/L. No seawater matrix effects were observed.
Six seawater samples were tested and detected 17 β-estradiol
by ELISA and chemical analysis at a concentration of 11 ng/L.
■ DRINKING WATER AND SWIMMING POOL
DISINFECTION BYPRODUCTS
Drinking Water DBPs. Unlike other contaminants that are
manmade, DBPs are formed in situ during drinking water (or
swimming pool) treatment when disinfectants (chlorine,
chloramines, ozone, chlorine dioxide, UV) react with natural
and anthropogenic organic matter, bromide, and iodide. DBPs
are an unintended consequence of killing harmful microbes in
drinking water or in swimming pool water to make it
microbially safe. While >700 DBP have been identified, only
11 are regulated in the United States. While natural organic
matter (NOM) is the predominant precursor in DBP
formation, anthropogenic pollutants can also serve as
precursors. For example, in this review, DBPs are reported
from pesticide metabolites, antibiotics, and algal toxins. DBPs
are one group of a handful of environmental contaminants, for
which documented adverse health effects have been observed
in human epidemiologic studies. These include bladder and
colorectal cancer, miscarriage, and birth defects (including
heart defects discovered in 2016).
Reviews. Several intriguing reviews are worthy of mention.
First, Li and Mitch published an outstanding review on the
multidisciplinary challenges and opportunities for drinking
water DBPs and human health effects.150 The authors discuss
new approaches being taken by chemists, engineers, toxicol-
ogists, and epidemiologists to characterize the DBP classes
driving drinking water toxicity. One particularly intriguing
complexity discussed in this review is the dynamic picture of
DBP evolution over drinking water treatment time scales. For
example, within 1 h, initial reaction products can include
hydroxybenzaldehydes, hydroxybenzoic acids, and phenols,
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
which can further transform into an array of halophenols,
halobenzaldehydes, and halobenzoic acids, and finally into the
lower molecular weight volatile/semivolatile DBPs that are
more traditionally measured. As a result, the contribution of
DBP classes to total organic halogen (TOX) is not static; this
can impact the mixture of DBPs that we are exposed to, which,
in turn, affects epidemiologic studies. GC-high-resolution MS
has enabled a large number of lower molecular weight DBPs to
be identified, and LC−MS has enabled the DBP precursors
and intermediates to be identified, along with highly polar
compounds. This review also discusses the conundrum of
NOM (e.g., not knowing its structure to be able to predict
DBP formation), changing disinfection practices, disinfection
optimization and toxicity drivers, advances in analytical
chemistry that shows the dynamic picture of DBP evolution,
closing the mass balance by predicting DBPs, frontiers in DBP
toxicology, challenges for epidemiology, and finally, translating
research into practice. This review is a must-read for DBP
researchers.
Yang et al. reviewed current methods for analyzing drinking
water DBPs, covering GC−MS, LC−MS, ion chromatography
(IC)-MS, ultrahigh-resolution MS, TOX, and fluorescence
methods.151 Challenges cited include low recovery of certain
polar DBPs on activated carbon used in the TOX method,
which could bias the TOX analysis. The authors suggest
exploration of modified activated carbon, as well as the use of
chemical ionization, atmospheric pressure chemical ionization
(APCI), and atmospheric pressure photoionization (APPI) for
helping to uncover additional DBPs that may be missed with
traditional electron ionization and ESI techniques.
Biomarkers were the focus of another review by Chen et al.,
who outlined exposure, effect, and susceptibility biomarkers
that can be used to study health effects of DBPs.152 Exposure
biomarkers include DBP parent compounds or their
metabolites that can be measured in biological samples, such
as urine, blood, or exhaled breath. Urinary trichloroacetic acid
(TCAA) is the most used biomarker in this regard for urine,
and trihalomethanes (THMs) are typically used as biomarkers
in blood and exhaled breath. Potential new biomarkers for
urine include total organic chlorine (TOCl), bromine (TOBr),
and iodine (TOI), which capture the bigger picture of total
organic halogen exposure (beyond known target halo-DBPs),
as well as total nitrosamines (TONO), which captures the total
nitrosamine exposure (beyond just a few known nitrosamines).
Effect biomarkers include DNA damage, DNA adducts,
chromosomal damage, and immune biomarkers. Susceptibility
biomarkers, which can evaluate lifetime exposures, include
glutathione-S-transferase theta-1 (GSTT1), GST zeta-1
(GSTZ1), CYP2E1, and DNA methylation.
DBP formation mechanisms were the focus of a review by
Kimura and Ortega-Hernandez, who discussed mechanisms of
formation for nitrogen-based DBPs, including N-halamines,
nitrosamines, haloacetonitriles, haloacetamides, and halonitro-
methanes.153 DBPs from AOPs, including UV/chlorine, are
also discussed. Also, importantly, key intermediates that were
recently discovered are highlighted in these reaction pathways.
DBPs from desalinated drinking water were the focus of
another review by Powers and Gonsior, who emphasized the
use of nontarget HRMS for their identification.154 Halogenated
DBPs, as well as halogenated CHO molecular signatures,
sulfur-containing DBPs, and nitrogen DBPs were revealed by
Fourier transform (FT)-MS. Differences in seawater vs
S DOI: 10.1021/acs.analchem.9b05269
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freshwater DBP precursors are also discussed, as well as
unknown DBPs yet to be identified in desalinated water.
Iodinated DBPs were the focus of two reviews. In the first,
Postigo et al. reviewed the main formation pathways of iodo-
DBPs during disinfection and highlighted the advances in the
field, with a focus on research published the last 2 years.155
Sources of iodine, as well as anthropogenic activities (e.g., oil
and gas extraction, the dairy industry, and seawater
desalination or advanced oxidation treatment with persulfate)
that can form iodo-DBPs were also discussed. Future research
needs include accounting for the unknown fraction of TOI,
new analytical approaches and methods to discover relevant
iodo-DBPs in the DBP mixture, further investigating iodo-DBP
formation mechanisms at real environmental conditions, and
formation of iodo-DBPs in reclaimed water. In the second
review by Dong et al., the formation, occurrence, and toxicity
of known and unknown iodo-DBPs was discussed, including
formation of six groups reported to-date: iodo-methanes, iodo-
acids iodo-acetamides, iodo-acetonitriles, iodo-acetaldehydes,
and iodo-phenols.156 Sources of iodine in iodo-DBP formation
are also discussed as well as unknown iodo-DBP identification
and TOI analysis.
New Methods. The “DBP Exposome” was the focus of a
new method by Kimura et al., who developed a new GC-MS
method that can simulataneously quantify 39 priority,
unregulated DBPs from six different chemical classes,
haloacetaldehydes, haloketones, haloacetamides, haloacetoni-
triles, halonitromethanes, and iodo-THMs, and analyze
unknown DBPs with a mass accuracy of <600 ppm under
full-scan conditions.157 At the heart of this method is a new
type of time-of-flight (TOF) mass spectrometer that combines
selected ion monitoring (SIM)-level sensitivity with mass
accuracy of ±0.05 Da. Method detection limits of 3−61 ng/L
were achieved. This method offered two advantages over
traditional quadrupole-MS: (1) full-scan data, which allows the
simultaneous identification of new unknown DBPs along with
providing additional confidence for quantitative analyses and
(2) two decimal places on the m/z values, which provides
additional confidence for target analytes and provides useful
information for molecular formula assignments for unknown
DBPs. This method was used to quantify 39 DBPs and identify
two new, previously unknown DBPs in drinking water: N,N-
dimethylacetamide and N-nitrosodibutylamine.
Another method published by Jiang et al. allows the
differentiation of isomeric C-chloro and N-chloro-tyrosyl
peptides in water.158 Normally, these different isomers cannot
be separated by LC−HRMS, but by using the selective
reductive nature of ascorbic acid, which selectively cleaves N−
Cl bonds, these isomers can be distinguished. Using this
approach, 36 new chlorinated DBPs were identified, including
mono-, di-, tri-, and tetra-Cl tyrosyl dipeptides.
The simultaneous analysis of 25 nitrogen-containing DBPs
(N-DBPs), haloacetonitriles, haloacetamides, and halonitro-
methanes, was the focus of a new liquid−liquid extraction
(LLE) GC−MS method by Carter et al.159 The use of a
programmable temperature injector minimized degradation of
thermally labile halonitromethanes, while maintaining efficient
volatilization of haloacetonitriles and haloacetamides. Detec-
tion limits of 0.8−1.7 μg/L were achieved, and the method was
validated using drinking water, swimming pool water, and spa
waters, where levels up to 41 μg/L of some of these N-DBPs
were found in pool waters.
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
SPE-LC−MS/MS was used in another method to
simultaneously measure iodinated haloacetic acids and
aromatic iodinated DBPs.160 Analytes included iodoacetic
acid (IAA), diiodoacetic acid (DIAA), 3,5-diiodo-4-hydroxy-
benzaldehyde, 3,5-diiodosalicylic acid, 2,6-diiodo-4-nitrophe-
nol, and 2,4,6-triiodophenol. SPE offered improved recoveries
for IAA and DIAA over previous LLE methods. Recoveries
ranged from 70 to 110%, quantification limits ranged from 0.06
to 0.19 ng/L, and detection limits ranged from 0.02 to 015 ng/
L. This method was used to measure these iodo-DBPs in nine
tap water samples, where levels up to 4.0 ng/L of IAA were
found.
Two new methods enabled the measurement of DBPs
without the need for extraction or preconcentration. For
example, direct injection-LC−ESI-MS/MS and HRMS were
used in a method by Planas et al. to simultaneously measure 11
haloacetic acids (HAAs) in drinking water.161 This method did
not require extraction or preconcentration and involved the
injection of 100 μL of water. Limits of detection (LODs)
ranged from 0.01 to 0.6 μg/L using triple quadrupole-MS/MS
and from 0.01 to 2 μg/L using a high-resolution Orbitrap mass
spectrometer. This simple method was demonstrated on tap
water from three drinking water treatment plants in Barcelona.
HAAs and nitrosamines were the focus of another method by
Alexandrou et al., who used LC−MS/MS with positive−
negative switching within a single run.162 Five HAAs and six
nitrosamines could be analyzed within 6 min without the need
for extraction or preconcentration. LODs of 0.05−0.1 μg/L
were reported.
Eight chlorophenylacetonitriles, a new class of DBP
identified recently, were the focus of a new SPE-GC−MS
method published by Zhang et al.163 Method detection limits
ranged from 0.15 to 0.37 ng/L, method quantification limits
ranged from 0.50 to 0.95 ng/L, and precision ranged from 5.8
to 11%. This method was demonstrated on nine drinking water
samples, where seven of the chlorophenylacetonitriles were
detected at concentrations between 0.8 and 155 ng/L in
chlorinated water and from 0.5 to 15 ng/L in chloraminated
drinking water.
Membrane introduction mass spectrometry (MIMS) was
used by Allard et al. for a new method to quantify
bromochloramine in water.164 To-date, there was not an
analytical method that could allow its quantification, free of
interferences. A LOD of 2.9 μM was achieved. Stable isotope
labeling (SIL) with SPE and LC−HRMS/MS was used in
another method by Liu et al. for the nontarget identification of
amino DBP precursors.165 Small amounts of deuterated
formaldehyde were used to label amino compounds in water,
which facilitated the tentative identification of 77 amino
compounds in a real source water sample.
Finally, Zhang et al. published a green pretreatment method
to measure nonionic TOX in water.166,167 This new method
helps to overcome an issue with the conventional TOX
method, when some compounds cannot be extracted using
activated carbon. Electrodialysis is used to separate nonionic
TOX and halides, after which, UV irradiation is used to
convert nonionic TOX into halides, which are analyzed using
IC. Electrodialysis was able to remove ≥98.5% of fluoride,
chloride, bromide, and iodide from all tested waters (up to
1000 mg/L) within 1.5 h and was able to recover 87.9% of 14
low molecular weight model compounds. UV irradiation was
able to recover >85.5% of each halide from 20 low-molecular
weight DBPs.
T DOI: 10.1021/acs.analchem.9b05269
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Brominated and Iodinated DBPs. Many brominated and
iodinated DBPs have been reported in the last 2 years,
including new DBPs not reported before. For example,
Liberatore et al. reported the first nontarget, comprehensive
analysis of iodinated DBPs formed in chloraminated produced
waters associated with hydraulic fracturing and conventional
gas formation.168 Using GC−HRMS, 56 new iodo-DBPs were
identified, and many were confirmed with authentic standards.
Four iodo-phenols, 2-iodophenol, 4-iodophenol, 2,4,6-triiodo-
phenol, and 4-iodo-2-methylphenol, were also investigated for
mammalian cell cytotoxicity. All were found to be cytotoxic,
especially 2,4,6-triiodophenol, which was more cytotoxic than
regulated THMs and most regulated HAAs. In addition,
interesting differences in cytotoxicity were noted for the two
iodo-phenol isomers. 4-Iodophenol (the para-substituted
isomer) was much more cytotoxic than 2-iodophenol (the
ortho-substituted isomer). Geogenic organic compounds in the
produced waters were also identified that could be precursors
of these DBPs.
Hydraulic fracturing DBPs were also the focus of another
study by Sumner and Plata, but this time without a traditional
disinfectant like chlorine or chloramine.169 This study
investigated the potential reaction of hydraulic fracturing
additives (e.g., corrosion inhibitors, oxidative breakers) with
halides under simulated subsurface conditions. Using GC ×
GC-TOF-MS, halogenated products were identified in
reactions of 5 of the 12 additives tested, including propargyl
alcohol, methyl isobutyl ketone, epichlorohydrin, cinnamalde-
hyde, and 2,2-dibromo-3-nitrilopropionamide. The cinnamal-
dehyde halogenation required the presence of ammonium
persulfate, the most frequently disclosed oxidant used in
hydraulic fracturing. The proposed mechanism involves a
multistep pathway, with the oxidation of halides to a reactive
species (e.g., HOCl, HOBr, or HOI) before addition to the
α,β-unsaturated bond. This was followed by degradation of
persulfate to a sulfate radical, which oxidizes Cl− rapidly to Cl2-
radical, which can react with organic compounds directly or
self-react to form Cl2. The chlorine can then hydrolyze to form
HOCl or OCl− (depending on pH) and can react with organic
material to form halogenated products.
Iodo-THMs were the focus of a large occurrence study of
Canadian drinking waters by Tugulea et al.170 Six iodo-THMs
were measured in source, finished, and distribution system
water samples from 65 drinking water treatment plants
(DWTPs), representing small, medium, and large systems.
One or more iodo-THMs were detected in 46 DWTPs during
the summer, and in 31 during the winter, up to 21.66 μg/L for
total iodo-THMs. Highest levels were seen at plants that had
high naturally occurring iodide and/or total iodine concen-
trations. Interestingly, two water systems had higher total iodo-
THMs than regulated THMs.
Iodinated tyrosyl dipeptide DBPs were reported for the first
time in drinking water by Huang et al.171 These DBPs were
initially discovered in chloramination reactions of tyrosyl
dipeptides in controlled laboratory reactions. Dipeptides are
commonly found in surface waters and were suspected as DBP
precursors. Following their initial identification using HRMS, a
SPE-LC−MS/MS method was created to probe for their
occurrence in real drinking waters. Four iodo-peptides were
subsequently identified in tap waters from three cities in
Canada: 3-iodo-tyrosylalanine, 3,5-diiodo-tyrosylalanine, 3-
iodo-tyrosylglycine, and 3,5-diiodo-tyrosylglycine. In a related
paper, Huang et al. reported new brominated and mixed halo-
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
tyrosyl dipeptides in chloraminated drinking water.172 These
were formed by the reaction of bromide, iodide, and
chloramine with three dipeptides, phenylalanylglycine, tyrosy-
lalanine, and tyrosylglycine, and were identified using direct-
infusion-ESI-quadrupole (Q)-time-of-flight (TOF)-MS. N-
Bromo, N,N-dibromo, N-bromo-N-chloro-, and N-bromo-3-
iodo-tyrosyl dipeptides were identified for the first time in the
reaction mixtures, and a more sensitive target SPE-LC−Q-ion
trap-MS method was used to probe real drinking waters for
these halopeptides, where 3,5-diiodo-tyrosylalanine and N-
bromo-tyrosylalanine were found.
Iodinated X-ray contrast media were the subject of two
studies. The first, by Postigo et al., identified one new
iodomethane (trichloroiodomethane), three new iodo-acids
(dichloroiodo-, chlorodiiodo, and bromochloroiodo-acetic
acid), and two new nitrogenous iodo-DBPs (iodoacetonitrile
and chloroiodoacetonitrile) in reaction mixtures of iopamidol
with chlorine.173 GC−HRMS was used for their identification;
several compounds were confirmed with authentic standards,
including one synthesized standard (chloroiodoacetonitrile). A
total of 21 regulated and unregulated DBPs, along with 11
target iodo-DBPs were also quantified. Interestingly, despite
the known genotoxicity of many of these DBPs, including
iodoacetonitrile, chlorination of the X-ray contrast media-
containing source water did not increase the mutagenicity
measured in the XAD resin extracts.
In the second study by Ackerson et al., the formation of
halogen-specific TOX (TOCl, TOBr, and TOI) were
measured along with chloro/iodo-DBP formation in reactions
of iopamidol with chlorine and chloramine in three different
source waters.174 TOI loss was ∼22−35% for each of the
source waters, and TOCl increased in all waters, with much of
it due to unknown TOCl molecules. Iopamidol was
determined to be a direct precursor for chloroform, trichloro-
acetic acid, and dichloroiodomethane. Low concentrations of
iodo-acids were also detected.
Formation and speciation of chloro-, bromo-, and iodo-
acetamides in simulated chloraminated drinking water was the
focus of another study by Fang et al.175 Reactions were carried
out using humic acid, bromide, and iodide and also with a
model compound, asparagine. Compared with bromide, iodide
demonstrated a much higher potential to be transformed into
haloacetamides during chloramination, with iodoacetamides
formed faster than chloro- or bromo-acetamides. A longer free
chlorine contact time before ammonia addition (to form
chloramines) resulted in reduced levels of diiodoacetamide,
due to oxidation of iodide to iodate by chlorine.
Haloacetamide DBPs were measured using liquid−liquid
extraction and GC-electron capture detection.
Halomethanesulfonic acids were the focus of a study by
Zahn et al., who used HRMS and NMR spectroscopy for
structural confirmation and a sensitive multilayer SPE (with
graphitized carbon black, WCX, and WAX SPE phases
separated by polyethylene frits) and hydrophilic interaction-
LC (HILIC)−MS/MS method to analyze them in drinking
water.176 These DBPs have only recently been reported, and
this was their first quantification in drinking water, where levels
ranged from 0.07 to 11.5 μg/L in tap water collected from six
countries in Europe. Interestingly, two surface waters also
contained halomethanesulfonic acids but at much lower levels
(∼100 ng/L).
The occurrence and stability of two chlorophenylacetoni-
triles was the subject of a study by Zhang et al., who
U DOI: 10.1021/acs.analchem.9b05269
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investigated the impact of pH, disinfectant residuals, and
quenching agents.177 2-Chlorophenylacetonitrile and 3,4-
dichlorophenylacetonitrile only slightly degraded with increas-
ing pH and chlorination after 5 days, and chloramination
showed no degradation. Of the quenching agents investigated,
only sodium sulfite showed negligible degradation. Levels
found at DWTPs ranged up to 530 ng/L for 2-
chlorophenylacetonitrile and up to 320 ng/L for 3,4-
dichlorophenylacetonitrile. Finally, mammalian cell cytotox-
icity was measured for the first time for these two new DBPs,
with an LC 50 of 133 and 83 μM observed for 2-
chlorophenylacetonitrile and 3,4-dichlorophenylacetonitrile,
respectively.
Ge et al. demonstrated that chlorinating a common green
algae (Chlorella vulgaris) can form the DBP, 2,6-dichloro-1,4-
benzoquinone (DCBQ).178 This algae is common in lakes and
rivers, and 0.3−2.1 μg/mgC of DCBQ was formed in
controlled laboratory reactions, with the highest levels at pH
8. Separation of the protein-rich intracellular organic matter
and the polysaccharide-rich extracellular fractions revealed
higher levels of DCBQ formed from the intracellular fraction
(1.4 μg/mg C) vs the extracellular fraction (0.7 μg/g C).
Finally, halogenated fatty amides were reported for the first
time by Kosyakov et al. as chlorine DBPs.179 LC−HRMS/MS
was used for their identification. They are believed to form by
the electrophilic addition of halogens to the double-bonds of
unsaturated fatty amides, and the proposed structures were
confirmed by conducting chlorination reactions with an
unsaturated oleamide standard. DBPs included chloro- and
bromohydrins as well as dichloro-derivatives of oleamide,
erucamide, palmito oleamide, and linoleamide. Precursors were
suggested to be either natural or from plastics.
Fate and Formation Mechanisms. A controlled
laboratory study by Vu et al. confirmed the mechanism of
formation for dichloroacetonitrile and dichloroacetamide via
the aldehyde reaction pathway.180 15N-Labeled monochlor-
amine and GC with low and high resolution-MS analysis was
used to verify the proposed pathway, which includes the
formation of 2,2-dichloro-1-(chloroamino)ethanol, followed by
two parallel reactions: (1) dehydration to form 1,1-dichloro-2-
(chloroimino)ethane, which decomposes to form dichloroace-
tonitrile and (2) oxidation by monochloramine to form N,2,2-
trichloroacetamide, which hydrolyzes to form dichloroaceta-
mide. Mammalian cytotoxicity analyses showed that N,2,2-
trichloroacetamide was more cytotoxic than N-chloroaceta-
mide but slightly less toxic than N,2-dichloroacetamide.
Cuthbertson et al. reported the most extensive granular
activated carbon (GAC) study of its kind, investigating the
removal and fate of 70 DBPs and speciated total organic
halogen (TOCl, TOBr, and TOI) over different service lives of
GAC (young-middle-old).181 Full-scale DWTPs using chlori-
nation with different source water impacts, algal, agricultural,
and industrial wastewater, were included. Overall, GAC was
effective for removing DBP precursors and reducing DBP
formation and total organic halogen. It was also effective at
removing preformed DBPs after prechlorination, including
highly toxic iodo-acid DBPs and haloacetonitriles. However,
seven highly toxic DBPs, mostly brominated and nitrogenous,
increased in formation after GAC treatment. This is because
GAC preferentially removes dissolved organic carbon (DOC)
over dissolved organic nitrogen (DON), and it does not
remove bromide. Therefore, the DON/DOC and Br-/DOC
ratios increase across GAC adsorbers, which may result in
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
increased formation of N- and Br-DBPs, due to increased
competition of HOBr.
As a result, while many DBPs were removed, a few highly
toxic DBPs increased with the use of GAC. However, the
calculated toxicity (using the TIC-Tox procedure) was still
reduced post-GAC, and prechlorination allowed further
reductions.
Hohner et al. provided a perspective on the formation and
fate of DBPs as a result of wildfires.182 Wildfires have increased
in intensity and severity in recent years, and they can
drastically alter forest vegetation and watershed processes
that control downstream water chemistry. Postfire rainstorms
can increase runoff, washing ash and soil, and increasing
turbidity, nutrient, and DOC levels in surface waters. These
impacts can persist, and the C and N released can cause DBPs
to increase in drinking water treatment, particularly N-DBPs.
These issues are discussed in detail in this article.
NDMA and Nitrosamine Methods, Formation, and
Fate. NDMA and other nitrosamines, which are currently
being considered for regulation by the U.S. EPA, continue to
be a hot topic of research. Sgroi et al. wrote an excellent review
on the precursors of NDMA in water and wastewater, along
with its formation and removal.183 Formation via nitrite,
chloramination, ozonation, and chlorine dioxide treatment
were discussed, along with sources of precursors, and different
removal strategies for NDMA and its precursors, including
biological treatment; coagulation, filtration, and lime softening;
adsorption; membrane filtration; UV treatment; and preox-
idation before chloramination.
In another paper, Huang et al. re-examined the role of
dichloramine in the high-yield formation of NDMA from N,N-
dimethyl-α-arylamines, including the popular pharmaceutical,
ranitidine.184 This study addressed the apparent contradiction
between practical experience and model precursor studies.
Practical studies had shown that dichloramine minimization
consistently reduces NDMA formation in real drinking water
and recycled wastewater, but mechanistic studies indicated that
minimizing dichloramine would not reduce NDMA formation
from N,N-dimethyl-α-arylamines. Results confirm that dichlor-
amine, rather than monochloramine, is the main reactant to
form NDMA, with substantially higher yields from dichlor-
amination for four N,N-dimethyl-α-arylamine compounds. The
authors suggest that dichloramine could be minimized using
preformed monochloramine or by applying chlorine before
ammonia in very well-nitrified wastewater as a cheap and viable
strategy for controlling nitrosamine formation.
Spahr et al. used stable isotope analysis to investigate
NDMA formation pathways from the chloramination of
tertiary amines.185 Nitrogen isotope ratios showed that
NH2Cl was the source of the nitrogen in the nitroso group
formed. Chloramination of four tertiary amines under slightly
different reaction conditions resulted in a consistent pattern of
carbon and nitrogen isotope fractionation in NDMA,
suggesting that these isotopes may be diagnostic for NDMA
precursors and formation pathways by chloramination.
A study in Japan by Hinneth et al. used the Japanese
Pollutant Release and Transfer Registers (PRTRs) to
investigate potential dimethylamine-containing compounds
that might form NDMA.186 In all, 31 compounds were
identified and were reacted with monochloramine in pure and
natural river waters containing NOM. Highest NDMA levels
formed from compounds with tertiary amines and aryl groups
in a β-position to the nitrogen in the dimethylamine group.
V DOI: 10.1021/acs.analchem.9b05269
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Fifteen compounds exceeded the Japanese guideline for
NDMA (100 ng/L), when assuming an accidental release of
0.144 mg C/L, similar to a previous accident in Japan in 2012.
Finally, Li et al. developed a new molecularly imprinted
polymer (MIP) for the measurement of N-nitrododiphenyl-
amine (NDPhA) in water.187 The MIPs were created using
precipitation polymerization with methacrylic acid as the
functional monomer, ethylene glycol dimethacrylate as the
cross-linker, and N,N-diphenylformamide as the template
molecule. An LOD and LOQ of 0.8 and 2.4 ng/L were
achieved, respectively. High selectivity for NDPhA was also
observed, along with good recovery of NDPhA in real samples
(92−107%) and % RSDs of 0.3−7.9%. This method was
subsequently demonstrated using real wastewater samples,
where NDPhA was detected in two samples, at 5.6 and 3.6 ng/
L, respectively.
Pollutant DBPs. While NOM is the traditional, main
precursor in the formation of DBPs, water contaminants can
also serve as precursors. For example, Wong et al. conducted a
new study to determine whether neonicotinoid pesticide
metabolites could form DBPs during chlorination in drinking
water treatment like the parent neonicotinoids.188 The authors
reported the first identification of desnitro-imidacloprid and
imidacloprid-urea in drinking water, with desnitro-imidacloprid
found up to 0.6 ng/L in 6 of the 9 plants sampled. LC−HR-
TOF-MS/MS was used to identify DBPs from the chlorination
of clothianidin, imidacloprid, desnitro-imidacloprid, imidaclo-
prid-urea, and hydrolysis products of thiamethoxam. DBP
formation was on a time-scale relevant to drinking water
treatment.
Algal toxins, β-N-methylamino-L-alanine (BMAA) and 2,4-
diaminobutyric acid (DAB), were the focus of another study
by Cao et al., who investigated DBP formation from
chlorination.189 These two algal toxins were measured in
Taihu Lake in China, up to 230.8 and 2.0 ng/L for BMAA and
DAB, respectively. THMs, HAAs, and haloacetonitriles
(HANs) formed at high yields, and reaction pathways were
proposed. THM and HAA formation was similar for the two
algal toxins, whereas HAN formation showed different
pathways for BMAA and DAB.
Antibiotic DBPs were the subject of a study by Neth et al.,
who investigated DBP formation of ciprofloxacin, trimetho-
prim, sulfamethoxazole, levofloxacin, and ofloxacin following
controlled laboratory reactions with chlorine.190 Antibacterial
activity was also measured in the reaction mixtures to
determine whether the DBPs retained their activity. Chlori-
nated and nonchlorinated DBPs were formed by all five
antibiotics, with those formed by ciprofloxacin, levofloxacin,
and ofloxacin retaining their antibiotic activity.
Swimming Pool DBPs. Several interesting swimming pool
DBP studies were published in the last 2 years. A total of 64
DBPs were targeted in swimming pools from Australia in an
extensive study from Carter et al.191 The target DBPs included
haloketones, haloacetaldehydes, haloacetamides, halonitro-
methanes, haloacetonitriles, HAAs, THMs, and nitrosamines.
GC−MS was used for their measurement. Approximately 70%
were detected in at least one pool, with concentrations greater
than reported previously for pools. Interestingly, trichloroace-
taldehyde accounted for up to 64% of the total molar DBP
concentration and >90% of the total calculated cytotoxicity in
these pool waters. Levels of trichloroacetaldehyde reached
1313 μg/L, HAAs reached 479 μg/L, haloacetamides reached
1093 ng/L, and nitrosamines reached 479 μg/L. Bromodi-
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
chloroacetaldehyde and bromochloroacetaldehyde were also
reported for the first time in pools.
Manasfi et al. investigated the transformation of five organic
UV filters in chlorinated seawater swimming pools and in
controlled laboratory reactions.192 UPLC−HRMS/MS and
GC−MS were used to comprehensively identify the DBPs.
Four of the UV filters, dioxybenzone, oxybenzone, avobenzone,
and 2-ethylhexyl-4-methoxycinnamate, formed brominated
DBPs; only octocrylene was stable in the presence of chlorine.
Due to the presence of bromide in the natural seawater, HOBr
is formed when chlorine is added, and this disinfectant species
was responsible for the brominated DBPs formed. Mono-, di-,
tri-, and tetra-bromo-DBPs were formed from the parent
compounds, along with other oxidation products and bromo-
form. Reaction pathways were proposed.
DBPs of the UV filter 2,4-dihydroxybenzophenone (BP-1)
in chlorinated swimming pools was the focus of another study
by Sun et al., who used UPLC−HRMS to identify the
products.193 Changes in genotoxicity were also monitored
during the reactions. Nine DBPs were tentatively identified,
including one chlorobenzoquinone, four phenyl benzoqui-
nones, and four polycyclic aromatic hydrocarbons. Reactions
were proposed to proceed by chlorine substitution, Baeyer−
Villiger oxidation, hydroylysis, and C−C coupling reactions.
The genotoxicity significantly increased with increasing
chlorine dose at acidic and neutral pH.
UV photolysis was the subject of another study by Cheema
et al., who investigated its use with chlorination for seawater
swimming pools.194 UV treatment is used sometimes in pools
to degrade harmful chloramines. THMs, HAAs, and
haloacetonitriles (HANs) were targeted in this study, using
GC−MS and GC-electron capture detection (ECD) methods.
Medium-pressure UV treatment increased the reactivity of
seawater pool water with chlorine, with increased formation of
brominated THMs and HANs following medium-pressure UV
and subsequent chlorination. The UV-chlorinated water was
predicted to have a higher toxicity based on the brominated
DBPs measured, although over time, UV can degrade Br-
HANs.
Finally, Yang et al. wrote a nice critical review on the
regulation, formation, exposure, and treatment of DBPs in
swimming pool water.195 Concentrations of different classes of
DBPs as well as factors affecting their formation (e.g., specific
disinfectant, disinfectant dose, precursors) in indoor vs
outdoor pool scenarios are also summarized and discussed as
well as treatments that can be used to reduce DBP levels.
■
SUNSCREENS/UV FILTERS
UV filters are used in products, such as sunscreens, shampoos,
cosmetics, and hair dyes, to protect against sun damage to skin
or hair. Organic UV filters absorb UV light, and inorganic UV
filters reflect and scatter UV light. Organic UV filters generally
have conjugated aromatic structures and are mostly lipophilic.
Multiple UV filters are usually present together in these
products. UV filters are prevalent in environmental waters,
introduced directly by activities such as swimming, or
indirectly, by treated wastewater. UV filters can be estrogenic,
developmentally toxic, or acutely toxic to aquatic organisms,
and they have been linked to the bleaching and death of coral
reefs. A new study by Mitchelmore et al. provides further
support for their impact on coral reefs.196 In this study, 13 UV
filters were measured in surface seawater, sediment, and coral
tissue from 19 sites in Oahu, Hawaii. Eight were detected in
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these three matrixes, with benzophenone-3 (BP-3) levels
reaching up to 136 ng/L in seawater from Waikiki Beach and
up to 241 ng/g (dry weight) in coral tissue. This was the first
report of UV filters in coral tissue from coastal waters in the
United States.
Mao et al. published a critical review on benzophenone-type
UV filters.197 Physicochemical properties, occurrence, fate, and
behavior of UV filters in the aquatic environment was
summarized and discussed. Of the 7 UV filters in this family,
BP-3 is the dominant species in the environment.
Photodegradation of 21 multiclass UV filters was the subject
of a study by Celeiro et al.198 LC−MS/MS and SPME-GC−
MS/MS were used to monitor their degradation by UVA,
UVC, UVA-TiO2, and UVC/H2O2. UVC degraded most UV
filters more than UVA, with yields >90% after 60 min of
exposure in pure water. When real water matrixes were used
(e.g., river, sea, and swimming pool water), degradation was
lower in waters with high organic matter content. UVA-TiO2
offered improved degradation, and UVC/H2O2 showed the
best removal efficiency in these more complex real-world
matrixes, with >90% degradation for most UV filters. In total,
19 photodegradation products were tentatively identified using
LC−HRMS.
Ozonation of UV filters was the focus of another fate study
by Hopkins et al., who measured second-order rate constants
and tentatively identified transformation products using LC−
MS/MS.199 Ozone reacted quickly with the phenolate group of
oxybenzone and moderately fast with the olefin group of
octinoxate, but only minimal reaction was observed for
octocrylene. Transformation products of these three UV filters
retained much of the structure of the parent molecules.
Finally, there were some new methods reported for the
measurement of UV filters in environmental waters. Liew
reported a fully automated sampling-sample preparation-
analysis platform using a modified vial, peristaltic pump,
mini-scale liquid−liquid extraction, evaporation, and GC−MS
to measure six UV filters.200 LODs ranged from 0.6 to 9.7 ng/
L, recoveries ranged from 62 to 80.7%, and good linearity was
observed for benzhydrol, 2-ethylhexyl salicylate, homosalate, 2-
hydroxy-methoxybenzophenone, 3-(4′-methylbenzylidene)-
camphor, and benzophenone. This new method was
subsequently demonstrated on swimming pool water, where
recoveries ranged from 85.4 to 118.2%, and it was
recommended for onsite water analysis.
Sun et al. developed a new molecularly imprinted polymer
(MIP), along with a miniaturized sorbent-based device to
extract benzophenone UV filters from water.201 This method
was used successfully to extract five benzophenones from
swimming pool water and human urine, where LODs of 0.12−
0.68 μg/L and 0.21−1.05 μg/L were achieved, respectively.
The MIP was also very selective for benzophenones. Finally,
Trujillo-Rodriguez et al. created a new headspace SPME
method for UV filters using polymeric ionic liquids.202 These
ionic liquid-cross-linked fibers could be used as alternatives to
commercial fibers. This new SPME method was combined
with GC−MS to provide a simple, solvent-free method that
does not require derivatization. LODs ranged from 2.8 to 26
ng/L and relative standard deviations from 2.5 to 15%. This
method was applied to tap water, swimming pool water, and
lake water, where most of the UV filters were detected and
quantified.
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■
BROMINATED AND EMERGING FLAME
RETARDANTS
Brominated flame retardants are still present in many
commercial products, including foam cushions in chairs and
sofas, children’s sleepwear, computers, plastics, and electronics.
Polyurethane foam can contain up to 30% by weight. While
flame retardants are used to protect human life, they are
environmentally persistent and can be transported long
distances in the environment. Polybrominated diphenyl ethers
(PBDEs) were commonly used in flame retardants for many
years until they were banned in several countries. The
Stockholm Convention recently listed deca-BDE as a persistent
o r g a n i c p o l l u t a n t ( P O P ) ( h t t p : / / c h m . po ps . i n t /
TheConvention/ThePOPs/ListingofPOPs/tabid/2509), and
China recently added it to their list of priority substances.
However, PBDEs can also be present in consumer products
previously sold, so that they continue to be released into the
environment during use and disposal. New replacement flame
retardants (e.g., organophosphates and chloro-organophos-
phates) are now found in the environment. De Boer and
Stapleton published a provocative perspective paper discussing
these “regrettable substitutions”, which all show harmful
effects. The authors lay out a better path forward with safer,
environmentally friendly alternatives, such as metal-based
compounds (e.g., zinc stannate, zinc borate, and aluminum
diethylphosphinate), as well as melamine polyphosphate.203
Also, while flame retardants may still be needed in such places
as airplanes, cars, insulation, and electronics, the authors
question whether they are really necessary in furniture,
children’s products, and other products like flags. In fact,
they point out that the use of flame retardants in residential
furniture only provides an additional ∼30 s to escape from a
flashover in a fire. It was recommended that authorities should
ban persistent, bioaccumulative, and toxic flame retardants as
soon as safer alternatives are available and to only allow on the
market ones that have been adequately tested for human
toxicity and environmental impacts. Interestingly, while
tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) was voluntar-
ily removed from children’s pajamas 3 decades ago when it was
deemed a risk to children, it has become a popular replacement
for pentabromodiphenyl ether in baby and children’s furniture
sold in the U.S.
Reviews. Several reviews have been published on flame
retardants in the last 2 years. For example, Pantelaki and
Voutsa summarized analytical methods and occurrence for
organophosphate flame retardants.204 Sample preparation,
extraction, cleanup, and analysis using GC−MS and LC−MS
were reviewed as well as occurrence in wastewater, river water,
seawater, drinking water, sediments, and sludge from several
different countries.
Occurrence and Fate. While this Water Analysis review is
focused on water, a recent wildlife exposure study is worth
noting. Marler et al. measured maternal transfer of legacy and
emerging flame retardants in sharks from the Western North
Atlantic Ocean.205 α-Hexabromocyclododecane (HBCDD)
diastereomers were measured using LC−MS/MS; other
flame retardants, 35 non-PBDE flame retardants and 20
PBDE congeners, were measured using GC−MS. Liver tissues
were measured from pregnant sharks from five species and
their embryos (n = 84). Concentrations ranged from 6.1 to
83.3 ng/g lipid weight (lw), 2.5−29.8 ng/g lw, and nondetect
to 32.6 ng/g lw for dechlorane analogues, tetrabromo-o-
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chlorotoluene, and hexabromobenzene, respectively. These
levels were 1−2 orders of magnitude lower than legacy PBDEs,
which ranged from 85.7 to 398 ng/g lw. Similar levels were
found in the different species of sharks, with 21 flame
retardants commonly found in the shark embryos, demonstrat-
ing maternal transfer in utero.
Several interesting occurrence studies were published in the
last 2 years. For example, Park et al. measured organo-
phosphorus flame retardants in tap water from South Korea.206
A total of 44 tap water samples were collected from eight major
cities served by four different watersheds. Total concentrations
ranged from 74 to 342 ng/L, with tris(2-chloroethyl)-
phosphate, tris(chloroisopropyl)phosphate, and tris(2-
butoxyethyl)phosphate predominant. No major differences in
flame retardants were found from the different regions.
Another study by Sutton et al. examined PBDEs and 52
additional brominated, chlorinated, or phosphate flame
retardants in water, sediment, bivalves, and harbor seal blubber
from San Francisco Bay.207 The highest levels were found in
the Bay water samples, with organophosphate flame retardants
as high as 5100 ng/L. The Amazon River and the tropical
North Atlantic Ocean was the focus of another interesting
occurrence study by Schmidt et al.208 Organophosphate flame
retardants (total concentration) reached 1300 ng/L in offshore
ocean waters, and a Lagrangian analysis confirmed that these
contaminants originated from the Amazon River plume,
transported >3000 km.
Arctic surface waters were the subject of another study
published by McDonough et al., who investigated the
distribution and net transport of organophosphate esters and
PBDEs through the Fram Strait in Canada.209 Passive
polyethylene samplers were used to sample deep seawater in
the strait and in surface waters from lakes and coastal sites in
the Canadian Arctic. Total organophosphate esters ranged
from 6.3 to 440 pg/L at deep water sites, and chlorinated
phosphate esters were dominant in surface waters (mean
ranging from < LOD to 4400 pg/L). PBDEs were found at
much lower levels (up to 14 pg/L). Several organophosphate
esters showed a net transport out of the Arctic, ranging from
17 kg/year to 3400 kg/year for ethylhexyldiphenylphosphate
and tris(2-chloroisopropyl)phosphate, respectively.
Organophosphate ester (OPE) transport, fate, and emissions
in Toronto was the topic of another paper by Rodgers et al.210
Three chlorinated OPEs and three nonchlorinated OPEs were
investigated. Modeling results indicate that measured stream
concentrations of ∼2000 ng/L for total OPEs originated from
urban air emissions transferred to water, mostly by
precipitation. Loadings to Lake Ontario from WWTPs were
estimated at 70%. In addition, tris(2-chloroethyl)phosphate,
tris(chloroisopropyl)phosphate, and tris(1,3-
dichloroisopropyl)phosphate could be considered persistent
and mobile organic compounds.
A new flame retardant, tris(2,4-di-tert-butylphenyl)-
phosphate, which was identified recently in e-waste dust, was
the focus of another study by Venier et al., who used GC−MS
to measure its concentrations in water, sediment, air, and in
dust from the Chicago area and the Indiana Harbor.211 Median
concentrations in water from the Indiana Harbor were 3700
pg/L, with much higher levels found in e-waste dust (14 400
ng/g) and house dust (4900 ng/g).
New Methods. Several new methods have been developed
for flame retardants in the last 2 years, including multianalyte
methods. For example, Hao et al. developed a new LC−MS/
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
MS direct injection method for measuring 19 organo-
phosphorus flame retardants in water.212 The removal of
sample extraction and concentration steps improved efficiency
and also reduced contamination commonly encountered in the
sample preparation process. Instrumental detection limits
ranged from 1.5 to 30 ng/L for 12 of these analytes. This
method was subsequently demonstrated on surface water and
wastewater from Ontario, where seven organophosphorus
flame retardants were detected, up to 10.3 and 10.2 μg/L,
respectively, for tris(2-butoxyethyl)phosphate.
Han et al. created a new SPE-UPLC−MS/MS method for
17 alternative flame retardants, including hexabromocyclodo-
decane (HBCD), tetrabromobisphenol-A (TBBPA), six
bromophenols, and nine organophosphate flame retardants in
water.213 Method detection limits (MDLs) were 0.1−2.5 ng/L
for HBCD, TBBPA, and the bromophenols and 0.10 ng/L for
the organophosphate flame retardants. The method was
applied to surface water, groundwater, raw source water,
finished drinking water, tap water, and bottled water samples.
Interestingly, several of these flame retardants were found in
tap water and bottled waters, up to high ng/L levels.
Finally, Zou et al. created a new in situ passive sampling
method using diffusive gradients in thin-films to measure
organophosphorus flame retardants in water.214 The method
was not limited by pH, ionic strength, or dissolved organic
matter. In addition, negligible competition effects between the
organophosphorus flame retardants were found, and validation
showed that WWTP effluent time-integrated measurements
over 12−16 days were comparable to those obtained by grab
sampling.
■ DIOXANE
1,4-Dioxane is used as a solvent stabilizer and is historically
connected with leaking underground storage tanks containing
chlorinated solvents, but it can also come from other sources,
such as landfill leachate, detergent manufacturing plants, and
chrome-plating plants.215 Despite its first detection in drinking
water more than 40 years ago and its classification as a
probable human carcinogen, 1,4-dioxane is still not regulated
in most countries. Recent data from the UCMR-3 indicate that
almost 30 million people in the U.S. have 1,4-dioxane levels
above the health reference level for cancer of 0.35 μg/L. 1,4-
Dioxane is listed on the U.S. EPA’s current CCL-4 and was
also listed on previous CCLs. As a result, an old chemical has
become an “emerging contaminant” again. 1,4-Dioxane is also
highly water-soluble, nonvolatile when dissolved in water, and
not well adsorbed by activated carbon, not readily oxidized by
common oxidants, or readily biodegraded in water.215 McElroy
et al. wrote an excellent review on analytical methods,
occurrence, and treatment approaches for 1,4-dioxane.215
Among the limited treatment options, advanced oxidation
technologies that generate hydroxyl radicals can be effective for
its removal, along with cometabolic biological treatment.
Pollitt et al. wrote an excellent review on 1,4-dioxane,
summarizing the state of the science and research needs.216
The authors discuss the environmental occurrence, co-
contaminants, environmental fate, routes of exposure (drinking
water, food, consumer products, bathing/showering), toxicity
and mechanisms of carcinogenesis, exposure assessment, health
effects in humans, and remediation methods, as well as
recommendations for future studies.
Carrera et al. published a study on the removal efficiency for
dioxanes and dioxolanes in each step of a drinking water
Y DOI: 10.1021/acs.analchem.9b05269
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treatment plant.217 SPE-GC−MS/MS was used for their
measurement. Ultrafiltration followed by reverse osmosis
showed the best removal for 1,4-dioxane, alkyl dioxanes, and
dioxolanes compared to ozonation followed by GAC filtration,
where some desorption processes were eventually observed.
Results also showed that the presence of 1,4-dioxane was not
only due to spills but also from other sources of contamination.
Background levels of ∼1 μg/L were measured in surface waters
and up to 11.6 μg/L in groundwater.
Contaminated groundwater sites in Western Germany were
the subject of a new study by Karges et al., who investigated
sites suspected to contain 1,4-dioxane.218 These sites included
ones known for volatile chlorinated hydrocarbon contami-
nation, representative landfill leachate characteristics, and
impacts from a detergent manufacturing plant. All sites
contained 1,4-dioxane, with levels ranging form 0.15 to 152
μg/L. When an aquifer containing a trichloroethylene (TCE)
plume was examined, a perfect match of TCE and 1,4-dioxane
was observed in vertical and horizontal distribution profiles.
This study represented one of the few studies carried out to-
date in Germany for 1,4-dioxane contamination in ground-
water.
A new sensor for 1,4-dioxane was created by Karim et al.219
The sensor was made from conducting polyaniline and SiO2
nanocomposites that were synthesized and deposited on a
glassy carbon electrode. Good reproducibility, long-term
stability, and high accuracy were reported for measuring 1,4-
dioxane in real environmental waters. The detection limit and
quantification limit were 16.0 and 53.3 pM, respectively.
■ ALGAL TOXINS
Algal toxins, released by harmful algae, are a global concern
and can cause fish kills, shellfish poisoning, and death and
illness in humans and animals. They have also been implicated
in cancer and were responsible for the deaths of 52 dialysis
patients in 1996.220,221 The rapid death of 12 dogs in 2017 in a
Berlin lake from anatoxin-a was a more recent reminder of
these concerns, as well as a state of emergency issued for eight
counties in Florida in 2018 due to massive, unprecedented
harmful algal blooms (HABs).220 These blooms have
continued in 2019, such that almost half of Florida’s water
bodies are now impacted, and many fish kills have occurred.
Eutrophication and climate change have been exasperating
these blooms, which can even occur in northern climates. Algal
toxins also threaten drinking water, and Toledo, Ohio was a
classic example of this in 2014, when winds blew a large algal
bloom directly over the drinking water intake in Lake Erie,
such that the drinking water treatment plant had to be
temporarily shut down due to the presence of microcystin
toxins. In fact, microcystins are the most commonly found algal
toxins in fresh waters, with nodularins, anatoxins, cylindro-
spermopsin, and saxitoxins and seawater brevetoxins also
commonly reported. The U.S. EPA lists several algal toxins on
its CCL-4, and several other countries have guideline limits.
These include Australia, Brazil, Canada, the Czech Republic,
France, Italy, Japan, Korea, New Zealand, Norway, Poland, and
Spain (for microcystins, anatoxin-a, and cylindrospermopsin,
limits from 1.0 to 1.5 μg/L).
Reviews. Several interesting reviews have been published in
the last 2 years. Jaramillo and O’Shea reviewed analytical
methods for measuring cyanotoxins in drinking water
sources.220 Indirect methods include enzyme-linked immuno-
sorbent assay (ELISA) antibody-based techniques, and direct
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
methods include LC−MS and matrix-assisted laser desorption
ionization (MALDI)-TOF-MS, electrochemical immunosen-
sors, qPCR of toxigenic genes, and aptamer detection.
Methods for microcystins, nodularins, anatoxin-a, and β-N-
methylamino-L-alanine (BMAA) are discussed as well as
multiclass toxin approaches.
Janssen published an intriguing review article on cyano-
bacterial peptides beyond microcystins, detailing the co-
occurrence, toxicity, and challenges for risk assessment for
these understudied and unknown toxins.221 While microcystins
are the most commonly measured, Janssen points out that
cyanobacteria produce an incredible diversity of hundreds of
cyanopeptides beyond microcystins. It is currently not known
whether they pose a human health risk. What is known from a
few limited studies is that these other cyanopeptides, including
cyanopeptolins and anabaenopeptins, can occur just as
frequently and at similar nanomolar concentrations to
microcystins in surface waters. The mechanisms of toxicity
are different, with cyanopeptolins, anabaenopeptins, aerugino-
sins, and microginins inhibiting proteases at the nanomolar
level, while microcystins exhibit phosphatase inhibition.
Cyanopeptolins, anabaenopeptins, aeruginosins also show
comparable toxicity to grazers as microcystins.
New Methods. Several new method have been published,
including three new sensor assays. Liu et al. created a new
PCR-assisted, optical fiber-based fluorescent biosensor for
early detection of cyanobacterial blooms, through the rapid
detection of microcystin synthetase A genes.222
A detection limit of 10 pM was achieved, with 87−102%
recoveries for Microcystis aeruginosa in mixed samples. Bickman
et al. developed a portable fluorescence optical biosensor using
an immunoassay in a disposable cartridge for the rapid and
simultaneous detection of multiple cyanobacterial toxins (8
microcystin congeners and cylindrospermopsin).223 Detection
limits were 0.4 and 0.7 μg/L for microcystin and
cylindrospermopsin, respectively. This sensor was validated
using 45 lake water samples from Colorado and Lake Erie,
which showed good correlation with existing ELISA methods.
Li et al. created an aptamer-based fluorescent sensor array
using a smart phone for detection and discrimination of four
cyanotoxins (anatoxin-a, cylindrospermopsin, nodularin, and
microcystin-LR) in parallel.224 Results could be achieved
within 5 min of reaction, and detection limits of <3 nM were
achieved. The sensor also showed good chemical specificity
against potential interfering compounds in water and was
validated in real lake water.
Stewart et al. reported the biosynthesis of 15N-labeled
microcystins by cultivating two different strains of Microcystis
using Na15NO3 as the sole nitrogen source. These labeled
standards could be used as internal calibrants to offer improved
quantification using LC−MS/MS.225 Yan et al. optimized a
SPE and LC−MS/MS method, with and without derivatization
(with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate), for
measuring dissolved BMAA in water.226 Best extractions were
accomplished using tandem C18 and MCX SPE cartridges.
The competition of NOM in natural water reduced BMAA
recovery, but it could be improved by lowering the pH to 3,
using a C18 cartridge for pretreatment and reducing sample
volumes to 50 mL. The optimized method yielded >88%
recovery in natural water and algal solutions.
Occurrence. Raw drinking waters (source waters) were the
focus of a study by Beversdorf et al., which revealed the
presence of many other toxins besides microcystin.227
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Temporal and spatial trends for four microcystins, three
cyanopeptolins, two anabaenopeptins, and microginins were
investigated in source waters and at six surface water locations
above the drinking water intakes. All but one of these were
found in the lake and source waters, with mean concentrations
of 3.9, 0.14, and 0.38 μg/L for microcystins, anabaenopeptins,
and cyanopeptolins, respectively, in two drinking water intakes.
The measurement method included lyophilization with 67%
methanol followed by LC−MS/MS analysis. These results
highlighted the co-occurrence of other toxins besides micro-
cystins.
Leon et al. investigated the fate of microcystin-LR (MC-LR),
nodularin, and cylindrospermopsin in controlled laboratory
studies with hydrolysis, chlorination, and photodegradation.228
UV irradiation resulted in rapid and complete degradation of
MC-LR and nodularin; partial degradation occurred under
sunlight conditions. Chlorination resulted in complete loss of
cyanotoxins. However, 12 transformation products were
identified using LC−QTOF-MS: six chlorination DBPs
(three from cylindrospermopsin and three from MC-LR),
four UV transformation products (from cylindrospermopsin),
and two sunlight transformation products (one from MC-LR
and one from nodularin).
He et al. investigated the influence of microcystin (MC)
structural difference on ELISA cross-reactivity and chlorination
effiency.229 Upon chlorination under all conditions tested,
MC-YR and MC-LY were completely eliminated, while
differential removal was observed for others, as measured
using LC−MS/MS. This was consistent with the reactivity of
the amino acids in their structures. ELISA gave apparently
higher concentrations than LC−MS/MS, depending on the
cross-reactivity of the congeners. Adda-containing DBPs
produced by chlorination also produced an elevated ELISA
result compared to LC−MS/MS, which could lead to false
positives for MCs.
Almuhtaram et al. investigated the extent of cyanobacteria
cell accumulation in different stages of drinking water
treatment from four plants in the Great Lakes region.230
Microscopic and ELISA methods were used to analyze
cyanobacteria and microcystins, anatoxin-a, saxitoxin, cylin-
drospermopsin, and BMAA. Under conditions of low cell
influxes (1000 cells/mL), significant cell accumulations (by a
factor of 12) were found in the clarifier sludge and filter
backwash samples. Thus, even in the absence of a visible algal
bloom, drinking water plants can still be at risk of toxic
cyanobacteria accumulation.
UV-chlorine degradation of microcysin-LR (MC-LR) was
the focus of another study by Duan et al.231 LC−MS/MS was
used to identify the transformation products. Surprisingly,
fewer chlorinated MC-LR products were detected with UV/
chlorine compared to chlorination. A transformation pathway
was proposed. The UV/chlorine treated samples also showed
lower cytotoxicity than chlorine-treated samples. It was
suggested that utilities that already use UV prior to the
addition of chlorine might consider adding chlorine before the
UV unit during an algal bloom event to prevent MC-LR from
entering the finished water.
■
MICROPLASTICS
Microplastics (MPs) have become a hot topic the past few
years, due to growing contamination in oceans, lakes, and
rivers worldwide. Defined as ≤5 mm in size, MPs can form by
degradation of larger plastics that enter the environment or
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Analytical Chemistry
from direct use in products. In 2015, the Microbead-Free
Waters Act banned microbeads in cosmetic products and
toothpaste manufactured or distributed in the United States
(www.congress.gov/bill/114th-congress/house-bill/1321/
text). Of the potential types of MPs, fibers are the most
predominant, and studies have shown that they are easily
released from clothes during washing (particularly from
polyester fleece).
While biodegradable plastics may seem like the answer,
polylactic acid and other biodegradable polymers are
essentially nondegradable in seawater.232 Thus, biodegradation
tests carried out in artificial environments can lack trans-
ferability to real conditions, and in a recent review article,
Haider et al. suggest that relevant field-testing conditions
should be developed.232 This review discusses the ecotoxico-
logical implications of biodegradable polymers, along with
social aspects.
We now have 4 decades of accumulation of MPs in the
environment, with major accumulations in the ocean gyres,
where “plastic islands” are formed. Many animals ingest MPs,
including seabirds, seals, sea lions, dolphins, whales, marine
reptiles, and zooplankton, such that the MPs can cause
obstruction in the digestive tract and internal organs as well as
transfer sorbed chemical contaminants. However, animals are
not the only ones ingesting MPs. It is estimated that humans
ingest an average of 5 g of plastic every week, the equivalent of
a credit card (www.cnn.com/2019/06/11/health/
microplastics-ingestion-wwf-study-scn-intl/index.html).
Microplastics in drinking water was the subject of another
review article by Eerkes-Medrano, who discussed the
occurrence of MPs in tap water, bottled water, source water,
and finished drinking water.233 Developed nations have higher
MP concentrations overall, with highest tap water levels in the
U.S. (9.24 particles/L) and Germany (0.91 particles/L) of the
14 countries analyzed. Most MPs were fibers (98%), ranging
from 0.10 to 5.00 mm in size. For bottled water, reusable
plastic bottles contained the highest levels, up to 4889
particles/L. The review also discusses drinking water sources
and pathways for MPs, potential implications for humans, and
recommendations for the future.
Human consumption of MPs was the subject of a study by
Cox et al., who examined 401 data points from 26 studies,
representing >3600 processed samples.234 When ∼15% of
American’s caloric intake was evaluated, consumption ranges
of 39 000 to 52 000 particles per year were estimated,
depending on age and sex. Dietary sources of MPs included
salt, alcohol (beer), seafood (fish, shellfish, and crustaceans),
added sugars (sugar and honey), and water. When inhalation is
also considered, these numbers increase to 74 100 and
121 000. People drinking bottled water may be ingesting an
additional 90 000 MPs per year compared to 4000 for people
who consume only tap water.
Export of plastic debris by rivers into the sea was the focus of
a study by Schmidt et al., who analyzed a global compilation of
data on plastic debris (micro- and macroplastic) in rivers and
calculated the global plastic debris inputs into the sea.235 The
top 10 ranked rivers were predicted to transport 88−95% of
the global plastic load into the sea. The global total was
estimated between 0.4(1−4) × 106 tons/year. In another
study, Alimi et al. estimated the loads of MPs and nanoplastics
in different environmental compartments and discussed factors
affecting their aggregation, deposition, and contaminant
cotransport.236 Polyethylene generally exhibits a greater
AA
Review
sorption capacity than other plastics. Key knowledge gaps
are also identified in this review.
Analytical chemistry methods for MPs was the focus of
another review by Silva et al., who covered sampling, sample
handling, identification, and quantification methods for water,
sediments, and biological tissues.237 Methods include optical
techniques, electron microscopy, infrared and Raman spec-
troscopy, and pyrolysis-GC−MS. Key challenges and a
roadmap for future research were also discussed.
New Methods. Magnetic extraction of MPs was the focus
of a new method by Grbic et al., who created hydrophobic Fe
NPs that bind to plastic and allow magnetic recovery.238 Using
this method, 92% of 10−20 μm polyethylene and polystyrene
beads and >1 mm MPs (polyethylene, polyethylene tereph-
thalate, polystyrene polyurethane, polyvinyl chloride, and
polypropylene) were recovered from seawater. Zhou et al.
developed a cloud-point extraction-thermal degradation-
pyrolysis GC−MS method for nanoplastics.239 An enrichment
factor of 500 was achieved for polystyrene and poly(methyl
methacrylate) nanoplastics without changing their original
morphology or size. When spiked into river water, recoveries of
85 and 92% were achieved for these two types of nanoplastics,
respectively, along with LODs of 1.1 μg/L and 0.6 μg/L,
respectively. The method was subsequently demonstrated on
real river water, seawater, and WWTP influent and effluent,
where good recoveries were achieved.
A new automated method for simultaneously identifying and
quantifying microfibers and MPs was created by Primpke et
al.240 This method involved concentrating the sample on
membrane filters, applying a BaF2 window on top of the filter,
and measurement using FT-infrared (IR) microscopy. By
covering the sample with the BaF2 window, fibers are arranged
in the focal plane of the microscope, allowing the analysis of
MPs and microfibers in a single measurement.
Erni-Cassola et al. reported a new high-throughput method
using Nile Red dye, fluorescence microscopy, and image
analysis software to detect and quantify small MPs (1 mm−20
μm) in environmental samples.241 Small polyethylene,
polypropylene, polystyrene, and nylon-6 particles could be
detected in environmental waters. This method helped to
resolve an underestimation of MPs in previous research.
Occurrence and Fate. Schymanski et al. published an
interesting study on the release of MPs into bottled water from
different kinds of bottles.242 Micro-Raman spectroscopy was
used to capture MPs less than 20 μm that can be missed with
other techniques. Bottled waters were purchased from grocery
stores in Germany including returnable and single-use plastic
bottles, beverage cartons, and glass bottles. Almost 80% of MPs
had a particle size between 5 and 20 μm. Average MP levels
were 118, 14, 11, and 50 particles/L in returnable plastic
bottles, single-use plastic bottles, beverage cartons, and glass
bottles, respectively. Most MPs in bottled water from
returnable plastics were polyester (primarily polyethylene
terephthalate, PET) (84%), with a minor amount from
polypropylene (7%). This corresponds to the composition of
the bottle and cap (PET and polypropylene, respectively),
demonstrating that the packaging itself can release MPs into
bottled water.
Flushable vs nonflushable wet wipes was the focus of a study
by Munoz et al., who used micro-Raman spectroscopy, FT-IR
spectroscopy, and fluorescence microscopy to investigate the
fiber composition.243 PET, high-density polyethylene (HDPE),
and polyethylene/vinyl acetate fibers were identified in some
DOI: 10.1021/acs.analchem.9b05269
Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
flushable wipes and PET in all the nonflushable ones. Other
polymers, polypropylene, low-density polyethylene (LDPE),
expanded polystyrene, and polyurethane, were also identified
as components of flushable wipes. Therefore, flushable wipes
could be a potential source of MP fibers in wastewater
effluents.
Landfill leachates were the focus of another study by He et
al., who investigated them as a source of MPs in the
environment.244 Twelve leachate samples were collected
from four active and two closed municipal solid waste landfills,
where 17 different types of plastics were identified, with
concentrations ranging from 0.42 to 24.58 items/L. Poly-
ethylene and polypropylene were the dominant polymer types,
and >99% of MPs were derived from the degradation of plastic
waste buried in the landfills. Thus, a case was made that
landfills are not necessarily the final sink for plastics but also a
potential source of MPs to the environment.
The journey of MPs from Yellowstone National Park to the
Pacific Ocean was the focus of an interesting study by Kapp
and Yeatman.245 Grab and plankton net samples were collected
from the top 25 cm of surface water every 80.5 km along the
Snake River (1735 km) to its confluence with the Columbia
River to the Pacific Ocean. MPs were found in 75% of the grab
samples and 93% of the net samples, with concentrations
ranging from 0 to 5.4 MP/L and 0−0.014 MP/L, respectively.
Sites with lower flow or farther down river had higher
numbers, and two hot spots were from locations with low
populations, but high agricultural use.
Fate of MPs during sterilization with chlorine was the focus
of a study by Kelkar et al., who used Raman spectroscopy and
differential scanning calorimetry to detect chemical and
physical changes.246 Virgin plastics were exposed to different
sterilization conditions relevant to drinking water, wastewater,
and heavily contaminated surfaces. Results demonstrated that
commonly used plastics can be chemically altered, even under
conditions used in wastewater treatment. HDPE and
polystyrene were the most reactive with chlorine, with shifts
in Raman peaks and the formation of new bonds. On the other
hand, polypropylene was resistant to chlorination.
Sorption of 17β-estradiol (E2) on MPs in seawater was the
focus of a paper by Liu et al.247 Salinity and dissolved organic
matter had only a minor effect on E2 sorption, but smaller
particle size increased sorption of E2. In another study by Yang
et al., plastics in the marine environment were determined to
be reservoirs for antibiotic and metal resistance genes (ARGs
and MRGs).248 The diversity, abundance, and co-occurrence
of ARGs and MRGs were measured in the microbial
communities on the plastics, where up to 1.21 × 10−2 and
4.82 × 10−2 copies per 16S rRNA were found, respectively. No
significant differences between macroplastic and microplastic
biota were observed, indicating that particle size had no effect
on resistance genes.
Finally phototransformation of brominated flame retardant-
containing plastics was investigated in a study by Khaled et
al.249 Infrared analysis showed an acceleration in photo-
degradation in flame retardant-polystyrene films vs pure
polystyrene films, and 14 brominated photoproducts were
observed, with lower molecular weights. Enhanced degradation
resulted in leaching (15%) of oxidation products from the
polystyrene films into water and into the gas phase.
AB
■
Review
AUTHOR INFORMATION
Corresponding Author
*E-mail: richardson.susan@sc.edu.
ORCID
Susan D. Richardson: 0000-0001-6207-4513
Notes
The authors declare no competing financial interest.
Biographies
Susan D. Richardson is the Arthur S. Williams Professor of Chemistry
at the University of South Carolina, and was formerly a research
chemist at the U.S. Environmental Protection Agency for many years.
She received her B.S. degree in Chemistry and Mathematics from
Georgia College in 1984 and her Ph.D. degree in Chemistry from
Emory University in 1989. Susan’s research has focused on the
identification, characterization, and quantification of new toxicolog-
ically important disinfection byproducts (DBPs), with special
emphasis on alternative disinfectants and polar byproducts. She is
particularly interested in promoting new health effects research so that
the risks of DBPs can be determined and minimized. She is also
interested in studying and minimizing emerging contaminants in
water reuse applications. Among her achievements, Susan was
recognized as an AAAS Fellow in 2019, an ACS Fellow in 2016,
and in 2020 will be joining the Editorial Advisory Board of Analytical
Chemistry. Susan is also currently serving as Associate Editor for
Environmental Science & Technology and is Vice President for
Programs/President-Elect for the American Society for Mass
Spectrometry.
Susana Y. Kimura is an Assistant Professor and Canadian Research
Chair Tier 2 in the Department of Chemistry at the University of
Calgary. Prior to her current appointment, she was a Postdoctoral
Fellow in the Department of Chemistry and Biochemistry at the
University of South Carolina. She received her M.S. and Ph.D.
degrees in Environmental Engineering from the University of Illinois
at Urbana−Champaign. Dr. Kimura’s research interests include the
chemical formation and toxicological mechanisms of priority
contaminants in drinking and reused waters using advanced mass
spectrometry instrumentation and techniques.
■
ACKNOWLEDGMENTS
S.D.R. would like to thank Jody Shoemaker of the U.S. EPA for
information on new EPA methods (she and others at the U.S.
EPA have created many great methods that are used in the
United States and throughout the world) and Stig Regli of the
U.S. EPA’s Office of Water for helpful information on new
regulations. I would also like to thank Despo Fatta-Kassinos for
new information on PFASs as well as for organizing an amazing
XENOWAC Conference in 2018, which led me to consider
introducing antibiotic resistance genes as important emerging
contaminants in this review. I would also like to thank Steve
Stein for providing new information on the upcoming NIST
2020 MS/MS library and Tony Williams of the U.S. EPA for
new information on EPA’s CompTox Dashboard. Finally, I
would like to thank the University of South Carolina
researchers and scholars who have created a very welcoming
and scientifically stimulating atmosphere for this next phase of
my career and my fabulous graduate students, undergrads, and
postdocs.
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AG DOI: 10.1021/acs.analchem.9b05269
Anal. Chem. XXXX, XXX, XXX−XXX