water analysis emerging contaminants and current issues

Published: June 14, 2011

r 2011 American Chemical Society 4614 dx.doi.org/10.1021/ac200915r |Anal. Chem. 2011, 83, 4614–4648

REVIEW

pubs.acs.org/ac

Water Analysis: Emerging Contaminants and Current IssuesSusan D. Richardson*,† and Thomas A. Ternes‡

†National Exposure Research Laboratory, U.S. Environmental Protection Agency, Athens, Georgia 30605, United States‡Federal Institute of Hydrology, Koblenz, D-56068 Germany

’CONTENTS

Background 4614Major Analysis Trends 4615Sampling and Extraction Trends 4616Chromatography Trends 4616Use of Nanomaterials in Analytical Methods 4616Other Particularly Creative Methods 4616Emerging Contaminants 4616

General Reviews 4617New Regulations/Regulatory Methods 4617

New Proposed Regulation for Perchlorate inU.S. Drinking Water 4617

The New Contaminant Candidate List-3 (CCL-3) 4618The Draft Third Unregulated Contaminants

Monitoring Rule (UCMR-3) 4618

New Regulatory Methods for Drinking Water 4618EPA Method 539: Hormones 4620EPA Method 538: Pesticides, Quinoline, and

Other Organic Contaminants 4620

EPA Method 524.3: Purgeable Organic Compounds 4620EPA Method 1615: Enteroviruses and Noroviruses 4620

Sucralose and Other Artificial Sweeteners 4621Antimony 4622Nanomaterials 4622PFOA, PFOS, and Other Perfluorinated Compounds 4623Pharmaceuticals and Hormones 4626

Environmental Impacts of Pharmaceuticals 4627Biological Transformation Products 4627Elimination/Reaction During Oxidative Water

Treatment 4628

Opiates and Other Drugs of Abuse 4628Antidepressants 4629Antiviral Drugs 4629Glucocorticoids 4629Antimycotics and Antibiotics 4629Thyroid Hormones 4629Drinking Water Analysis 4629Beta-Blockers 4629Multiresidue Methods 4629New SPE Materials/Procedures 4630New Derivatization Method 4630Enantiomers 4630

Bioassays 4630Drinking Water and Swimming Pool DisinfectionBy-Products 4630Drinking Water DBPs 4630Combining Chemistry with Toxicology 4631Discovery of New DBPs 4631New Methods 4631Near Real-Time Methods 4632Improved Method for Total Organic Chlorine and

Bromine 4632

Alternative Disinfection Technologies Using Iodine,UV, and Other Treatments 4632

Nitrosamines 4633Mechanisms of Formation 4634DBPs of Pollutants 4635New Swimming Pool Research 4635

Sunscreens/UV Filters 4636Brominated Flame Retardants 4637Benzotriazoles 4638Dioxane 4638Siloxanes 4638Naphthenic Acids 4638Musks 4639Pesticide Transformation Products 4639Perchlorate 4640Algal Toxins 4641Microorganisms 4642Contaminants on the Horizon: Ionic Liquids 4643

Biographies 4644Acknowledgment 4644References 4644

’BACKGROUND

This biennial review covers developments in water analysis foremerging environmental contaminants over the period of2009�2010. A few significant references that appeared betweenJanuary and February 2011 are also included. Analytical Chem-istry’s policy is to limit reviews to a maximum of 250 significant

Special Issue: Fundamental and Applied Reviews in AnalyticalChemistry

4615 dx.doi.org/10.1021/ac200915r |Anal. Chem. 2011, 83, 4614–4648

Analytical Chemistry REVIEW

references and to mainly focus on new trends. Even with a morenarrow focus, only a small fraction of the quality researchpublications could be discussed. As a result, as with the previousreview on Water Analysis in 2009,1 this review will not becomprehensive but will highlight emerging contaminant groupsand discuss representative papers. I write a similar review articleon Environmental Mass Spectrometry, which also focuses onemerging contaminants.2 That review article is somewhatdifferent from this one, in that it focuses on mass spectrometrymethods and applications and includesmeasurements of air, soil/sediments, and biological samples, in addition to water. ThisReview on Water Analysis focuses only on water measurementsand applications but includes other methodologies besidesmass spectrometry. I am excited to have Thomas Ternes joinme this year (as in 2005) to cover the section on Pharmaceuticalsand Hormones. Because Thomas is an international leader in thisarea, this Review will be much better with his contribution. Wewelcome any comments you have on this Review ([email protected]).

Numerous abstracts were consulted before choosing the bestrepresentative ones to present here. Abstract searches werecarried out using Web of Science, and in many cases, full articleswere obtained. A table of acronyms is provided (Table 1) as aquick reference to the acronyms of analytical techniques andother terms discussed in this Review. A table of usefulWebsites isalso provided (Table 2).Major Analysis Trends.One of the hottest trends is the use of

high resolution mass spectrometry (MS) with liquid chromatog-raphy (LC) to identify unknown contaminants or to providefurther selectivity for known analytes. Full scan and high resolu-tion mass spectrometry have been used with gas chromatography(GC) in a similar fashion for decades, enabling the identificationof many environmental contaminants. With recent instrumentaldevelopment for LC/mass spectrometers, especially time-of-flight (TOF), this full scan and high resolution/accurate massbenefit is now being utilized both for target analytes and also foridentifying nontarget analytes that are highly polar, nonvolatile,or of high molecular weight and are not amenable to GC. As aresult, within a single analytical run, both target and nontargetanalytes can be analyzed or identified. In comparison to triplequadrupole mass spectrometers, which operate at unit resolutionand generally in the selected reaction monitoring (SRM) ormultiple reaction monitoring (MRM) modes for specific targetanalytes, TOF-mass spectrometers are capable of acquiring full-scan mass spectra at high resolution for all analytes without lossin sensitivity. Because most TOF mass spectrometers have aresolution of at least 10 000 at full-width-half-maximum (fwhm)peak height, isotopic patterns are evident and empirical formulasand chemical structures can be proposed for unknowns orconfirmed for target analytes. This also makes it possible to usemass spectral libraries and enable the data file to be reinterro-gated months later to find additional unknown contaminants.

Table 1. List of Acronyms

APCI atmospheric pressure chemical ionization

APPI atmospheric pressure photoionization

BP-3 benzophenone-3

BSTFA bis(trimethylsilyl)trifluoroacetamide

CCL Contaminant Candidate List

DBPs disinfection byproducts

E1 estrone

E2 17β-estradiol

E3 estriol

EE2 17R-ethinylestradiolECD electron capture detection

EDCs endocrine disrupting compounds

ELISA enzyme-linked immunosorbent assay

EPA Environmental Protection Agency

ESA ethane sulfonic acid

ESI electrospray ionization

FT Fourier-transform

FTOHs fluorinated telomer alcohols

GC gas chromatography

HAAs haloacetic acids

HXLPP hypercrosslinked polymer resin

IC ion chromatography

ICP inductively coupled plasma

IR infrared

LC liquid chromatography

MALDI matrix-assisted laser desorption ionization

4-MBC 4-methylbenzylidene camphor

MCL maximum contaminant level

MIMS membrane introduction mass spectrometry

MRM multiple reaction monitoring

MS mass spectrometry

MSTFA N-methyl-N-trimethylsilyltrifluoroacetamide

MX 3-chloro-(4-dichloromethyl)-5-hydroxy-2(5H)-furanone

NCI negative chemical ionization

NDMA N-nitrosodimethylamine

NMR nuclear magnetic resonance

NOM natural organic matter

N-EtFOSAA N-ethyl perfluorooctane sulfonamide acetate

OC octocrylene

ODPABA octyl-dimethyl-p-aminobenzoic acid

PCBs polychlorinated biphenyls

PBDEs polybrominated diphenyl ethers

PFCs perfluorinated compounds

PFCAs perfluorocarboxylic acids

PFDA perfluorodecanoic acid

PFHxA perfluorohexanoic acid

PFHpA perfluoroheptanoic acid

PFNA perfluorononanoic acid

PFOA perfluorooctanoic acid

PFOS perfluorooctane sulfonate

PFOSA perfluorooctane sulfonamide

PFPrA perfluoropropanoic acid

PFUnDA perfluoroundecanoic acid

REACH Registration, Evaluation, and Authorization of Chemicals

SPE solid phase extraction

Table 1. ContinuedSPME solid phase microextraction

THMs trihalomethanes

TOF time-of-flight

UCMR-3 the third Unregulated Contaminants Monitoring Rule

UPLC ultraperformance liquid chromatography

WWTP wastewater treatment plant



In addition to TOF-mass spectrometers, linear ion trap-Fouriertransform (FT)-Orbitrap mass spectrometers are also now beingused for similar high resolution-full scan applications. Examplesof the use of high resolution-MS in this Review include theidentification of pharmaceutical and pesticide transformationproducts and naphthenic acids.Researchers are also increasingly using isotopically labeled

standards (deuterated or 13C-labeled) to allow more accuratequantification in a variety of sample matrixes (especially for waste-water samples, where matrix effects and ion suppression can besubstantial). Atmospheric pressure photoionization (APPI) is alsoincreasingly being used with LC/MS because it provides improvedionization for more nonpolar compounds, such as nanomaterials(e.g., fullerenes), polybrominated diphenyl ethers (PBDEs), andnaphthenic acids discussed in this Review. Finally, nuclear magneticresonance (NMR) spectroscopy is increasing in use, as it canprovide detailed structural information to confirm tentativestructures proposed by LC/MS/MS. In this regard, it is increas-ingly used to confirm structures of pharmaceutical transformationproducts. Because NMR is not as sensitive as MS, preparative LCis often used to collect enough material in fractions to enable theanalysis of unknowns in complex environmental mixtures.Sampling and Extraction Trends. Solid phase extraction

(SPE) remains the most popular means of extraction andconcentration, and a new SPE device called Bag extraction wasreported during the last 2 years. This bag-SPE consists ofpolystyrenedivinylbenzene enclosed in a woven polyester fabric,which can be immersed in water samples for solid phaseextraction. Measured concentrations of pharmaceuticals have beenshown to be comparable for bag-SPE vs Oasis HLB extraction.Benefits include the ease of handling, unattended water extrac-tion, and that no filtration is needed. In addition, new SPEsorbents are available, including Oasis MCX and hypercross-linked polymer resin (HXLPP) that are being used to capture abroader range of analytes within a single extraction. Solventlessextraction techniques, such as solid phase microextraction (SPME),single-drop microextraction (SDME), stir bar sorptive extraction,and hollow-fiber membrane microextraction, also continue to beused in many applications. Polar organic chemical integrativesamplers (POCIS) are also popular. These POCIS extractiondevices have membranes that allow polar contaminants to bepassively extracted from water and wastewater and can allowhigher concentration factors and a more integrated sampling (vsspot sampling) over time.The use of molecularly imprinted polymers (MIPs) for selective

extraction of environmental contaminants has also continued togrow. MIPs are synthetic polymers made with specific recogni-tion sites that are complementary in shape, size, and functionalgroup to the analyte of interest. The recognition sites mimic thebinding sites of antibodies and enzymes. Because they are highlyspecific to the target analytes of interest,MIPs can be used to extractand isolate them from other matrix components in a complexmixture.MIPs have now been synthesized for a number of emergingcontaminants, including pharmaceuticals, pesticides, pesticidemetabolites, endocrine disrupting compounds (EDCs), and algaltoxins. Examples are cited in this Review for pharmaceuticals.Chromatography Trends. The fastest growing chromatog-

raphy trend continues to be the use of ultraperformance liquidchromatography (UPLC). UPLC is a recently developed LCtechnique that uses small diameter particles (typically 1.7 μm) inthe stationary phase and short columns, which allow higherpressures and, ultimately, narrower LC peaks (5�10 s wide). In

addition to providing narrow peaks and improved chromato-graphic separations, UPLC dramatically shortens analysis times,often to 10min or less. Another significant chromatography trend isthe use of two-dimensional GC (GC�GC). GC�GC enablesenhanced separations of complex mixtures through greaterchromatographic peak capacity and allows homologous seriesof compounds to be easily identified. It also enables the detectionof trace contaminants that would not have been identifiedthrough traditional GC. TOF-MS is often used as the detectorfor GC�GC because of its rapid acquisition capability. Examplesof the use of GC�GC in this Review include the measurement ofbenzotriazoles, benzothiazoles, and benzosulfonamides.Use of Nanomaterials in Analytical Methods. In addition to

nanomaterials being a class of emerging contaminant, they arealso being applied in creative ways to aid in the measurement ofother emerging contaminants. For example, carbon nanohornswere used in electrochemical immunosensors to enable the rapiddetection of microcystin-LR (an algal toxin) in water. Goldnanoparticle labeling was also usedwith ICP-MS in a newmethodtomeasureE. coli O157:H7 inwater. Thismethod took advantage ofthe signal amplification property of gold nanoparticles, mono-clonal antibody recognition, and the high sensitivity of ICP-MS.Other Particularly Creative Methods. In addition to the

creative use of nanomaterials mentioned above, the last 2 yearshas seen other particularly creative methods worthy of mention.One such method involved a new microsensor array imprintedonto ordinary compact discs (CDs) to measure microcystins inwater. Immunoreactions were detected with a DVD drive, whichdisplayed the readouts in minutes. This method was simple,sensitive, and rapid and could be used in a high-throughputcapacity for field use. Another creative method for UV filtersinvolved the use of direct analysis in real-time (DART)-MS todirectly analyze the surface of a polydimethylsiloxane-coated stirbar previously used to extract the UV filters from water. Whilestir-bar sorptive extraction is commonly used in many environ-mental applications, the direct analysis of analytes sorbed onto thesestir bars is a new, creative application that makes the method muchmore simple and rapid and still allows low ng/L detection limits.Emerging Contaminants. This year, there is one new con-

taminant class added as a “contaminant on the horizon” to watch:ionic liquids. Ionic liquids are organic salts with a low meltingpoint (<100 �C) that are being promoted as “green chemistry”replacements to traditional solvents used in industry becausethey have low volatility and flammability. They are currently oneof the hottest areas in chemistry, with many papers and reviewshighlighting ionic liquids as a state-of-the-art, innovative ap-proach to sustainable chemistry. However, there is limitedtoxicity and environmental data for these new “green solvents”,and there is the potential that they may pose a threat to aquaticand terrestrial ecosystems. While not volatile, most ionic liquidsare highly water-soluble and chemically and thermally stable,creating the potential for entry and persistence in the environ-ment. The state-of-the-science on their environmental fate andtoxicity, along with a discussion of their properties and uses,appears at the end of this Review.Other emerging contaminants discussed include sucralose

(and other artificial sweeteners), nanomaterials, perfluorinatedcompounds (PFCs), pharmaceuticals, hormones, drinking waterdisinfection byproducts (DBPs), sunscreens/UV filters, brominatedflame retardants (including polybrominated diphenyl ethers),benzotriazoles, naphthenic acids, antimony, siloxanes, musks, algaltoxins, perchlorate, dioxane, pesticide transformation products,



and microorganisms. These continue to be intense areas ofresearch. An ongoing trend in research for most of theseemerging contaminants continues to be investigating ways toremove them from environmental waters (e.g., through advancedoxidation, photolysis, microbial degradation, etc.). Because re-searchers often find that the contaminants are not completelyremoved with these technologies, the identification of intermediatesand degradation products becomes important, as well as theevaluation of resulting toxicity or biological activity for the transfor-mation products. In this regard, there are many more researcherswho are combining analytical chemistry with effects research.

’GENERAL REVIEWS

This section includes general reviews relating to water analysisand emerging contaminants. Reviews that relate to specific areas(e.g., PFCs, pharmaceuticals, DBPs) can be found in thosespecific sections. Many reviews have been published over thelast two years that relate to environmental mass spectrometry,and a few focus specifically on emerging contaminants. My otherbiennial review on Environmental Mass Spectrometry publishedin 2010 discussed advances in mass spectrometry research for thesame emerging contaminants discussed in this current Review,along with melamine�cyanuric acid.2

Rubio and Perez-Bendito published an excellent review on therecent advances in environmental analysis, including discussionsof sampling and sample preparation techniques, separation anddetection techniques, calibration, and environmetrics (dataanalysis).3 Emerging contaminants were the focus of severalreviews over the past 2 years. For example, Alvarez and Jones-Lepp published a new review on sampling and analysis ofemerging contaminants in surface water, groundwater, and soiland sediment pore water.4Wells et al., discussed occurrence, fate,treatment, modeling, and toxicity/risk assessment of emergingpollutant studies published in 2009.5 Murray et al. reviewedoccurrence and toxicity data for three classes of trace pollutantsand emerging contaminants (industrial chemicals, pesticides,pharmaceuticals, and personal care products) and prioritizedthem for potential regulation and treatment.6

Verlicchi et al. discussed hospital effluents as a source ofemerging pollutants and outlined different treatment options forremoving them, including physicochemical treatment, biologicaltreatment, reverse osmosis, nanofiltration, ozonation, advancedoxidation processes, disinfection, and use of constructed wetlands.7

Contaminants highlighted included pharmaceuticals, radionu-clides, solvents, and disinfectants. Snow et al. reviewed the detection,occurrence, and fate of emerging contaminants in agriculturalenvironments, which included discussions of pharmaceuticals,hormones, veterinary antibiotics, antibiotic resistant genes, andprions.8 Matamoros et al. reviewed the advances in determiningdegradation intermediates for personal care products in the

environment.9 Contaminants included stimulants, fragrances,sunscreens, antimicrobials, and insect repellents.

Several reviews focused on LC/MS trends for measuringemerging contaminants. For example, Petrovic et al. reviewedLC/MS methods used for pharmaceuticals, drugs of abuse, polarpesticides, PFCs, and nanomaterials.10 Krauss et al. reviewed theuse of LC with high resolution-MS for target screening andidentification of unknowns.11 The development of highly re-solved and accurate hybrid tandem mass spectrometers, such asquadrupole (Q)-TOF and linear ion trap/Orbitrap instruments,as well as improved automated software, have enabled morereliable target analysis of highly polar compounds, as well asscreening for unknowns. Similarly, Pitarch et al. discuss ananalytical strategy based on the use of LC and GC with triplequadrupole and TOF mass spectrometers for measuring targetorganic contaminants in wastewater.12 This strategy was demon-strated for 60 compounds from different chemical families, manyof which are priority contaminants in the European UnionWaterDirective, and was also effective for identifying nontarget com-pounds, due to accuratemass and full scan capability of TOF-MS.

UPLC/MS was the focus of a review by Guillarme et al., whodiscussed its use for analyzing environmental samples, biologicalfluids, foods, and plant extracts.13 Applications to metabolomicswere also highlighted. The application of capillary electrophoresis(CE)/MS in the trace analysis of environmental and food con-taminants was the focus of another review by Robledo and Smyth.14

Low molecular weight amines, nitroaromatics, alkylphosphonicacids, azo dyes, antidepressants, and antibiotics were included.

While not reviews themselves, a few additional papers arenoteworthy for general applicability in analyzing emerging con-taminants in environmental samples. Two papers focused on theuse of computer-aided techniques for identifying organic con-taminants and transformation products. In the first, Kern et al.combined LC/high resolution-MS with a target list of predictedmicrobial degradation products to screen for transformationproducts of 52 pesticides, biocides, and pharmaceuticals insurface waters from Switzerland.15 Using this procedure, 19transformation products were identified, including some thatare rarely reported. In the second, Rosal et al. detailed thedevelopment and interlaboratory verification of LC/MS librariesfor identifying environmental contaminants, including pesti-cides, illicit drugs, and pharmaceuticals.16 When comparinglibrary searching results, the libraries from two manufacturers’instruments exhibited different ion abundance ratios in theirmass spectra, but the NIST search engine match probability was96% or greater for 64 out of 67 compounds evaluated.

’NEW REGULATIONS/REGULATORY METHODS

NewProposed Regulation for Perchlorate in U.S. DrinkingWater. The big news for this year is that the U.S. Environmental

Table 2. Useful Websites

Website comments

www.epa.gov U.S. EPA’s Website

www.epa.gov/safewater/methods/analyticalmethods.html U.S. EPA approved methods for drinking water compliance monitoring

www.epa.gov/microbes/ordmeth.htm drinking water methods developed by U.S. EPA’s National Exposure Research Laboratory

www.standardmethods.org/ link to Standard Methods Online

www.astm.org link to ASTM International methods

http://ec.europa.eu/environment/chemicals/reach/reach_intro.htm REACH Website



Protection Agency (EPA) has decided to regulate perchlorateunder the Safe Drinking Water Act (http://water.epa.gov/drink/contaminants/unregulated/perchlorate.cfm). This deci-sion reverses a 2008 preliminary determination. Perchlorate ishighly water-soluble, is environmentally stable, accumulates inplants, and is of concern because it can disrupt the thyroid’sability to produce hormones needed for normal growth anddevelopment. As such, it has been a concern for the U.S. EPA,dating back to 1998 when it was placed on the original Con-taminant Candidate List for drinking water (CCL-1) and later onthe CCL-3. National data collected from the Unregulated Con-taminants Monitoring Rule (UCMR) revealed that more than4% of the public drinking water systems in the U.S. haddetectable perchlorate, and the U.S. EPA decided there was ameaningful opportunity for health risk reduction for 5 to 16million people. The U.S. EPA intends to publish the proposedregulation for public review and comment within 24 months,with a proposed maximum contaminant limit (MCL) at thattime. A final regulation would be promulgated within 18 monthsafterward. Interestingly, two states had already regulated per-chlorate earlier: California (2007), with an MCL of 6 μg/L, andMassachusetts (2006), with an MCL of 2 μg/L.Another new direction being considered by the U.S. EPA in its

new drinking water strategy is to address contaminants as groupsrather than individually. Of course, this was done in the pastsomewhat with regulating trihalomethanes (THMs) and haloa-cetic acids (HAAs) but has not generally been used for othercontaminants. This group approach is intended to speed upaction on new and emerging threats to drinking water, and thefirst group selected for consideration is 16 volatile organiccompounds (VOCs) that may cause cancer (http://water.epa.gov/lawsregs/rulesregs/sdwa/dwstrategy/upload/FactSheet_DrinkingWaterStrategy_VOCs.pdf). Recent U.S. Rules and Reg-ulations are summarized in Table 3.The New Contaminant Candidate List-3 (CCL-3). In Sep-

tember 2009, the U.S. EPA published the final CCL-3, which is adrinking water priority contaminant list for regulatory decisionmaking and information collection. The listed contaminants areknown to occur or anticipated to occur in drinking water systemsand will be considered for potential regulation. This final CCL-3contains 104 chemicals or chemical groups and 12 microbialcontaminants (Table 4) and is somewhat different than theoriginal proposed CCL-3 in 2008. This final CCL-3 now includesperfluorooctanoic acid (PFOA) and perfluorooctane sulfonate(PFOS), 3 pharmaceuticals (erythromycin, 17R-ethinylestradiol[EE2], and nitroglycerin [also used as an explosive]), 8 hor-mones (17R-estradiol, 17β-estradiol, equilenin, equilin, estriol,estrone, mestranol, and norethindrone), and several DBPs(chlorate, formaldehyde, acetaldehyde, and 5 nitrosamines), aswell as pesticides, pesticide degradation products, metals, indus-trial solvents/ingredients, and specific algal toxins (microcystin-LR, anatoxin-a, and cylindrospermopsin). The U.S. EPA is also

currently considering available occurrence, toxicity, bioaccu-mulation, and other data for the chemical contaminants on theCCL-3 to make a preliminary decision whether to regulate anyof them.For this CCL-3 effort, there was a major change in how it was

developed. The U.S. EPA undertook a broader and morecomprehensive screening process of potential contaminants andused a new mechanism for allowing the general public, stake-holders, agencies, and industry to nominate chemicals, micro-organisms, or other materials for consideration. In the newprocess, a broadly defined “universe” of potential drinking watercontaminants was identified, assessed, and reduced to a prelimin-ary CCL (PCCL) using simple screening criteria that indicatepublic health risk and the likelihood of occurrence in drinkingwater. The PCCL contaminants were then assessed inmore detailusing available occurrence and toxicity data, and a draft CCL-3was proposed. Outside expert panels (including the ScienceAdvisory Board) were then asked to comment on this draft list,and the list changed substantially following their recommenda-tion. Further details on theCCL-3 process can be found at http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm.The Draft Third Unregulated Contaminants Monitoring

Rule (UCMR-3). The Draft UCMR-3 was proposed on February17, 2011 (http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/ucmr3/index.cfm) and is an updated version of the earlierUCMR-1 (1999) and UCMR-2 (2007). Table 5 lists the con-taminants proposed to be monitored under the UCMR-3, alongwith their approved methods. Contaminants include hormones,PFCs, VOCs, metals, dioxane, chlorate, and viruses. The UCMR-3 requires drinking water utilities to monitor for 30 contaminants(28 chemicals and 2 viruses) during 2013�2015. Twenty-four ofthese contaminants are also on the CCL-3. The 6 chemicals noton the CCL-3 include testosterone, 4-androstene-3,17-dione,and 4 PFCs: perfluorobutanesulfonic acid (PFBS), perfluoro-heptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS),and perfluorononanoic acid (PFNA). The UCMR is used toprovide national occurrence data for priority unregulated con-taminants for future regulatory consideration. This Rule helps tosupport the Safe Drinking Water Act and Amendments, whichrequires that, at least once every five years, theU.S. EPA identify alist of no more than 30 unregulated contaminants to be mon-itored. The Draft UCMR-3 is divided up into two groups ofcontaminants (Table 5). All public water systems serving morethan 10 000 people and a representative sample of 800 systemsserving 10 000 or fewer people are required to conduct Assess-ment Monitoring (List 1) during a continuous 12-month periodduring January 2013�December 2015. In addition, a targetedgroup of 800 systems serving 1000 or fewer people will conductprescreen testing for two “List 3” viruses during a 12-monthperiod from January 2013�December 2015.New Regulatory Methods for Drinking Water. Four new

drinking water methods were developed by the U.S. EPA

Table 3. Recent U.S. Rules/Regulations

rule/regulation Website

Stage 2 D/DBP Rule http://water.epa.gov/lawsregs/rulesregs/sdwa/stage2/regulations.cfm

Contaminant Candidate List (CCL)-3 http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm

Draft Third Unregulated Contaminants Monitoring

Rule (UCMR-3) http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/ucmr3/index.cfm

UCMR-2 national occurrence data http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/data.cfm#ucmr2010



Table 4. Final Contaminant Candidate List-3 (CCL-3)

Chemical Contaminants

1,1,1,2-Tetrachloroethane

1,1-Dichloroethane

1,2,3-Trichloropropane

1,3-Butadiene

1,3-Dinitrobenzene

1,4-Dioxane

17R-Estradiol1-Butanol

2-Methoxyethanol

2-Propen-1-ol

3-Hydroxycarbofuran

4,40-Methylenedianiline

Acephate

Acetaldehyde

Acetamide

Acetochlor

Acetochlor ethanesulfonic acid (ESA)

Acetochlor oxanilic acid (OA)

Acrolein

Alachlor ethanesulfonic acid (ESA)

Alachlor oxanilic acid (OA)

R-HexachlorocyclohexaneAniline

Bensulide

Benzyl chloride

Butylated hydroxyanisole

Captan

Chlorate

Chloromethane (Methyl chloride)

Clethodim

Cobalt

Cumene hydroperoxide

Cyanotoxins (Anatoxin-a, Microcystin-LR, and Cylindrospermopsin)

Dicrotophos

Dimethipin

Dimethoate

Disulfoton

Diuron

Equilenin

Equilin

Erythromycin

Estradiol (17β-estradiol)

Estriol

Estrone

Ethinyl estradiol (17R-ethinyl estradiol)Ethoprop

Ethylene glycol

Ethylene oxide

Ethylene thiourea

Fenamiphos

Formaldehyde

Germanium

Halon 1011 (bromochloromethane)

HCFC-22

Table 4. ContinuedHexane

Hydrazine

Mestranol

Methamidophos

Methanol

Methyl bromide (Bromomethane)

Methyl tert-butyl ether

Metolachlor

Metolachlor ethanesulfonic acid (ESA)

Metolachlor oxanilic acid (OA)

Molinate

Molybdenum

Nitrobenzene

Nitroglycerin

N-Methyl-2-pyrrolidone

N-Nitrosodiethylamine (NDEA)

N-Nitrosodimethylamine (NDMA)

N-Nitroso-di-n-propylamine (NDPA)

N-Nitrosodiphenylamine (NDPhA)

N-Nitrosopyrrolidine (NPYR)

Norethindrone (19-Norethisterone)

n-Propylbenzene

o-Toluidine

Oxirane, methyl-

Oxydemeton-methyl

Oxyfluorfen

Perchlorate

Perfluorooctane sulfonic acid (PFOS)

Perfluorooctanoic acid (PFOA)

Permethrin

Profenofos

Quinoline

RDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine)

sec-Butylbenzene

Strontium

Tebuconazole

Tebufenozide

Tellurium

Terbufos

Terbufos sulfone

Thiodicarb

Thiophanate-methyl

Toluene diisocyanate

Tribufos

Triethylamine

Triphenyltin hydroxide (TPTH)

Urethane

Vanadium

Vinclozolin

Ziram

Microbial Contaminants

Adenovirus

Caliciviruses

Campylobacter jejuni

Enterovirus



(Table 6): Method 539 (hormones), 538 (pesticides, quinoline,and other organic contaminants), 524.3 (purgeable organiccompounds), 1615 (enteroviruses and noroviruses). These aremostly directed toward the measurement of CCL/UCMRchemicals in drinking water. The U.S. EPA’s Office of Wateralso has a nice Website that lists all EPA approved methods fordrinking water compliance, which include methods developedfor inorganics (including metals), radionuclides, and organiccontaminants (http://water.epa.gov/scitech/drinkingwater/lab-cert/analyticalmethods.cfm). Note that this Website address isdifferent from past years. ThisWebsite provides a link not only toEPA Methods but also to methods developed by ASTM Inter-national, StandardMethods, theU.S. Geological Survey (USGS),the U.S. Department of Homeland Security, Waters Corp., andother organizations, which are approved to use for drinking watercompliance in the United States.EPA Method 539: Hormones. In 2010, a new EPA method

was created for measuring 7 hormones in drinking water: EPAMethod 539, Determination of Hormones in Drinking Water bySolid phase Extraction (SPE) and Liquid Chromatography Electro-spray Ionization TandemMass Spectrometry (LC/ESI-MS/MS)(http://water.epa.gov/scitech/drinkingwater/labcert/upload/met539.pdf). The hormones include 16R-hydroxyestradiol (estriol),17β-estradiol, 17R-ethinylestradiol, testosterone, estrone,4-androstene-3,17-dione, and equilin. Most of these hormonesare included on the U.S. EPA’s new CCL-3. Detection limitsrange from 0.04 to 2.9 ng/L.EPA Method 538: Pesticides, Quinoline, and Other Organic

Contaminants. In 2009, a new EPA method was created formeasuring pesticides, quinoline, and other organic contaminantsin drinking water: EPA Method 538, Determination of SelectedOrganic Contaminants in Drinking Water by Direct AqueousInjection-Liquid Chromatography/Tandem Mass Spectrometry(DAI-LC/MS/MS) (www.epa.gov/microbes/Method%20538_Final.pdf). Analytes include acephate, aldicarb, aldicarb sulfoxide,dicrotophos, diisopropyl methylphosphonate (DIMP), fenamiphossulfone, methamidophos, oxidemeton-methyl, quinoline, and thio-fanox. Minimum reporting levels ranged from 0.011 to 1.5 μg/L.EPAMethod524.3: PurgeableOrganicCompounds. In 2009,

a new EPA method was created for measuring purgeable organiccompounds in drinking water: Measurement of Purgeable OrganicCompounds inWater by Capillary ColumnGas Chromatography/Mass Spectrometry (www.epa.gov/ogwdw000/methods/pdfs/methods/met524-3.pdf). A total of 86 analytes can be measuredwith this purge-and-trap GC/MS method, including a few newanalytes that were not part of previous versions of this method: 1,3-butadiene, chlorodifluoromethane, diisopropyl ether (DIPE),methyl acetate, tert-amyl ethyl ether (TAEE), tert-amyl methylether (TAME), tert-butyl alcohol (TBA), and tert-butyl ethyl ether(ETBE). Detection limits range from 7.7 to 140 ng/L.

EPA Method 1615: Enteroviruses and Noroviruses. InDecember 2010, a new EPA method was created for measuringenteroviruses and noroviruses in water (http://www.regulations.

Table 4. ContinuedEscherichia coli (0157)

Helicobacter pylori

Hepatitis A virus

Legionella pneumophila

Mycobacterium avium

Naegleria fowleri

Salmonella enterica

Shigella sonnei

Table 5. Draft Unregulated Contaminants Monitoring Rule(UCMR)-3 Contaminants and Approved Methods

List 1. Assessment MonitoringContaminant Method

Hormones

17β-Estradiol EPA Method 539

17R-Ethinylestradiol(ethinyl estradiol)

EPA Method 539

16R-Hydroxyestradiol (estriol) EPA Method 539

Equilin EPA Method 539

Estrone EPA Method 539

Testosterone EPA Method 539

4-Androstene-3,17-dione EPA Method 539

Volatile Organic Compounds

1,2,3-Trichloropropane EPA Method 524.3

1,3-Butadiene EPA Method 524.3

Chloromethane (methyl chloride) EPA Method 524.3

1,1-Dichloroethane EPA Method 524.3

n-Propylbenzene EPA Method 524.3

Bromomethane (methyl bromide) EPA Method 524.3

sec-Butylbenzene EPA Method 524.3

Chlorodifluoromethane (HCFC-22) EPA Method 524.3

Bromochloromethane (halon 1011) EPA Method 524.3

Synthetic Organic Compounds

1,4-Dioxane EPA Method 522

Metals

Vanadium EPA 200.8 Rev 5.4, ASTM D5673

Molybdenum EPA 200.8 Rev 5.4, ASTM D5673

Cobalt EPA 200.8 Rev 5.4, ASTM D5673

Strontium EPA 200.8 Rev 5.4, ASTM D5673

Oxyhalide Anion

Chlorate EPA Method 300.1, ASTM

D6581�08, Standard Methods

4110D (1997)

Perfluorinated Compounds

Perfluorooctane sulfonate (PFOS) EPA Method 537.1

Perfluorooctanoic acid (PFOA) EPA Method 537.1

Perfluorononanoic acid (PFNA) EPA Method 537.1

Perfluorohexane sulfonic

acid (PFHxS)

EPA Method 537.1

Perfluoroheptanoic

acid (PFHpA)

EPA Method 537.1

Perfluorobutane sulfonic

acid (PFBS)

EPA Method 537.1

Prescreening Testing (List 3)

Contaminant Method

Enteroviruses EPA Method 1615

Noroviruses EPA Method 1615



gov/#!documentDetail;D=EPA-HQ-OW-2009-0090-0029).This method uses filtration, extraction of RNA, and real-timequantitative polymerase chain reaction (PCR) for detection.Detection limits are reported in terms of most probablenumber (MPN) of infectious units per liter; detection limitsare 0.01 MPN/L (surface water) and 0.002 MPN/L (ground-water).

’SUCRALOSE AND OTHER ARTIFICIAL SWEETENERS

Sucralose (also known as Splenda or SucraPlus) is a relativelynew artificial sweetener that is now widely used in NorthAmerican and Europe. It may seem like an odd compound toinclude as an emerging contaminant, but it is now being found inenvironmental waters and is extremely persistent (half-life up toseveral years).2 It is made by chlorinating sucrose, where threehydroxyl groups are replaced by chlorine atoms. Sucralose is heatstable, which is why it has replaced other artificial sweeteners(such as aspartame) for baking and is now widely used in softdrinks because of its long shelf life. So far, at least 9 researchgroups have investigated its occurrence and fate in the environ-ment: the Norwegian Institute for Air Research,2 the SwedishEnvironmental Research Institute,2 and the European Commis-sion’s Joint Research Centre17 and most recently from research-ers at the University of North Carolina-Wilmington,18 the WaterTechnology Center in Karlsruhe, Germany,19,20 the Swiss Fed-eral Research Station inW€adenswil, Switzerland,21 theUniversityof Colorado,22 and Link€oping University (Sweden) togetherwith the Swiss Federal Institute of Aquatic Science and Technol-ogy (EAWAG).23 In the groundbreaking multicountry study inEurope,17 Loos et al. used a SPE-LC/negative ion-electrosprayionization (ESI)-MS/MS method with isotope dilution to mea-sure sucralose at a detection limit of∼10 ng/L. One hundred andtwenty samples were collected from rivers in 27 Europeancountries, and sucralose was found up to 1 μg/L, predominantlyin samples from the United Kingdom, Belgium, The Nether-lands, France, Switzerland, Spain, Italy, Norway, and Sweden,with only minor levels (<100 ng/L) detected in samples fromGermany and Eastern Europe, suggesting a lower use of sucralosein those countries. Mead et al. presented the first findings ofsucralose in the United States, as well as the first measurements incoastal and open ocean waters.18 SPE, derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), and quan-tification by GC/MS were used to measure sucralose in estuarineand coastal waters fromNorth Carolina (NC), Louisiana, and theFlorida Keys. The highest concentrations were from treatedwastewater effluents (119 μg/L) in NC, with decreasing con-centrations in the receiving waters of the Cape Fear River Estuary(NC) (372 ng/L), and levels up to 67, 147, and 392 ng/L inwaters from the Gulf Stream, Northern Florida Keys, andMiddleFlorida Keys, respectively. This study highlighted the persistenceand widespread distribution of sucralose, with incorporation intoa major oceanographic current (the Gulf Stream), where globaldistribution could take place.

Scheurer et al. reported a new SPE-LC/ESI-MS/MS methodfor measuring 7 artificial sweeteners (sucralose, acesulfame,cyclamate, saccharin, aspartame, neotame, and neohesperidindihydrochalcone (NHDEC)) in environmental waters and usedthis method to measure their occurrence in German wastewatertreatment plants, surface waters, and soil aquifer treatmenteffluents.19 Quantification limits ranged from 1 to 10 ng/L, withno substantial ion suppression. Four artificial sweeteners(sucralose, acesulfame, saccharin, and cyclamate) were foundin the wastewater influent and effluent samples, at concentrationsranging from 34 to 50 μg/L for acesulfame and saccharin, up to190 μg/L for cyclamate, and below 1 μg/L for sucralose ininfluents. Acesulfame and sucralose were not well removed inwastewater treatment, whereas saccharin and cyclamate wereremoved at >94%. Acesulfame was more persistent during soilaquifer treatment than in conventional wastewater treatment,such that acesulfame was still present in groundwater after aresidence time of 1.5 year. In surface waters, acesulfame was thepredominant artificial sweetener found, with concentrationsexceeding 2 μg/L; saccharin and cyclamate were found at levelsbetween 50 and 150 ng/L, and sucralose was found at 60 to80 ng/L, with one sample exceeding 100 ng/L.

Following this wastewater study, Scheurer et al. also investi-gated the effectiveness of drinking water treatment in removingfour artificial sweeteners: sucralose, acesulfame, saccharin, andcyclamate.20 Six full-scale drinking water treatment plants wereinvestigated, which used bank filtration, artificial recharge, floc-culation, ozonation, granular activated carbon (GAC) filtration,and disinfection with chlorine and chlorine dioxide. Acesulfameand sucralose proved to be the most recalcitrant. Acesulfame wasthe only artificial sweetener detected in finished drinking water,up to several hundred ng/L. Acesulfame and sucralose were notbiodegraded during river bank filtration, and sucralose waspersistent against ozone, with transformation <20% in lab andfield tests. However, remaining levels could be subsequentlyremoved using GAC filtration. On the other hand, acesulfamereacted readily with ozone, but ozone levels typically used indrinking water treatment would only remove 18�60%. Theremaining acesulfame could then be somewhat removed usingGAC filtration. Ozonation byproducts are yet to be identified.Saccharin and cyclamate were removed completely in all drinkingwater treatment plants using river bank filtration or artificialgroundwater recharge. One point of interest was that thestructurally similar acesulfame and saccharin (both with asulfonamide moiety in their ring structures) behaved completelydifferent during ozonation, and the initial point of attack forozone on the molecules is not known.

Buerge et al. developed an online-SPE-LC/MS/MS methodtomeasure 4 artificial sweeteners (sucralose, acesulfame, saccharin,and cyclamate) in environmental waters.21 All 4 artificialsweeteners were found in most samples analyzed, with acesul-fame detected at the highest levels. Acesulfame was consistentlydetected in untreated and treated wastewater (12�46 μg/L), in

Table 6. New Regulatory Methods

method analytes Website

EPA Method 539 hormones http://water.epa.gov/scitech/drinkingwater/labcert/upload/met539.pdf

EPA Method 538 pesticides, quinoline, and other organic contaminants www.epa.gov/microbes/Method%20538_Final.pdf

EPA Method 524.3 purgeable organic compounds www.epa.gov/ogwdw000/methods/pdfs/methods/met524-3.pdf

EPA Method 1615 enteroviruses and noroviruses http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OW-2009-0090-0029



most surface waters (up to 2.8 μg/L), in 65% of the groundwatersamples investigated (up to 4.7 μg/L), and even in several tapwater samples (up to 2.6 μg/L) in Switzerland. Because of itrecalcitrance to transformation, acesulfame was viewed as anideal marker for the detection of domestic wastewater inenvironmental waters, particularly groundwater. Using acesul-fame as a chemical marker, the percent contribution of domesticwastewater to environmental waters could be determined. Forexample, acesulfame levels were used to estimate a ∼10�20%contribution from domestic wastewater to groundwater in thelower Glatt valley in Switzerland. This method is sensitiveenough to detect as low as a 0.05% contribution.

Ferrer and Thurman developed a SPE-LC/TOF-MS methodto measure sucralose, aspartame, and saccharin in wastewater,surface water, groundwater, and soft drinks.22 The presence ofthe artificial sweeteners could be confirmed by accurate massmeasurements. Analysis of several wastewater, surface water, andgroundwater samples revealed relatively high levels of sucralose,up to 2.4 μg/L. Sucralose was frequently detected, whereassaccharin was only detected in one wastewater sample, andaspartame was not detected in any samples. It is likely thataspartame and saccharin are easily biodegraded, due to reactivechemical moieties in these molecules. Finally, Neset et al.combined substance-flow modeling with water and wastewatersampling to establish the current extent of sucralose emissionsfrom consumption.23 Sucralose was measured in wastewatertreatment plant influents and effluents in Sweden and alsoupstream and downstream of the receiving stream and in anearby lake. Samples were measured using a SPE-LC/Orbitrap-MS/MS method. This study revealed that several small sourcescontributed to the loading coming from households, smallbusinesses, and industry, which was in contrast to a consumptionpattern seen two years earlier.

’ANTIMONY

Antimony, which can have both acute and chronic toxicityeffects, is regulated in drinking water in the United States,Canada, Europe, and Japan at action levels ranging from 2 to 6μg/L. Antimony contamination can result from copper or leadsmelting or from petroleum refineries, but new studies haveshown that it can also leach from polyethylene terephthalate(PET) plastic water bottles.2 Antimony trioxide is used as acatalyst in the manufacture of PET plastics, which can contain>100 mg/kg of antimony. Keresztes et al. used inductivelycoupled plasma ICP-MS to measure antimony leaching fromPET bottles into carbonated (sparkling) and noncarbonated(still) mineral waters purchased in Europe.24 Storage conditions(time, temperature, exposure to light) were also investigated. Ingeneral, antimony levels were higher in the carbonated waters,and levels exceeded 2 μg/L under extreme light and temperaturestorage conditions (60�70 �C, 23 W daylight lamp for 116 h).Antimony leaching varied over an order of magnitude among thewaters investigated.

Reimann used ICP-MS to investigate the type of bottle on theleaching of antimony (and other metals/elements) into bottledwater.25 Glass bottles, hard PET bottles, and soft PET bottles ofdifferent colors were investigated by purchasing bottled waters insupermarkets across Europe, rinsing the bottles and refilling withhigh purity (deionized) water at pH 6.5 and also at pH 3.5 toinvestigate the effect of pH. Antimony was found to have a 21�higher concentration when sold in PET bottles, but glass could

also leach antimony in acidified waters, up to 0.45 μg/L after 150days in a dark green glass bottle. For plastic bottles, the soft PETbottles and dark blue hard PET bottles leached the mostantimony at near-neutral pH (6.5). Finally, Cheng et al. assessedantimony and othermetal leaching into water from plastic bottlesthat had been previously recycled.26 They investigated factorsthat could affect leaching, including cooling with frozen water,heating with boiling water, microwave, low pH, outdoor sunlightirradiation, and in-car storage. Heating and microwaving led tothe highest antimony leaching relative to controls, whereas lowpH, outdoor sunlight irradiation, and in-car storage had nosignificant effect. Results also revealed partial antimony leachingfrom PET bottles comes from the plastic surface during themanufacturing process, while major antimony leaching comesfrom conditional changes.

’NANOMATERIALS

There remains an ongoing research boom in the area ofnanomaterials, with many companies and universities expandingtheir efforts. New university departments have been developedaround the study of nanomaterials, and government investmentin nanotechnology has dramatically increased in the last 10 years.In my searching on Web of Science this year, nearly 5000citations appeared in the literature for just the last 2 year periodthat this Review covers. This included 565 review articles onnanomaterials. There is even a monthly journal called ACS Nano(created in 2008). Most nanomaterial research is centered ondeveloping new uses for nanomaterials and new products withunique properties, but on the other side, there is also significantconcern regarding nanomaterials as environmental contami-nants. As such, nanomaterials are the focus of a large initiativeat the U.S. EPA, under which research on nanomaterial fate,transport, and health effects is being conducted. Nanomaterialsare 1 to 100 nm in size and can have unique properties, includinghigh strength, thermal stability, low permeability, and highconductivity. In the near future, nanomaterials are projected tobe used in areas such as chemotherapy, drug delivery, andlabeling of food pathogens (“nanobarcodes”). The chemicalstructures of nanomaterials are highly varied, including fuller-enes, nanotubes, quantum dots, metal oxanes, TiO2 nanoparti-cles, nanosilver, and zerovalent iron nanoparticles.

Most environmental concerns center on the potential humanand ecological effects, and most methods use techniques otherthan mass spectrometry, such as transmission electron micro-scopy (TEM), scanning electron microscopy (SEM), atomicforce microscopy (AFM), quartz crystal microbalance, energydispersive X-ray spectroscopy (EDS), X-ray photoelectron spec-troscopy, static light scattering (SLS), particle electrophoresis,LC/UV, Raman spectroscopy, and NMR spectroscopy. In addi-tion, most studies are carried out in “clean” systems and not inreal environmental systems.

As mentioned earlier, there were numerous reviews publishedfor nanomaterials, even in the environmental arena. As a result,only a very few reviews could be cited here, such that I could alsohighlight new studies. In 2010, a special series of 8 nano papers(4 reviews and 4 technical papers) was published in Journal ofEnvironmental Quality. Top experts in the field led off this specialissue with a review of the environmental occurrence, behavior, fate,and ecological effects of nanoparticles.27 Within this review articleare discussions of risks and release of engineered nanomaterials,key research areas and needs, and sustainable development of



engineered nanomaterials. Important questions raised include:How much will be released? In which environmental compart-ments will they reside? What are the environmentally relevantforms of the material? How do environmental conditions deter-mine the engineered nanomaterial form? Lin et al. publishedanother review in this series on the fate and transport ofengineered nanomaterials in the environment, which includedaggregation and suspension behavior, and how factors such asnatural colloids, natural organic matter, pH, and ionic strengthcan influence this behavior.28 Future research directions andoutlook were also presented. The authors also point out how fewstudies have investigated nanomaterials in the natural aquaticenvironment, and how such studies are needed. Hotze et al.reviewed nanomaterial aggregation and outlined challenges tounderstanding transport and reactivity in the environment.29

Techniques for assessing the colloidal properties of engineerednanoparticles were highlighted by Chen et al. in another review,and they also discussed recent findings for fullerene C60 andmultiwalled carbon nanotubes.30 Techniques discussed includedtransmission electron microscopy (TEM), scanning electronmicroscopy (SEM), and atomic force microscopy (AFM)(for particle size and imaging); energy dispersive X-ray spectro-scopy (EDS) (for measuring elemental bulk composition); X-rayphotoelectron spectroscopy (for characterizing surface composi-tion and charge), particle electrophoresis (for determining aparticle’s migration rate and electrokinetic properties); and staticlight scattering (SLS) (for studying aggregate structures), amongother techniques.

Isaacson et al. published a thorough review on the quantitativeanalysis of fullerene nanomaterials, which included a report onthe state-of-the-art analytical methods for quantifying them,analytical challenges to overcome, and how improvements inanalytical methodologies will play an essential role in advancingour understanding of fullerene nanomaterial occurrence, trans-port, and effects.31 In particular, analytical methods need toprovide chemically explicit information, such as molecular weightand the number and identity of surface functional groups (whichcan be achieved with mass spectrometry), and increased avail-ability is needed for well characterized authentic standards,reference materials, and isotopically labeled internal standards.Ecotoxicity and analysis of nanomaterials in the aquatic environ-ment was the focus of another review by Farr�e et al.32 Ecotoxicitydata crossed several different species of aquatic organisms,including zebra fish, Daphnia magna, Vibrio fischeri, and rainbowtrout. Analysis techniques summarized included dynamic lightscattering (DLS), TEM, SEM, atomic absorption spectroscopy,anodic stripping voltammetry, UV�vis spectroscopy, and LC/MS techniques. The analysis, behavior, and ecotoxicity of carbon-based nanomaterials were the focus of another review by Perezet al., with special emphasis on surface properties and interac-tions with natural organic matter.33

Previous studies have investigated the release of nanosilverfrom socks and other clothing treated with nanosilver; Bennet al. followed up this early work with an investigation ofnanosilver release from many consumer products, including ashirt, a medical mask and cloth, toothpaste, shampoo, deter-gent, a towel, a toy teddy bear, and two humidifiers.34 Silverconcentrations ranged from 1.4 to 270 000 μg Ag per g ofproduct. Products were washed with 500 mL of tap water toassess potential release of silver. SEM confirmed the presence ofsilver nanoparticles in most products, as well as in the washwater samples.

In one of the few published MS methods for nanomaterials,Isaacson and Bouchard used asymmetric flow field-flow fractio-nation (AF4), DLS, and LC/APPI-MS to determine aggregatesize distributions of C60 fullerenes in aqueous systems.

35 This isthe first method to use AF4 for fractionating a colloidal suspen-sion of aqueous C60, which provided improved particle sizecharacterization. The authors also made a strong case for the useof MS over other detection techniques, due to the unambiguousdetermination of the mass of C60 in each size fraction. With thismethod, aqueous C60 aggregates were shown to contain sizedistributions between 80 and 150 nM (for 58% of the mass),<80 nm (5% of the mass), and 150 to 260 nm (14% of the mass).Farr�e et al. reported the first determination of C60 and C70

fullerenes and N-methylfulleropyrrolidine C60 in suspendedmaterial of wastewater effluents.36 Ultrasonic extraction was usedto extract the nanomaterials from suspended solids, and LC/MS/MS was used for quantification. Fullerenes were reported tobe found in 50% of the samples analyzed from 22 wastewatertreatment plants in Catalonia (Spain), with nine samples re-ported in the μg/L concentration range.

Quantum dots were the focus of another study by Navarroet al. who investigated natural organic matter-mediated phasetransfer in the aquatic environment.37 This study presented thefirst evidence of the stabilization of quantum dots in water byhumic substances in real environmental samples. Holbrook et al.reported the impact of source water quality on multiwalledcarbon nanotube coagulation.38 Results indicated that multi-walled carbon nanotube coagulation in the natural environmentis likely to be limited and that potential removal in drinking watertreatment by coagulation is likely to be highly variable, such thatother removal processes downstream, such as filtration, will beimportant in their removal.

The effect of UV irradiation on nanomaterials was the focus ofseveral studies. For example, Hwang and Li investigated thephotolysis of aqueous C60 under environmentally relevantconditions.39 Surface oxygenation and hydroxylation were ob-served after UVA irradiation, as detected using X-ray photoelec-tron spectroscopy (XPS) and attenuated total reflectance(ATR)-FT-infrared (IR) analysis; complete mineralization wasnot observed. Qu et al. investigated aggregation behavior of nC60

nanoparticles before and after UVA irradiation.40 In NaClsolutions, surface oxidation induced by UV irradiation increasedthe nC60 stability, due to an increased negative surface charge andreduced particle hydrophobicity. In contrast, UV irradiationreduced nC60 stability in CaCl2, due to interactions of Ca2þ

with the negatively charged functional groups on the UV-irradiated nC60 surface, and consequent neutralization of charge.These results highlighted the importance of nC60 surface chem-istry in its environmental transport and fate.

’PFOA, PFOS, AND OTHER PERFLUORINATEDCOMPOUNDS

Perfluorinated compounds (PFCs), also referred to as fluor-otelomer acids, alcohols, and sulfonates, have beenmanufacturedfor more than 50 years and have been used to make stainrepellents (such as polytetrafluoroethylene and Teflon) thatare widely applied to fabrics and carpets. They are also used inthe manufacture of paints, adhesives, waxes, polishes, metals,electronics, fire-fighting foams, and caulks, as well as grease-proofcoatings for food packaging (e.g., microwave popcorn bags,French fry boxes, hamburger wrappers, etc.). PFCs are unusual



chemically, in that they are both hydrophobic (repel water) andlipophobic (repel lipids/grease), and they contain one of thestrongest chemical bonds (C�F) known. Because of theseproperties, they are highly stable in the environment (and inbiological samples) and have unique profiles of distribution in thebody. During 2000�2002, an estimated 5 million kg/yr wasproduced worldwide, with 40% of this in North America. Two ofthese PFCs, perfluorooctane sulfonate (PFOS) and perfluorooc-tanoic acid (PFOA), have received themost attention. PFOSwasonce used to make the popular Scotchgard fabric and carpetprotector, and since 2002, it is no longer manufactured in theU.S., due to concerns about widespread global distribution in theblood of the general population and in wildlife, including remotelocations in the Arctic and North Pacific Oceans. Like PFOS,PFOA is ubiquitous at low levels in humans, even in those livingfar from any obvious sources.1

In January 2005, the U.S. EPA issued a draft risk assessment ofthe potential human health effects associated with exposure toPFOA (www.epa.gov/oppt/pfoa/pubs/pfoarisk.html), and inJanuary 2006, the U.S. EPA invited PFC manufacturers toparticipate in a global stewardship program on PFOA and relatedchemicals (www.epa.gov/oppt/pfoa/pubs/stewardship). Parti-cipating companies agreed to reduce PFOA from emissions andproduct content by 95% by 2010 and to work toward eliminatingPFOA in emissions and products by 2015. The U.S. EPA has nowlisted PFOA and PFOS on the new CCL-3 (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). In Europe, theEuropean Food Safety Authority has established tolerable dailyintakes for PFOA and PFOS (www.efsa.europa.eu/en/efsajour-nal/pub/653.htm), and there are new restrictions on the use ofPFOS as part of the European Union’s REACH program(http://ec.europa.eu/enterprise/sectors/chemicals/files/reach/restr_inventory_list_pfos_en.pdf).

Potential health concerns include developmental toxicity,cancer, and bioaccumulation. Research questions include under-standing the sources of PFOA and other PFCs, their environ-mental fate and transport, pathways for human exposure anduptake, and potential health effects. It is hypothesized that thewidespread occurrence of PFOA and other fluoro-acids is partlydue to the atmospheric or oceanic transport of the more volatilefluorinated telomer alcohols (FTOHs) and subsequent transfor-mation into PFOA and other fluoro-acids via metabolism andbiodegradation. Recent studies support this hypothesis. There isalso evidence that PFOA itself is volatile.

PFOS, PFOA, and other PFCs are included in the NationalHealth and Nutrition Examination Survey (NHANES) beingconducted by the Centers for Disease Control and Prevention(CDC) to provide a better assessment of the distribution of thesechemicals in adults and children in theUnited States (www.cdc.gov/nchs/nhanes.htm). TheNational Toxicology Program is also study-ing PFOA and several other perfluorocarboxylic acids (PFCAs) andperfluorosulfonates (PFSAs) to better understand their toxicity andpersistence in human blood (http://ntp.niehs.nih.gov).

While PFOS and PFOA were the first fluorinated surfactantsto receive considerable attention, research has rapidly expandedbeyond these two contaminants to other long-chain perfluori-nated acids and various precursors. In addition, there is increasedfocus on shorter chain forms, e.g., perfluorobutanoic acid(PFBA) and PFBS, as manufacturers are beginning to shift tolower molecular weight PFCs. Rayne and Forest published anextensive critical review of physicochemical properties, levels,and patterns in waters and wastewaters and treatment methods

for perfluoroalkylsulfonic and carboxylic acids.41 Ahrens pub-lished a critical review on the occurrence and fate of PFCs in theaquatic environment, which also identified knowledge gapsand presented recommendations for future work.42 Theserecommendations included research on key loss processes anddeposition, the relationship between sources and aqueous en-vironmental concentrations, solid/water partitioning or air�water exchange, transport mechanisms, and the extent to whichPFCs undergo long-range global transport, seasonality, and long-term changes, as well as the need to establish a global monitoringprogram for PFCs in river water and seawater.

Martin et al. published a thought-provoking review and perspec-tive on PFOS precursors (which the authors called “PreFOS”) asdeterminants of human and environmental PFOS exposure.43

This PreFOS material and the fate processes that transform itinto PFOS and contribute to exposure are not well characterized.The authors point out that the yield of PFOS from abioticdegradation of commercially important PreFOS material is negli-gible, but in vivo biotransformation is important. Ocean waterscan vary in the proportion of PFOS vs PreFOS, as well as whalesand humans who are exposed in different regions. The authorspresent two new source tracking principles, which are based onPFOS isomer patterns and PFOS enantiomers in human serum.

Newmethods tomeasure PFCs in water include an interestingnew use of nanoparticles to extract PFCs from water. In thismethod, Zhang et al. synthesized chitosan-coated octadecyl-functionalized magnetite nanoparticles and used them as anadsorbent to extract PFCs from water.44 LC/MS/MS was usedfor detection. Concentration factors of 1000 could be achievedwith 500 mL of water, and detection limits of 0.24, 0.093, 0.24,0.14, 0.075, 0.24, and 0.17 ng/L were obtained for PFOA, PFOS,PFNA, perfluorodecanoic acid (PFDA), perfluoroundecanoicacid (PFUnDa), perfluorododecanoic acid (PFDoDa), and per-fluorotetradecanoic acid (PFTA), respectively, in wastewater.Willie et al. developed a new method for 14 PFCs in surfacewater, seawater, and wastewater using LC/TOF-MS.45 The useof very narrow mass tolerance windows (<10 ppm) resulted inhigh selectivity for these analytes. Limits of quantification rangedfrom 2 to 200 ng/L. Using this method, the authors were alsoable to detect PFCs in waters from the North Sea, the Scheldtestuary, and harbors on the Belgian coast. Another method usingautomated in-tube SPME coupled to LC/MS was developed bySaito et al. for measuring PFOA and PFOS.46 This methodoffered detection limits of 1.5 and 3.2 ng/L for PFOA and PFOS,respectively, and LC/MS separations could be achieved in 10min for a 40 μL water sample.

Tap water was the focus of new occurrence studies the past 2years. For example, Mak et al. conducted a large multicountrystudy, measuring 20 PFCs in drinking water from China, Japan,India, the U.S., and Canada between 2006 and 2008.47 LC/ESI-MS/MS was used for measurement. PFOS, PFHxS, PFBS,perfluoropropane sulfonate (PFPrS), perfluoroethane sulfonate(PFEtS), perfluorooctane sulfonamide (PFOSA), N-ethyl per-fluorooctane sulfonamide acetate (N-EtFOSAA), PFDoDa, PF-UnDa, PFDA, PFNA, PFHpA, perfluorohexanoic acid (PFHxA),perfluoropentanoic acid (PFPeA), PFBA, and perfluoropropa-noic acid (PFPrA) were all detectable in the tap water samples.Drinking water from Shanghai (China) contained the highestconcentrations of total PFCs (mean of 130 ng/L). Interestingly,Beijing (China) had the lowest overall levels (mean of 0.71 ng/L),which was attributed to the use of activated carbon in theirdrinking water treatment. In general, tap water from the U.S. and



Canada contained similar levels to those found in China. Levelswere low in India, but only a single tap water sample wascollected from the 3 cities in India sampled. In addition to PFOAand PFOS, shorter-chain PFCs (including PFBA, PFBS, PFHxA,and PFHxS) were also prevalent in drinking water. Quinete et al.measured PFCs in tap water, surface water, and biota in Brazil.48

This study represents one of the first to measure PFCs in waterfrom South America. PFOS, PFOA, and PFHxS were detected inall drinking water samples at levels up to 6.7, 2.8, and 1.0 ng/L,respectively. Profiles were somewhat different from those inother countries.

Quinones and Snyder measured PFCs in drinking water andassociated surface, ground, and wastewater in the U.S.49 Sevendrinking water plants located in different regions of the U.S. weresampled 4 times a year during 2008, including some that arehighly impacted by treated wastewater. In treated wastewater, theaverage total PFC concentrations ranged from 70 to 260 ng/L,with predominant contributions from PFHxA, PFOA, andPFOS. For drinking water plants, the plant regarded as non-impacted (by wastewater) had no detectable PFCs, whereasthose impacted by treated wastewater had frequent detection forPFCs. PFCs containing 8 carbons or less were the mostfrequently detected in finished drinking water, and PFOA hadthe highest overall concentration at any site.

Loos et al. carried out a large multicountry European study ofpolar organic persistent pollutants in groundwater, which in-cluded PFCs, as well as pharmaceuticals, hormones, pesticides,pesticide transformation products, benzotriazoles, alkylphenolcompounds, caffeine, diethyltoluamide (DEET), and triclosan.50

PFOS, PFOA, PFHpA, and PFHxS were among the chemicalsdetected the most often at the highest concentrations, withmaximum levels of 135, 39, 21, and 19 ng/L, respectively.Compared to river water, groundwater was less contaminated,in general. Interestingly, compounds found at the highestfrequency were not always those found at the highest concentra-tions; for example, PFOA had the highest frequency of detection(66%), but its maximum concentration was lower than PFOSand some other chemicals measured in this study. In anotherpaper, Pistocchi and Loos provided a map of Europeanemissions and concentrations of PFOS and PFOA.51 A spatiallydistributed data set of PFOS and PFOA concentrations wereused together with average river flow to estimate their overallaqueous emissions in Europe. The total discharge across thewhole European river network to coastal areas was estimatedto be 20 and 30 tons/year for PFOS and PFOA, respectively(for 2007).

The flux of PFCs through wet deposition (rain) was the focusof a study by Kwok et al., who collected samples from Japan, theU.S., France, China, and India.52 This is one of the few studies to-date to measure occurrence of PFCs in precipitation, and ithelped in understanding the scavenging of PFCs in rainwater.Higher total PFCs were found in the first rain even when a largerrainfall occurred in a second event. PFPrA was detected in all ofthe rain samples, and average total PFC concentrations rangedfrom 1.40 to 18.1 ng/L for the 7 cities studied. The greatest levelswere found in Tsukuba, Japan, and the lowest levels were inPatna, India. PFPrA, PFOA, and PFNAwere the dominant PFCsin Japanese and U.S. rainwater.

Eschauzier et al. published an interesting study of PFCs ininfiltrated Rhine River water and rainwater in coastal dunes fromTheNetherlands.53 PFBS was found at the highest concentrationof all PFCs, up to 37 ng/L in infiltrated river water. These levels

were significantly higher than those found in infiltrated rainwater,and it is in stark contrast to the more typical higher levels ofPFOA and PFOS generally reported in the environmentalwaters. Concentrations of PFOA, PFHxA, PFHpA, PFBS, PFOS,and PFHxS in infiltrated river water showed an increasing trendwith decreasing age of water. Nakayama et al. carried out a studyof PFCs in the Upper Mississippi River Basin (U.S.), one of thelargest watersheds in the world.54 PFCs were found in 94% of the177 samples collected, with 80% of these <10 ng/L. The mostabundant PFCs were PFBA, PFOS, PFHxA, and PFHpA; thehighest levels were from PFBA (458 ng/L), PFOS (245 ng/L),and PFOA (125 ng/L). Relatively high levels of PFBA likelyreflect a shift toward the manufacture of lower molecularweight PFCs in the U.S. Results indicated multiple sources anda continuous increase in PFC loading as the river flowedthrough the basin. Many localized areas with elevated PFCinputs were identified. Lake Superior water was the focus of astudy by Scott et al. who investigated the trends and sources ofPFCs.55 PFOA was the major PFC in Lake Superior, withconcentrations ranging from 0.07 to 1.2 ng/L, which weregenerally 1.5�2� greater than PFOS levels. Wastewater treat-ment plants contributed up to 20� higher concentrations ofPFOA relative to intake water from Lake Superior. Overall,tributaries and precipitation were estimated to be the majorsources of PFCAs and perfluoroalkanesulfonates (PFSs), andPFCAs were found throughout the water column, into thedeepest areas of the lake.

The Atlantic Ocean was the focus of a study by Ahrens et al.,who measured PFCs in waters collected on a sampling trip fromLas Palmas (Spain) to St. Johns (Canada) and from the Bay ofBiscay (Spain) to the South Atlantic Ocean.56 This studyprovided the first concentration data for PFOSA, PFHxA, andPFHpA in the Atlantic Ocean. Results showed decreasingconcentrations from the Bay of Biscay to the South AtlanticOcean, and a concentration drop-off close to the Labrador Sea.Maximum levels were found for PFOSA, PFOS, and PFOA at302, 291, and 229 pg/L, respectively. In samples south of theequator, only PFOSA was detected, and below 4 degrees South,no PFCs were detected. Goksoyr et al. measured PFCs and othercontaminants in the Pacific Ocean during the Norwegian Tan-garoa Balsa Raft expedition that crossed the Pacific (from Peru toPolynesia) in 2006.57 Semipermeable membrane devices(SPMDs) were used for sampling, and this raft provided a uniqueopportunity for minimal disturbance of the environment duringsampling because no machinery or generators were used. Thisraft was constructed of balsa from the rainforests of Ecuadoraccording to ancient traditions of the Peruvian Indians(incidentally, a photo of this raft is given in the article, and it isa must-see). Of the PFCs, only PFOS was detected in the oceanwaters at subpg/L levels. Overall, most contaminants either werenot detected or were detected at only minute levels.

Initially, PFCs were measured in the U.S., Japan, and WesternEurope, but measurements are now expanding to many othercountries, including China, India, Thailand, and Brazil. Forexample, Yeung et al. measured PFCs in surface water and biotain the Ganges River and other water bodies in India.58 PFOS wasthe dominant compound found, up to 3.91 ng/L in river water.Long-chain PFCAs were not detected in the waters, but inter-estingly, were found in biota.

Several fate and transport studies have also been conducted.For example, Murakami et al. investigated sources of PFCs ingroundwater inTokyo.59 PFOSwasmore abundant in groundwater



than in river waters, wastewaters, and street runoff, indicatingthat it was likely produced by degradation of precursors. Soilcolumn tests also supported this. Wastewater and surface runoffcontributed 54�86% and 16�46%, respectively, of PFCAs togroundwater. Stemmler and Lammel investigated pathways ofPFOA to the Arctic, including oceanic currents and atmospherictransport.60 A spacially resolved global multicompartment modelsuggested that oceanic transport was the dominant source ofPFOA to the Arctic, delivering an estimated 14.8 t/a. Benskinet al. applied an isomer profiling method to assess the contribu-tion of electrochemical and telomer manufacturing processes toPFCs measured in North America, Asia, and Europe.61 Electro-chemical fluorination produces a mixture of branched and linearisomers, whereas telomerization typically produces more linearstructures. A sensitive LC/MS/MS method was then used toquantify these isomers to allow this source attribution. With theexception of 3 sites in Japan, >80% of the total PFOA was fromelectrochemical manufacturing.

In another study, Fr€omel and Knepper investigated biotrans-formation as a source of fluorotelomer ethoxylates in theenvironment.62 These compounds, which are polyethoxylated2-perfluoroalkylethanols, have been largely disregarded in pre-vious studies of PFCs, despite their high production and applica-tion amounts. Aerobic biotransformation tests showed that acommercial fluorotelomer ethoxylate mixture rapidly trans-formed, with a half-life of approximately 1 day. LC/MS/MSwas used to elucidate the structures of the transformation products,which revealed oxidation of the ethoxylate to the carboxylic acid,followed by sequential shortening of the ethoxylate units, leadingto fluorotelomer carboxylates, including a small amount of PFOAand PFHxA. Plumlee et al. investigated the indirect photolysis(with hydroxyl radical) of PFCs, including N-ethyl perfluorooc-tane sulfonamidoethanol (N-EtFOSE), N-EtFOSAA, and per-fluorooctane sulfonamide acetate (FOSAA).63 A proposed reactionpathway for the degradation of N-EtFOSE to other perfluoroalk-anesulfonamides and PFOA included oxidation and N-dealkyla-tion steps. PFOSA and PFOA were the final degradationproducts. Indirect photolysis was suggested to be an importantpathway, due to the slow rates expected for biotransformationand weak sorption.

Finally, Qu et al. investigated the photoreductive defluorina-tion of PFOA in water, as a potential removal technology.64 Inthese experiments, UV photolysis led to the generation ofhydrated electrons, which were able to efficiently defluorinatePFOA (98% release of fluoride). Besides fluoride, additionalintermediates were identified and quantified, including formicacid, acetic acid, 6 short-chain PFCAs (C1�C6), trifluoromethane,and hexafluoroethane. With these data, two major defluorinationpathways were proposed (1) direct cleavage of C�F bondsattacked by hydrated electrons as the nucleophiles and (2)stepwise removal of CF2 by UV irradiation and hydrolysis.

’PHARMACEUTICALS AND HORMONES

Pharmaceuticals and hormones have become crucial emergingcontaminants, due to their presence in environmental waters(following incomplete removal in wastewater treatment or point-source contaminations), threat to drinking water, and concernabout possible estrogenic and other effects, both to wildlife andhumans. A major concern for pharmaceuticals also includes thedevelopment of bacterial resistance (creation of “Super Bugs”)from the release of antibiotics to the environment, and there are

also new concerns that antibiotics will decrease biodegradation ofleaf and other plant materials, which serves as the primary foodsource for aquatic life in rivers and streams. It is estimated thatapproximately 3000 different substances are used as pharmaceu-tical ingredients, including painkillers, antibiotics, antidiabetics,betablockers, contraceptives, lipid regulators, antidepressantsand impotence drugs. However, only a very small subset of thesecompounds has been investigated in environmental studies sofar. Pharmaceuticals are introduced not only by humans, but alsothrough veterinary use for livestock, poultry, and fish farming.Various drugs are commonly given to farm animals to preventillness and disease and to increase the size of the animals. Onelingering question is whether the relative low environmentalconcentration levels of pharmaceuticals (generally ng/L range)would cause adverse effects in humans or wildlife. Pharmaceu-ticals and hormones are now included on the U.S. EPA’s finalCCL-3 (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). One typical pharmaceuticals (erythromycin) andone explosive (nitroglycerin) that is also be used as pharmaceu-tical and nine natural and synthetic hormones (17R-ethinyles-tradiol [EE2], 17R-estradiol, 17β-estradiol [E2], equilenin,equilin, estriol [E3], estrone, mestranol, and norethindrone)are included as priority drinking water contaminants, based onhealth effects and occurrence in environmental waters. For therevision of the list of priority substances within the EU waterframework directive (2000) describing the chemical status ofEuropean rivers, streams, and lakes) two pharmaceuticals (di-clofenac and ibuprofen) and two hormones (EE2 and E2) aresuggested. There are also increasing “source-to-tap” studiesconsidering the fate of pharmaceuticals from wastewaters toriver waters, to source waters, and to finished drinking water,such that the complete cycle of pharmaceutical fate is beingconsidered.

Innovative analytical instrumentation, such as hybrid massspectrometry enables the identification and quantification oforganic pollutants including pharmaceuticals and hormones downto the lower nanogram per liter and nanogram per kg range inenvironmental matrices and drinking water. While most organiccontaminants are entering wastewater without being metabolized,pharmaceuticals are frequently transformed in the body and acombination of non-altered pharmaceuticals and their metabolitesare excreted by humans.65 Microbial transformation products(TPs) of pharmaceuticals and hormones can be formed duringbiological wastewater treatment, from contact with sediment andsoil, as well as during bank filtration. Furthermore, TPs can beformed by UV irradiation in surface waters and during oxidativetreatment processes, such as ozonation and chlorine disinfection.

Still, LC/tandem-MS is the method of choice for the determina-tion of all classes of pharmaceuticals in aqueous matrices. ESI andAPCI are the most commonly used LC interfaces. Major innova-tions have beenmade in modern hybridmass spectrometry systems(e.g., linear ion trap/FT-MS, Q-TOF-MS) coupled to liquidchromatography, providing accurate masses of the analytes andinformation for mass fragments, which can be used to identify thechemical structures. Radjenovi�c et al. published a review of theliterature using MS to elucidate the formation of pharmaceuticalTPs during oxidative wastewater and drinking water treatment.66 Afew rapid biochemical techniques, such as biosensors and immu-noassays, have also been recently developed for selected pharma-ceuticals. Further innovations have been made in rapid on-lineextraction and bag extraction, as well as on-line derivatizationtechniques in combination with GC/MS(/MS) detection.



Environmental Impacts of Pharmaceuticals. While manypharmaceuticals can have an acute or chronic effect on aquatic orother organisms, most of the lowest observed effect concentra-tions (LOECs) are substantially above the environmental con-centrations that have been observed (ng/L to low μg/L).However, there are a few notable exceptions, where chronictoxicity LOECs approach levels observed in wastewater effluents.For chronic toxicity, these include salicylic acid, diclofenac,propranolol, clofibric acid, carbamazepine, and fluoxetine. Forexample, for diclofenac, the LOEC for fish toxicity was in therange of wastewater concentrations, and the LOEC of propra-nolol and fluoxetine for zooplankton and benthic organisms wasnear the maximum measured in wastewater effluents. Theantibiotic ciprofloxacin has also been shown to have effects onplankton and algae growth at environmentally relevantconcentrations.1 Estrogenic effects on wildlife are quite possiblewith the contraceptive 17R-ethinylestradiol (EE2), as it caninduce estrogenic effects in fish at extremely low concentrations(low and sub-ng/L). Effects include alteration of sex ratios andsexual characteristics, and decreased egg fertilization in fish.1 Anarticle in Nature (Oaks et al., 2004) highlighted that residues ofveterinary used diclofenac probably caused renal failure ofvultures and hence lead to a dramatic decline (> 95 %) of thevulture population in Pakistan.67 Experts estimate the vultureloss at 40 million, and it is being called the “worst case of wildlifepoisoning ever”, far eclipsing the numbers of birds affected byDDT a few decades ago.Biological Transformation Products. Even though TPs have

gained increasing interest as water contaminants, only a fewstudies have investigated the formation and fate of biological TPsof pharmaceuticals in contact with biologically active matrixes,such as activated sludge or sediments. One reason is thechallenge of structural elucidation of TPs present at low con-centrations in natural matrixes. Sophisticated analytical techniquesare needed, such as hybrid high-resolution mass spectrometryand NMR.68 Although the target compound is known, with a fewexceptions of very simple reactions (e.g., hydrolysis of amidesand esters), quadrupole-MS and even high resolution-MS (e.g.,LC/Orbitrap-MS) are often not sufficient to obtain or confirmchemical structures of TPs. The TP structure suggestions basedon exact masses and mass fragments have to be confirmed byalternative analytical methods or chemical reactions specificallyaltering the new functional moieties formed. Possibilities ofanalytical methods include a wide variety of currently availableNMR techniques or, to a much less extent, IR spectroscopy.However, a drawback of both techniques is the elevated quantityand the high purity needed for isolated standards. In those cases,where no authentic standard is available and only MS spectra ofTPs have been obtained, we might better define the suggestionsof the chemical TP structures as “tentative identifications” unlessfurther plausibility criteria are fulfilled, confirming the proposedchemical structures. A comprehensive overview of the literatureregarding the detection and identification of pharmaceutical TPsuntil 2008 is provided by Celiz et al.69

Several recent studies indicated that the majority of pharma-ceutical TPs formed under aerobic conditions have a slightlymodified molecular structure featuring increased polarity, due tothe introduction of hydroxyl, carboxyl, or keto moieties.70,71 Onthe basis of the similarity of their molecular structure to theparent compound, a significant number of TPs are expected topossess comparable biological activity as their chemicalprecursors.72 However, the enhanced polarity improves the

permeability of these compounds for several water treatmentprocesses such as adsorptive filtration (e.g., activated carbon),underground soil passage, or bank filtration. As consequence, thelikelihood increases that TPs are contaminating groundwater anddrinking water.73

Several enzyme-catalyzed reactions are quite commonly in-volved in the transformation of pharmaceuticals: mono- anddihydroxylation, alcohol and aldehyde oxidation, ester and amidehydrolysis, N-dealkylation, N-deacetylation, and decarboxyla-tion. For the first time, Radjenovi�c et al. have elucidated theamide hydrolysis of the betablocker atenolol to atenolol acid and thehydroxylation of the hypoglycemic agent glibenclamide in con-tact with activated sludge. LC/Qq-TOF-MS and LC/Qq-linearion trap-MS techniques were used for measurement.74 Helblinget al. reported for the first time the amide hydrolysis of theantiepileptic levitiracetam by LC/Orbitrap-MS.75 Furthermore,they found in contact with activated sludge the demethylation ofdiazepam, which is already known from human metabolism, aswell as the hydroxylation of diazepam. By the same authors, TPsof the antihypertensive valsertan were identified using LC/Orbitrap-MS. Transformation took place by amide hydrolysis,transamination, and subsequent oxidation to a carboxylic acid.Trautwein et al. described the dealkylation of the antihyperten-sive verapamil76 using LC/ion trap-MS, and Kern et al. showed,in addition to verapamil, the dealkylation of the antidepressantvenlaflaxine by LC/Orbitrap-MS.77 Calza et al. reported theidentification of 11 TPs of the antibiotic spiramycin by LC/MS/MS in river water by hydroxylation, N-demethylation, andcleavage of sugar moieties.78 Using LC/Qq-TOF-MS, Kosjeket al. reported the identification of 2 TPs for diclofenac duringnitrification formed by (a) decarboxylation and (b) amideformation, as well as the formation of p-chlorophenol from theether cleavage of clofibric acid.79 The oxidation of the antihista-mine ranitidin at the amine and the thiol moiety forming two TPswas reported by Kern et al. using LC/Orbitrap-MS.80 ApplyingLC/Qq-linear ion trap-MS and 1H and 13C NMR, Schulz et al.81

and Kormos et al.68,73 identified 46 TPs from four X-ray contrastmedia (iopromide, iomeprol, iopamidol, and iohexol) formed byN-dealkylation, N-deacetylation, oxidation, and decarboxylation.Twelve of these TPs have been reported in surface water,groundwater, and drinking water, up to several hundreds of ng/L.O-Desmethylnaproxen, the main metabolite of naproxen, wasidentified by enantioselective-GC/MS in surface water and waste-water treatment plant (WWTP) effluents at high ng/L levels.Prasse et al. reported the biotransformation of the two antiviraldrugs, acyclovir (ACV) and penciclovir (PCV), in contact withactivated sludge.82 TPs were identified using LC/Orbitrap-MSand 1 D (1H NMR, 13C NMR) and 2D (1H, 1H-COSY, 1H-13C-heteronuclear single quantum coherence [HSQC]) NMR spec-troscopy. Structural elucidation of TPs revealed that transforma-tion took place at the side chain, leaving the guanine moietyunaltered. The oxidation of the primary hydroxyl group in ACVresulted in the formation of carboxy-acyclovir. For PCV, severalenzymatic reactions occurred, such as the oxidation of terminalhydroxyl groups and β-oxidation followed by acetate cleavage.Carboxy-ACV was detected in surface and drinking water, withconcentrations up to 3200 ng/L and 40 ng/L, respectively.Perez-Parada et al. reported the identification of TPs of theantibiotic amoxicillin in wastewater and surface water using LC/Q-TOF-MS.83 The cleavage of the beta lactam ring led todiastereomers of amoxilloic acid and amoxicillin diketopipera-zine. The latter has been detected in wastewater and river water.



The biological transformation of the contraceptive EE2 wasinvestigated by several authors.84,85 Skotnicka-Pitak et al. eluci-dated the formation of a TP after hydrolysis and oxidation of theethinyl group, as well as a hydroxylated TP by LC/ion trap-MSand 1H NMR.84 The hydroxylated TP was also reported by Yiand Harper, and additionally, the formation of a sulfate conjugateusing thin layer chromatography (TLC) and 1H NMR.85 Tes-tosterone was shown to be very stable to biological degradation,but it can be slowly transformed under solar irradiation. Severalphotoproducts, such as hydroxylated derivatives resulting fromphotohydration of the enone group, a spiro-compound, or(1,5,10)-cyclopropyl-17β-hydroxyandrostane, were identifiedby TOF-MS, LC/MS, GC/MS, IR, and NMR.The identification of nitrophenolic TPs of acetaminophen in

samples from full-scaleWWTPs indicated that abiotic nitration isoccurring in biological wastewater treatment.86 Wick et al.reported that the opium alkaloid codeine was transformed withactivated sludge into at least 18 TPs, when applying a multistepapproach with LC/Orbitrap-MS and 1D and 2D NMR.87 Mostof the TPs identified had only slightly modified molecularstructures, featuring double bond shifts, introduction of hydroxylmoieties, or amine demethylation. The transformation pathwayof codeine with activated sludge was characterized by a combina-tion of biologically and chemically mediated reactions. Formorphine, 10 TPs similar to those observed for codeine weredetected, including the main TPs morphinone and 14-hydro-xymorphinone. In addition to the codeine-like TPs, an additionalnine TPs were tentatively identified for morphine, including themorphine dimer pseudomorphine and 2-nitro-derivatives. Sincenitrophenolic compounds are frequently of toxicological con-cern, the role of abiotic reactions for the transformation of micro-pollutants deserves further attention. Finally, dihydrocodeinewas transformed into hydrocodone and isodihydrocodeine.87

Elimination/Reaction During Oxidative Water Treatment.Several studies confirmed the efficiency of oxidation processes,such as ozonation, advanced oxidation, or ferrate (Fe(VI)), for thetransformation of micropollutants. However, it cannot be ruledout that oxidation leads to persistent oxidation products which areof toxicological concern. This might be even more relevant forchlorination, since chlorinated products frequently possess a hightoxicological potential. It is, therefore, crucial to identify theoxidation products formed. This is only possible when advancedmass spectrometry is used, such as LC/Q-TOF-MS, LC/Orbitrap-MS, or LC/Qq-linear ion trap-MS, and NMR techniques.Hollender et al. showed that ozone transformed most inves-

tigated pharmaceuticals and their metabolites (>70) whenapplied in full-scale post-treatment of a municipal WWTP.88

This was especially true for those pharmaceuticals that containelectron-rich moieties. Dodd et al. investigated the ozonationTPs of beta-lactam antibiotics penicillin G and cephalexin.89 TheTPs were identified as (R)-sulfoxides, using 1HNMR, 13CNMR,and LC/Orbitrap-MS. While penicillin G-sulfoxide was recalci-trant toward ozone but readily transformed by OH radicals(HO•), the cephalexin sulfoxides were degraded by both ozoneand OH radicals. According to Dodd et al., ozonation leads tostructural modification sufficient to eliminate the antibacterialactivity for 13 antibiotics from 9 structural classes.90 Using LC/Qq-linear ion trap-MS, Benner et al. identified a large number ofoxidation products after ozonating membrane concentratescontaining elevated concentrations of pharmaceuticals, such asthe beta-blockers propranolol and metoprolol.91,92 The beta-blockers were attacked by ozone at the secondary amino group,

yielding hydroxyl amine and aldehyde moieties, due to ring-opening on the aromatic rings.A novel oxidation technology using ferrate [Fe (VI)] in water

and wastewater treatment were reported by Lee et al.93 andHu et al.94 Lee et al. showed that pharmaceuticals containingelectron-rich moieties are transformed by more than 85%.93

Although Fe (VI) treatment was slightly less effective than ozone,it has the benefit of the simultaneous removal of phosphate. Huet al. reported that Fe (VI) was able to transform the antiepilepticcarbamazepine.94 Similar to ozone, it attacks olefinic moieties inthe central heterocyclic ring, leading to ring-opening and forma-tion of several TPs, which were identified by LC/ESI-MS/MS. Theoxidation by KMnO4 led to comparable TPs, without showing apH dependence. However, similar to ozonation, neither Fe(VI)nor KMnO4 mineralized the target pharmaceuticals.The chlorination of water containing EE2 and bromide led to

halogenated TPs, such as 4-chloro-, 2,4-dichloro-, 4-bromo-, or2,4-dibromo-EE2.95 The authors concluded that bromine pro-duced from oxidation of Br� is mainly responsible for thehalogenation of EE2. Mash reported that the synthetic androgentrenbolone is highly reactive toward hypochlorite.96 Chlorina-tion leads to a large number of TPs containing up to two chlorineatoms and up to two additional oxygen atoms. Quintana et al.investigated the transformation of seven acidic pharmaceuticalsand two metabolites by LC/Q-TOF-MS.97 The authors ob-served chlorinated and brominated products of salicylic acid,naproxen, and diclofenac. The nonhalogenated diclofenac wasfurther transformed by decarboxylation and hydroxylation. It isinteresting to note that halogenated derivatives of salicylic acidwere detected in wastewater and even in drinking water usingLC/MS/MS. The oxidation of seven fluoroquinolones and threestructurally related amines with ClO2 revealed that the piper-azine ring is the primary reactive center, leading to dealkylation,hydroxylation, and an intramolecular ring closure at the piper-azine moiety.98 The formation of halogenated products was notobserved.Yuan et al. reported the degradation of four pharmaceuticals

(ibuprofen, phenazone, diphenhydramin, and phenytoin) byUV/H2O2 and UV.99 Several photodegradation intermediateswere identified by GC/MS. The suitability of UV/H2O2 treat-ment for the removal of pharmaceuticals was also mentioned byRosario-Ortiz et al.100 They clearly demonstrated that theefficacy of UV/H2O2 treatment is influenced by the effluentorganic matter and its reactivity toward OH radicals. X-raycontrast media can be transformed by advanced oxidationprocesses. The second order reaction rate constants with HO•

ranged between 9.58� 108 (diatrizoate) and 3.42� 109M�1s�1

(iopamidol).Opiates and Other Drugs of Abuse. Several analytical

methods have been reported for the determination of drugs ofabuse in wastewater and environmental samples, primarily usingLC/MS/MS. The determination of these drugs in wastewaterand surface water can be used for environmental forensicinvestigations, which is possible due to the high sensitivity ofthe analytical methods.Analytical methods and environmental occurrence of amphe-

tamines and methamphetamines are reviewed by Boles andWells.101 Opioids (oxycodone and methadone) and other phar-maceuticals, such as muscle relaxants, were detected by LC/MS/MS at elevated concentrations, up to 1700 μg/L (oxycodone)and 3800 μg/L (metaxolone) in WWTP effluents connected topharmaceutical formulation facilities.102 Median concentrations of



4 compounds (methadone, oxycodone, metaxolone, and butalbital)ranged from 3.4 to >400μg/L in thisWWTP effluent, indicating thatformulation facilities are a potential source for environmental phar-maceutical contamination.Vazquez-Roig et al. developed an analyticalmethod using SPE and LC/MS/MS for the determination of 14drugs of abuse and their metabolites (e.g., cannabinoids, ampheta-mine-like compounds, opiates, and cocainics).103 The best recoverieswere obtained using Oasis HLB (200 mg), after comparing sevendifferent SPE materials. Limits of quantification of <1 ng/L wereachieved. Bijlsma et al. usedOasisMCX for SPE andUPLC/MS/MSwhen determining amphetamines, amphetamine-like stimulants,cocaine, its metabolites, and a cannabis metabolite in surface waterand wastewater.104 A direct injection method for LC/MS/MSdetection was described by Bisceglia et al., who simultaneouslydetermined 23 different drugs of abuse down to <50 ng/L.105

Gonzales-Marino et al. compared MIPs with mixed mode (OasisMCX) and hydrophilic balance (Oasis HLB) sorbents.106 Theyconcluded thatMIPs rendered cleaner extracts with lessmatrix effectsand lower limits of detection, aswell as better recoveries andprecision.The amphetamines MDA and MDMA (also known as “Ecstasy”)were found afterMIP extraction and LC/MS/MS detection at 4�20ng/L levels. GC/MS detection after derivatization by MSTFA wasdescribed for the determination of drugs of abuse, such as cocaine andits metabolite benzoylecgonine. A spatial and seasonal variation ofcocaine and its metabolite benzoylecgonine was investigated inBelgium by van Nuijs et al. using SPE and hydrophilic interactionliquid chromatography (HILC)/MS/MS detection.107 On thebasis of the measurements, the authors found in the WWTPBrussel-Noord no significant differences between cocaine con-sumption during the investigated seasons (summer/autumn2007, winter 2007/2008) but a constant monthly use andelevated peaks during the weekends.Antidepressants. Ferrer and Thurman reported for the first

time the determination of the antidepressant lamotrigine and itsconjugate 2-N-glucruonide by SPE and LC/Q-TOF-MS inwastewater, surface water, groundwater, and drinking water.108

A surprisingly high mean concentration of 209 ng/L of theglucuronide conjugate was found in surface water, indicating thatthis conjugate is passing WWTPs without a major cleavage. Onthe basis of these results, it should be recommended to includethe conjugates (N- and O-glucuronides) in current monitoringprograms in order to get the entire loads of pharmaceuticalspresent in wastewater and environmental matrixes. However, thelack of commercially available reference standards of glucuronideconjugates has to be solved. Antidepressants were also detectedin two U.S. streams, due to point discharges of WWTPeffluents.109 Metcalfe et al. reported the analysis of 6 antidepres-sants and 5 human metabolites in Canadian WWTPs and riverwater.110 Maximum concentrations were found for venlafaxineand its two metabolites O- and N-desmethyl venlafaxine, withmean concentration levels in a municipal WWTP of 2.1 and 1.1μg/L and in rivers of 0.109 and 0.047 μg/L, respectively. Calistoet al. reported the results of a review on occurrence, persistence,fate, toxicity, and analytical methods for psychiatric pharmaceu-ticals, including sedatives, aniolytics, hypnotics, and antidepres-sants in environmental matrixes.111 A MIP SPE was applied byDemeestere et al. prior to the detection of antidepressants byUPLC/MS/MS.112 Matrix effects were significantly reduced dueto the selectively of the MIP retaining serotonin reuptakeinhibitors paroxetine, fluoxetine, and citalopam.Antiviral Drugs. A LC/ESI-MS/MS method was developed

for the determination of 9 antiviral drugs (acyclovir, abacavir,

lamivudine, nevirapine, oseltamivir, penciclovir, ribavirin, stavu-dine, and zidovudine) and one active metabolite (oseltamivircarboxylate) in raw and treated wastewater, as well as surfacewater.113 Concentrations in surface waters were mostly in thelower ng/L range, with a maximum of 190 and 170 ng L�1 foracyclovir and zidovudine, respectively. The antiviral metaboliteoseltamivir carboxylate was detected in WWTP effluents andrivers in Japan using UPLC/MS/MS.114 During the flu seasons,the authors detected concentrations of oseltamivir carboxylate inWWTP effluents up to 293 ng/L and in rivers up to 190 ng/L.Glucocorticoids. Schriks et al. reported an innovative study

on the detection of glucocorticoids in various Dutch wastewatersusing LC/Orbitrap-MS.115 In hospital wastewater, they identi-fied cortisone, cortisol, prednisone, prednisolone, and triamci-nolone amide, with concentrations between 13 and 1918 ng/L,concluding that triamcinolone amide, dexamethasone, and pre-dnisolone are mainly contributing to the glucocorticogenicactivity detected in wastewater.Antimycotics and Antibiotics. Lindberg et al. described the

analysis of six antimycotics in wastewater and sludge by SPE andLC/MS/MS detection.116 Fluconazole was the only antimycoticdetected in raw wastewater and WWTP effluent, with concen-trations ranging from 90 to 140 ng/L. In contrast, clotrimazole,ketoconazole, and econazole were present in all sludge samplesbut not in the WWTP effluents. For the determination of 6tetracyclines and 10 of their human metabolites, an analyticalmethod was developed by Jia et al. using Oasis HLB extraction,cleanup by Oasis MAX (mixed mode strong anion exchange),and LC/MS/MS detection.117 SPME with micellar desorptioncoupled to LC-fluorescence detection was applied for thedetermination of five fluorochinolones.118 Limits of quantifica-tion (LOQs) of less than 1 ng/L were attained.Thyroid Hormones. Svanfelt et al. developed an analytical

method for the determination of thyroid hormones (thyroninederivatives) in different types of waters.119 They applied SPE andLC/tandem-MS and attained LOQs down to 10.5�84.9 ng/Lfor raw wastewater and 1.1�13.3 ng/L in tap water. In WWTPinfluents and effluents, 3,5,30,5-tetraiodo-L-thyronine was foundat 64 and 22 ng/L, respectively.Drinking Water Analysis. In U.S. drinking water and accom-

panying source waters, Benotti et al. monitored 51 emergingpollutants between 2006 and 2007.120 Among the most fre-quently detected compounds were several pharmaceuticals (e.g.,atenolol, carbamazepine, gemfibrozil, naproxen, sulfamethoxa-zole, and trimethoprim). Median concentrations were <10 ng/L,except sulfamethoxazole, which was 12 ng/L.Beta-Blockers. Seasonal variations in the occurrence and fate

of beta-blockers and the antiepileptic carbamazepine were in-vestigated in a Swedish river-lake system by Daneshvar et al.121

They identified a significant natural attenuation of the beta-blocker loads in the summer time and less reduction of the loadsin the winter time, probably mainly due to biodegradation. Carba-mazepine loads were not reduced at all. Scheurer et al. reportedenormousmatrix effects for the determination of beta-blockers inwastewater and sludge using LC/ESI-MS/MS.122 Only the use ofappropriate 13C- or 2H-labeled surrogate standards were able tocompensate these losses to an acceptable level.Multiresidue Methods. Huerta-Fontela et al. reported a

multiresidue method to determine 49 pharmaceuticals and 5metabolites using UPLC/MS/MS within 9 min.123 A rapidscreening method was described by Gros et al., who were ableto detect 73 pharmaceuticals in surface water and wastewater



using LC/Qq�linear ion trap-MS.124 Loos et al. described a firstpan-European reconnaissance of the occurrence of polar organicpersistent compounds, including pharmaceuticals, in Europeangroundwater from 23 countries.125 Carbamazepine was the onlypharmaceutical that was present above the quality standard forpesticides in groundwater of 0.1 μg/L.New SPE Materials/Procedures. Bag-SPE, consisting of

20 mg of polystyrenedivinylbenzene enclosed in a woven polye-ster fabric, was immersed into 20 mL samples for solid phaseextraction.126,127 Although recoveries were lower in compar-ison to Oasis HLB, the concentrations determined in raw andtreated wastewater were comparable for most pharmaceuticals(e.g., diclofenac,metoprolol, oxazepam, cyclofosfamide, gemfibrozil,and furosemide). Benefits the authors mentioned included theease of handling, unattended water extraction, and that nofiltration is needed. Ten pharmaceuticals were detected in coastalwater, with concentrations ranging from 4 to 210 ng/L. Hyper-crosslinked polymer resin (HXLPP), a mixed-mode polymericsorbent in the form of monodisperse microspheres, was usedoff-line and online.128,129 For online extraction of river water(250 mL) and WWTP effluents (100 mL), the HXLPP wasmodified with 1,2-ethylenediamine (EDA) moieties, enabling itsapplication as a weak anion exchange (WAX) sorbent. Onlinesolid phase extraction of large-volume (10 mL) injectionscoupled to LC/MS/MS was applied for simultaneous quantifica-tion of 14 organic trace pollutants, including 8 pharmaceuticals.130

Detection limits ranged from 0.6 to 6 ng/L.New Derivatization Method. Migowska et al. described a

new derivatization method using trimethylsilyldiazomethane(TMSD) for the determination of nonsteroidal anti-inflammatorydrugs (NSAIDs) byGC/MS.131 The instrumental detection limitsof ibuprofen, ketoprofen, and naproxen were down to 2 ng.Enantiomers. Barreiro et al. developed an analytical method to

determine the enantiomers of omeprazole in wastewater andestuarine water samples by a two-dimensional LC system using acolumn-switching method.132 An octyl restricted-access mediabovine serum albumin column (RAM-BSA C8) was used toexclude macromolecules, followed by a polysaccharide-based chiralcolumn coupled to UV/vis or ion trap-MS. On the basis of theelevated limit of detection of 5μg/L, the enantiomerswere detectedin the influent of municipal WWTPs but not in the effluents.Bioassays. Bahlmann et al. developed an enzyme-linked

immunosorbent assay (ELISA) for the detection of the anti-epileptic carbamazepine in surface water and wastewater.133 Theimmunoassay is based on monoclonal antibodies and a novelenzyme conjugate that links the hapten via a hydrophilic peptide(triglycine) spacer to horseradish peroxidase. They achieveddetection limits of 24 ng/L and a quantification range of 50�50 000 μg/L. The ELISA displayed cross-reactivities for 10,11epoxy-carbamazepine and 2-hydroxy-carbamazepine of 83 and14%, respectively.

’DRINKING WATER AND SWIMMING POOL DISIN-FECTION BY-PRODUCTS

Drinking Water DBPs. Drinking water DBPs are formed bythe reaction of disinfectants (chlorine, chloramines, ozone,chlorine dioxide, etc.) with natural organic matter (NOM) andbromide or iodide in source waters. They can also form by thereaction of disinfectants with other organic contaminants, andthere is an increasing amount of research in this area. Oneparticularly important discovery in this regard was the formation

of high levels of N-nitrosodimethylamine (NDMA) in drinkingwater that resulted from the reaction of ozone with a microbialtransformation product of a fungicide (tolylfluanid) used inEurope.2 New areas in drinking water DBP research includethe study of highly genotoxic or carcinogenic DBPs that havebeen recently identified, issues with increased formation of manyof these with the use of alternative disinfectants (e.g., chlora-mines and ozone), and routes of exposure besides ingestion. Inthis regard, there have been several recent studies of DBPs inswimming pools. Other trends include the development ofUPLC/MS/MS methods and the combination of analyticalchemistry with toxicology to account for toxicological effects withDBPs measured. In addition, near real-time methods are beingdeveloped, which could give drinking water utilities a betterunderstanding and control over DBP levels received by con-sumers and improve exposure characterizations for epidemiolo-gic studies.Toxicologically important DBPs include brominated, iodi-

nated, and nitrogen-containing DBPs (“N-DBPs”). BrominatedDBPs are generally more carcinogenic than their chlorinatedanalogues, and new research is indicating that iodinated com-pounds are more toxic than their brominated analogues.1 Bro-minated and iodinated DBPs form due to the reaction of thedisinfectant (such as chlorine) with natural bromide or iodidepresent in source waters. Coastal cities, where groundwaters andsurface waters can be impacted by salt water intrusion, and someinland locations, whose surface waters can be impacted by naturalsalt deposits from ancient seas or oil-field brines, are examples oflocations that can have high bromide and iodide levels. Asignificant proportion of the U.S. population and several othercountries now live in coastal regions that are impacted bybromide and iodide; therefore, exposures to brominated andiodinated DBPs are of growing interest. Early evidence inepidemiologic studies indicates that brominated DBPs may beassociated with reproductive and developmental effects, as well ascancer. Brominated and iodinated DBPs of interest include iodo-acids, bromonitromethanes, iodo-trihalomethanes (iodo-THMs),brominated forms of MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), haloaldehydes, and haloamides. Iodi-nated DBPs are increased in formation with chloramination, andbromonitromethanes are increased with the use of preozonation.Besides haloamides, other N-DBPs of interest include NDMAand other nitrosamines, which can form with either chloramina-tion or chlorination (if nitrogen-containing coagulants are usedin treatment). Five nitrosamines (NDMA, N-nitrosodiethyla-mine, N-nitrosodipropylamine, N-nitrosodiphenylamine, andN-nitrosopyrrolidine), as well as formaldehyde (which is a DBPfrom treatment with ozone, chlorine dioxide, or chlorine), arecurrently listed on the U.S. EPA’s new Contaminant CandidateList (CCL-3) (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). Chloramination has become a popular alternativeto chlorination for plants that have difficulty meeting the regula-tions with chlorine, and its use has increased with the new Stage 2Disinfectants (D)/DBP Rule (http://water.epa.gov/lawsregs/rulesregs/sdwa/stage2/regulations.cfm).Potential health risks from DBPs include cancer and repro-

ductive/developmental effects, with bladder cancer showing themost consistency in human epidemiologic studies from severalcountries. While this Review does not typically cover toxicologyor epidemiology studies, an important epidemiologic study wasjust published that bears mentioning here. Cantor et al. con-ducted a new case-control bladder cancer study and found an



enhanced risk for bladder cancer (odds ratio 5.9) for people witha particular genotype, which can be found in approximately 25%of the U.S. population.134 Their study also found that dermal/inhalation exposure from showering, bathing, and swimming wasa significant risk factor. The findings strengthen the hypothesisthat DBPs cause bladder cancer and suggest possible mechan-isms, as well as classes likely to be implicated.Several reviews have been published the last 2 years on DBPs.

For example, Krasner published a review on the formation andcontrol of emerging DBPs of health concern.135 Emerging DBPsdiscussed included iodo-THMs, haloaldehydes, halonitromethanes,and nitrosamines. Some emerging DBPs are associated withimpaired drinking water supplies (e.g., impacted by treatedwastewater, algae, and iodide). Examples of treatment techniquesto control their formation are given, including predisinfectionwith chlorine, chlorine dioxide, or ozone to destroy precursorsfor NDMA formation and the use of biofiltration to reduce levelsof ozone DBPs. Charrois published a nice review on the analysisof emerging DBPs in drinking water, which included detaileddiscussions on different analytical techniques that can be used tomeasure classes of emerging DBPs.136 In addition, Charroispresented a nice historical perspective on the beginnings of thisresearch area, with mention to the Water Chlorination Confer-ences begun by Robert Jolley (also published in a series ofbooks), on up to the establishment of a Gordon ResearchConference on Drinking Water DBPs in 2006. Swimming poolDBPs were also discussed.Richardson published a new review on DBP formation and

occurrence in drinking water.137 This review provides a compre-hensive listing of >600 DBPs identified from different disinfec-tants and disinfectant combinations (updating a 1998 encyclo-pedia article containing these original comprehensive lists) andincludes discussion of formation and occurrence, issues withalternative disinfectants, route of exposure, and formation of“pollutant” DBPs. Weinberg reviewed modern approaches foranalyzing DBPs in drinking water, which included a summary ofmethods for measuring regulated and emerging DBPs, includingiodo-THMs, halonitromethanes, nitrosamines, haloacetamides,and halofuranones.138

Combining Chemistry with Toxicology. More studies arecombining DBP identification/measurement efforts with toxi-cology to understand their potential health effects. For example,Pressman et al. report the second phase of a large integratedmultidisciplinary study (called the Four Lab Study) involving thecollaboration of chemists, toxicologists, engineers, and riskassessors from the 4 National Research Laboratories of theU.S. EPA, as well as collaborators from academia and the waterindustry.139 This paper described a new procedure for producingchlorinated drinking water concentrates for animal toxicologyexperiments, the comprehensive identification of >100 DBPs,and quantification of 75 priority and regulated DBPs. Complexmixtures of DBPs were produced by concentrating natural sourcewaters with reverse osmosis membranes, followed by addition ofbromide and treatment with chlorine. When the NOM wasconcentrated first and disinfected with chlorine afterward, DBPs(including volatiles and semivolatiles) were formed and main-tained in a water matrix suitable for animal studies. DBPs wererelatively stable over the course of the animal studies (125 days)with multiple chlorination events (every 5�14 days), and asignificant proportion of the total organic halogen was accountedfor through a comprehensive identification approach. ManyDBPs were reported for the first time, including previously

undetected and unreported haloacids and haloamides. Thenew concentration procedure not only produced a concentrateddrinking water suitable for animal experiments but also provideda greater TOC concentration factor (136�), enhancing thedetection of trace DBPs that are often below detection usingconventional approaches.Discovery of New DBPs. Increasingly, ESI-MS/MS is being

used to discover new, highly polar DBPs. For example, Qin et al.reported the first haloquinone DBP found in drinking water, 2,6-dichloro-1,4-benzoquinone, using SPE and LC/MS/MS.140

Quantitative structure-toxicity relationship (QSTR) analysishad predicted that haloquinones are highly toxic and may beformed during drinking water treatment. The chronic lowestobserved adverse effect levels (LOAELs) of haloquinones arepredicted to be in the lowμg/kg bodyweight per day range, whichis 1000� lower than most regulated DBPs, except bromate. Thisnew DBP was found in drinking water treated with chlorine andchloramines, as well as chloramines and UV irradiation, at levelsranging from 5.3 to 54.6 ng/L. It has a predicted LOAEL of 49μg/kg body weight per day. This effort was followed up byanother effort from Li’s research group, in which 3 additionalhaloquinones were identified for the first time in drinking waterusing LC/ESI-MS/MS: 2,6-dichloro-3-methyl-1,4-benzoqui-none, 2,3,6-trichloro-1,4-benzoquinone, and 2,6-dibromo-1,4-benzoquinone.141 Following their discovery in chlorinated drink-ing water, they were quantified, along with 2,6-dichloro-1,4-benzoquinone. Levels ranged from 0.5 to 165 ng/L. An unusualfeature about these compounds is that, using negative ion-ESI,they form (M þ H)� ions through a reduction step, rather thanthe classic (M � H) � ions that are typically observed withnegative ionization. The authors used tandem-MS and accuratemass measurements to confirm the identity of these unusual ions.Ding and Zhang used UPLC/ESI-MS/MS to provide a more

comprehensive picture of polar iodinated DBPs formed indrinking water.142 Precursor scans of iodine (m/z 126.9) allowediodinated DBPs to be detected in simulated drinking waterstreated with chlorine, monochloramine, and chlorine�chloramine.A total of 17 iodo-DBPs were tentatively identified, with chlor-amination producing the most iodo-DBPs, followed by chlorine�chloramine, then chlorination. Tentatively identified compoundsincluded iodoacetic acid, chloroiodoacetic acid, (E)- and (Z)-iodobutenedioic acid, 4-iodobenzoic acid, 3-iodophthalic acid,2,4-diiodobenzoic acid, 5,6-diiodosalicylic acid, and 5,6-diiodo-3-ethylsalicylic acid. In addition, two nitrogenous iodo-DBPs werefound in chloraminated and chlorine�ammonia treated waters,but the ion abundances were too low to propose structures forthem. In another paper, Zhai and Zhang developed a new ESI/MS/MS method for differentiating ESI adducts of commondrinking water DBPs from higher molecular weight DBPs.143

Using this method, they also proposed structures for several newbrominated DBPs in simulated drinking water. Finally, Peter andvon Gunten used SPME-GC/MS/olfactory detection to identify2,4,6-trichloroanisole, following a taste and odor episode in adrinking water system in Switzerland.144 This DBP has a very lowodor threshold of 30 pg/L, and it was found up to 24 ng/L indrinking water but only in distribution systems and not in the rawsource waters or finished waters from the plant. Laboratorystudies showed that trichlorophenol was an important precursor,chlorine played a key role as a residual disinfectant, and 2,4,6-trichloroanisole was only formed in the presence of biofilms.New Methods. Several other methods have been developed

for DBPs. Shi and Adams created a rapid ion chromatography



(IC)/ICP-MS method for simultaneously measuring iodoaceticacids, bromoacetic acids, iodate, bromate, iodide, and bromide.145

Method detection limits ranged from 0.33 to 0.72 μg/L foriodinated DBPs, and 1.36 to 3.28 μg/L for brominated DBPs.However, mono-, di-, and trichlorinated species could not bedetected because the sensitivity of ICP-MS for chlorine is poor.This method was successfully applied to measuring brominatedand iodinated DBPs in drinking water, groundwater, surfacewater, and swimming pool water.Several methods focused on derivatizing reagents to improve

the analysis/identification of DBPs. For example, Vincenti et al.synthesized a novel derivatizing agent, 5-chloro-2,2,3,3,4,4,5,5-octafluoropentyl chloroformate (ClOFPCF), and used it forthe direct derivatization of highly polar DBPs in drinkingwater.146 This derivatizing agent was specifically designed toderivatize carboxyl, hydroxyl, and amine groups, forming multi-ply substituted nonpolar derivatives that can be easily extractedfrom water and determined by GC/negative chemical ionization(NCI)-MS. The entire procedure from raw aqueous samples toready-to-inject hexane solutions of the derivatives requires <10min. Using this method, 13 unknown highly polar DBPs wereidentified in ozonated fulvic and humic acid solutions and in realozonated drinking water. Kubwabo et al. developed a newmethod using N-methyl-bis-trifluoroacetamide (MBTFA) deri-vatization and GC/ion trap-MS/MS to measure MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) in drinkingwater.147 This new method resulted in a significant reductionin analysis time and improved detection limits (7.7 ng/L) overprevious methods. The trifluoroacylated MX was shown to bestable for 30 days in an excess of the derivatization reagent, andthis method was used to measure MX in several drinking watersamples, where it was detected up to 517 ng/L. Finally, Banosand Silva used in situ derivatization/preconcentration withdansylhydrazine, which was first adsorbed on a reverse phase-C18 mini-column, to allow low ng/L detection of aldehydes inwater.148 This simple method required only 10mL of sample andused LC with chemiluminscence for detection.Near Real-TimeMethods. Researchers continue to pursue the

development of new instruments to enable real-time measure-ments of DBPs in drinking water, which would be a tremendousbenefit to drinking water utilities and to epidemiologists, whocould obtain more accurate exposure information for their studies.To this end, Emmert’s group at the University of Memphis hasbeen very active in designing such instruments. The latest devel-opment by his group includes a new instrument that can selectivelymeasure THMs andHAAs in near real-time directly from drinkingwater distribution systems.149 The instrument uses a capillarymembrane sampler-flow injection analyzer and is based on thefluorescence of the reaction of nicotinamide in basic solution withTHMs and HAAs. The analyzer alternates sampling between twosample loops connected to a capillary membrane sampler, whichdiscriminates between the volatile THMs and the nonvolatileHAAs. Method detection limits for the 4 regulated THMs and 5regulated HAAs (chloro-, dichloro-, trichloro-, bromo-, and di-bromoacetic acid) were 2.5 and 3.3 μg/L, respectively. Thismethod compared favorably to EPA Methods 502.2 and 552.3in chlorinated and chloraminated distribution systems and pro-vided automated online sampling with hourly sample analysis rates.Improved Method for Total Organic Chlorine and Bro-

mine.A few years ago,Minear’s group at the University of Illinoispioneered the development of a method to speciate total organichalogen (TOX), such that total organic chlorine (TOCl), total

organic bromine (TOBr), and total organic iodine (TOI) couldbe differentiated. This method involves the sorption of analytesonto activated carbon, followed by removal of inorganic analytes,combustion of the activated carbon, bubbling the combustion gasinto ultrapure water, and injection of this water onto an ionchromatograph for measurement of chloride, bromide, andiodide. The original TOX measurement served a useful purposein providing an idea of the total halogenated material formed inchlorinated and other disinfected waters, so that it could bedetermined how much of the halogenated DBPs were beingaccounted for through quantification of targeted DBPs. Thismeasurement has been widely used and has revealed that morethan 50% of the halogenated DBPs in drinking water are still notaccounted for. The development of the TOCl/TOBr/TOImethod allowed an even finer distinction of these DBPs andhas become an important measurement because of increasedtoxicity among the brominated and iodinated DBPs. Li et al.discovered that a portion of the TOCl (∼20%) can be reduced tochloride by the activated carbon, which can lead to an under-estimation of TOCl. The authors discovered that ozone can beused to oxidize the activated carbon to eliminate this problem.150

A follow-up paper by Li et al. revealed that ∼10% of TOBr canalso sometimes be reduced by the activated carbon, and theauthors were able to use aqueous solutions of ozone to improvethe TOBr measurement.151 Interestingly, TOI does not appearto suffer from the same issues.Alternative Disinfection Technologies Using Iodine, UV,

and Other Treatments. Two papers investigated DBP forma-tion from point-of-use treatments. In the first, Smith et al.measured the formation of iodo-DBPs (iodo-THMs and iodo-acids) and nitrosamines from 3 different iodine point-of-usetreatments that are used for the military in remote locations(iodine tincture), campers and hikers (iodine tablets), and thenew Lifestraw, a reusable device marketed toward rural con-sumers in developing countries that uses an iodinated anionexchange resin material with activated carbon post-treatment.152

Controlled laboratory experiments were carried out using fourdifferent source waters with widely ranging dissolved organiccarbon, specific UV absorbance (SUVA), and bromide levels.GC/EI-MS and derivatization with GC/NCI-MS were used tomeasure the iodo-THMs and iodo-acids, respectively; GC/CI-MS/MS (EPA Method 521) was used to measure the nitrosa-mines. TOCl, TOBr, and TOI were also measured using thecombustion-IC method described earlier. Iodoform was thepredominant iodo-DBP formed and was substantial, at roughly20�60% on a molar basis of the chloroform formation observedduring treatment of the same waters with a 6-fold higher oxidantconcentration. Iodine tincture produced the highest levels iodo-form, which ranged from 114 to 268 μg/L for treatments.Despite higher iodine residuals, iodoform formation duringtreatment with iodine tablets was lower, ranging from 74 to132 μg/L. While dichloroiodomethane and chlorodiiodo-methane were detected, they were more than an order ofmagnitude lower concentration than iodoform. Iodoacetic acid,bromoiodoacetic acid, diiodoacetic acid, (E)-3-bromo-3-iodo-propenoic acid, and (E)-2-iodo-3-methylbutenedioic acid werealso formed with iodine tincture treatment, with diiodoacetic acidand iodoacetic acid dominant in this class, but present at <11% ofthe iodoform levels. Lifestraw, which showed no iodine residual,produced the lowest iodo-DBPs among the 3 iodine treatments,with iodoform detected in only one of the disinfected waters at23 μg/L. TOI dominated with iodine tincture, while TOCl



dominated with chlorine and chloramine treatment, carried outfor comparison. On the basis of previous measurements of mamma-lian cell cytotoxicity of the individual THMs, a person consumingdrinking water treated with iodine tincture would receive thesame THM-associated cytotoxic exposure in 4�19 days as aconsumer of the same waters treated with a 6-fold higher dose ofchlorine over 1 year. Finally, nitrosamines were measured in samplesfrom the Lifestraw because nitrosamines can form from thecontact of oxidants with ion-exchange resins. While nitrosamineswere initially observed in the first few flushes of water through theLifestraw, they rapidly declined to low levels (3�4 ng/L).In another study, Lantagne et al. investigated DBP formation

in sodium dichloroisocyanurate point-of-use treatment that isused in Tanzania.153 THMs were measured in 6 source waters,some of which were highly turbid waters. No sample collectedat 1, 8, or 24 h after disinfection exceeded the World HealthOrganization (WHO) guideline values for individual or total THMs.Chlorine residual and THM formation were not significantlydifferent than when sodium hypochlorite treatment (a form ofchlorine commonly used in full-scale drinking water treatmentplants) is used.UV treatment is gaining popularity in the U.S. because it is

effective against resistant pathogens, including Cryptosporidium,and it has not been found to directly produce DBPs. However,studies are finding that when UV (particularly medium pressure-UV) is used along with postchlorination, it can enhance theformation of some DBPs. Low-pressure UV emits only 254 nmlight, but medium-pressure UV emits a much broader spectrum(often 200�400 nm). Dotson et al. investigated DBP formationfrom the use of UV and UV/H2O2 (advanced oxidation).

154 At aUV dose of 1000 mJ/cm2, THM levels increased by up to 4 μg/mg-C and 13 μg/mg-C when treated with low- and medium-pressure UV, respectively. Addition of hydrogen peroxide wasshown to increase THM formation up to 25 μg/mg-C and 37μg/mg-C, respectively. In another study, Reckhow observed anincrease in formation of trichloronitromethane (chloropicrin)and 1,1,1-trichloropropanone when medium-pressure UV wasfollowed by chlorination.155 In contrast, low-pressure UV did notcause an increase in trichloronitromethane formation. Theauthors propose that photonitration leads to the formation ofnew nitroorganics during UV treatment and these form haloni-tromethanes during subsequent chlorination.The formation of iodo-DBPs from the use of manganese(IV)

dioxide treatment was investigated by Gallard et al.156

Manganese(IV) dioxide is sometimes used as a catalyst indrinking water treatment to oxidize Mn(II) to Mn(IV) dioxideso that it can be subsequently removed by filtration. BecauseMn(IV) dioxide was previously shown to oxidize iodide to iodineat neutral pH, the authors investigated the potential for iodo-DBP formation. In the presence of NOM, adsorbable organiciodine (AOI) was observed following treatment with Mn(IV)dioxide, and iodoacetic acid and iodoform were measured asDBPs. At very high NOM/Mn(IV) dioxide ratios, iodoform wasnot observed, due to inhibition of the catalytic effect of Mn(IV)dioxide by NOM sorbing onto the manganese dioxide.Nitrosamines. Nitrosamines continue to be of interest, since

they were discovered to be DBPs in 2002. NDMA is a probablehuman carcinogen, and there are toxicological concerns regard-ing other nitrosamines. NDMA was initially discovered inchlorinated drinking waters from Ontario, Canada, and has sincebeen found in other locations. The detection of NDMA indrinking water is largely due to improved analytical techniques

that have allowed its determination at low ng/L concentrations.NDMA is generally present at low ng/L in chloraminated/chlorinated drinking water, but it can be formed at much higherlevels in wastewater treated with chlorine. It was also recentlyshown to form when waters containing a microbial degradationproduct of the fungicide, tolylfluanid, were ozonated.2 NDMA isnot currently regulated in the United States for drinking water,but it is regulated in Ontario, Canada, at 9 ng/L under Ontario’sSafe Drinking Water Act (http://www.e-laws.gov.on.ca/html/regs/english/elaws_regs_030169_e.htm). A Canadian nationaldrinking water guideline for NDMA is also under development(www.hc-sc.gc.ca/ewh-semt/consult/_2010/ndma/draft-ebauche-eng.php). NDMA was included in the U.S. EPA’s secondUnregulated Contaminants Monitoring Rule (UCMR-2), alongwith 5 other nitrosamines (N-nitrosodiethylamine, N-nitrosodi-butylamine,N-nitrosopropylamine,N-nitrosomethylethylamine,and N-nitrosopyrrolidine), and national occurrence data arecurrently available (http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/data.cfm#ucmr2010). In addition, NDMA and 4other nitrosamines are also on the U.S. EPA’s final CCL-3(http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm).Zhao et al. investigated the role of diphenylamine as a

precursor in the formation of N-nitrosodiphenylamine (NDPhA)and determined the effect of pH and chloramination conditionson its formation.157 Diphenylamine was determined to be a keyprecursor, and controlled experiments revealed that chloraminesare also essential to NDPhA formation, with increasing forma-tion at increasing pH (from 4 to 10). In addition, two new DBPs,phenazine and a chlorinated phenazine derivative, were identifiedfor the first time using LC/MS/MS and GC/MS. These newDBPs were detected only in the treated water and not in theraw water.A fascinating study by Kemper et al. investigated the role of

several consumer products (shampoos, laundry detergents, dishwashing liquids, and fabric softeners) in the formation ofnitrosamines.158 This study was conducted in order to addressthe question surrounding relatively high levels of nitrosamines intreated wastewaters that are correlated with wastewaters impacts,rather than total dissolved organic nitrogen. Nitrosamines wereformed from several of these products when they were reactedwith monochloramine or chlorine, and the authors showed clearevidence that quaternary amines (including polymers) used inthese products form nitrosamines. In fact, the quaternary aminepolymers were more reactive than the monomers, and preozona-tion or prechlorination did not significantly reduce nitrosamineformation. EPAMethod 521 (GC/CI-MS/MS) was used for themeasurements. There was also important new information onthe reaction of monochloramine and chlorine with the poly-DADMAC polymers used as coagulants in drinking watertreatment. Results showed that the polymers themselves arereacting with chlorine to form NDMA and other nitrosamines.This was proven by synthesizing polyDADMAC (to control thepurity and eliminate contribution of monomers). These findingsare important because nitrosamine formation is often attributedto lower order amine impurities, but these results clearly showthat quaternary amine polymers can form NDMA.Other new studies investigated the role of anion-exchange

resins and water treatment polymers in the formation of nitro-samines. For example, strong base anion-exchange resins wereinvestigated in a study by Kemper et al.159 These resins (whichcontain quaternary amine functional groups) represent an im-portant option for water utilities and homeowners to address



growing concerns with nitrate, arsenate, and perchlorate contam-ination. Nitrosamines were released from the resins when theywere new (up to 10 ng/L), but levels decreased with time aftermultiple regeneration cycles, indicating that releases may even-tually subside. When chlorinated or chloraminated water waspassed through the resins, nitrosamine levels increased to20�100 ng/L. Dimethylnitramine (DMNA) was also formedwith chlorine at significant levels; trichloronitromethane(chloropicrin) was formed to a lesser extent. EPA Method 521was used to measure nitrosamines and DMNA. NoN-DBPs werefound in the cation exchange-based point-of-use devices that areused by homeowners. Water treatment polymers (includingpolyamines and poly(diallyldimethylammonium chloride)[polyDADMAC]) were investigated as sources of nitrosaminesby Park et al.160 Overall, polyamines had greater NDMA forma-tion potential than polyDADMAC, and NDMA formation fromboth polymers was strongly related to polymer degradation anddimethylamine release during chloramination. The tertiary aminechain of the polyamines plays a major role, while the quaternaryammonium group of polyDADMAC played a major role.Goslan et al. published the first nitrosamine occurrence in

Scotland, in which nitrosamines and other N-DBPs were measured,and the impact of secondary disinfectants was investigated.161

There is not currently a regulation in the UK for nitrosamines,but there is a guideline that requires water utilities to contact localhealth professionals if concentrations exceed 10 ng/L. EPAMethod 521 (GC/CI-MS/MS) was used to measure nitrosa-mines, and a modified EPA Method 551.1 (GC-electron capturedetection [ECD]) was used to measure haloacetonitriles andchloropicrin. Over the 3 seasons sampled among 7 water utilitiesin Scotland, NDMA was found in only one of the utilitiessampled, up to 26 ng/L in drinking water treated with chlor-amines. Templeton andChen reportedmeasurements of NDMAand 7 other nitrosamines in the United Kingdom.162 NDMAwasfound only in a few samples from one distribution system, slightlyabove the detection limit of 0.9 ng/L. Otherwise, the majority ofthe samples collected from 6 systems contained no detectablelevels. However, N-nitrosobutylamine (NDBA) was consistentlydetected on one distribution system, up to 6.4 ng/L.DBPs from wastewater effluents were the focus of another

occurrence study by Krasner et al.163 Chlorinated wastewatersfrom 23 wastewater treatment plants in the U.S. were studiedacross different seasons. Nitrosamines, iodo-THMs, haloacetal-dehydes, halonitromethanes, and THMs were measured usingGC/MS and GC/ECD. Disinfection and oxidation practices hada profound impact on the types and levels of DBPs formed.Wastewater treatment plants that did not achieve breakpointchlorination (which would effectively have chloramination con-ditions) formed lower levels of halogenated DBPs but produceda substantial amount of NDMA (up to 3165 ng/L). N-Nitroso-morpholine was also frequently detected. On the other hand,plants that achieved breakpoint chlorination formed consider-able amounts of THMs, HAAs, haloacetaldehydes, and haloace-tonitriles. This study revealed how wastewater treatment plantdischarges can be a source of a wide range of halogenated andnonhalogenated DBPs of health concern, which is important foran increasing number of water reclamation programs in aridregions of the United States.Mechanisms of Formation. Typically, HOCl is assumed to

be the active oxidant when chlorine is used in drinking watertreatment. However, Sivey et al. provided evidence that a little-known chlorine monoxide (Cl2O) species is the predominant

chlorinating agent during the chlorination of the herbicidedimethenamid.164 The influence of free available chlorine andpH and the kinetics of these reactions were consistent with Cl2Obeing the active species under typical drinking water treatmentconditions. Some early reports identifying Cl2O as an activechlorinating species appeared in the 1970s and 1980s, but theliterature has been quiet since on this topic; it is quite likely that itcould have been the active reactant species in other reactions buthas not been considered. As a consequence, the authors suggestthat some apparent rate constants in the literature may not bevalid. Chu et al. investigated precursors of dichloroacetamide, themost common haloamide formed in chlorinated and chlorami-nated drinking water.165 In a reservoir in China, dissolved organicmatter was separated into 6 fractions by a series of resin elutions,and hydrophilic dissolved organic matter was found to form thehighest levels of dichloroacetamide. Fluorescence excita-tion�emission matrix spectra revealed that a mass of protein-like substances in this fraction, made up of amino acids, werelikely the dichloroacetamide precursors. Subsequent reactions of20 amino acids with chlorine revealed that 7 amino acids(aspartic acid, histidine, tyrosine, tryptophan, glutamine, aspar-agine, and phenylalanine) could form dichloroacetamide duringchlorination, with yields of 0.231, 0.189, 0.153, 0.104, 0.078,0.058, and 0.050 mmol/mol amino acid.Halonitromethane formation was the focus of another study

by Hu et al.166 Formation potential tests confirmed earlier workshowing that ozonation followed by postchlorination producedthe highest halonitromethane levels, and fractionation of NOMrevealed a significantly higher reactivity of hydrophilic NOMthan hydrophobic or transphilic NOM. The best correlationbetween halonitromethane formation and various water qualityparameters was with the ratio of dissolved organic carbon todissolved organic nitrogen. Dabrowska and Nawrocki carried outa study to address past controversies regarding the formation oftrichloroacetaldehyde (chloral hydrate, CH) in drinking water.167

Haloaldehydes are the third most prevalent class of DBP (behindthe THMs and HAAs), and CH is the most common one in thisclass. The authors carried out reactions in different source watersin Poland (with widely different TOC and water quality). Inaddition, finished drinking water samples were collected fromfull-scale plants. Results showed that CH formation dependsmore on the type of NOM than on its quantity and thatincreasing chlorine dose leads to higher concentrations of CH,with reactions taking place with NOM as long as chlorine isavailable in the water. Higher pH forms higher levels of CH, andpreozonation significantly increases its formation, as observedpreviously in the literature. Further, biological filtration did notremove all CH precursors.Finally, Krasner et al. published a nice study on the impact of

wastewater treatment processes on organic carbon, organicnitrogen, and DBP precursors in effluent organic matter.168 Thisstudy represents the first large-scale assessment of the criticalwater quality parameters that affect the formation of DBPsduring drinking water treatment relative to the discharge ofupstream wastewater treatment plants. Source waters are in-creasingly receiving treated wastewater, and as such, there isindirect, unintentional reuse of wastewater in many drinkingwater systems. In this study, 23 wastewater treatment plants weresampled, and regulated and priority unregulated DBPs weremeasured. Results showed that nitrification has a profoundimpact on many measures of effluent water quality, includingformation potentials for a diverse group of priority DBPs of



health concern. Complete nitrification reduced biodegradableorganic carbon (BDOC) levels and changed the ratio of BDOC/dissolved organic carbon (DOC). Nitrification reduced the UVabsorbance at 254 nm, but it also increased the specific UVA/DOC ratio, which was attributed to the preferential removal ofthe nonhumic fraction of DOC during biological treatment. Theeffluent organic carbon was composed of hydrophilic andbiodegradable DOM, as well as hydrophobic and recalcitrantDOM, whose proportions changed with advanced biologicaltreatment. The onset of nitrification in these plants producedlower precursor levels for HAAs and nitrogenous DBPs(halonitriles and NDMA), but THM precursors were relativelyunaffected by the level of wastewater treatment.DBPs of Pollutants. Studies of DBPs are going beyond the

“classic” DBPs formed by the reaction of NOM with disinfec-tants, such that reactions of environmental pollutants withdisinfectants are increasingly being studied. Contaminant DBPshave been recently reported from herbicides, pharmaceuticals,personal care products, microcystins, and terpenoids. Some ofthis research has been conducted in order to find ways to degradeand remove these contaminants from wastewater effluents anddrinking water sources, but some of this research is beingconducted to determine the fate of these contaminants indrinking water treatment. It is not surprising that DBPs canform from these contaminants, as many of them have activatedaromatic rings or other structural groups that can readily reactwith oxidants like chlorine and ozone. However, until recently,these types of DBPs were not investigated.DBPs formed by the reaction of chlorine with triazine

herbicides were the focus of an article by Brix et al.169 UPLC-Q-TOF-MS/MS was used to tentatively identify 4 new DBPsfrom ametryn, prometryn, and terbutryn, which had highertoxicities than the parent herbicides. Wang et al. investigatedDBPs formed by chlorine dioxide treatment of fluoroquinoloneantibiotics and structurally related amines.170 The piperazine ringof the fluoroquinolones was the primary reactive center towardchlorine dioxide, followed by fragmentation, dealkylation, hydro-xylation, and intramolecular ring closure at the piperazinemoiety. However, the quinolone ring remained mostly intact,which is strongly related to the antimicrobial property. Chlorina-tion byproducts of the cyanobacterial toxin microcystin-LR werethe focus of a new study by Merel et al., who used linear ion trap-Q-Orbitrap-MS to identify the products.171 Microcystin-LR wastotally transformed within 2 min, and 8 new byproducts wereidentified, including chloro-microcystin, chloro-dihydroxy-mi-crocystin, dichloro-dihydroxy-microcystin, trichloro-hydroxy-microcystin, and several dihydroxy-microcystins.Also, several other examples were highlighted earlier in the

Pharmaceuticals and Hormones section. These included ozonebyproducts of antibiotics and beta-blockers; chlorine byproductsof EE2, trenbolone, salicyclic acid, naproxen, diclofenac, andfluoroquinolones; UV/H2O2 byproducts of X-ray contrastmedia; and ferrate byproducts of carbamazepine.New Swimming Pool Research. Swimming pools are being

recognized as an important source of exposure to DBPs. Healthconcerns include increased risk of bladder cancer from exposureto indoor pools and increased risk of asthma for both indoor andoutdoor pools.1 Richardson et al. carried out a comprehensiveDBP characterization and assessed the mutagenicity in twopublic swimming pools, one chlorinated and one brominated,that were part of a human exposure study focused on respiratoryand genotoxicity biomarkers.172 More than 100 DBPs were

measured, including many nitrogenous DBPs likely formed bynitrogen-containing inputs from human inputs (urine, sweat,skin cells). In addition, several new DBPs were identified thathave not previously been reported for either swimming poolwater or drinking water. Bromoform levels were higher in thebrominated pool, but brominated DBPs were also identified inthe chlorinated pool, due to source waters (from Barcelona) thatwere already high in bromide. Mutagenicity results showed thatthese pool waters had a similar mutagenicity to chlorinateddrinking water, but the toxicity was higher.Volatile DBPs in a chlorinated indoor swimming pool were the

focus of a study by Weaver et al., who used membrane ionizationmass spectrometry (MIMS) for their measurement.173 Elevenpools were investigated over a 6 month period, and 11 volatileDBPs were identified as follows: monochloramine, dichloramine,trichloramine, chloroform, bromoform, bromodichloromethane,dibromochloromethane, cyanogen chloride, cyanogen bromide,dichloroacetonitrile, and dichloromethylamine. In a fascinatingstudy involving continuous real-time measurements, Kristensenused MIMS for online monitoring of the dynamics of THMconcentrations in a warm public swimming pool.174 The MIMSinstrument performed unsupervised for more than a year, withonly short interruptions for filament replacements every 6�8weeks. Online monitoring revealed the daily cycles of chloroformand bromodichloromethane concentrations, which increasedduring the pools’ closing hours and decreased during openinghours. Daily concentrations of 30�100 μg/L for chloroformwere observed, and 5�10 μg/L levels of bromodichloromethanewere observed, except for short bursts in bromodichloromethanelevels (up to 100 μg/L) that were linked to salt addition (sodiumchloride) used to electrolytically generate chlorine for disinfec-tion. Lower THM levels correlated to the operation of a strongwater jet system.Blatchley and Cheng conducted experiments to elucidate the

reaction mechanism of free chlorine with urea.175 Urea is animportant swimming pool precursor, introduced by human urine,and it is known to react with chlorine to form trichloramine, arespiratory irritant that is suspected in the cases of asthma of eliteswimmers. Results showed multiple N-chlorination steps, withinitial formation ofN-chlorourea, subsequent formation of a fullychlorinated urea molecule, which undergoes further hydrolysisand additional chlorination to yield trichloramine as an inter-mediate. Trichloramine can then be hydrolyzed to yield mono-chloro- and dichloramine, with subsequent decay to stable endproducts, including N2 and nitrate. Conversion of urea-nitrogento nitrate was found to be pH dependent. The aquatic fate ofsunscreen agents in model swimming pools was the focus of astudy by Nakajima et al., who used GC/MS to identify thechlorination byproducts.176 Octyl-4-methoxycinnamate (OMC)and octyl-4-dimethylaminobenzoate (ODPABA) reacted withhypochlorite to produce chlorine-substituted products as inter-mediates, which were weakly mutagenic in Salmonella (TA 100).Finally, Kulshrestha et al. reported a new total N-nitrosamine

(TONO) assay for application to swimming pools.177 Thismethod was a modified version of a method previously devel-oped for the measurement of nitrite, S-nitrosothiols, andN-nitrosamines in biological samples and involves their reductionto nitric oxide by acidic tri-iodide, followed by chemiluminescentdetection of the evolved nitric oxide in the gas phase. Methoddetection limits of 62 pM (5 ng/L as NDMA) were achieved for1 L pool water samples extracted with liquid�liquid extraction.Evaluation of potential interfering species indicated that only



nitrite and S-nitrosothiols were a concern, and both interferenceswere effectively eliminated using group-specific sample pretreat-ments previously used for biological samples. This method wassubsequently applied to TONOmeasurements in pools and theircorresponding tap water sources.

’SUNSCREENS/UV FILTERS

UV filters used in sunscreens, cosmetics, and other personalcare products have increased in interest due to their presence inenvironmental waters and their potential for endocrine disrup-tion and developmental toxicity. A few UV filters have beenshown to have estrogenic effects similar to E2 (a naturalestrogen), as well as the potential for developmental toxicity.1

Environmental levels of UV filters are not far below the doses thatcause toxic effects in animals. There are two types of UV filters:organic UV filters, which work by absorbing UV light, andinorganic UV filters (TiO2, ZnO), which work by reflectingand scattering UV light. Organic UV filters are increasingly usedin personal care products, such as sunscreens, cosmetics, beautycreams, skin lotions, lipsticks, hair sprays, hair dyes, and sham-poos. Examples include benzophenone-3 (BP-3), ODPABA,4-methylbenzylidene camphor (4-MBC), ethylhexyl methoxy-cinnamate (EHMC), octocrylene (OC), iso-amylmethoxycinna-mate (IAMC), and phenylbenzimidazole sulfonic acid (PBSA).The majority of these are lipophilic compounds (low watersolubility) with conjugated aromatic systems that absorb UVlight in the wavelength range of 280�315 nm (UVB) and/or315�400 nm (UVA). Most sunscreen products contain severalUV filters, often in combination with inorganic micropigments.Because of their use in a wide variety of personal care products,these compounds can enter the aquatic environment indirectlyfrom bathing or washing clothes, via wastewater treatment plantsand directly from recreational activities, such as swimming andsunbathing in lakes and rivers.

Diaz-Cruz and Barcel�o published a review on UV filters,summarizing analytical methods and ecotoxicological effects.178

The authors discussed the fact that biological activity is not wellpredicted from the chemical data alone and that EC50 values forhormonally active UV filters were similar to those for otherknown environmental xenoestrogens (in the low μM range).Gaps in knowledge pointed out by the authors include a need toassess and understand the activity of mixtures of UV filters andthe need for integrated chemical and biological testing.

New methods continue to be developed, including ones usingUPLC/MS, LC/MS, direct analysis in real-time (DART)-MS,SPME-GC/MS, and dispersive liquid�liquid microextraction(DLLME)-GC/MS. Wick et al. developed a multiresidue meth-od using LC/ESI-MS/MS and LC/APCI-MS/MS for determin-ing 36 emerging contaminants, including 5 UV filters, in raw andtreated wastewater, activated sludge, and surface water.179 Quan-tification limits ranged from 0.5 to 5 ng/L and 2.5�50 ng/L insurface waters and wastewater, respectively. Maximum concen-trations up to 5.1 and 3.9 μg/L were found in raw wastewater forthe BP-4 and PBSA, respectively. This method also allowed thefirst identification of an antidandruff compound (climbazole) inwastewater up to 1.4 μg/L. Pedrouzo et al. created the UPLC/MS/MS method using stir-bar sorptive extraction to measure 4UV filters (DHMB, BP-3, OC, and ODPABA) and antimicrobialcompounds (triclosan and triclocarban) in surface water andwastewater.180 Detection limits of 2.5 ng/L (river water) and5�10 ng/L (raw and treated wastewater) were achieved. Using

this method, BP-3 was found up to 127 ng/L in wastewaterinfluents and up to 28 ng/L in river waters.

DART-MS was used in a creative method by Haunschmidtet al. to measure 7 UV filters in environmental waters.181 Stir-barsorptive extraction was used to extract analytes from the water,and DART-MS was used to directly analyze the analytes from thesurface of the polydimethylsiloxane-coated stir bars. Detectionlimits of <40 ng/L were achieved, and the newmethod was cross-confirmed using a thermodesorption-GC/MS method, whichproduced comparable concentrations when tested on lake watersamples. SPME-GC/MS/MS was the focus of a method byNegreira et al., who measured 3 UV filters and hydroxylatedbenzophenones in water.182 The analytes were extracted andconcentrated onto a SPME fiber, followed by on-fiber silylationand measurement with GC/MS/MS. The entire process took 40min and provided limits of quantification of 0.5 to 10 ng/L.DLLME-GC/MSwas used in a newmethod by Tarazone et al. tomeasure hydroxylated benzophenones UV filters in seawatersamples.183 Under optimized conditions, 1000 μL of acetone(dispersive solvent), containing 60 μL of chloroform (extractionsolvent), was injected into a 5 mL aqueous sample (adjusted topH 4 and containing 10%NaCl). DLLME extracts were evaporatedunder an air stream and reconstituted with bis(trimethylsilyl)-trifluoroacetamide (BSTFA) to derivatize the target analytes totheir trimethylsilyl derivatives, followed by analysis with GC/MS.Detection limits ranged from 32 to 50 ng/L. Oliveira et al. created anew automated sample pretreatment/detectionmethod using in-line SPE with multisyringe-lab-on-valve and LC/diode array-UVdetection.184 Samples could be automatically processed every 9min, and detection limits ranged from 0.45 to 3.2 μg/L.

New occurrence studies include one from Fent et al. whodemonstrated the widespread occurrence of estrogenic UV filtersin aquatic ecosystems in Switzerland.185 POCIS was used withLC/MS/MS and GC/MS to measure the UV filters in biota andriver water sampled at 10 sites above and below wastewatertreatment plants. BP-3, 4-MBC, and EHMC ranged from 6 to 68ng/L in river water, and EHMC was accumulated in biota.Wastewater was found to be the most important source of theseUV filters, and no significant in-stream removal was observed inthe rivers. Leal et al. measured UV filters and other xenobioticcontaminants in gray water and investigated biological treatmentsystems (aerobic, anaerobic, and combined anaerobic�aerobic)for their removal.186 Due to limited freshwater resources, graywater, which is the effluent from domestic washing activities (e.g.,laundry, dishwashing, bathing), is increasingly being explored forreuse in applications, such as landscape irrigation and toiletflushing. In this study, all xenobiotics were detected in gray watersamples at low μg/L levels, with lower levels following biologicaltreatment. Generally, removal efficiencies were higher underaerobic conditions, however, most xenobiotics were still detectedin the biologically treated gray water. The UV filters PBSA andEHMC were among the most persistent compounds found.Estimated estrogenic potential of the effluent ranged from 0.07to 0.72 ng/L of 17β-estradiol equivalents.

Several good fate studies have also been published on UVfilters. For example, Rodil et al. investigated the photostability ofUV filters used in sunscreens and combined this with investiga-tions of toxicity of the resulting photolysis products.187 Duringexposure to artificial sunlight over 72 h, 3 of the UV filters werefound to degrade, with half-lives of 20�59 h. Structural changesincluded isomerization and polymerization for IAMC, EHMC,and 4-MBC, and dealkylation for ODPABA, which formed stable



photoproducts. Stir-bar sorptive extraction with GC/MS andliquid desorption-LC/MSwere used to analyze theUV filters andtheir degradation products. A few of the UV filters were found tobe toxic for algae, but EHMC, IAMC, and ODPABA degradedquickly during UV radiation, and the corresponding phytotoxi-city of the reactionmixtures was low. OC, BP-3, and 4-MBCwerestable to irradiation. Finally, as mentioned earlier in the DBPsection, Nakajima et al. investigated the fate of OMC andODPABA (used in sunscreens) in model chlorinated swimmingpool waters using GC/MS.176 ODPABA was found to reactrapidly with free chlorine at pH 7.0, whereas OMC reacted ratherslowly under the same conditions. Both produced chlorine-substituted byproducts as intermediates, which decomposedvia cleavage of the ester bonds. These byproducts were weaklymutagenic in Salmonella TA 100 (Ames assay).

’BROMINATED FLAME RETARDANTS

Brominated flame retardants have been used for many years ina variety of commercial products including children’s sleepwear,foam cushions in chairs, computers, plastics, and electronics.Brominated flame retardants work by releasing bromine freeradicals when heated, and these free radicals scavenge other freeradicals that are part of the flame propagation process. The use ofthese flame retardants is believed to have successfully reducedfire-related deaths, injuries, and property damage. However,there is concern because of their widespread presence in theenvironment and in human and wildlife samples, as well as theirpresence in locations far fromwhere they were produced or used.Polybrominated diphenyl ethers (PBDEs) have been a popularingredient in flame retardants since the polybrominated biphe-nyls were banned about 30 years ago. They are environmentallypersistent, lipophilic, and bioaccumulate in animals and humans.PBDEs are made up of 209 possible congeners containingbetween 1 and 10 bromine atoms, and of these, 23 congenersare of environmental significance.1 In recent years, PBDE levelshave been increasing significantly. The greatest health concerncomes from recent reports of developmental neurotoxicity inmice, but there are also concerns regarding the potential forhormonal disruption and, in some cases, cancer. In 2004, theEuropean Union banned the use of the penta- and octa-BDEsand, later in 2008, banned deca-BDEs.1

In 2004, the major U.S. manufacturer of PBDE-based flameretardants (Great Lakes Chemical) voluntarily stopped produ-cing the penta- and octa-BDEs. However, deca-BDE is still beingmanufactured and used. Earlier studies had suggested that deca-BDE was too large to bioaccumulate and would not be a risk tohumans. However, research now shows that it can accumulate inanimal tissues (including people) and that it can debrominate inthe environment and metabolically form the lower brominatedspecies (including the octa- and penta-BDEs).1 Several U.S.states banned the penta- and octa-BDEs in 2006, and inDecember 2009, two U.S. producers of deca-BDE agreed tovoluntarily phase it out in the United States (www.epa.gov/oppt/existingchemicals/pubs/actionplans/deccadbe.html). Inaddition, the U.S. EPA issued a new rule in 2006 to complementthe phase-out of the octa- and penta-BDEs, ensuring that no newmanufacture or importation of these chemicals can occur withoutfirst being subject to U.S. EPA evaluation (www.epa.gov/EPA-TOX/2006/June/Day-13/t9207.htm).

However, despite the halt in manufacture of most of thesePBDEs in North America and Europe, they are still present in

many consumer products sold previously and can be releasedinto the environment during use and disposal. In addition, thereis still the possibility of importing products that contain them.Four of the PBDEs (2,20,4,40-tetra-BDE (BDE-47), 2,20,4,40,5-penta-BDE (BDE-99), 2,20,4,40,5,50-hexa-BDE (BDE-153), and2,20,4,40,6-penta-BDE (BDE-100)) and another brominatedflame retardant (2,20,4,40,5,50hexabromobiphenyl (HBB)) wereon the UCMR-2 in the U.S., and national occurrence data arenow available (http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/data.cfm#ucmr2010).

Many review articles have been published on brominatedflame retardants, and one is highlighted here. Daso et al. reviewedthe sources of brominated flame retardants and routes of humanexposure.188 Consumption of contaminated food and water andinhalation and ingestion of dust, as well as dermal absorption,were considered important pathways of exposure. Fatty foods,especially fish, meat, dairy products, and human milk constituteimportant routes for human exposure to these contaminants.Ruan et al. reported the discovery of a new brominated flameretardant, tris(2,3-dibromopropyl)isocyanurate, in the environ-ment.189 This compound was identified in river water, sediment,soils, and biota in a factory-polluted area in southern China, up to163 ng/L in river water. Results also showed a high Kow (log Kow =7.37) and bioaccumulation factor (log BAF = 4.30).

New methods for measuring brominated flame retardantsinclude those using LC/APPI-MS/MS and GC/MS. Bacaloniet al. described a new LC/negative ion-APPI-MS/MS methodfor measuring tetrabisphenol A and 5 PBDEs (BDE-47, BDE-99,BDE-100, BDE-153, and BDE-154) in water.190 A mobile phaseconsisting of methanol/acetone/water was used, where acetoneserved as the dopant for APPI. Method quantification limitsranged from 0.2 to 20.3 ng/L. Fontana et al. used cloud pointextraction with ultrasound-assisted back-extraction-GC/MS in anew method to measure PBDEs in water and soil.191 A nonionicsurfactant (Triton X-114) was used to extract the PBDEs, andmethod detection limits of 1�2 ng/L were achieved.

Studies continue to explore the fate of PBDEs in the environ-ment. For example, Steen et al. investigated the photochemical fateof hydroxylated PBDEs and their chlorinated derivatives.192 Halo-genated dioxins were formed when the four hydroxylated PBDEs(OH-PBDEs) and polybrominated/chlorinated diphenyl etherswere photolyzed under sunlight in river and lake water. Dioxinyields of 0.7�3.6% were found, with higher yields for 6-hydroxy-BDE-47. Wan et al. conducted a study to determine the origin ofOH-PBDEs.193 Results showed that metabolism can also formOH-PBDEs from the corresponding methylated PBDEs, which repre-sents a new mechanism that has not been previously explored.

Robrock et al. investigated the aerobic biotransformation ofPBDEs in bacteria using GC/ECD and GC/MS.194 Two PCB-degrading strains of bacteria were found to transform all of themono- through penta-BDEs, and one strain transformed one ofthe hexa-BDEs. The extent of transformation was inverselyproportional to the degree of bromination. This is the first reportof aerobic transformation of these PBDEs, as well as the firstreport of the stoichiometric release of bromide during PBDEtransformation. Finally, Bogdal et al. investigated sources ofPBDEs and polychlorinated biphenyls (PCBs) in a Swiss lake.195

For lower brominated PBDEs, ∼70% and 30% of input to thelake originated from atmospheric deposition and from tributaries,respectively. For heavier PBDEs and all PCBs, rivers delivered themajor load (64�92%). Wastewater effluents were a minorsource, and 50�90% was buried in the permanent sediment.



’BENZOTRIAZOLES

Benzotriazoles are complexing agents that are widely used asanticorrosives (e.g., in engine coolants, aircraft deicers, or anti-freeze liquids) and for silver protection in dish washing liquids.The two common forms, benzotriazole and tolyltriazole, aresoluble in water, resistant to biodegradation, and only partiallyremoved in wastewater treatment. There is also new evidence forestrogenic effects in vitro but, so far, not in vivo, in recent fishstudies.1 Because of their water solubility, LC/MS and LC/MS/MS methods have been recently developed for their measure-ment in environmental waters. While reports of benzotriazolesare fairly recent (last 6�7 years), studies indicate that they arelikely ubiquitous environmental contaminants. Benzothiazolesand benzosulfonamides are also increasingly being measured inenvironmental samples. Benzothiazoles are high productionchemicals used as corrosion inhibitors, as biocides in paper andleather manufacturing, and in the production of rubber. Benzo-sulfonamides are widely used as plasticizers and intermediates inthe synthesis of sweeteners and can be metabolites of corrosioninhibitors.1

New methods developed include one by Jover et al. whoinvestigated the use of GC�GC-TOF-MS to measure benzo-triazoles, benzothiazoles, and benzosulfonamides in environmen-tal waters.196 SPEwas used for extraction, andGC�GC improvedseparations, enabling the identification of minor components thatmight be overlooked with other methods. This method was thenused to measure these analytes in river water, effluent from awastewater treatment plant, and raw sewage. Orbitrap-MS wasused in another method by van Leerdam et al., who measured 6benzotriazoles and benzothiazoles in water.197 This LC/linear iontrap-Orbitrap-MSmethod enabled improved mass accuracies anddetection limits down to 0.01 μg/L. Finally, Wick et al. developeda multiresidue method using LC/MS/MS that included ben-zothiazoles, which could be measured at ng/L levels.179

The occurrence and fate of benzotriazoles and benzothiazolesin constructed wetlands and a wastewater treatment plant wasinvestigated by Matamoros et al., who used GC�GC-TOF-MS.198 Benzotriazole removal efficiencies ranged from 65 to70% and 89 to 93% in the conventional wastewater treatmentplant and in the constructed wetlands, respectively. Benzothia-zole removal efficiencies ranged from 0 to 80% and 83 to 90% inthe conventional wastewater treatment plant and in the con-structed wetlands, respectively. Higher degradation in theconstructed wetlands was attributed to the possibility of biode-gradation, photodegradation, and plant uptake. Finally, in the pan-European studymentioned earlier by Loos et al., 1H-benzotriazoleand methylbenzotriazole were measured in >50% of the ground-waters sampled, up to 1.03 and 0.52 μg/L, respectively.50

’DIOXANE

1,4-Dioxane is a widespread industrial contaminant in envir-onmental waters (often exceeding water quality criteria andguidelines), has also been found in drinking water, and is aprobable human carcinogen. Dioxane is a high productionchemical and is used as a solvent stabilizer in the manufactureand processing of paper, cotton, textile products, automotivecoolants, cosmetics, and shampoos, as well as a stabilizer in 1,1,1-trichloroethane (TCA), a popular degreasing solvent. In 2002,more than 500 t of dioxane were produced or imported in theUnited States.1 The U.S. EPA has identified dioxane as a highpriority contaminant, and it is currently listed on the new CCL-3

(http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). There is also an EPA Method (522) for its measurement(www.epa.gov/microbes/Method%20522_final%20for%20OG-WDW%2009_22_08.pdf). Dioxane is problematic to extract andmeasure because it is miscible with water. It is also difficult toremove from water by air stripping or carbon adsorption.

Environmental investigation and remediation of dioxane andother solvent stabilizers was the focus of a new book by Mohr.199

This book included a discussion of the chemistry, uses, andoccurrence; environmental fate and transport; sampling andanalysis; toxicology; regulation and risk assessment; remediationtechnologies; case studies of releases, treatment and drinkingwater contamination; and forensic applications. Lee et al. in-vestigated occurrence patterns and removal efficiencies in waste-water treatment for dioxane and other micropollutants.200

Removal efficiency of dioxane in most treatment processes waslow (1.1�16%). However, dissolved air floatation/chemicalcoagulation reactor processes and activated carbon filtrationshowed relatively high removal efficiencies (>80%).

’SILOXANES

Siloxanes have become a new area of research. They includecyclic siloxanes, octamethylcyclotetrasiloxane (D4), decamethyl-cyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6),and tetradecamethylcycloheptasiloxane (D7) and linear silox-anes, which are used in a number of products, such as cosmetics,deodorants, soaps, hair conditioners, hair dyes, car waxes, babypacifiers, cookware, cleaners, furniture polishes, and water-re-pellent windshield coatings. There is concern about potentialtoxicity and transport into the environment. They have beenpreviously measured in wastewater, river water, and landfillbiogases.1,2 Price et al. used a Geographic Information System(GIS)-based water quality model to predict concentrations of D5

in two UK rivers.201 A wastewater flux of 2.4 mg/cap-day wasdetermined, which was consistent with effluent concentrations.

’NAPHTHENIC ACIDS

Naphthenic acids (NAs) are a complex mixture of alkyl-substituted acyclic and cyclo-aliphatic carboxylic acids that dissolvein water at neutral or alkaline pH and have surfactant-like proper-ties. They occur naturally in crude oil deposits across the world (upto 4% by weight) and have also been recently discovered in coal,which could be a source of contamination for groundwater.202 Inthis new study of contaminated groundwater, NAs were found tobe leaching from coal deposits intowells thatwere distant from anypetroleum sources. NAs are toxic to aquatic organisms, includingphytoplankton, daphnia, fish, and mammals, and are also endo-crine disrupting.Most research has focused onNAs in the oil sandsregion in Alberta, Canada, which is one of the highest producers ofcrude oil in the world. Caustic hot water is used in the extraction ofcrude oil from oil sands, which results in a residual tailing water(0.1 to 0.2 m3 of tailings per ton of oil sands processed) thatcontains high levels of NAs (80 to 120 mg/L) and is very toxic.The total volume of tailing ponds is projected to exceed 109 m3 bythe year 2020. Little is known about the environmental fate ofNAs. NAs are challenging to measure because they are present asa complex mixture of isomers and homologues. Understandingwhy NAs persist in tailing waters may help in the developmentof remediation technologies.

Headley et al. reviewed mass spectrometry techniques forcharacterizing NAs in environmental samples and included



discussions of EI, ESI, APCI, GC/MS, LC/MS, GC�GC, and highresolution techniques, includingTOF-MS,magnetic sector-MS, andFT-ion cyclotron resonance (ICR)-MS.203Data analysis techniques,such as Kendrick and van Krevelen plots, are also discussed.

Thomas et al. published an effects-directed identification studyof NAs in discharges from offshore oil production in the NorthSea.204 NAs were weak estrogen receptor agonists, accountingfor as much as 65% of the unknown estrogen receptor agonistpotency in the produced waters. Derivatization with GC/highresolution-TOF-MS was used to measure the NAs, and the YeastEstrogen (YES) assay and Yeast Androgen Receptor BindingAssay (YAS) were used to measure effects of the water fractionscollected. Han et al. estimated the in situ biodegradation of NAsin oil sands process waters using LC/high resolution-MS.205 Aprevious laboratory study had revealed several potential biomar-kers ofmicrobial degradation ofNAs, and this study examined forthese signatures in aged oil sands process water. Results sug-gested that the least cyclic fraction undergoes rapid biodegrada-tion in active settling basins, but other fractions appear to berecalcitrant, with half-lives of 12.8�13.6 years.

New methods continue to be developed, including one byBarrow et al., which used APPI and ESI-FT-ICR-MS.206 Use ofAPPI led to the observation of the greatest number of compo-nents in Athabasca oil sands process water. Oxygenated speciespredominated, including NAs. NAs with higher hydrogen defi-ciencies (potentially naphthenoaromatic compounds) weremore abundant using APPI vs ESI. The authors stressed theimportance of the use of different techniques to more fullycharacterize these complex mixtures because the overall toxicityis not expected to depend on the NAs alone. Kavanagh et al.created a simple and rapid method using synchronous fluores-cence spectroscopy, which could detect the presence of aromaticacids closely associated with NAs in <5 min without the need forpretreatment.207 It was suggested that this method could be usedas a rapid screening tool for the movement of oil sands processwater into the environment.

’MUSKS

Synthetic musk compounds are widely used as fragranceadditives in many consumer products, including perfumes, lotions,sunscreens, deodorants, and laundry detergents. They can havenitroaromatic structures, as in the case ofmusk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene) or musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone), or polycyclic structures, asin the case of 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthalene (AHTN; trade name, tonalide) 1,3,4,6,7,8-hexahy-dro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB;trade name, galaxolide, 4-acetyl-6-tert-butyl-1,1-dimethylindan(ADBI; trade name, celestolide), dihydropentamethylindanone(DPMI; trade name, cashmeran), or 5-acetyl-1,1,2,3,3,6-hexamethy-lindan (AHMI, trade name phantolide). Because they are widelypresent in environmental samples, including wildlife and hu-mans, there is growing concern. Musks are highly lipophilic, sothey tend to accumulate in sediments, sludges, and biota. Up to190 ng/g lipid has been reported in humans.2

New methods utilize SPME and stir bar sorptive extraction.For example, Silva and Nogueira created a new method using stirbar sorptive extraction with large volume injection-GC/MS formeasuring celestolide, galaxolide, tonalide, and musk ketone inenvironmental waters at 12�19 ng/L detection limits.208 Themethod, which used 30 mL sample volumes, was demonstrated

on tap water, river water, seawater, and urban wastewater.Another stir bar sorptive extraction method was created byRamirez et al. who used thermal desorption-GC/MS for detec-tion of 9 musks in wastewater, surface water, and RO-treatedwater.209 Detection limits of 0.02�0.3 ng/L could be achieved.Galaxolide was the most abundantmusk found in wastewater (upto 2069 and 1432 ng/L in influents and effluents, respectively).Cashmeran, phantolide, and tonalide were also found, up to 94,26, and 88 ng/L, respectively. Although nitromusks are prohib-ited for use in cosmetics in Europe, musk xylene andmusk ketonewere still detected in wastewater effluents and river samples.Gomez created a new GC/MS method using large-volumeinjection with backflushing to measure musks and several othercontaminants in wastewaters and surface waters.210 Methoddetection limits ranged from 1 to 36 ng/L. In addition, theauthors report a new synthetic fragrance metabolite, 4-aminomusk xylene, which was identified by full scan electron ionization(EI)-MS. This compound was not present in the NIST library.

Sumner et al. investigated inputs and distributions of syntheticmusk fragrances in estuarine and coastal environments.211 Highconcentrations of galaxolide and tonalide were present in waste-water treatment effluents, up to 2098 and 159 ng/L, respectively,which discharged into the Tamar and Plym Estuaries (UK).Lower concentrations of celestolide, phantolide, musk xylene,and musk ketone were found (4�30 ng/L). Levels were rapidlydiluted in the coastal outfall waters. Reiner and Kannanmeasuredpolycyclic musks in water, sediment, and fish from the UpperHudson River in New York.212 Galaxolide and tonalide weredetected in water, up to 26 and 23 ng/L, respectively, andbioaccumulation was observed in several fish species. Claraet al. measured the occurrence of several musks in wastewaterand surface waters and investigated their fate during wastewatertreatment and anaerobic sludge digestion.213 Major sources ofpolycyclic musks were households, whereas industrial inputswere minor. For galaxolide and cashmeran, 100% of the load insurface waters was derived from treated wastewater discharges.Overall removal efficiencies ranged from 50% to >95%, withsludge being the main removal pathway.

Finally,Wombacher andHornbuckle examined the occurrenceof 8 synthetic musk fragrances in source water and their removalin different stages of conventional drinking water treatment thatused lime softening.214 The compounds were measured in thewater, waste sludge, and air throughout the plant. Galaxolide andtonalide were detected in 100% of the samples. Total removalaveraged between 67 and 89% and was dominated by adsorptionto water softener sludge. Volatilization, chlorine disinfection, anddisposal of backwash water played a minor role in their removal.Following drinking water treatment, galaxolide and tonalide werestill found, at low levels in finished waters, with average concen-trations of 2.2 and 0.51 ng/L, respectively.

’PESTICIDE TRANSFORMATION PRODUCTS

Herbicides and pesticides continue to be the focus of muchenvironmental research. Recent studies have focused more ontheir transformation products because their hydrolysis, oxida-tion, biodegradation, or photolysis transformation products canbe present at greater levels in the environment than the parentpesticide and can be as toxic or more toxic. Several pesticidedegradation products are on the U.S. EPA’s new CCL-3: alachlorethanesulfonic acid (ESA), alachlor oxanilic acid (OA), aceto-chlor ESA, acetochlor OA, metolachlor ESA, metolachlor OA,



3-hydroxycarbofuran, and terbufos sulfone (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm), as well as onthe UCMR-2 (alachlor ESA and OA, acetochlor ESA and OA,and metolachlor ESA and OA).

LC/MS and LC/MS/MS are now common place for measur-ing pesticide degradates, which are generally more polar than theparent pesticides, making LC/MS ideal for their detection. Inaddition, researchers are increasingly using UPLC to enablesimultaneous analysis of larger groups of pesticides, and TOF-MS and Q-TOF-MS are being used to identify new pesticidedegradates. Vidal et al. published an extensive review on extrac-tion and detection methods for pesticide transformation pro-ducts in environmental, biological, and food samples andincluded a discussion of problems that can be encountered withtheir extraction.215 The analysis of target analytes as well as theidentification of unknown compounds with high resolution-MSare also discussed, and a comprehensive listing of >100 transfor-mation products of 49 different pesticides is provided.

Helbling et al. published a new high-throughput procedure forthe elucidation of transformation products (TP) for a broad anddiverse group of pesticides.75 Samples coming from batchreactors seeded with activated sludge were separated by LCand analyzed by linear ion trap-Orbitrap-MS. TPs were tenta-tively identified using a postacquisition data processing method,which was based on target and nontarget screening of full-scanMS data, and structures were proposed by interpretation of MSandMS/MS fragments. Using this procedure, newmicrobial TPswere reported for the pesticides. Results showed that thecomplementary use of target and nontarget screening allowedfor more comprehensive identification of TPs. UPLC-MS/MSwas used by Benvenuto et al. for a newmethod to simultaneouslydetermine triazine and their TPs in surface water and waste-waters.216 Quantification and confirmation could be performedat ng/L levels. UPLC/MS/MS was also used by Kowal et al. tomeasure the polar pesticide transformation product, N,N-di-methylsulfamide, in environmental waters.217 The only samplepreparation step was the addition of an internal standard;10 ng/L detection limits were achieved. Using this method,>600 samples of drinking water, surface, water, and groundwaterswere measured in the Rhine and Ruhr region of the North RhineRiver (Germany); approximately 65% of the samples containedmeasurable levels, up to 63 μg/L.

While most analytical methods developed utilize sophisticatedMS methods, two simpler ones were created recently formeasuring pesticides and their metabolites. For example, San-chez-Bayo published a new LC/electrochemical (EC) detectionmethod to measure amitrole, glyphosate, and its aminomethyl-phosphonic acid metabolite in environmental waters.218 Passivesamplers were used for concentration, and detection limits of0.03 to 0.3 μg/L were achieved. Dispersive liquid�liquid micro-extraction (DLLME) was used with LC-UV detection in anothermethod by Zhou et al. for measuring dichlorodiphenyltrichlor-oethane (DDT) and its metabolites in environmental waters.219

Detection limits ranged from 0.32 to 0.51 μg/L.Occurrence and fate studies continue to be conducted for

pesticides and their metabolites. In the pan-European surveymentioned earlier by Loos et al., pesticide transformationproducts were included and were among the most frequentlydetected and highest concentration of the many analytes mea-sured in European groundwaters.125 For example, desethylatra-zine and desethylterbutylazine were found in 55 and 49% of thesamples, up to 487 and 266 ng/L, respectively. Occurrence and

degradation of N-chloridazon was the focus of a study byButtiglieri et al., who measured >500 samples of groundwater,surface water, and wastewaters using SPE and GC/MS and LC/MS/MS.220 N-Chloridazon was measured up to 0.89 μg/L, andits degradation product, desphenyl-chloridazon (DPC), wasfound at much higher levels, up to 7.4 μg/L. Methylated-DPC,another degradation product, was also detected in surface waters.In separate aerobic degradation tests, N-chloridazon was com-pleted converted to DPC, which was stable up to 98 days. Chironet al. measured pesticides and their transformation products insouthern France.221 MCPA [(4-chloro-2-methylphenoxy)aceticacid] was found to transform by photolysis according to thefollowing sequence: MCPAf 4-chloro-2-methylphenol (CMP)f4-chloro-2-methyl-6-nitrophenol (CMNP). CMNP was moreenvironmentally persistent than the parent compound. Whilenitration of chlorophenols typically reduces their acute toxicity,there is concern over the genotoxic effects of nitro compounds.Irradiation experiments suggested that the photonitration ofCMP to CMNP involved nitrogen dioxide, generated from thephotolysis of nitrate and photooxidation of nitrite by OH radical.Fe(III) is also believed to play a role. Finally, Wang et al.identified hydrolysis products of dyfonate, an organophosphorusinsecticide, in simulated water treatment using UV and GC/MSdetection.222 Two hydrolysis products were identified: thiophe-nol and phenyl disulfide.

’PERCHLORATE

Perchlorate became an important environmental issue follow-ing its discovery in a number of water supplies in the westernUnited States. It has since been found in environmental watersacross the United States and in other parts of the world at μg/Llevels, as well as in fresh produce, foods, wines, and beveragesfrommany countries, including those in Europe and the Far East.Perchlorate has also been found in biological samples, and it canbe transported by pregnant mothers to their developing babyacross the placental barrier. Perchlorate is increasingly beingfound in environmental waters following fireworks displays. As aresult, it is now recognized as a worldwide environmental issue,rather than only being limited to the United States. Ammoniumperchlorate has been used in solid propellants used for rockets,missiles, and fireworks, as well as highway flares. There is alsopotential contamination from fertilizers (e.g., Chilean nitrate,where perchlorate co-occurs naturally), and new work hasrevealed other natural sources of perchlorate. In addition, per-chlorate can be a contaminant in sodium hypochlorite (liquidbleach) that is used in drinking water treatment. Perchlorate is ananion that is very water-soluble and environmentally stable. It canaccumulate in plants (including lettuce, wheat, and alfalfa), whichcan contribute to exposure in humans and animals. In addition,perchlorate is not removed by conventional water treatmentprocesses, so human exposure could also come through drinkingwater. Health concerns arise from perchlorate’s ability to displaceiodide in the thyroid gland, which can affect metabolism, growth,and development.

Due to these concerns and due to the proportion of the U.S.population exposed to it, the U.S. EPA has now decided toregulate perchlorate under the Safe Drinking Water Act (http://water.epa.gov/drink/contaminants/unregulated/perchlorate.cfm). The regulation is currently being developed, and there isnot a proposed MCL as of yet. (See earlier section onNew Regulations/Regulatory Methods for further details.)



Perchlorate was previously on the U.S. EPA’s CCL (CCL-1 andCCL-2 and is now on the CCL-3; http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). Perchlorate was also includedin the first UCMR (http://water.epa.gov/lawsregs/rulesregs/sdwa/ucmr/data.cfm). The U.S. EPA established a referencedose of 0.0007 mg/kg/day, which translates to a drinking waterequivalent level (DWEL) of 24.5 μg/L.1 Prior to this nationaldecision to regulate, California had already issued a state regula-tion of 6 μg/L (in 2007) (www.cdph.ca.gov/certlic/drinking-water/Pages/Perchlorate.aspx), and several states had issuedadvisory levels, ranging from 1 to 18 μg/L (www.epa.gov/fedfac/documents/perchlorate_links.htm#state_adv). Thereare several EPA Methods for measuring perchlorate in water,including EPAMethod 314.2 (2-dimensional IC with suppressedconductivity detection), EPA Method 331 (LC/ESI-MS/MS),and EPA Method 332 (IC/ESI-MS/MS) (www.epa.gov/safe-water/methods/analyticalmethods_ogwdw.html; www.epa.gov/nerlcwww/ordmeth.htm).

Parker reviewed the occurrence of perchlorate in the environ-ment and provided evidence of widespread natural occurrence.223

Furdui and Tomassini published a fascinating study of trends andsources of perchlorate in Arctic snow.224 Samples from theDevon Island ice cap in Canada were used to calculate the annualinput of atmospherically formed perchlorate. Ice cores weredated between 1996 and 2005, and IC/ESI-MS/MS was usedfor measurement. Concentrations varied between 1 and 18 ng/Land were correlated with total ozone levels from this area. Datasuggested that perchlorate from the Arctic snow was formed inthe atmosphere by two different mechanisms: (1) Stratosphericchlorine radicals reacted with ozone year-round, producingconcentrations of perchlorate correlated with the total ozonelevel; (2) During the summer months, perchlorate was likelyformed in the troposphere. Interestingly, a deep ice core samplerevealed that perchlorate was present in precipitation at similarconcentrations more than 2000 years ago. The total estimatedamount that reached the Arctic in 2005 was 41�86 t.

Jackson et al. evaluated the isotopic composition of naturalperchlorate indigenous to the southwestern U.S. to understandits origins.225 Stable isotope ratios were measured for perchlorate(δ18O,Δ17O, δ37Cl) and associated nitrate in groundwater fromthe southern High Plains of Texas and New Mexico and theMiddle Rio Grande Basin in New Mexico, unsaturated subsoil inthe southern High Plains, and nitrate-rich deposits near DeathValley, California. Results showed that natural perchlorate in thesouthwestern U.S. has a wide range of isotopic compositions thatare distinct from those reported previously from the AtacamaDesert of Chile, as well as for synthetic perchlorate. Results fromDeath Valley samples indicated partial atmospheric formation viareaction with ozone. In contract, perchlorate isotope ratios fromwestern Texas and NewMexico indicated that they were affectedby postdepositional oxygen isotope exchange. This study pro-vides important new information on the possibility of divergentperchlorate formation mechanisms and isotopic exchange inbiologically active environments.

Rao investigated perchlorate formation by ozone oxidation ofaqueous chlorine/oxy-chlorine species (Cl�, OCl�, ClO2

�,ClO3

�, and ClO2).226 Higher reaction rates were observed for

higher oxidation states of chlorine, except for ClO3�, which did

not react with ozone. The slow rate of perchlorate productionfrom Cl� suggested minimal potential for perchlorate formationin drinking water or wastewater systems that use ozone fortreatment. A potential formation pathway for perchlorate from

Cl� was proposed, which involved ClO2 and higher oxy-chlorineradicals and intermediates (e.g., Cl2O6) in its formation.

Recent studies have addressed perchlorate occurrence in drinkingwater. For example, Brandhuber et al. compiled data from thefirst UCMR, as well as from state surveys carried out in Arizona,California, Massachusetts, and Texas.227 Perchlorate was detectedin 26 states, including ∼5% of the large public drinking watersystems (serving >10 000 people each). Due to perchloratecontamination, many potable water systems have been takenoff-line (estimated at 50 mgd). When detected, perchlorate wasgenerally present at <12 μg/L levels. In another study, Blountet al. investigated perchlorate, nitrate, and iodide intake throughdirect and indirect consumption of tap water.228 Median per-chlorate levels measured in tap water were 1.16 μg/L, which werebelow the U.S. EPA’s drinking water equivalent level of 24.5 μg/L.Significant correlations were found between perchlorate andnitrate. Using individual tap water consumption data and bodyweight, the median perchlorate dose attributable to tap water was9.11 ng/kg-day.

New methods for perchlorate include a creative one byGertsch et al., who developed amicrochip electrophoresis systemto measure perchlorate in drinking water at ppb levels.229 Thissystem was inexpensive and rapid, offering portability, highselectivity, minimal sample pretreatment, and reduced analysistime relative to IC methods. In tap water, detection limits of 5.6μg/L were reported. Finally, Sturchio et al. explored the use of36Cl measurements for improving the discrimination of perchlo-rate sources.230 Stable chlorine and oxygen isotope ratios hadbeen used previously to distinguish sources of perchlorate, butthe additional use of 36Cl data from accelerator mass spectro-metry measurements was able to provide a clear distinctionamong the 3 principal perchlorate source types in the environ-ment: synthetic perchlorate, natural perchlorate from soils andgroundwater of the Atacama Desert, and natural perchloratefrom the southwestern U.S.

’ALGAL TOXINS

Algal toxins (mostly cyanobacterial toxins produced fromblue-green algae) continue to be of increasing interest in theUnited States and in other countries around the world. Increaseddischarges of nutrients (from agricultural runoff and from waste-water discharges) have led to increased algal blooms and anaccompanying increased incidence of shellfish poisoning, largefish kills, and deaths of livestock and wildlife, as well as illness anddeath in humans. Toxins produced by these algae have beenimplicated in the adverse effects. There was even a recent reportof the death of rhinoceros and other large animals in a nationalpark in South Africa, where microcystin-LR was responsible.231

An unusually high hippopotamus density had led to high urineand fecal loadings, which caused an increased growth of Micro-cystis aeruginosa and subsequent release of extraordinarily highlevels of microcystins.

The most commonly occurring algal toxins are microcystins,nodularins, anatoxins, cylindrospermopsin, and saxitoxins. “Redtide” toxins are also often found in coastal waters. Micro-cystins and nodularins are hepatotoxic high molecular weight,cyclic peptide structures. Anatoxins, cylindrospermopsin, andsaxitoxins are heterocyclic alkaloids; anatoxins and saxitoxins areneurotoxic, and cylindrospermopsin is hepatotoxic. “Red tide”toxins include brevetoxins, which have heterocyclic polyetherstructures and are neurotoxic. Microcystins (of which, more than



70 different variants have been isolated and characterized) are themost frequently reported of the algal toxins.

The most common microcystins are cyclic heptapeptides thatcontain the amino acids leucine and arginine in their structures.Nearly every part of the world that uses surface water as a drinkingwater source has encountered problems with cyanobacteria andtheir toxins. Algal toxins were on the U.S. EPA’s previous CCLs(CCL-1 and CCL-2) in a general way, “cyanobacteria (blue-green algae, other freshwater algae, and their toxins”, and now,the CCL-3 has specifically named three cyanobacterial toxins:anatoxin-a, microcystin-LR, and cylindrospermopsin for the newlist (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm). Several countries, including Australia, Brazil, Canada,France, and New Zealand, have guideline values for microcystins,anatoxin-a, and cylindrospermopsin (ranging from 1.0 to1.5 μg/L). Many of these toxins have relatively high molecularweights and are highly polar. New methods for algal toxinsinclude those using UPLC/MS, IR-MALDI-TOF-MS, and fluor-escent immunochromatography, as well as new sensors.

In 2010, a special issue of the journal Toxicon, on “HarmfulAlgal Blooms and Natural Toxins in Fresh and Marine Waters”,included 14 papers on the exposure, occurrence, detection,toxicity, control, management, and policy.232 This issue is a must-read for the latest state-of-the science for algae and their toxins.

New methods include a particularly clever one from Moraiset al., who created a new microsensor array on the polycarbonateside of ordinary compact discs (CDs) to measure microcystins inwater.233 The method was based on the principle of indirectcompetitive microimmunoassay, where free microcystin-LRcompetes with immobilized conjugate for a specific monoclonalantibody. Each disk surface was designed with 48 arrays; thehydrophobic nature of the polycarbonate side of the disk, alongwith the array distance and low sample volume used, preventedcross-contamination of samples. The article includes nice photosshowing the arrays on the CDs. Immunoreactions were detectedwith a DVD drive, which displayed the readouts in minutes.Detection limits of 1.04 μg/L could be achieved over a linearrange of 0.12 to 2.0 μg/L, which encompasses the WHO upperlimit in drinking water and is comparable to other screeningmethods. This method was simple, sensitive, and rapid and couldbe used in a high-throughput capacity for field use. Precoateddiscs were stable for at least 7 weeks without losing theiranalytical performance. The assay also showed high congenerreactivity to microcystin-LY, -LA, -LF, -LW, -YR, and nodularin.The applicability of this method was tested on 42 samples of riverwater, where the effect of the water matrix was found to benegligible.

Another clever method involved the use of carbon nanohornsin electrochemical immunosensors for rapid detection of micro-cystin-LR in water.234 The single-walled carbon nanohorns(SWNHs) were functionalized by covalently binding microcystin-LR to the carboxylic groups on the cone-shaped tips of the SWNHsin the presence of linkage reagents. They were characterized usingRaman spectroscopy, X-ray photoelectron spectroscopy, scanningelectron microscopy, and transmission electron microscopy.SWNHs were determined to be more sensitive than single-walled carbon nanotubes, and a detection limit of 0.03 μg/Lcould be achieved, with a linear response of 0.05 to 20 μg/L.Good agreement was shown with reference values.

UPLC/MS/MS was used in a method by Oehrie et al. toimprove chromatographic resolution and increase the speed ofanalysis for cyanotoxins.235 With UPLC, the cyanotoxins,

including cylindrospermopsin, anatoxin-a, nodularin, and micro-cystin-LR, -RR, -YR, -LA, -LY, -LW, and -LF, could be resolvedand analyzed in <8 min. Without sample enrichment, analytescould be detected at 0.5 ppb levels. Another method developedby Meisen et al. coupled thin layer chromatography (TLC) andUV spectroscopy with IR-MALDI-TOF-MS to measure micro-cystin-LR and nodularin.236 Detection limits were 5 ng for UVdetection and 3 ng for MS. Mekebri et al. developed a LC/ESI-MS/MS method to measure 6 microcystins in water, bivalves,and fish, providing improved detection limits from other meth-ods in the literature.237 Detection limits between 0.2 and 1 pg on-column (0.01�0.03 μg/L in water) were possible. Further, thismethod allowed the detection of microcystin metabolites,desmethyl-LR and desmethyl-RR, which were subsequently identi-fied and measured in real lake samples, along with the parentmicrocystins. Microcystin-RR, -LR, and -YR were found at averagesof 68.2, 76.5, and 1.68 μg/L in lake water samples impacted by anatural algal bloom of Microcystis aeruginosa. Desmethyl-RR anddesmethyl-LR were found at averages of 70.2 and 66.5 μg/L,respectively. Finally, fluorescent immunochromatography was usedin a new method by Khreich et al. for measuring microcystins andnodularins.238 Monoclonal antibodies labeled with fluorescentliposomes (called immunoliposomes) were developed as tracersto allow the detection of a large number of microcystins andnodularin variants in water samples. The fluorescent signalgenerated by these immunoliposomes can be measured andquantified using a small transportable, easy-to-use fluorometer.This method proved to be 10� more sensitive than a previousimmunochromatographic test using colloidal gold for labeling.Detection limits of 0.06 μg/L for microcystin-LR were achieved.

Several good fate studies have been published recently. Forexample,Wormer et al. investigated the natural photodegradation ofmicrocystins (-LR, -RR, and -YR) and cylindrospermopsin.239

LC with photodiode array detection was used to measure themicrocystins; UPLC/MS/MS was used to measure cylindros-permopsin. Photodegradation of cylindrospermopsin was highlydependent on UV-A and was very low under natural conditions.Microcystin photodegradation was higher at all 3 radiation bandstested (photosynthetic active radiation [PAR], UV-A, and UV-B),with UV-A and PAR being more pronounced. Results showedthat photodegradation can play an important role in the fate ofmicrocystins in some situations, including shallow waters or thinmixed layers in deep, stratified systems.

Studies continue to investigate the oxidation of algal toxins. Forexample, asmentioned earlier in theDBPs of Pollutants Section, 8new chlorination byproducts of microcystin-LR and cylindros-permopsin were identified: chloro-microcystin, chloro-dihy-droxy-microcystin, dichloro-dihydroxy-microcystin, trichloro-hydroxy-microcystin, and several dihydroxy-microcystins.171 Ina follow-up review article, Merel et al. discussed the chlorinationof cylindrospermopsin, saxitoxins, and nodularin, as well asmicrocystins.240 All algal toxins were efficiently transformed bychlorine and showed a resulting loss in acute toxicity. DBPswere identified for microcystins and cylindrospermopsin. Incontrast, anatoxin-a exhibited slow reaction kinetics, suggest-ing that it is resistant to chlorination.

’MICROORGANISMS

Outbreaks of waterborne illness in the United States and otherparts of the world have necessitated improved analytical methodsfor detecting and identifying microorganisms in water and other



environmental samples. Several microorganisms are included onthe new CCL-3 (http://water.epa.gov/scitech/drinkingwater/dws/ccl/ccl3.cfm) (Table 4). The U.S. EPA’s National Expo-sure Research Laboratory in Cincinnati has developed severalmethods for measuring microorganisms in water (www.epa.gov/nerlcwww). These includemethods forCryptosporidium,Giardia,E. coli, Aeromonas, coliphages, viruses, total coliforms, andenterococci. E. coli O157:H7 and H1N1 (swine flu) havecaptured a lot of attention recently because they have caused anumber of outbreaks and deaths around the world. Traditionalbiological methods are often used for detection of microorgan-isms, including cell culture, immunological methods, polymerasechain reaction (PCR), and microscopic identification, but ESIand MALDI-MS methods are also often used.

In a new review article, Vikesland and Wigginton discussed apromising but currently underdeveloped area for the future ofdrinking water pathogen monitoring: nanomaterial-enabledbiosensors.241 The authors summarize the state-of-the-science for nanoenabled biosensors but highlight the fact thatonly a few studies have focused on detection of whole cells andwaterborne pathogens, suggesting this as a significant oppor-tunity for environmental monitoring. While a wide variety ofnanomaterial-enabled bioassays have been developed forpathogens, their suitability under environmental conditionshas not been established. Problems, such as nonspecificbinding, particle size variation, nanoparticle aggregation, andnanoparticle stability, must be addressed to make thesetechniques useful for environmental monitoring. In addition,the differentiation of viable from nonviable cells and thedetection of viable but noncultural organisms is not yetpossible with these techniques.

In another review, Girones et al. discuss the pros and cons ofmolecular techniques for detection of pathogens in water.242

They discuss the fact that the range of methods has increased,which has facilitated the identification, genotyping, enumera-tion, viability assessment, and source-tracking of human andanimal contamination. Also, recent improvements have allowedthe simultaneous detection of multiple targets in a single assay.However, the authors discuss the need for yet improvedmethods that can be applied to diverse matrixes, includingdisinfected waters, which may affect the viability of pathogens,whose numbers can be overestimated by molecular techniques.Jofre and Blanch published a review outlining the feasibility ofmethods based on nucleic acid amplification techniques foranalysis of microorganisms.243 Positive aspects of nucleic acidmethods include the potential for identifying isolates fromconventional culture methods, providing data on culturableand nonculturable microorganisms, information on the pre-sence of pathogens in waters, determining the causes of water-borne outbreaks, and in some cases, detecting emergingpathogens. Challenges discussed include the varied compositionof water samples, low numbers of target microorganisms, variedwater quality required for different uses, and the physiologicalstate of the microorganisms, as well as the need for standardizedmolecular techniques.

New microorganism methods include one by Wildeboer et al.that uses a hand-held fluorescence detector for the rapid detec-tion of E. coli in water.244 This method is based on the use of4-methyl-umbelliferone-β-D-glucuronide as a substrate. Resultsobtained with the hand-held device compared favorably to thoseobtained with an established fluorescent substrate assay and byquantifying microbial growth on a chromogenic medium. This

method was used to analyze samples obtained from the RiverThames. The miniaturized fluorescence detector allowed re-duced incubation times, making the device portable and rapid.E. coli levels as low as 7 cfu/mL could be detected in a riversample. It was pointed out that this technique can be used inconjunction with different fluorescent substrates to target otherorganisms.

A real-time PCR assay was developed by Yanez et al. tomeasure Helicobacter pylori in water.245 This method is based onthe amplification of a fragment of a gene specific to H. pylori andthe use of an external standard for quantification. Linearity andspecificity of the method were excellent, and quantification limitswere 607 genomic copies. This method was demonstrated using69 water samples, including drinking water, surface water, andwastewater. Three wastewater samples were found to be positivefor H. pylori; all other samples were negative.

Gold nanoparticle labeling was used with ICP-MS in a newmethod by Li et al. to measure E. coli O157:H7 in water.246

This method took advantage of the signal amplificationproperty of gold nanoparticles, monoclonal antibody recogni-tion, and the high sensitivity of ICP-MS, which enabled thedetection of as few as 500 E. coli O157:H7 cells in a 1 mLsample. Specificity was excellent, as nonpathogenic forms ofE. coli did not bind or adsorb to the antibody-conjugated goldnanoparticles, and tests with these showed only backgroundsignals equivalent to the blanks. The specificity of this assay isdue to the specific antibodies used for E. coli O157:H7. The assaywas also very rapid, requiring only 40 min. Because of the abilityof ICP-MS to detect a wide range of elements, the applicability ofthis technique could be extended to other nanoparticles (includingsilver and rare earth nanoparticles), and potentially be used in ahigh throughput capacity to enable multiple bacterial cells to bemeasured simultaneously, through the use of different antibodiesfor different cells.

Quantification of viable but nonculturable (VBNC) E. coliO157:H7was the focus of a newmethod by Liu et al.247 This one-step quantification method combined reverse transcription andreal-time quantitative PCR and was capable of quantifying as fewas 7 E. coli O157:H7 cells in pure culture, 9 culturable cells in tapwater and river water, and 23 VBNC cells in river water, which arethe best quantification limits to-date for environmental waters.Measurement of a selective marker in VBNC E. coli O157:H7that was not present in dead cells or the negative controls servesas the basis for this method, which showed a linear dynamic range>6 orders of magnitude and >90% amplification efficiency fortap and river water samples. This technique is important becauseE. coli O157:H7 easily becomes VBNC under environmentalstresses (including disinfection) and escapes detection by currentmethods. An earlier paper by Liu previously demonstratedhow E. coli O157:H7 could enter a VBNC state followingchloramination in tap water but could resuscitate themselvesback into an infective form.248 As a result, it is important to beable to detect these VBNC forms that can remain a potentialhealth risk.

’CONTAMINANTS ON THE HORIZON: IONIC LIQUIDS

Ionic liquids are organic salts with a low melting point(<100 �C) that are being promoted as “green chemistry”replacements to traditional solvents used in industry.249,250 Theyare currently one of the hottest areas in chemistry, with manypapers and reviews highlighting ionic liquids as a state-of-the-art,



innovative approach to sustainable chemistry, due to their lowvapor pressures and flammability. However, there is limitedtoxicity and environmental data for these new “green solvents”,and there is the potential that they may pose a threat toaquatic and terrestrial ecosystems. While not volatile, most ionicliquids are highly water-soluble and chemically and thermallystable, creating the potential for entry and persistence in theenvironment. Ionic liquids have unique properties includingtunable viscosity, miscibility, and electrolytic conductivity, whichmake them useful for many applications, including organicsynthesis and catalysis, production of fuel cells, batteries, coat-ings, oils, and nanoparticles, as well as other chemical engineeringand biotechnology applications. Their chemical structures typicallyinvolve a cationic or anionic polar headgroup with accompanyingalkyl side chains. Cationic head groups include imidazolium,pyridinium, pyrrolidinium, morpholinium, piperidium, quinoli-nium, quaternary ammonium, and quaternary phosphoniummoieties; anionic head groups include tetrafluoroborate(BF4

�), hexafluorophosphate (PF6�), bis(trifluoromethylsulfonyl)-

imide [(CF3SO2)2N�], dicyanamide [(CN)2N

�], chloride, andbromide.249 Pham et al. wrote an excellent, thought-provokingreview on the environmental fate and toxicity of ionic liquids,outlining these concerns and summarizing the toxicitydata, antibacterial activity, chemical and biodegradation, andsorption in environmental systems.249 Current data show thationic liquids are toxic in nature and that their toxicities varyconsiderably across organisms and trophic levels. Introduction ofpolar groups to the alkyl chains has been shown to decrease theirtoxicity and increase biodegradation, suggesting the possibility oftailoring the chemical structures to produce more environmen-tally friendly compounds. A recent review by Sun and Armstrongsummarizes recent analytical chemistry papers devoted to ionicliquids, including those covering extractions, GC, LC, CE, MS,electrochemistry, sensors, and spectroscopy.250

’BIOGRAPHIES

Susan D. Richardson is a research chemist at the U.S.Environmental Protection Agency’s National Exposure ResearchLaboratory in Athens, GA. She received her B.S. degree inChemistry and Mathematics from Georgia College in 1984 andher Ph.D. degree in Chemistry from Emory University in 1989.Her research has focused on the identification, characterization,and quantification of new toxicologically important disinfectionbyproducts (DBPs), with special emphasis on alternative disin-fectants and polar byproducts. She is particularly interested inpromoting new health effects research so that the risks of DBPscan be determined and minimized.

Thomas A. Ternes graduated with an undergraduate degree inChemistry from the University of Mainz (Germany) in 1989. In1993, he completed his Ph.D. at the University of Mainz inAnalytical Chemistry. In January 2001, he completed hishabilitation and became an official lecturer at the Universityof Mainz. Since 1995, his research has focused on the analysisand fate of organic pollutants, such as pharmaceuticals andpersonal care products (PPCPs), in various kinds of environ-mental matrixes. Dr. Ternes was the coordinator of the Pharma-cluster project POSEIDON (http//www.eu-poseidon.com)dealing with the removal of PPCPs in wastewater and drinkingwater treatment, soil aquifer treatment, and environmentalrisk assessment. Since May 2003, he has been at the Federal

Institute of Hydrology (BfG) in Koblenz, Germany, where he isthe head of the water chemistry department and is responsiblefor the coordination and management of research projects inthe field of organic pollutants and their removal during waste-water treatment and drinking water treatment.

’ACKNOWLEDGMENT

S.R. would like to thank Jody Shoemaker and Jean Munch ofthe U.S. EPA for information on new EPA methods (they havedeveloped many for EPA), Shay Fout of the U.S. EPA forinformation on the new EPAMethod 1615, Stig Regli of the U.S.EPA’s Office of Water for helpful information on the newproposed perchlorate regulation, Jon Martin of the Universityof Alberta, Mary Kaiser of DuPont, and Tom Jenkins of the U.S.EPA for helpful information on PFCs, John Sumpter of BrunelUniversity for the incredible presentation he gave recently thatalerted me to the issue with the vultures and diclofenac, RobertLoos of the European Commission's Joint Research CentreInstitute for Environment and Sustainability for helpful informa-tion on algal toxins, Jim Evans of SRA International for designingour nice TOC art, and David Humphries of the Alberta ResearchCouncil for daily inspiration. This paper has been reviewed inaccordance with the U.S. EPA’s peer and administrative reviewpolicies and approved for publication. Mention of trade names orcommercial products does not constitute endorsement or re-commendation for use by the U.S. EPA.

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