Japan Environment and Children’s Study
JECS
Worldwide trends in tracing PFAS in
the environment
OECD Webinar Series | 11 June 2020
Shoji F. Nakayama, MD, PhD
Deputy Director
Japan Environment and Children’s Study Programme Office
National Institute for Environmental Studies

Japan Environment and Children’s Study
JECS
Coauthors/Acknowledgement
National Institute for Environmental Studies
• Yukiko Nishihama
• Miyuki Iwai-Shimada
• Mai Takagi
• Yayoi Kobayashi
• Tomohiko Isobe
IDEA Consultants, Inc.
• Mitsuha Yoshikane
• Yu Onoda
US Environmental Protection Agency
• Andrew Lindstrom
• Mark Strynar
• Marc Mills
The findings and conclusions of this article
are the sole responsibility of the authors
and do not represent the official views of
the Japanese government or the National
Institute for Environmental Studies (NIES).
Any mention of trade names or commercial
products does not constitute NIES
endorsement or recommendation for use.
2For details, please refer to the publication: https://doi.org/10.1016/j.trac.2019.02.011

Japan Environment and Children’s Study
JECS
Forever chemicals facts
‣ Poly and perfluoroalkyl substances, shortly PFAS as plural noun, consist of a vast cosmos of chemicals
with one or more perfluoroalkyl (–CnF2n–) moieties.
‣ More than 4,000 PFAS are currently on the global market.
‣ PFAS are widely used and distributed everywhere.
‣ Some PFAS are persistent in humans and the environment. Recent substitutes are aimed to break down
faster and be eliminated quicker.
‣ Some PFAS have been found toxic both to humans and ecosystem.
‣ Perfluoroalkyl (–CnF2n–) moieties are so beneficial that they would not retire from market.
‣ Research, especially in environmental health, is not sufficient to fully unveil PFAS’ impacts on our health.
‣ PFAS are chemicals that demand ‘FOREVER’ research!
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PFAS to name a few
‣ Perfluoroalkyl acids
- Carboxylic acids (PFCAs)
- Sulphonic acids (PFSAs)
- Phosphoric acids (PFPAs)
- Phosphinic acids (PFPiAs)
‣ Iodides (PFAIs)
‣ Fluorotelomer (polyfluoro) acids
- Carboxylic acids (FTCAs)
- Sulphonic acids (FTSAs)
- Unsaturated carboxylic acids (FTUCAs)
‣ Perfluoroalkanes
- Sulphonamides (FASAs)
- Sulphonamido acetic acids (FASAAs)
- Sulphonamido ethanols (FASEs)
‣ Perfluoroethers
- Sulphonic acids (PFESAs)
- Carboxylic acids (PFECAs), e.g HFPO-DA
‣ Fluorotelomer olefins (FTOs)
‣ Fluorotelomer alcohols (FTOHs)
‣ Fluorotelomer iodides (FTIs)
‣ Phosphate diester/triester
- Ammonium bis(N-ethyl-2-
perfluorooctylsulfonaminoethyl)phosphate
(diSAmPAP)
- Ammonium tris(N-ethyl-2-
perfluorooctylsulfonaminoethyl)phosphate
(triSAmPAP)
‣ Cyclic perfluoroalkyl sulphonic acids
‣ Fluorotelomer acrylates (FTACs)
‣ Fluorotelomer methacrylates (FTMACs)
‣ Polyfluoroalkyl phosphate esters
- Monoesters (monoPAPs)
- Diesters (diPAPs)
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Methods overview
‣ Sampling
- Conventional
• Manual sampling/large volume sampling
- Evolving
• Small volume–online analysis
‣ Extraction/clean-up
- Conventional
• Liquid–liquid/ion-pair extraction (LLE/IPE)
• Solid phase extraction (SPE)
• Solid phase micro-extraction (SPME)
• Accelerated solvent extraction (ASE)
- Evolving
• Vortex-assisted/dispersive liquid–liquid micro-
extraction (VALLME/DLLME)
• Multiple monolithic fibre solid-phase micro-
extraction (MMF-SPME)
• Supported liquid extraction (SLE), …
‣ Instrumental analysis
- Conventional
• GC-MS
• LC-MS/MS
- Evolving
• GC-MS/MS
• LC-HRMS
• GC x GC/LC x LC-HRMS
• Online-SPE LC-MS/MS
• Combustion ion chromatography (CIC)
• Particle-induced gamma-ray emission (PIGE)
spectroscopy
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Air samples
‣ Target PFAS
- Volatile and neutral PFAS, e.g. FTOHs, FASEs, FASAs
‣ Sample collection
- PUF/XAD/PUF
- Solvent-impregnated polyurethane foam (SIP)
- SPE cartridges, e.g. ISOLUTE ENV+, Oasis HLB, C18/WAX
- Air volume: 300–2,000 m3 (outdoor), 20–200 m3 (indoor), 0.2–8 m3 (indoor recently)
‣ Extraction/clean-up
- PUF/XAD/PUF: Soxhlet extraction with acetone/ether
- SIP: Soxhlet extraction
- SPE cartridges: methanol elution
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Air samples
‣ Instrumental analysis
- Neutral PFAS: EI/CI GC-MS
- Ionic PFAS: ESI LC-MS/MS
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Study Year Findings
Global Atmospheric
Passive Sampling
(GAPS)
2009–2015
• FTOHs (polar region): < 0.4–21 pg/m3
• FTOHs (urban sites): 40–238 pg/m3
• PFSA increased but not FTOHs, FASAs, FASEs, PFCAs
Arctic Monitoring and
Assessment Program
(AMAP)
2006–2014
• FTOHs: < 0.17–30 pg/m3
• FASAs: < 0.014–0.82 pg/m3
• FASEs: < 0.10–4.8 pg/m3
Indoor air, China 2015
• FTOHs (houses ≃ hotels): 246–62,100 pg/m3
• PFCAs/PFSAs (houses > hotels): 86.8–1,970 pg/m3
• FASAs/FASEs (houses < hotels): ND–2,460 pg/m3
Indoor air, Norway 2013-2014
• FTOHs: 170–446,000 pg/m3
• FASAs/FASEs: ND–78,300 pg/m3

Japan Environment and Children’s Study
JECS
Aqueous matrices
‣ Samples
- Drinking water, ground/surface/sea water, wastewater
‣ Target PFAS
- PFCAs, PFSAs, FOSAs, FOSEs, FTSAs, FTOHs, emerging PFAS
‣ Sample collection
- Grab samples in HDPE, PP or glass containers
- Volume: 0.1–5000 mL
‣ Extraction/clean-up
- SPE: Oasis HLB, ENVI-Carb, Oasis WAX, bamboo charcoal
- MMF-SPME
- SBSE/DLLME/VALLME, i.e. green chemistry
- Direct injection (DI)
- Online-SPE
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Aqueous matrices
‣ Instrumental analysis
- GC-MS or MSMS
- ESI or APCI/APPI (U)HPLC-MSMS or HRMS (Orbitrap, TOFMS)
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Study Year Findings
River/coastal water,
China
2010–2016
• PFOS: 0.13–881 ng/l
• PFOA: 1.28–24,700 ng/l
WWTP, Australia 2014
• PFCAs (C6–12): 0.3–20 ng/l
• PFSAs (C4, 6): 0.11–25 ng/l
Tap water, South Korea 2017 • PFCAs (C5–14)/PFSAs (C4–10): ND–189.6 ng/l
Ground water, China 2016
• PFCAs: ND–290 ng/l
• PFSAs: ND–143 ng/l
• 6:2 Cl-PFESA/6:2 FTSA: 0.17–8.54 ng/l
Surface water, CN, US,
UK, SE, GE, NL, KR
2016
• HFPO-DA: 0.95 ng/l (median)
• HFPO-TA: 0.21 ng/l (median)
• 6:2 Cl-PFESA: 0.31 ng/l (median)

Japan Environment and Children’s Study
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Abiotic solid metrics
‣ Samples
- Sediments, soil, sludge, dust
‣ Target PFAS
- PFCAs, PFSAs, FOSAs, FOSEs, FTCAs, FTSAs, FTOHs, PAPs, SAmPAP, ADONA,…
‣ Sample collection
- Stainless-steel grab sampler, bottom sampler, hand trowel, knife
- Volume: 0.5–5 g (soil, sediment, sludge, biosolids), ~100 mg (dust)
‣ Extraction/clean-up
- Soxhlet, PLE, SLE followed by ENVI-Carb, WAX, HLB, C18
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Japan Environment and Children’s Study
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Abiotic solid metrics
‣ Instrumental analysis
- GC-MS or MSMS
- ESI or APCI/APPI (U)HPLC-MSMS or HRMS (Orbitrap, TOFMS)
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Study Year Findings
Sediments, Canada 2005–2018
• PFOS: ND–623 ng/g
• PFOA: ND–16 ng/g
Sludge, China 2010–2011
• ∑PFSA: ND–220 ng/g
• ∑FTSA: ND–18.9 ng/g
• ∑Cl-PFESA: 0.31–241 ng/g
Soil, Sweden 2017
• PFCAs: ND–8.3 ng/g
• PFSAs: ND–1.7 ng/g
• FASA: ND–0.65 ng/g
House dust, Finland 2014/2015
• PFAS (LC): ND–1,360 ng/g
• PFAS (GC): ND–514 ng/g

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Wildlife and humans
‣ Samples
- Fish, frog, eel, marine organisms, etc.
- Human: blood, urine, nail, hair, etc.
‣ Target PFAS
- PFCAs, PFSAs, PFPiAs, PFPAs, FOSAs, FOSEs, FTSAs, FTOHs, FTUCAs, emerging PFAS
‣ Sample collection
- HDPE, PP containers
- Volume: 0.1–1 g (tissue), 25 µl–1 mL (serum), 1–50 ml (urine)
‣ Extraction/clean-up
- SLE, LLE, IPE
- Alkaline digestion, protein precipitation
- Focused ultrasound solid-liquid extraction (FUSLE), turbulent flow chromatography (TFC)
- Online SPE
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Wildlife and humans
‣ Instrumental analysis
- ESI (U)HPLC-MSMS
- Online SPE (U)HPLC-MSMS
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Study Year Findings
Frog, China 2016
• 6:2 Cl-PFESA: 0.13–119 ng/g ww
• HFPO-TA: 6.51–27.3 ng/g ww
Fish, birds, dolphins,
North America
2004–2011
• ∑PFCA: 65–3,171 ng/g ww
• ∑PFSA: 96–2,337 ng/g ww
• PFPA: ND
• ∑PFPiA: 0.33–5.0 ng/g ww
Serum, Norway 2014
• PFCA, PFSA: ND–2,140 ng/ml, ND–10,499 ng/ml
• FTSA: ND–171 ng/ml
• monoPAP, diPAP: ND–0.19 ng/ml, ND–0.94 ng/ml
• PFPA, PFPiA: ND, ND–0.09 ng/ml
• FASA, FASAA: ND–0.97 ng/ml, ND–0.72 ng/ml
• Cl-PFESA: ND–1.39 ng/ml

Japan Environment and Children’s Study
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Non-target/non-specific analysis
‣ Non-target analysis
- Many ‘as-yet-unknown’ PFAS have been identified by HRMS
- Dilution, SPE clean-up, SLE, SLE–ENVI-Carb are commonly used for pre-treatment
- GC x GC or LC x LC TOFMS have also been used
- In-source fragmentation or MSE TOFMS used for many ‘new’ PFAS identification
‣ Non-specific analysis
- Combustion ion chromatography (CIC) for extractable/absorbable organic fluorine
- Total oxidisable precursor (TOP) assay for precursors oxidisable to PFAAs
- Particle-induced gamma ray emission (PIGE) spectroscopy
- 19F- NMR
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Challenges and future direction
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Challenges Future direction
‣ Ever growing list of PFAS
- Limits of the current management scheme
- Lack of analytical standards including isotopic labelled
ones
- Lack of harmonised methods for global PFAS monitoring
‣ New/sound management scheme
- Submission of reference standards w/ registration
- Global harmonisation on monitoring framework
- Especially global human biomonitoring programme
‣ Little known about effect of most of the PFAS on
humans and ecosystem thus difficult to determine what
PFAS to be monitored
- Any toxic equivalency factor (TEF) development for
PFAS?
‣ Strategic utilisation of humans and ecosystem studies
- Population studies are required
- Harmonisation/co-ordination of epidemiological studies
- Computer based effect modelling
‣ Statistical models to deal with many kinds of PFAS
analysis data is lacking
- How to analyse mixture data?
- How to deal with left censored data? E.g. how to sum
PFAS concentrations with NDs?
‣ Systematic support for statistical model development
- Self-organising map (SOM) model
- Weighted quantile sum (WQS) model
- Bayesian kernel machine regression (BKMR)
- Non-parametric approach for left censored data
- Multiple imputation to impute NDs, e.g. mi-WQS